The Scientific World Journal: Neuroscience The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Effect of Opioid on Adult Hippocampal Neurogenesis Tue, 05 Apr 2016 06:08:50 +0000 During the past decade, the study of the mechanisms and functional implications of adult neurogenesis has significantly progressed. Many studies focus on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells, including addictive drugs such as opioid. Here, we review the most recent works on opiate drugs’ effect on different developmental stages of adult hippocampal neurogenesis, as well as the possible underlying mechanisms. We conclude that opiate drugs in general cause a loss of newly born neural progenitors in the subgranular zone of dentate gyrus, by either modulating proliferation or interfering with differentiation and maturation. We also discuss the consequent impact of regulation of adult neurogenesis in animal’s opioid addiction behavior. We further look into the future directions in studying the convergence between the adult neurogenesis field and opioid addiction field, since the adult-born granular cells were shown to play a role in neuroplasticity and may help to reduce the vulnerability to drug craving and relapse. Yue Zhang, Horace H. Loh, and Ping-Yee Law Copyright © 2016 Yue Zhang et al. All rights reserved. Simultaneous Cranioplasty and Subdural-Peritoneal Shunting for Contralateral Symptomatic Subdural Hygroma following Decompressive Craniectomy Mon, 23 Mar 2015 12:48:59 +0000 Background. Contralateral subdural hygroma caused by decompressive craniectomy tends to combine with external cerebral herniation, causing neurological deficits. Material and Methods. Nine patients who underwent one-stage, simultaneous cranioplasty and contralateral subdural-peritoneal shunting were included in this study. Clinical outcome was assessed by Glasgow Outcome Scale as well as Glasgow Coma Scale, muscle power scoring system, and complications. Results. Postoperative computed tomography scans demonstrated completely resolved subdural hygroma and reversed midline shifts, indicating excellent outcome. Among these 9 patients, 4 patients (44%) had improved GOS following the proposed surgery. Four out of 4 patients with lethargy became alert and orientated following surgical intervention. Muscle strength improved significantly 5 months after surgery in 7 out of 7 patients with weakness. Two out of 9 patients presented with drowsiness due to hydrocephalus at an average time of 65 days after surgery. Double gradient shunting is useful to eliminate the respective hydrocephalus and contralateral subdural hygroma. Conclusion. The described surgical technique is effective in treating symptomatic contralateral subdural hygroma following decompressive craniectomy and is associated with an excellent structural and functional outcome. However, subdural-peritoneal shunting plus cranioplasty thoroughly resolves the subdural hygroma collection, which might deteriorate the cerebrospinal fluid circulation, leading to hydrocephalus. Muh-Shi Lin, Tzu-Hsuan Chen, Woon-Man Kung, and Shuo-Tsung Chen Copyright © 2015 Muh-Shi Lin et al. All rights reserved. The “Gender Factor” in Wearing-Off among Patients with Parkinson’s Disease: A Post Hoc Analysis of DEEP Study Tue, 20 Jan 2015 14:02:33 +0000 Background. The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson’s disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena. Methods. Patients on dopaminergic treatment for ≥1 year were included in this multicenter observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19-item wearing-off questionnaire (WOQ-19); WO was defined for scores ≥2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect to WO. Results. Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists’ judgment (61.9% versus 53.8%, ) and the WOQ-19 analysis (72.5% versus 64.0%, ). In patients with WO (WOQ-19), women experienced ≥1 motor symptom in 72.5% versus 64.0% in men and ≥1 nonmotor symptom in 44.5% versus 36.7%, in men. Conclusions. Our results suggest WO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender-effect. Delia Colombo, Giovanni Abbruzzese, Angelo Antonini, Paolo Barone, Gilberto Bellia, Flavia Franconi, Lucia Simoni, Mahmood Attar, Emanuela Zagni, Shalom Haggiag, and Fabrizio Stocchi Copyright © 2015 Delia Colombo et al. All rights reserved. Whole Body Vibration at Different Exposure Frequencies: Infrared Thermography and Physiological Effects Wed, 14 Jan 2015 07:56:39 +0000 The aim of this study was to investigate the effects of whole body vibration (WBV) on physiological parameters, cutaneous temperature, tactile sensitivity, and balance. Twenty-four healthy adults ( years) participated in four WBV sessions. They spent 15 minutes on a vibration platform in the vertical mode at four different frequencies (31, 35, 40, and 44 Hz) with 1 mm of amplitude. All variables were measured before and after WBV exposure. Pressure sensation in five anatomical regions and both feet was determined using Von Frey monofilaments. Postural sway was measured using a force plate. Cutaneous temperature was obtained with an infrared camera. WBV influences the discharge of the skin touch-pressure receptors, decreasing sensitivity at all measured frequencies and foot regions (). Regarding balance, no differences were found after 20 minutes of WBV at frequencies of 31 and 35 Hz. At 40 and 44 Hz, participants showed higher anterior-posterior center of pressure (COP) velocity and length. The cutaneous temperature of the lower limbs decreased during and 10 minutes after WBV. WBV decreases touch-pressure sensitivity at all measured frequencies 10 min after exposure. This may be related to the impaired balance at higher frequencies since these variables have a role in maintaining postural stability. Vasoconstriction might explain the decreased lower limb temperature. Anelise Sonza, Caroline C. Robinson, Matilde Achaval, and Milton A. Zaro Copyright © 2015 Anelise Sonza et al. All rights reserved. Plasticity of Mesenchymal Stem Cells from Mouse Bone Marrow in the Presence of Conditioned Medium of the Facial Nerve and Fibroblast Growth Factor-2 Mon, 29 Dec 2014 00:10:39 +0000 A number of evidences show the influence of the growth of injured nerve fibers in peripheral nervous system as well as potential implant stem cells (SCs). The SCs implementation in the clinical field is promising and the understanding of proliferation and differentiation is essential. This study aimed to evaluate the plasticity of mesenchymal SCs from bone marrow of mice in the presence of culture medium conditioned with facial nerve explants and fibroblast growth factor-2 (FGF-2). The growth and morphology were assessed for over 72 hours. Quantitative phenotypic analysis was taken from the immunocytochemistry for glial fibrillary acidic protein (GFAP), protein OX-42 (OX-42), protein associated with microtubule MAP-2 (MAP-2), protein β-tubulin III (β-tubulin III), neuronal nuclear protein (NeuN), and neurofilament 200 (NF-200). Cells cultured with conditioned medium alone or combined with FGF-2 showed morphological features apparently similar at certain times to neurons and glia and a significant proliferative activity in groups 2 and 4. Cells cultivated only with conditioned medium acquired a glial phenotype. Cells cultured with FGF-2 and conditioned medium expressed GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200. This study improves our understanding of the plasticity of mesenchymal cells and allows the search for better techniques with SCs. Eudes Euler de Souza Lucena, Fausto Pierdoná Guzen, José Rodolfo Lopes de Paiva Cavalcanti, Maria Jocileide de Medeiros Marinho, Wogelsanger Oliveira Pereira, Carlos Augusto Galvão Barboza, Miriam Stela Mariz de Oliveira Costa, Expedito Silva do Nascimento Júnior, and Jeferson Sousa Cavalcante Copyright © 2014 Eudes Euler de Souza Lucena et al. All rights reserved. Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury Sun, 21 Dec 2014 10:13:23 +0000 Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-κβ, disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury (SCI) includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it. Mehar Naseem and Suhel Parvez Copyright © 2014 Mehar Naseem and Suhel Parvez. All rights reserved. Effects of L-Theanine on Posttraumatic Stress Disorder Induced Changes in Rat Brain Gene Expression Sun, 03 Aug 2014 12:24:30 +0000 Posttraumatic stress disorder (PTSD) is characterized by the occurrence of a traumatic event that is beyond the normal range of human experience. The future of PTSD treatment may specifically target the molecular mechanisms of PTSD. In the US, approximately 20% of adults report taking herbal products to treat medical illnesses. L-theanine is the amino acid in green tea primarily responsible for relaxation effects. No studies have evaluated the potential therapeutic properties of herbal medications on gene expression in PTSD. We evaluated gene expression in PTSD-induced changes in the amygdala and hippocampus of Sprague-Dawley rats. The rats were assigned to PTSD-stressed and nonstressed groups that received either saline, midazolam, L-theanine, or L-theanine + midazolam. Amygdala and hippocampus tissue samples were analyzed for changes in gene expression. One-way ANOVA was used to detect significant difference between groups in the amygdala and hippocampus. Of 88 genes examined, 17 had a large effect size greater than 0.138. Of these, 3 genes in the hippocampus and 5 genes in the amygdala were considered significant () between the groups. RT-PCR analysis revealed significant changes between groups in several genes implicated in a variety of disorders ranging from PTSD, anxiety, mood disorders, and substance dependence. Tomás Eduardo Ceremuga, Stephanie Martinson, Jason Washington, Robert Revels, Jessica Wojcicki, Damali Crawford, Robert Edwards, Joshua Luke Kemper, William Luke Townsend, Geno M. Herron, George Allen Ceremuga, Gina Padron, and Michael Bentley Copyright © 2014 Tomás Eduardo Ceremuga et al. All rights reserved. Phytoestrogen α-Zearalanol Improves Memory Impairment and Hippocampal Neurogenesis in Ovariectomized Mice Mon, 21 Jul 2014 00:00:00 +0000 Estrogen is known to provide robust protection of memory in postmenopausal women, but the fact that estrogen may increase the incidence of uterine and breast tumors has undoubtedly limited the clinical use of estrogen. In the present study, the effect of α-zearalanol (α-ZAL), a plant-derived phytoestrogen with low side-effect on uterine and breast, on memory has been evaluated in ovariectomized (OVX) mice when using 17β-estradiol (17β-E2) as an estrogen positive control. Our findings demonstrated that OVX resulted in impaired spatial learning and memory and reduced numbers of newborn neurons in the dentate gyrus of the hippocampus, while 17β-E2 or α-ZAL treatment significantly improved memory performance and restored hippocampal neurogenesis. We also found the reduction of brain derived neurotrophic factor (BDNF) and TrkB expression in OVX mice, which were ameliorated by 17β-E2 or α-ZAL supplementation. These results indicated that α-ZAL may improve memory impairments induced by OVX and modulate the expression of BDNF-TrkB benefit to neurogenesis which may be involved in the memory protection from α-ZAL, in a manner similar to that of 17β-E2. The present findings suggested that α-ZAL may be a plausible substitute of 17β-E2 in improving memory in postmenopausal women. Yilong Dong, Aimei Jiang, Hongju Yang, Huicheng Chen, and Yanmei Wang Copyright © 2014 Yilong Dong et al. All rights reserved. miR-16-1 Promotes the Aberrant α-Synuclein Accumulation in Parkinson Disease via Targeting Heat Shock Protein 70 Mon, 23 Jun 2014 12:03:20 +0000 There is striking evidence that heat shock protein 70 (Hsp70) negatively regulates α-synuclein aggregation, which plays a significant role in the formation and progression of Parkinson disease (PD). However, how the Hsp70 in neurons fails to prevent or even reverse α-synuclein aggregation and toxicity in PD still remains to be determined. In the present study, we constructed an α-synuclein-overexpressed human neuroblastoma cell line, SH-SY5Y-Syn, in which the blockage of Hsp70 promoted α-synuclein aggregation. And we also found that miR-16-1 downregulated Hsp70 and promoted α-synuclein aggregation in the SH-SY5Y-Syn cells. This study revealed a novel regulatory mechanism of Hsp70 expression, which might contribute to the PD development. Zhelin Zhang and Yan Cheng Copyright © 2014 Zhelin Zhang and Yan Cheng. All rights reserved. Benefits of Repetitive Transcranial Magnetic Stimulation (rTMS) for Spastic Subjects: Clinical, Functional, and Biomechanical Parameters for Lower Limb and Walking in Five Hemiparetic Patients Tue, 29 Apr 2014 08:27:42 +0000 Introduction. Spasticity is a disabling symptom resulting from reorganization of spinal reflexes no longer inhibited by supraspinal control. Several studies have demonstrated interest in repetitive transcranial magnetic stimulation in spastic patients. We conducted a prospective, randomized, double-blind crossover study on five spastic hemiparetic patients to determine whether this type of stimulation of the premotor cortex can provide a clinical benefit. Material and Methods. Two stimulation frequencies (1 Hz and 10 Hz) were tested versus placebo. Patients were assessed clinically, by quantitative analysis of walking and measurement of neuromechanical parameters (H and T reflexes, musculoarticular stiffness of the ankle). Results. No change was observed after placebo and 10 Hz protocols. Clinical parameters were not significantly modified after 1 Hz stimulation, apart from a tendency towards improved recruitment of antagonist muscles on the Fügl-Meyer scale. Only cadence and recurvatum were significantly modified on quantitative analysis of walking. Neuromechanical parameters were modified with significant decreases in Hmax⁡ /Mmax⁡ and T/Mmax⁡ ratios and stiffness indices 9 days or 31 days after initiation of TMS. Conclusion. This preliminary study supports the efficacy of low-frequency TMS to reduce reflex excitability and stiffness of ankle plantar flexors, while clinical signs of spasticity were not significantly modified. Luc Terreaux, Raphael Gross, Fabien Leboeuf, Hubert Desal, Olivier Hamel, Jean Paul Nguyen, Chantal Pérot, and Kévin Buffenoir Copyright © 2014 Luc Terreaux et al. All rights reserved. Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain Thu, 03 Apr 2014 11:52:44 +0000 The pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer’s disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the production of amyloid-β peptides (Aβ) and phosphorylation of microtubule-associated protein tau in DM rats and elucidate the role of GSK-3 and Akt (protein kinase B, PKB) in these processes. Streptozotocin injection-induced DM rats displayed an increased GSK-3 activity, decreased activity and expression of Akt. And Aβ40 and Aβ42 were found overproduced and the microtubule-associated protein tau was hyperphosphorylated in the hippocampus. Furthermore, selective inhibition of GSK-3 by lithium could attenuate the conditions of Aβ overproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of Aβ and the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects. Zhong-Sen Qu, Liang Li, Xiao-Jiang Sun, Yu-Wu Zhao, Jin Zhang, Zhi Geng, Jian-Liang Fu, and Qing-Guo Ren Copyright © 2014 Zhong-Sen Qu et al. All rights reserved. A Robust Nonlinear Observer for a Class of Neural Mass Models Thu, 20 Mar 2014 14:21:02 +0000 A new method of designing a robust nonlinear observer is presented for a class of neural mass models by using the Lur’e system theory and the projection lemma. The observer is robust towards input uncertainty and measurement noise. It is applied to estimate the unmeasured membrane potential of neural populations from the electroencephalogram (EEG) produced by the neural mass models. An illustrative example shows the effectiveness of the proposed method. Xian Liu, Dongkai Miao, and Qing Gao Copyright © 2014 Xian Liu et al. All rights reserved. Personality, Category, and Cross-Linguistic Speech Sound Processing: A Connectivistic View Thu, 13 Mar 2014 11:12:36 +0000 Category formation of human perception is a vital part of cognitive ability. The disciplines of neuroscience and linguistics, however, seldom mention it in the marrying of the two. The present study reviews the neurological view of language acquisition as normalization of incoming speech signal, and attempts to suggest how speech sound category formation may connect personality with second language speech perception. Through a questionnaire, (being thick or thin) ego boundary, a correlate found to be related to category formation, was proven a positive indicator of personality types. Following the qualitative study, thick boundary and thin boundary English learners native in Cantonese were given a speech-signal perception test using an ABX discrimination task protocol. Results showed that thick-boundary learners performed significantly lower in accuracy rate than thin-boundary learners. It was implied that differences in personality do have an impact on language learning. Yizhou Lan and Will X. Y. Li Copyright © 2014 Yizhou Lan and Will X. Y. Li. All rights reserved. A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury Sun, 23 Feb 2014 11:50:12 +0000 Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S) protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS) induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH). Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH. Yong-Peng Yu, Xiang-Lin Chi, and Li-Jun Liu Copyright © 2014 Yong-Peng Yu et al. All rights reserved. Alternative Paradigm of Selective Vagus Nerve Stimulation Tested on an Isolated Porcine Vagus Nerve Thu, 06 Feb 2014 11:02:35 +0000 Alternative paradigm for spatial and fibre-type selective vagus nerve stimulation (VNS) was developed using realistic structural topography and tested in an isolated segment of a porcine cervical left vagus nerve (LVN). A spiral cuff (cuff) containing a matrix of ninety-nine electrodes was developed for selective VNS. A quasitrapezoidal stimulating pulse (stimulus) was applied to the LVN via an appointed group of three electrodes (triplet). The triplet and stimulus were configured to predominantly stimulate the B-fibres, minimizing stimulation of the A-fibres and by-passing the stimulation of the C-fibres. To assess which fibres made the most probable contribution to the neural response (NR) during selective VNS, the distribution of conduction velocity (CV) within the LVN was considered. Experimental testing of the paradigm showed the existence of certain parameters and waveforms of the stimulus, for which the contribution of the A-fibres to the NR was slightly reduced and that of the B-fibres was slightly enlarged. The cuff provided satisfactory fascicle discrimination in selective VNS as well as satisfactory fascicle discrimination during NR recording. However, in the present stage of development, fibre-type VNS remained rather limited. Polona Pečlin and Janez Rozman Copyright © 2014 Polona Pečlin and Janez Rozman. All rights reserved. The Patient’s Experience of the Psychosocial Process That Influences Identity following Stroke Rehabilitation: A Metaethnography Tue, 28 Jan 2014 07:45:32 +0000 Background and Purpose. Patient experience is increasingly being recognised as a key health outcome due to its positive correlation with quality of life and treatment compliance. The aim of this study was to create a model of how patient’s experiences of rehabilitation after stroke influence their outcome. Methods. A metaethnography of qualitative articles published since 2000 was undertaken. A systematic search of four databases using the keywords was competed. Original studies were included if at least 50% of their data from results was focused on stroke survivors experiences and if they reflected an overarching experience of stroke rehabilitation. Relevant papers were appraised for quality using the COREQ tool. Pata analysis as undertaken using traditional processes of extracting, interpreting, translating, and synthesizing the included studies. Results. Thirteen studies were included. Two themes (1) evolution of identity and (2) psychosocial constructs that influence experience were identified. A model of recovery was generated. Conclusion. The synthesis model conceptualizes how the recovery of stroke survivors’ sense of identity changes during rehabilitation illustrating changes and evolution over time. Positive experiences are shaped by key psychosocial concepts such as hope, social support, and rely on good self-efficacy which is influenced by both clinical staff and external support. E. Hole, B. Stubbs, C. Roskell, and A. Soundy Copyright © 2014 E. Hole et al. All rights reserved. Chronic Administration of 5-HT1A Receptor Agonist Relieves Depression and Depression-Induced Hypoalgesia Thu, 23 Jan 2014 12:10:00 +0000 Previous studies have shown that depressed patients as well as animal models of depression exhibit decreased sensitivity to evoked pain stimuli, and serotonin is indicated to be involved in depression-induced hypoalgesia. The purpose of this study was to investigate the potential role of 5-HT1A receptor in the depression-induced hypoalgesia. Acute or chronic administration of 5-HT1A receptor agonist, 8-OH-DPAT, was performed in olfactory bulbectomy (OB) and sham-operated rats. The depression-like behavior and pain thresholds were measured using open-field test and radiant heat thermal pain test, respectively. We found that acute administration of 8-OH-DPAT increased locomotor activity and pain thresholds in the sham rats but had no effect on the OB rats. In contrast, chronic administration of 8-OH-DPAT reduced locomotor activity and pain thresholds and restored them to normal level. Increased pain thresholds were also observed in the sham rats after the chronic administration. These results demonstrated that chronic administration of 8-OH-DPAT reversed the depression-induced decrease in pain sensitivity in rats, suggesting that 5-HT1A receptor may play a role in the depression-associated hypoalgesia. Zhao-Cai Jiang, Wei-Jing Qi, Jin-Yan Wang, and Fei Luo Copyright © 2014 Zhao-Cai Jiang et al. All rights reserved. Eyes as Gateways for Environmental Light to the Substantia Nigra: Relevance in Parkinson’s Disease Wed, 22 Jan 2014 07:34:18 +0000 Recent data indicates that prolonged bright light exposure of rats induces production of neuromelanin and reduction of tyrosine hydroxylase positive neurons in the substantia nigra. This effect was the result of direct light reaching the substantia nigra and not due to alteration of circadian rhythms. Here, we measured the spectrum of light reaching the substantia nigra in rats and analysed the pathway that light may take to reach this deep brain structure in humans. Wavelength range and light intensity, emitted from a fluorescent tube, were measured, using a stereotaxically implanted optical fibre in the rat mesencephalon. The hypothetical path of environmental light from the eye to the substantia nigra in humans was investigated by computed tomography and magnetic resonance imaging. Light with wavelengths greater than 600 nm reached the rat substantia nigra, with a peak at 709 nm. Eyes appear to be the gateway for light to the mesencephalon since covering the eyes with aluminum foil reduced light intensity by half. Using computed tomography and magnetic resonance imaging of a human head, we identified the eye and the superior orbital fissure as possible gateways for environmental light to reach the mesencephalon. Stefania Romeo, Daniela Di Camillo, Alessandra Splendiani, Marta Capannolo, Cristina Rocchi, Gabriella Aloisi, Irene Fasciani, Giovanni U. Corsini, Eugenio Scarnati, Luca Lozzi, and Roberto Maggio Copyright © 2014 Stefania Romeo et al. All rights reserved. C-Reactive Protein and Cognition Are Unrelated to Leukoaraiosis Wed, 22 Jan 2014 06:59:51 +0000 Elevated serum levels of C-reactive protein (CRP) have been associated with leukoaraiosis in elderly brain. However, several studies indicate that leukoaraiosis is associated with an increased risk of cognitive impairment. It is unknown how the effect of CRP on cognition is mediated by leukoaraiosis. The purpose of this study is to assess the relationship between serum levels of CRP, the presence of leukoaraiosis, and cognitive impairment in a population of coronary patients over 50 years old. CRP levels explained 7.18% (: 0.002) of the variance of the MMSE. The adjustment for the presence of leukoaraiosis little changed this variance (5.98%, : 0.005), indicating that only a small portion of the CRP influence on cognition was mediated via leukoaraiosis. Patients with CRP levels ≥5.0 had 2.9 (95% CI: 1.26–6.44) times more chance to present cognitive impairment (: 0.012). We found that elevated serum levels of CRP were associated with increased risk of cognitive impairment in elderly and it was not mediated by presence of leukoaraiosis. Liara Rizzi, Fabricio Correia Marques, Idiane Rosset, Emilio Hideyuki Moriguchi, Paulo Dornelles Picon, Marcia Lorena Fagundes Chaves, and Matheus Roriz-Cruz Copyright © 2014 Liara Rizzi et al. All rights reserved. Effect of Receptor Antagonist (CGP35348) on Learning and Memory in Albino Mice Sun, 19 Jan 2014 12:49:18 +0000 The present study was designed to demonstrate the potential effect of CGP 35348 (GABAB receptor antagonist) on the learning, memory formation, and neuromuscular coordination in albino mouse. Mice were intrapertoneally injected with 1 mg CGP 35348/mL of distilled water/Kg body weight, while the control animals were injected with equal volume of saline solution. A battery of neurological tests was applied following the intrapertoneal injections. Results of rota rod indicated that CGP 35348 had no effect on neuromuscular coordination in both male () and female () albino mice. CGP 35348 treated females demonstrated poor exploratory behavior during open filed for several parameters (time mobile (), time immobile (), rotations (), and anticlockwise rotations ()). The results for Morris water maze (MWM) retention phase indicated that CGP 35348 treated male mice took shorter latency to reach the hidden platform () than control indicating improved memory. This observation was complemented by the swim strategies used by mice during training days in MWM as CGP 35348 treated males used more direct and focal approach to reach the platform as the training proceeded. Quratulane Gillani, Shahid Iqbal, Fatima Arfa, Saba Khakwani, Atif Akbar, Asmat Ullah, Muhammad Ali, and Furhan Iqbal Copyright © 2014 Quratulane Gillani et al. All rights reserved. Dynamic Principal Component Analysis with Nonoverlapping Moving Window and Its Applications to Epileptic EEG Classification Thu, 16 Jan 2014 07:39:19 +0000 Classification of electroencephalography (EEG) is the most useful diagnostic and monitoring procedure for epilepsy study. A reliable algorithm that can be easily implemented is the key to this procedure. In this paper a novel signal feature extraction method based on dynamic principal component analysis and nonoverlapping moving window is proposed. Along with this new technique, two detection methods based on extracted sparse features are applied to deal with signal classification. The obtained results demonstrated that our proposed methodologies are able to differentiate EEGs from controls and interictal for epilepsy diagnosis and to separate EEGs from interictal and ictal for seizure detection. Our approach yields high classification accuracy for both single-channel short-term EEGs and multichannel long-term EEGs. The classification performance of the method is also compared with other state-of-the-art techniques on the same datasets and the effect of signal variability on the presented methods is also studied. Shengkun Xie and Sridhar Krishnan Copyright © 2014 Shengkun Xie and Sridhar Krishnan. All rights reserved. Significance of Normalization on Anatomical MRI Measures in Predicting Alzheimer’s Disease Mon, 06 Jan 2014 06:48:04 +0000 This study establishes a new approach for combining neuroimaging and neuropsychological measures for an optimal decisional space to classify subjects with Alzheimer’s disease (AD). This approach relies on a multivariate feature selection method with different MRI normalization techniques. Subcortical volume, cortical thickness, and surface area measures are obtained using MRIs from 189 participants (129 normal controls and 60 AD patients). Statistically significant variables were selected for each combination model to construct a multidimensional space for classification. Different normalization approaches were explored to gauge the effect on classification performance using a support vector machine classifier. Results indicate that the Mini-mental state examination (MMSE) measure is most discriminative among single-measure models, while subcortical volume combined with MMSE is the most effective multivariate model for AD classification. The study demonstrates that subcortical volumes need not be normalized, whereas cortical thickness should be normalized either by intracranial volume or mean thickness, and surface area is a weak indicator of AD with and without normalization. On the significant brain regions, a nearly perfect symmetry is observed for subcortical volumes and cortical thickness, and a significant reduction in thickness is particularly seen in the temporal lobe, which is associated with brain deficits characterizing AD. Qi Zhou, Mohammed Goryawala, Mercedes Cabrerizo, Warren Barker, Ranjan Duara, and Malek Adjouadi Copyright © 2014 Qi Zhou et al. All rights reserved. Anti-Tumor Effect of Rutin on Human Neuroblastoma Cell Lines through Inducing G2/M Cell Cycle Arrest and Promoting Apoptosis Sun, 29 Dec 2013 13:54:24 +0000 Aims. To further investigate the antineuroblastoma effect of rutin which is a type of flavonoid. Methods. The antiproliferation of rutin in human neuroblastoma cells LAN-5 were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chemotaxis of LAN-5 cells was assessed using transwell migration chambers and scratch wound migration assay. The cell cycle arrest and apoptosis in a dose-dependent manner was measured by flow cytometric and fluorescent microscopy analyses. The apoptosis-related proteins BAX and BCL2 as well as MYCN mRNA express were determined by RT-PCR analysis. Secreted TNF-α level were determined using specific enzyme-linked immunosorbent assay kits. Results. Rutin significantly inhibited the growth of LAN-5 cells and chemotactic ability. Flow cytometric analysis revealed that rutin induced G2/M arrest in the cell cycle progression and induced cell apoptosis. The RT-PCR showed that rutin could decrease BCL2 expression and BCL2/BAX ratio. In the meantime, the MYCN mRNA level and the secretion of TNF-α were inhibited. Conclusion. These results suggest that rutin produces obvious antineuroblastoma effects via induced G2/M arrest in the cell cycle progression and induced cell apoptosis as well as regulating the expression of gene related to apoptosis and so on. It supports the viability of developing rutin as a novel therapeutic prodrug for neuroblastoma treatment, as well as providing a new path on anticancer effect of Chinese traditional drug. Hongyan Chen, Qing Miao, Miao Geng, Jing Liu, Yazhuo Hu, Lei Tian, Jingkun Pan, and Yi Yang Copyright © 2013 Hongyan Chen et al. All rights reserved. The Influence of Negative Emotion on the Simon Effect as Reflected by P300 Thu, 26 Dec 2013 19:03:27 +0000 The Simon effect refers to the phenomenon that reaction time (RT) is faster when stimulus and response location are congruent than when they are not. This study used the priming-target paradigm to explore the influence of induced negative emotion on the Simon effect with event-related potential techniques (ERPs). The priming stimuli were composed of two kinds of pictures, the negative and neutral pictures, selected from the International Affective Picture System (IAPS). The target stimuli included chessboards of two color types. One was red and black the other one was green and black. Each chessboard was presented on the left or the right of the screen. The participants were asked to press the response keys according to the colors of the chessboards. It was called the congruent condition if the chessboard and the response key were on the same side, otherwise incongruent condition. In this study, the emotion-priming Simon effect was found in terms of RT and P300. Negative emotion compared with neutral emotion significantly enhanced the Simon effect in the cognitive process, reflected by a larger difference of P300 latency between the incongruent and congruent trials. The results suggest that the induced negative emotion influenced the Simon effect at the late stage of the cognitive process, and the P300 latency could be considered as the reference measure. These findings may be beneficial to researches in psychology and industrial engineering in the future. Qingguo Ma and Qian Shang Copyright © 2013 Qingguo Ma and Qian Shang. All rights reserved. Pharmacological Effects of Active Compounds on Neurodegenerative Disease with Gastrodia and Uncaria Decoction, a Commonly Used Poststroke Decoction Thu, 14 Nov 2013 15:19:49 +0000 Neurodegenerative diseases refer to the selective loss of neuronal systems in patients. The diseases cause high morbidity and mortality to approximately 22 million people worldwide and the number is expected to be tripled by 2050. Up to now, there is no effective prevention and treatment for the neurodegenerative diseases. Although some of the clinical therapies target at slowing down the progression of symptoms of the diseases, the general effectiveness of the drugs has been far from satisfactory. Traditional Chinese medicine becomes popular alternative remedies as it has been practiced clinically for more than thousands of years in China. As neurodegenerative diseases are mediated through different pathways, herbal decoction with multiple herbs is used as an effective therapeutic approach to work on multiple targets. Gastrodia and Uncaria Decoction, a popular TCM decoction, has been used to treat stroke in China. The decoction contains compounds including alkaloids, flavonoids, iridoids, carotenoids, and natural phenols, which have been found to possess anti-inflammatory, antioxidative, and antiapoptotic effects. In this review, we will summarize the recent publications of the pharmacological effects of these five groups of compounds. Understanding the mechanisms of action of these compounds may provide new treatment opportunities for the patients with neurodegenerative diseases. Stanley C. C. Chik, Terry C. T. Or, D. Luo, Cindy L. H. Yang, and Allan S. Y. Lau Copyright © 2013 Stanley C. C. Chik et al. All rights reserved. Perioperative Variables Contributing to the Rupture of Intracranial Aneurysm: An Update Tue, 12 Nov 2013 08:24:38 +0000 Background. Perioperative aneurysm rupture (PAR) is one of the most dreaded complications of intracranial aneurysms, and approximately 80% of nontraumatic SAHs are related to such PAR aneurysms. The literature is currently scant and even controversial regarding the issues of various contributory factors on different phases of perioperative period. Thus this paper highlights the current understanding of various risk factors, variables, and outcomes in relation to PAR and try to summarize the current knowledge. Method. We have performed a PubMed search (1 January 1991–31 December 2012) using search terms including “cerebral aneurysm,” “intracranial aneurysm,” and “intraoperative/perioperative rupture.” Results. Various risk factors are summarized in relation to different phases of perioperative period and their relationship with outcome is also highlighted. There exist many well-known preoperative variables which are responsible for the highest percentage of PAR. The role of other variables in the intraoperative/postoperative period is not well known; however, these factors may have important contributory roles in aneurysm rupture. Preoperative variables mainly include natural course (age, gender, and familial history) as well as the pathophysiological factors (size, type, location, comorbidities, and procedure). Previously ruptured aneurysm is associated with rupture in all the phases of perioperative period. On the other hand intraoperative/postoperative variables usually depend upon anesthesia and surgery related factors. Intraoperative rupture during predissection phase is associated with poor outcome while intraoperative rupture at any step during embolization procedure imposes poor outcome. Conclusion. We have tried to create such an initial categorization but know that we cannot scale according to its clinical importance. Thorough understanding of various risk factors and other variables associated with PAR will assist in better clinical management as well as patient care in this group and will give insight into the development and prevention of such a catastrophic complication in these patients. Tumul Chowdhury, Ronald B. Cappellani, Nora Sandu, Bernhard Schaller, and Jayesh Daya Copyright © 2013 Tumul Chowdhury et al. All rights reserved. Left Prefrontal Activity Reflects the Ability of Vicarious Fear Learning: A Functional Near-Infrared Spectroscopy Study Tue, 05 Nov 2013 16:00:02 +0000 Fear could be acquired indirectly via social observation. However, it remains unclear which cortical substrate activities are involved in vicarious fear transmission. The present study was to examine empathy-related processes during fear learning by-proxy and to examine the activation of prefrontal cortex by using functional near-infrared spectroscopy. We simultaneously measured participants’ hemodynamic responses and skin conductance responses when they were exposed to a movie. In this movie, a demonstrator (i.e., another human being) was receiving a classical fear conditioning. A neutral colored square paired with shocks () and another colored square paired with no shocks () were randomly presented in front of the demonstrator. Results showed that increased concentration of oxygenated hemoglobin in left prefrontal cortex was observed when participants watched a demonstrator seeing compared with that exposed to . In addition, enhanced skin conductance responses showing a demonstrator's aversive experience during learning object-fear association were observed. The present study suggests that left prefrontal cortex, which may reflect speculation of others’ mental state, is associated with social fear transmission. Qingguo Ma, Yujing Huang, and Lei Wang Copyright © 2013 Qingguo Ma et al. All rights reserved. The Protective Role of Carnosic Acid against Beta-Amyloid Toxicity in Rats Thu, 24 Oct 2013 16:00:26 +0000 Oxidative stress is one of the pathological mechanisms responsible for the beta- amyloid cascade associated with Alzheimer’s disease (AD). Previous studies have demonstrated the role of carnosic acid (CA), an effective antioxidant, in combating oxidative stress. A progressive cognitive decline is one of the hallmarks of AD. Thus, we attempted to determine whether the administration of CA protects against memory deficit caused by beta-amyloid toxicity in rats. Beta-amyloid (1–40) was injected by stereotaxic surgery into the Ca1 region of the hippocampus of rats in the Amyloid beta (Aβ) groups. CA was delivered intraperitoneally, before and after surgery in animals in the CA groups. Passive avoidance learning and spontaneous alternation behavior were evaluated using the shuttle box and the Y-maze, respectively. The degenerating hippocampal neurons were detected by fluoro-jade b staining. We observed that beta-amyloid (1–40) can induce neurodegeneration in the Ca1 region of the hippocampus by using fluoro-jade b staining. Also, the behavioral tests revealed that CA may recover the passive avoidance learning and spontaneous alternation behavior scores in the Aβ + CA group, in comparison with the Aβ group. We found that CA may ameliorate the spatial and learning memory deficits induced by the toxicity of beta-amyloid in the rat hippocampus. H. Rasoolijazi, N. Azad, M. T. Joghataei, M. Kerdari, F. Nikbakht, and M. Soleimani Copyright © 2013 H. Rasoolijazi et al. All rights reserved. Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals Tue, 22 Oct 2013 14:34:34 +0000 In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent [31]P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, [31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain -NTP (direct measure of adenosine triphosphate), -NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse. George H. Trksak, Bethany K. Bracken, J. Eric Jensen, David T. Plante, David M. Penetar, Wendy L. Tartarini, Melissa A. Maywalt, Cynthia M. Dorsey, Perry F. Renshaw, and Scott E. Lukas Copyright © 2013 George H. Trksak et al. All rights reserved. Antipsychotic-Like Effect of Trimetazidine in a Rodent Model Tue, 22 Oct 2013 09:06:32 +0000 Trimetazidine (TMZ) has been used as an anti-ischemic agent for angina pectoris, chorioretinal disturbances, and vertigo. Also, it can induce extrapyramidal type adverse reaction such as parkinsonism, gait disorder, and tremor via blockade of D2 receptors. In the present study, we evaluated the effect of TMZ on novelty-induced rearing behavior and apomorphine-induced stereotypy behavior in male rats. Four groups of rat () were administrated with TMZ (10 and 20 mg/kg, i.p.), chlorpromazine (1 mg/kg, i.p.), or isotonic saline. One hour later, apomorphine (2 mg/kg, s.c.) was administrated to each rat. Our results showed that both doses of TMZ significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. TMZ also decreased the stereotypy scores in a dose-dependent manner. We concluded that TMZ has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, with its antioxidative and cytoprotective properties, TMZ is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug. Oytun Erbaş, Hüseyin Serdar Akseki, Betül Eliküçük, and Dilek Taşkıran Copyright © 2013 Oytun Erbaş et al. All rights reserved. Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal Mon, 21 Oct 2013 13:39:49 +0000 Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans. Raffaele Nardone, Yvonne Höller, Monica Storti, Monica Christova, Frediano Tezzon, Stefan Golaszewski, Eugen Trinka, and Francesco Brigo Copyright © 2013 Raffaele Nardone et al. All rights reserved. Cognitive Intraindividual Variability and White Matter Integrity in Aging Mon, 23 Sep 2013 14:26:39 +0000 The intraindividual variability (IIV) of cognitive performance has been shown to increase with aging. While brain research has generally focused on mean performance, little is known about neural correlates of cognitive IIV. Nevertheless, some studies suggest that IIV relates more strongly than mean level of performance to the quality of white matter (WM). Our study aims to explore the relation between WM integrity and cognitive IIV by combining functional (fMRI) and structural (diffusion tensor imaging, DTI) imaging. Twelve young adults (aged 18–30 years) and thirteen older adults (61–82 years) underwent a battery of neuropsychological tasks, along with fMRI and DTI imaging. Their behavioral data were analyzed and correlated with the imaging data at WM regions of interest defined on the basis of (1) the fMRI-activated areas and (2) the Johns Hopkins University (JHU) WM tractography atlas. For both methods, fractional anisotropy, along with the mean, radial, and axial diffusivity parameters, was computed. In accord with previous studies, our results showed that the DTI parameters were more related to IIV than to mean performance. Results also indicated that age differences in the DTI parameters were more pronounced in the regions activated primarily by young adults during a choice reaction-time task than in those also activated in older adults. Nathalie Mella, Sandrine de Ribaupierre, Roy Eagleson, and Anik de Ribaupierre Copyright © 2013 Nathalie Mella et al. All rights reserved. Effects of MRP8, LPS, and Lenalidomide on the Expressions of TNF-α, Brain-Enriched, and Inflammation-Related MicroRNAs in the Primary Astrocyte Culture Sat, 21 Sep 2013 15:09:20 +0000 Astrocytes are now recognized as a heterogeneous class of cells with many important and diverse functions in healthy and diseased central nervous system (CNS). MicroRNAs (miRNAs) are small, noncoding RNAs which may have key roles in astrocytes activation in response to various stimuli. We performed quantitative real-time PCR (qPCR) to detect changes in the expressions of brain-enriched miRNAs (124, 134, 9, 132, and 138), inflammation-related miRNAs (146a, 21, 181a, 221, and 222), and tumor necrosis factor alpha (TNF-α) in the rat primary astrocyte cultures after stimulation with myeloid-related protein 8 (MRP8) and lipopolysaccharides (LPS). Further, we inhibited the expression of TNF-α in the astrocytes by using TNF-α inhibitor (lenalidomide) and tested for the first time the effect of this inhibition on the expressions of the same tested miRNAs. Stimulation of the astrocytes with MRP8 or LPS leads to significant upregulation of miRNAs (124, 134, 9, 132, 146a, 21, 181a, 221, and 222), while miRNA-138 was downregulated. TNF-α inhibition with lenalidomide leads to opposite expressions of the tested miRNAs. These miRNAs may play an important role in activation of the astrocytes and may be a novel target for cell-specific therapeutic interventions in multiple CNS diseases. Ahmed Omran, Muhammad Usman Ashhab, Na Gan, Huimin Kong, Jing Peng, and Fei Yin Copyright © 2013 Ahmed Omran et al. All rights reserved. Amniotic Fluid or Its Fatty Acids Produce Actions Similar to Diazepam on Lateral Septal Neurons Firing Rate Mon, 24 Jun 2013 14:32:05 +0000 Human amniotic fluid (AF) contains eight fatty acids (FATs), and both produce anxiolytic-like effects in adult rats and appetitive responses in human newborns. The medial amygdala and lateral septal nucleus function are related to social behavior, but the action of AF or its FATs in this circuit is known. We obtained 267 single-unit extracellular recordings in Wistar rats treated with vehicle (1 mL, s.c.; ), human AF (1 mL, s.c.; ), a FAT mixture (1 mL, s.c.; ), diazepam (1 mg/kg, i.p.; ), and fluoxetine (1 mg/kg, p.o.; ). Compared with the vehicle group, the spontaneous septal firing rate in the AF, FAT mixture, and diazepam groups was the lowest and in the fluoxetine group the highest. Cumulative peristimulus histograms indicated that the significant change in septal firing occurred only in the AF and FAT mixture groups and exclusively in those neurons that increased their firing rate during amygdala stimulation. We conclude that human AF and its FATs produce actions comparable to anxiolytic drugs and are able to modify the responsivity of a circuit involved in social behavior, suggesting facilitation of social recognition processes by maternal-fetal fluids. Ana G. Gutiérrez-García, Carlos M. Contreras, and Diana Idania Vásquez-Hernández Copyright © 2013 Ana G. Gutiérrez-García et al. All rights reserved. Anxiolytic-Like Actions of Fatty Acids Identified in Human Amniotic Fluid Tue, 30 Apr 2013 16:15:23 +0000 Eight fatty acids (C12–C18) were previously identified in human amniotic fluid, colostrum, and milk in similar proportions but different amounts. Amniotic fluid is well known to be the natural environment for development in mammals. Interestingly, amniotic fluid and an artificial mixture of fatty acids contained in amniotic fluid produce similar anxiolytic-like actions in Wistar rats. We explored whether the lowest amount of fatty acids contained in amniotic fluid with respect to colostrum and milk produces such anxiolytic-like effects. Although a trend toward a dose-response effect was observed, only an amount of fatty acids that was similar to amniotic fluid fully mimicked the effect of diazepam (2 mg/kg, i.p.) in the defensive burying test, an action devoid of effects on locomotor activity and motor coordination. Our results confirm that the amount of fatty acids contained in amniotic fluid is sufficient to produce anxiolytic-like effects, suggesting similar actions during intrauterine development. Rosa Isela García-Ríos, Juan Francisco Rodríguez-Landa, and Carlos M. Contreras Copyright © 2013 Rosa Isela García-Ríos et al. All rights reserved. The Effects of Whole-Body Vibration on the Cross-Transfer of Strength Mon, 10 Dec 2012 14:53:31 +0000 This study investigated whether the use of superimposed whole-body vibration (WBV) during cross-education strength training would optimise strength transfer compared to conventional cross-education strength training. Twenty-one healthy, dominant right leg volunteers ( years) were allocated to a strength training (ST, , ), a strength training with WBV (ST + V, , ), or a control group (no training, , ). Training groups performed 9 sessions over 3 weeks, involving unilateral squats for the right leg, with or without WBV (35 Hz; 2.5 mm amplitude). All groups underwent dynamic single leg maximum strength testing (1RM) and single and paired pulse transcranial magnetic stimulation (TMS) prior to and following training. Strength increased in the trained limb for the ST (41%; ) and ST + V (55%; ) groups, which resulted in a 35% () strength transfer to the untrained left leg for the ST group and a 52% () strength transfer to the untrained leg for the ST + V group, when compared to the control group. No differences in strength transfer between training groups were observed . For the untrained leg, no differences in the peak height of recruitment curves or SICI were observed between ST and ST + V groups . Strength training with WBV does not appear to modulate the cross-transfer of strength to a greater magnitude when compared to conventional cross-education strength training. Alicia M. Goodwill and Dawson J. Kidgell Copyright © 2012 Alicia M. Goodwill and Dawson J. Kidgell. All rights reserved. Maxwellian Eye Fixation during Natural Scene Perception Sun, 25 Nov 2012 14:58:49 +0000 When we explore a visual scene, our eyes make saccades to jump rapidly from one area to another and fixate regions of interest to extract useful information. While the role of fixation eye movements in vision has been widely studied, their random nature has been a hitherto neglected issue. Here we conducted two experiments to examine the Maxwellian nature of eye movements during fixation. In Experiment 1, eight participants were asked to perform free viewing of natural scenes displayed on a computer screen while their eye movements were recorded. For each participant, the probability density function (PDF) of eye movement amplitude during fixation obeyed the law established by Maxwell for describing molecule velocity in gas. Only the mean amplitude of eye movements varied with expertise, which was lower in experts than novice participants. In Experiment 2, two participants underwent fixed time, free viewing of natural scenes and of their scrambled version while their eye movements were recorded. Again, the PDF of eye movement amplitude during fixation obeyed Maxwell’s law for each participant and for each scene condition (normal or scrambled). The results suggest that eye fixation during natural scene perception describes a random motion regardless of top-down or of bottom-up processes. Jean Duchesne, Vincent Bouvier, Julien Guillemé, and Olivier A. Coubard Copyright © 2012 Jean Duchesne et al. All rights reserved. Analysis of EMG Signals in Aggressive and Normal Activities by Using Higher-Order Spectra Wed, 24 Oct 2012 12:31:22 +0000 The analysis and classification of electromyography (EMG) signals are very important in order to detect some symptoms of diseases, prosthetic arm/leg control, and so on. In this study, an EMG signal was analyzed using bispectrum, which belongs to a family of higher-order spectra. An EMG signal is the electrical potential difference of muscle cells. The EMG signals used in the present study are aggressive or normal actions. The EMG dataset was obtained from the machine learning repository. First, the aggressive and normal EMG activities were analyzed using bispectrum and the quadratic phase coupling of each EMG episode was determined. Next, the features of the analyzed EMG signals were fed into learning machines to separate the aggressive and normal actions. The best classification result was 99.75%, which is sufficient to significantly classify the aggressive and normal actions. Necmettin Sezgin Copyright © 2012 Necmettin Sezgin. All rights reserved. Oxytocin and the Biopsychology of Performance in Team Sports Mon, 10 Sep 2012 16:11:36 +0000 Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sport. Gert-Jan Pepping and Erik J. Timmermans Copyright © 2012 Gert-Jan Pepping and Erik J. Timmermans. All rights reserved. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration Mon, 10 Sep 2012 14:05:38 +0000 After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD). This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA) derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise. Carlos Rodrigo Camara-Lemarroy, Emmanuel Irineo Gonzalez-Moreno, Francisco Javier Guzman-de la Garza, and Nancy Esthela Fernandez-Garza Copyright © 2012 Carlos Rodrigo Camara-Lemarroy et al. All rights reserved. An Emerging New Paradigm in Opioid Withdrawal: A Critical Role for Glia-Neuron Signaling in the Periaqueductal Gray Thu, 02 Aug 2012 11:23:43 +0000 The chronic use of opiates (i.e., narcotics such as the natural derivatives of opium including morphine or codeine) or opioids (i.e., semisynthetic derivatives of opium and other molecules that activate opioid receptors) induces dependence, which is associated with various specific behavioral and somatic signs after their withdrawal or after the administration of an opioid antagonist. Among the brain regions implicated in opiate dependence and withdrawal, the periaqueductal gray area (PAG) appears to be critical in regulating the complex signs and symptoms of opioid withdrawal. Numerous neurochemical mechanisms in the PAG have been identified that may contribute to the opioid withdrawal syndrome. Accumulating evidence suggests that glial activation leading to the release of proinflammatory molecules acting on neurons is important in the complex syndrome of opioid dependence and withdrawal. This paper focuses on the recent advances in our understanding of the vital role that glia-neuron interactions play in opioid dependence and withdrawal within the PAG. We summarize those neurochemical mechanisms associated with opioid withdrawal including the recently defined importance of TNFα release from activated glial cells that communicate with TNF receptors on PAG neurons. Handong Ouyang, Shue Liu, Weian Zeng, Roy C. Levitt, Keith A. Candiotti, and Shuanglin Hao Copyright © 2012 Handong Ouyang et al. All rights reserved. Peripheral Nerve Repair with Cultured Schwann Cells: Getting Closer to the Clinics Mon, 04 Jun 2012 15:14:58 +0000 Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiated in vitro into Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated bone marrow mesenchymal cells can be associated with nerve conduits and afterward transplanted. Experimental studies provide evidence of functional, histological, and electromyographical improvement following transplantation of bone-marrow-derived cells in animal models of peripheral nerve injury. This paper focuses on this new therapeutic approach highlighting its direct translational and clinical utility in promoting regeneration of not only acute but perhaps also chronic cases of peripheral nerve damage. Maria Carolina O. Rodrigues, Antonio Antunes Rodrigues Jr., Loren E. Glover, Julio Voltarelli, and Cesario V. Borlongan Copyright © 2012 Maria Carolina O. Rodrigues et al. All rights reserved. Motion Streaks Do Not Influence the Perceived Position of Stationary Flashed Objects Thu, 03 May 2012 08:13:42 +0000 In the present study, we investigated whether motion streaks, produced by fast moving dots Geisler 1999, distort the positional map of stationary flashed objects producing the well-known motion-induced position shift illusion (MIPS). The illusion relies on motion-processing mechanisms that induce local distortions in the positional map of the stimulus which is derived by shape-processing mechanisms. To measure the MIPS, two horizontally offset Gaussian blobs, placed above and below a central fixation point, were flashed over two fields of dots moving in opposite directions. Subjects judged the position of the top Gaussian blob relative to the bottom one. The results showed that neither fast (motion streaks) nor slow moving dots influenced the perceived spatial position of the stationary flashed objects, suggesting that background motion does not interact with the shape-processing mechanisms involved in MIPS. Andrea Pavan and Rosilari Bellacosa Marotti Copyright © 2012 Andrea Pavan and Rosilari Bellacosa Marotti. All rights reserved. Serotonin Receptors in Hippocampus Wed, 02 May 2012 16:28:14 +0000 Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. Laura Cristina Berumen, Angelina Rodríguez, Ricardo Miledi, and Guadalupe García-Alcocer Copyright © 2012 Laura Cristina Berumen et al. All rights reserved. Long-Term Efficacy of Prism Adaptation on Spatial Neglect: Preliminary Results on Different Spatial Components Wed, 02 May 2012 14:38:03 +0000 This study describes the long-term effectiveness on spatial neglect recovery of a 2-week treatment based on prism adaptation (PA). Seven right-brain-damaged patients affected by chronic neglect were evaluated before, after two weeks of the PA treatment and at a follow-up (variable between 8 and 30 months after the end of PA). Neglect evaluation was performed by means of BIT (conventional and behavioral), Fluff Test, and Comb and Razor Test. The results highlight an improvement, after the PA training, in both tasks performed using the hand trained in PA treatment and in behavioral tasks not requiring a manual motor response. Such effects extend, even if not significantly, to all BIT subtests. These results support previous findings, showing that PA improves neglect also on imagery tasks with no manual component, and provide further evidence for long-lasting efficacy of PA training. Dissociations have been found with regard to PA efficacy on peripersonal, personal, and representational neglect, visuospatial agraphia and neglect dyslexia. In particular, we found no significant differences between the pre-training and post-training PA session in personal neglect measures, and a poor recovery of neglect dyslexia after PA treatment. The recruitment of a larger sample could help to confirm the effectiveness of the prismatic lenses with regard to the different clinical manifestations of spatial neglect. Maria Luisa Rusconi and Laura Carelli Copyright © 2012 Maria Luisa Rusconi and Laura Carelli. All rights reserved. Striatal Input- and Rate-Dependent Effects of Muscarinic Receptors on Pallidal Firing Tue, 01 May 2012 15:58:51 +0000 The globus pallidus (GP) plays a key role in the overall basal ganglia (BG) activity. Despite evidence of cholinergic inputs to GP, their role in the spiking activity of GP neurons has not received attention. We examine the effect of local activation and blockade of muscarinic receptors (MRs) in the spontaneous firing of GP neurons both in normal and ipsilateral striatum-lesioned rats. We found that activation of MRs produces heterogeneous responses in both normal and ipsilateral striatum-lesioned rats: in normal rats the response evoked by MRs depends on the predrug basal firing rate; the inhibition evoked by MRs is higher in normal rats than in striatum-lesioned rats; the number of neurons that undergo inhibition is lower in striatum-lesioned rats than in normal rats. Our data suggest that modulation of MRs in the GP depends on the firing rate before their activation and on the integrity of the striato-pallidal pathway. Enrique Querejeta, Alberto Alatorre, Alain Ríos, Rafael Barrientos, Aldo Oviedo-Chávez, Rosa Amalia Bobadilla-Lugo, and Alfonso Delgado Copyright © 2012 Enrique Querejeta et al. All rights reserved. Lack of Association of Childhood Partial Epilepsy with Brain Derived Neurotrophic Factor Gene Tue, 01 May 2012 15:47:59 +0000 Brain-derived factor (BDNF) is a member of neurotrophin family and is localized and upregulated in areas implicated in epileptogenesis. Several lines of evidence make the BDNF gene a plausible candidate gene for predisposition to epilepsy. In this study, we tested that BDNF might be involved in the etiology of childhood PE. To assess whether BDNF gene C270T polimorphism could be implicated in vulnerability to PE, we conducted a case-control association analysis (112 partial epileptic and 100 controls) in Turkish children. Epileptic children were divided into two groups: 1—idiopathic (𝑛=85) and 2—symptomathic epilepsy (𝑛=27). There was no significant difference in genotypic distribution and allelic frequencies of the BDNF gene C270T polimorphism between the PE and control groups. However, the BDNF gene TT genotype was more frequently seen in the epileptic children (15 versus 11 patients, resp.). Interestingly, in the epilepsy group, both two children with TT genotype have posttraumatic epilepsy. The data indicate a possible association with the 270T genotype of the BDNF gene with a posttraumatic epilepsy. To draw any conclusion, further studies using larger sample sizes should be carried out in various ethnic populations in childhood epilepsies. Aycan Unalp, Elcin Bora, Tufan Cankaya, Ozlem Giray Bozkaya, Derya Ercal, Aysel Ozturk, and Ayfer Ulgenalp Copyright © 2012 Aycan Unalp et al. All rights reserved. Brain Reorganization in Patients with Brachial Plexus Injury: A Longitudinal Functional MRI Study Tue, 01 May 2012 15:44:40 +0000 The aim of this study is to assess plastic changes of the sensorimotor cortex (SMC) in patients with traumatic brachial plexus injury (BPI) using functional magnetic resonance imaging (fMRI). Twenty patients with traumatic BPI underwent fMRI using blood oxygen level-dependent technique with echo-planar imaging before the operation. Sixteen patients underwent their second fMRI at approximately one year after injury. The subjects performed two tasks: a flexion-extension task of the affected elbow and a task of the unaffected elbow. After activation, maps were generated, the number of significantly activated voxels in SMC contralateral to the elbow movement in the affected elbow task study (𝑁af) and that in the unaffected task study (𝑁unaf) were counted. An asymmetry index (AI) was calculated, where AI=(𝑁af−𝑁unaf)/(𝑁af+𝑁unaf). Ten healthy volunteers were also included in this fMRI study. The AI of the first fMRI of the patients with BPI was significantly lower than that of the healthy subjects (𝑃=0.035). The AI of the second fMRI significantly decreased compared with that of the first fMRI (𝑃=0.045). Brain reorganization associates with peripheral nervous changes after BPI and after operation for functional reconstruction. Takeharu Yoshikawa, Naoto Hayashi, Yasuhito Tajiri, Yoshirou Satake, and Kuni Ohtomo Copyright © 2012 Takeharu Yoshikawa et al. All rights reserved. Distribution of Extrasynaptic NMDA Receptors on Neurons Mon, 30 Apr 2012 13:41:35 +0000 NMDA receptors are found in both synaptic and extrasynaptic locations on neurons. NMDA receptors also can be found on neurons in early stages prior to synaptogenesis, where they may be involved in migration and differentiation. Extrasynaptic NMDA receptors typically are associated with contacts with adjacent processes such as axons and glia. Extrasynaptic NMDA receptor clusters vary in size and may form associations with scaffolding proteins such as PSD-95 and SAP102. The best-characterized extrasynaptic NMDA receptors contain NR1 and NR2B subunits. Extrasynaptic NMDA receptors may be activated by glutamate spillover from synapses or from ectopic release of glutamate. Consequently, extrasynaptic NMDA receptor activation may occur under different circumstances than that for synaptic NMDA receptors, indicating different functional consequences for the neuron. In some cases, activation of extrasynaptic NMDA receptors may have a negative influence on the neuron, leading to cell damage and death, as may occur in some major diseases of the nervous system. Ronald S. Petralia Copyright © 2012 Ronald S. Petralia. All rights reserved. Perceiving Numbers Affects the Internal Random Movements Generator Thu, 26 Apr 2012 15:38:52 +0000 According to the evidence of direct relationships among space, numbers, and finger representations, a random movement generation (RMG) task was employed in order to investigate whether numerical exposure can influence the finger selection of healthy humans. To this purpose a group of participants were asked to generate random finger movements during the exposure to several numerical cues. Although participants were explicitly asked to move finger as random as possible, results showed that left-hand fingers were moved more frequently than right-hand fingers when low numerical cues (from 1 to 3) were presented, and, vice versa, right-hand fingers were moved more frequently than left-hand fingers when high numerical cues (ranged from 7 to 9) were presented. The current result suggests that spontaneous actions can be affected by abstract information, providing an evidence that numerical concepts can influence low-level, non-goal-directed behaviours. Carmelo Mario Vicario Copyright © 2012 Carmelo Mario Vicario. All rights reserved. Impact of Environmental Thermal Stimulation on Activation of Hypothalamic Neuronal Nitric Oxide Synthase during the Prenatal Ontogenesis in Muscovy Ducks Thu, 19 Apr 2012 13:08:28 +0000 The aim of the study is to investigate the influence of prenatal temperature stimulation on neuronal NO synthase (nNOS) expression in the anterior hypothalamus of Muscovy duck embryos. Experiments were performed on embryonic day (E) E20, E23, E28, and E33 using histochemistry for identification of the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) as marker of NOS-containing neurons. Until the experiments, all duck embryos were incubated under standard temperature conditions (37.5∘C). During 3 hours before the start of the experiments, one group was incubated at 37.5∘C (control group), the second was warm-experienced at 39∘C, and the third was cold-experienced at 34∘C. In normal and warm-incubated duck embryos, nNOS activity could be first detected on E23. Particularly, after cold stimulation, a significant increase in nNOS activity was found in all embryos investigated even on day 20. Warm stimulation obviously induces the opposite effect, but at later embryonic age (E33). It can be concluded that probably in late-term bird embryos NO acts as a mediator of the neuronal cold pathway in the anterior hypothalamus, which might be improved by prenatal cold stimulation. Valery Dunai and Barbara Tzschentke Copyright © 2012 Valery Dunai and Barbara Tzschentke. All rights reserved. Do β-Defensins and Other Antimicrobial Peptides Play a Role in Neuroimmune Function and Neurodegeneration? Thu, 19 Apr 2012 13:01:06 +0000 It is widely accepted that the brain responds to mechanical trauma and development of most neurodegenerative diseases with an inflammatory sequelae that was once thought exclusive to systemic immunity. Mostly cationic peptides, such as the β-defensins, originally assigned an antimicrobial function are now recognized as mediators of both innate and adaptive immunity. Herein supporting evidence is presented for the hypothesis that neuropathological changes associated with chronic disease conditions of the CNS involve abnormal expression and regulatory function of specific antimicrobial peptides. It is also proposed that these alterations exacerbate proinflammatory conditions within the brain that ultimately potentiate the neurodegenerative process. Wesley M. Williams, Rudy J. Castellani, Aaron Weinberg, George Perry, and Mark A. Smith Copyright © 2012 Wesley M. Williams et al. All rights reserved. Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s Disease Sun, 01 Apr 2012 09:27:59 +0000 Lipids play an important role as risk or protective factors in Alzheimer’s disease (AD). Previously it has been shown that plasmalogens, the major brain phospholipids, are altered in AD. However, it remained unclear whether plasmalogens themselves are able to modulate amyloid precursor protein (APP) processing or if the reduced plasmalogen level is a consequence of AD. Here we identify the plasmalogens which are altered in human AD postmortem brains and investigate their impact on APP processing resulting in Aβ production. All tested plasmalogen species showed a reduction in γ-secretase activity whereas β- and α-secretase activity mainly remained unchanged. Plasmalogens directly affected γ-secretase activity, protein and RNA level of the secretases were unaffected, pointing towards a direct influence of plasmalogens on γ-secretase activity. Plasmalogens were also able to decrease γ-secretase activity in human postmortem AD brains emphasizing the impact of plasmalogens in AD. In summary our findings show that decreased plasmalogen levels are not only a consequence of AD but that plasmalogens also decrease APP processing by directly affecting γ-secretase activity, resulting in a vicious cycle: Aβ reduces plasmalogen levels and reduced plasmalogen levels directly increase γ-secretase activity leading to an even stronger production of Aβ peptides. Tatjana L. Rothhaar, Sven Grösgen, Viola J. Haupenthal, Verena K. Burg, Benjamin Hundsdörfer, Janine Mett, Matthias Riemenschneider, Heike S. Grimm, Tobias Hartmann, and Marcus O. W. Grimm Copyright © 2012 Tatjana L. Rothhaar et al. All rights reserved. Cell Cycle Inhibition without Disruption of Neurogenesis Is a Strategy for Treatment of Aberrant Cell Cycle Diseases: An Update Sun, 01 Apr 2012 09:16:23 +0000 Since publishing our earlier report describing a strategy for the treatment of central nervous system (CNS) diseases by inhibiting the cell cycle and without disrupting neurogenesis (Liu et al. 2010), we now update and extend this strategy to applications in the treatment of cancers as well. Here, we put forth the concept of “aberrant cell cycle diseases” to include both cancer and CNS diseases, the two unrelated disease types on the surface, by focusing on a common mechanism in each aberrant cell cycle reentry. In this paper, we also summarize the pharmacological approaches that interfere with classical cell cycle molecules and mitogenic pathways to block the cell cycle of tumor cells (in treatment of cancer) as well as to block the cell cycle of neurons (in treatment of CNS diseases). Since cell cycle inhibition can also block proliferation of neural progenitor cells (NPCs) and thus impair brain neurogenesis leading to cognitive deficits, we propose that future strategies aimed at cell cycle inhibition in treatment of aberrant cell cycle diseases (i.e., cancers or CNS diseases) should be designed with consideration of the important side effects on normal neurogenesis and cognition. Da-Zhi Liu and Bradley P. Ander Copyright © 2012 Da-Zhi Liu and Bradley P. Ander. All rights reserved. Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120: Mechanistic and Therapeutic Implications Wed, 01 Feb 2012 12:23:25 +0000 The blood-brain barrier (BBB) is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain. We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120) as a model. Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP) injection] or chronic [using SV(gp120), an experimental model of ongoing production of gp120] disrupted the BBB, and led to leakage of vascular contents. Gp120 was directly toxic to brain endothelial cells. Abnormalities of the BBB reflect the activity of matrix metalloproteinases (MMPs). These target laminin and attack the tight junctions between endothelial cells and BBB basal laminae. MMP-2 and MMP-9 were upregulated following gp120-injection. Gp120 reduced laminin and tight junction proteins. Reactive oxygen species (ROS) activate MMPs. Injecting gp120 induced lipid peroxidation. Gene transfer of antioxidant enzymes protected against gp120-induced BBB abnormalities. NMDA upregulates the proform of MMP-9. Using the NMDA receptor (NMDAR-1) inhibitor, memantine, we observed partial protection from gp120-induced BBB injury. Thus, (1) HIV-envelope gp120 disrupts the BBB; (2) this occurs via lesions in brain microvessels, MMP activation and degradation of vascular basement membrane and vascular tight junctions; (3) NMDAR-1 activation plays a role in this BBB injury; and (4) antioxidant gene delivery as well as NMDAR-1 antagonists may protect the BBB. Jean-Pierre Louboutin and David S. Strayer Copyright © 2012 Jean-Pierre Louboutin and David S. Strayer. All rights reserved. Aqp 9 and Brain Tumour Stem Cells Wed, 04 Jan 2012 11:14:36 +0000 Several studies have implicated the aquaporins (aqp) 1, 4, and 9 in the pathogenesis of malignant brain tumours, suggesting that they contribute to motility, invasiveness, and oedema formation and facilitate metabolism in tumour cells under hypoxic conditions. We have studied the expression of aqp1, 4, and 9 in biopsies from glioblastomas, isolated tumour stem cells grown in a tumoursphere assay and analyzed the progenitor and differentiated cells from these cultures. We have compared these to the situation in normal rat brain, its stem cells, and differentiated cells derived thereof. In short, qPCR in tumour tissue showed presence of aqp1, 4, and 9. In the tumour progenitor population, aqp9 was markedly more highly expressed, whilst in tumour-derived differentiated cells, aqp4 was downregulated. However, immunostaining did not reveal increased protein expression of aqp9 in the tumourspheres containing progenitor cells; in contrast, its expression (both mRNA and protein) was high in differentiated cultures. We, therefore, propose that aquaporin 9 may have a central role in the tumorigenesis of glioblastoma. Guri Fossdal, Einar O. Vik-Mo, Cecilie Sandberg, Mercy Varghese, Mari Kaarbø, Emily Telmo, Iver A. Langmoen, and Wayne Murrell Copyright © 2012 Guri Fossdal et al. All rights reserved. Assessing Topographical Orientation Skills in Cannabis Users Tue, 03 Jan 2012 17:09:35 +0000 The long-term effects of cannabis on human cognition are still unclear, but, considering that cannabis is a widely used substance and, overall, its potential use in therapeutic interventions, it is important to evaluate them. We hypothesize that the discrepancies among studies could be attributed to the specific cognitive function investigated and that skills subserved by the hippocampus, such as the spatial orientation abilities and, specifically, the ability to form and use cognitive maps, should be more compromised than others. Indeed it has been showed that cannabis users have a reduced hippocampus and that the hippocampus is the brain region in which cannabis has the greatest effect since it contains the highest concentration of cannabinoid receptors. To test this hypothesis we asked 15 heavy cannabis users and 19 nonusers to perform a virtual navigational test, the CMT, that assesses the ability to form and use cognitive maps. We found that using cannabis has no effect on these hippocampus-dependent orientation skills. We discuss the implications of our findings and how they relate to evidence reported in the literature that the intervention of functional reorganization mechanisms in cannabis user allows them to cope with the cognitive demands of navigational tasks. Liana Palermo, Filippo Bianchini, Giuseppe Iaria, Antonio Tanzilli, and Cecilia Guariglia Copyright © 2012 Liana Palermo et al. All rights reserved. The Limbic System Conception and Its Historical Evolution Thu, 08 Dec 2011 00:00:00 +0000 Throughout the centuries, scientific observers have endeavoured to extend their knowledge of the interrelationships between the brain and its regulatory control of human emotions and behaviour. Since the time of physicians such as Aristotle and Galen and the more recent observations of clinicians and neuropathologists such as Broca, Papez, and McLean, the field of affective neuroscience has matured to become the province of neuroscientists, neuropsychologists, neurologists, and psychiatrists. It is accepted that the prefrontal cortex, amygdala, anterior cingulate cortex, hippocampus, and insula participate in the majority of emotional processes. New imaging technologies and molecular biology discoveries are expanding further the frontiers of knowledge in this arena. The advancements of knowledge on the interplay between the human brain and emotions came about as the legacy of the pioneers mentioned in this field. The aim of this paper is to describe the historical evolution of the scientific understanding of interconnections between the human brain, behaviour, and emotions. Marcelo R. Roxo, Paulo R. Franceschini, Carlos Zubaran, Fabrício D. Kleber, and Josemir W. Sander Copyright © 2011 Marcelo R. Roxo et al. All rights reserved. Interaction between 𝛼-Synuclein and Other Proteins in Neurodegenerative Disorders Mon, 24 Oct 2011 00:00:00 +0000 Protein aggregation is a common characteristic of many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, evidence increasingly indicates considerable overlap between synucleinopathies and tauopathies or other protein-misfolding diseases. Inclusions, characteristics of these disorders, also occurring in other neurodegenerative diseases, suggest interactions of pathological proteins engaging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Parkinson and Alzheimer diseases have confirmed correlations/overlaps between these and other neurodegenerative disorders. The synergistic effects of α-synuclein, hyperphosphorylated tau, amyloid-β, and other pathologic proteins, and the underlying molecular pathogenic mechanisms, including induction and spread of protein aggregates, are critically reviewed, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, although the etiology of most of these processes is still mysterious. Kurt A. Jellinger Copyright © 2011 Kurt A. Jellinger. All rights reserved. A Showcase of Bench-to-Bedside Regenerative Medicine at the 2010 ASNTR Sun, 23 Oct 2011 00:00:00 +0000 Insight into the expanding themes of regenerative medicine is provided by the American Society for Neural Therapy and Repair's annual meeting. The 17th meeting covered a wide range of neurodegenerative disorders, exploring methods to elucidate the currently unknown mechanisms behind the disorders, as well as possible treatments ranging from the use of growth factors, gene therapy to cell transplantation. The importance of growth factors, both as a contributing factor to a disease and as a possible treatment either solo, or as a consequence of, or in conjunction with, stem cell therapy, was highlighted. The potential for viral vectors was also explored either for cells prior to transplantation or as a direct treatment regime into the brain itself. Identification of biomarkers that would allow early detection of a disease is an important factor in our fight against disease. The ability to now perform whole genome analysis and biomolecular profiling provides hope that such markers could be identified which not only could identify this likely to suffer from a disorder but also could allow its progress to be monitored. A few preclinical and clinical cell transplantation trials were also introduced as potential areas of followup in the years to come. David J. Eve, Cesar V. Borlongan, and Paul R. Sanberg Copyright © 2011 David J. Eve et al. All rights reserved. The Three-Layer Concentric Model of Glioblastoma: Cancer Stem Cells, Microenvironmental Regulation, and Therapeutic Implications Sun, 23 Oct 2011 00:00:00 +0000 Tumors arising in the central nervous system are thought to originate from a sub-population of cells named cancer stem cells (CSCs) or tumor initiating cells (TICs) that possess an immature phenotype, combined with self-renewal and chemotherapy resistance capacity. Moreover, in the last years, these cells have been identified in particular brain tumor niches fundamental for supporting their characteristics. In this paper, we report studies from many authors demonstrating that hypoxia or the so called “hypoxic niche” plays a crucial role in controlling CSC molecular and phenotypic profile. We recently investigated the relationship existing between Glioblastoma (GBM) stem cells and their niche, defining the theory of three-concentric layers model for GBM mass. According to this model, GBM stem cells reside preferentially within the hypoxic core of the tumour mass, while more differentiated cells are mainly localized along the peripheral and vascularized part of the tumour. This GBM model provides explanation of the effects mediated by the tumour microenvironment on the phenotypic and molecular regulation of GBM stem cells, describing their spatial distribution in the tumor bulk. Moreover, we discuss the possible clinical implications of the creation of this model for future GBM patient management and novel therapeutic strategies development. Luca Persano, Elena Rampazzo, Alessandro Della Puppa, Francesca Pistollato, and Giuseppe Basso Copyright © 2011 Luca Persano et al. All rights reserved. Neuroscience of Meditation Mon, 01 Jan 1900 00:00:00 +0000 Dhyana-Yoga is a Sanskrit word for the ancient discipline of meditation, as a means to Samadhi or enlightenment. Samadhi is a self-absorptive, adaptive state with realization of one’s being in harmony with reality. It is unitive, undifferentiated, reality-consciousness, an essential being, which can only be experienced by spontaneous intuition and self-understanding. Modern neuroscience can help us to better understand Dhyana-Yoga. This article discusses topics including brain-mind-reality, consciousness, attention, emotional intelligence, sense of self, meditative mind, and meditative brain. A new hypothesis is proposed for a better understanding of the meditative mind. Meditation is an art of being serene and alert in the present moment, instead of constantly struggling to change or to become. It is an art of efficient management of attentional energy with total engagement (poornata, presence, mindfulness) or disengagement (shunyata, silence, emptiness). In both states, there is an experience of spontaneous unity with no sense of situational interactive self or personal time. It is a simultaneous, participatory consciousness rather than a dualistic, sequential attentiveness. There is a natural sense of well being with self-understanding, spontaneous joy, serenity, freedom, and self-fulfillment. It is where the ultimate pursuit of happiness and the search for meaning of life resolve. One realizes the truth of one’s harmonious being in nature and nature in oneself. It is being alive at its fullest, when each conscious moment becomes a dynamic process of discovery and continuous learning of the ever-new unfolding reality. Vinod D. Deshmukh Copyright © 2006 Vinod D. Deshmukh. All rights reserved. Opioid-Induced Glial Activation: Mechanisms of Activation and Implications for Opioid Analgesia, Dependence, and Reward Mon, 01 Jan 1900 00:00:00 +0000 This review will introduce the concept of toll-like receptor (TLR)–mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward). Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference) and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine) level of analysis. Moreover, a novel antagonism of TLR4 by (+)- and (˗)-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia) and unwanted (tolerance, dependence, and reward) actions of opioids, thereby improving the safety and efficacy of their use. Mark R. Hutchinson, Sondra T. Bland, Kirk W. Johnson, Kenner C. Rice, Steven F. Maier, and Linda R. Watkins Copyright © 2007 Mark R. Hutchinson et al. All rights reserved. Quality of Life Philosophy III. Towards a New Biology: Understanding the Biological Connection between Quality of Life, Disease, and Healing Mon, 01 Jan 1900 00:00:00 +0000 This paper addresses (in a philosophical way) the complex and enigmatic interface between matter, life, and consciousness in modern medical science. The problem today in understanding living matter is not at the molecular level, but at the macro level where all molecular activities in the individual cell are coordinated, and especially at a higher level, where the activities of all the organism’s cells are coordinated. Although we understand very much of the body’s chemistry, we have only just started to get the gist of the tremendous organization of living matter. We are just beginning to acknowledge the enormous flow of information that is needed to make everything function in a healthy organism, including consciousness, where every cell does exactly what it has to do to make the organs function.A concept that seems to be able to bridge the scientifically very different domains of matter, life, and consciousness seems to be “biological information”. If a cell is seen as a liquid crystal in which the cell’s molecules constantly connect in firm mutual relationships only to dissolve again and become fluid and free, whenever the cell needs it, the backbone of the cell seems to be the information that organizes the cell. For example, in cell motion a cell is able to crawl with the help of a skeleton of fibers that can be created guided by biological information, whenever the cell needs the solidity provided by the fibers. The moment it has finished crawling or intends to crawl in another direction, these fibers will dissolve again. The fibers are made of millions of molecules that connect in an arranged pattern, and they dissolve when these molecules again let go of each other. How the cell precisely regulates such processes is today a complete mystery. How cells cocreate consciousness is also an enigma. All we can do is describe the cell and the organisms arising from its cells as filled with energy and information as well as an unbeatable ability to organize itself way down to the molecular level, where apparently the cell is in control of almost every single molecule.Our understanding today of how the information is stored and how it flows through living matter is still very limited. The source of the qualities (the qualia) characterizing the human being as a whole — like joy, love, motivation, consciousness, free will, wisdom, intuitive competence — is still practically unknown and scientifically unexplained, more than 50 years after science has turned itself towards these fundamental problems. We believe that we need a radically new biology and medicine to give the scientific explanations of the structure, dynamics, and quality of life, and of its consciousness. Soren Ventegodt, Niels Jørgen Andersen, and Joav Merrick Copyright © 2003 Soren Ventegodt et al. All rights reserved. White Matter Lesions and Cognitive Impairment as Silent Cerebral Disease in Hypertension Mon, 01 Jan 1900 00:00:00 +0000 Although the pathogenesis and clinical significance of cerebral white matter lesions remain controversial, it is well established that age and hypertension are the most important factors related to the presence of these lesions. Hypertension is known to be the most important factor for developing stroke and vascular dementia. In addition, the presence of cerebral white matter lesions is an important prognostic factor for the development of stroke, and also for cognitive impairment and dementia. The mechanisms underlying hypertension-related cognitive changes are complex and are not yet fully understood. Correlations between cerebral white matter lesions and elevated blood pressure provide indirect evidence that structural and functional changes in the brain over time may lead to lowered cognitive functioning when blood pressure control is poor or lacking.Some authors have suggested that the presence of white matter lesions in hypertensive patients could be considered an early marker of brain damage. Cristina Sierra and Antonio Coca Copyright © 2006 Cristina Sierra and Antonio Coca. All rights reserved. The Israeli Rett Syndrome Center. Evaluation and Transdisciplinary Play-Based Assessment Mon, 01 Jan 1900 00:00:00 +0000 Rett syndrome (RS) is a neuro-developmental syndrome of genetic origin, which mainly affects women. Individuals diagnosed with RS exhibit a variety of functional difficulties, which impair their quality of life. The variety of impairments and the differences between each child makes it necessary to administer skilled treatment, individually tailored to each client. Since the foundation of proper treatment is based on a structured, well administered, insightful assessment, the individual with RS with her complex array of difficulties should benefit from such a procedure. This notion has led to the establishment of the Israel Rett Syndrome Center. The center includes a medical branch located at the Safra Shildren's Medical Center at Tel Hashomer and an education/rehabilitation team, who performs assessments in special education facilities and residential settings throughout Israel. The assessment team works by means of arena assessment according to the concept of play-based assessment. This article presents the working model used by the education/rehabilitation team at the Israeli Rett Syndrome Center. The principles and working characteristics of the Israel Rett Syndrome Center team are suggested here as a potential model for establishing additional teams, presenting similar evaluation services for other individuals with RS as well as for analogous populations. Meir Lotan, Iris Manor-Binyamini, Cochavit Elefant, Judy Wine, Einat Saraf, and Yael Yoshei Copyright © 2006 Meir Lotan et al. All rights reserved. Role Of Cgrp In Sensitization Of Dura Mater Mon, 01 Jan 1900 00:00:00 +0000 The mammalian dura mater encephali is richly supplied by trigeminal nerve fibers, a considerable proportion of which contains calcitonin gene-related peptide (CGRP). As plasma levels of CGRP are increased in some forms of headaches, the question is in which way CGRP is involved in nociceptive mechanisms within the peripheral and the central trigeminovascular system. K. Messlinger Copyright © 2001 K. Messlinger. All rights reserved. Visceral Afferent Pathways and Functional Brain Imaging Mon, 01 Jan 1900 00:00:00 +0000 The application of functional imaging to study painful sensations has generated considerable interest regarding insight into brain dysfunction that may be responsible for functional pain such as that suffered in patients with irritable bowel syndrome (IBS). This review provides a brief introduction to the development of brain science as it relates to pain processing and a snapshot of recent functional imaging results with somatic and visceral pain. Particular emphasis is placed on current hypotheses regarding dysfunction of the brain-gut axis in IBS patients. There are clear and interpretable differences in brain activation following somatic as compared with visceral noxious sensation. Noxious visceral distension, particularly of the lower gastrointestinal tract, activates regions associated with unpleasant affect and autonomic responses. Noxious somatic sensation, in contrast, activates regions associated with cognition and skeletomotor responses. Differences between IBS patients and control subjects, however, were far less clear and interpretable. While this is in part due to the newness of this field, it also reflects weaknesses inherent within the current understanding of IBS. Future use of functional imaging to examine IBS and other functional disorders will be more likely to succeed by describing clear theoretical and clinical endpoints. Stuart W.G. Derbyshire Copyright © 2003 Stuart W.G.�Derbyshire. All rights reserved. Zebrin II Expressing Purkinje Cell Phenotype—Related and—Unrelated Cerebellar Abnormalities in Ca˅2.1 Mutant, Rolling Mouse Nagoya Mon, 01 Jan 1900 00:00:00 +0000 Rolling mouse Nagoya is an ataxic mutant mouse that carries a mutation in a gene encoding for the alpha 1A subunit of the voltage-gated P/Q-type Ca2+ channel (Ca˅2.1). This report summarizes our studies and others concerning cerebellar abnormalities in rolling mice based on chemical neuroanatomy. While there are no obvious cerebellar deformations in this mutant mouse, the altered functions of Purkinje cells can be revealed as a reduced expression of type 1 ryanodine receptor (RyR1) in all Purkinje cells uniformly throughout the cerebellum, and as an ectopic expression of tyrosine hydroxylase (TH) in the Purkinje cell subsets with the zebrin II—immunopositive phenotype. As the mutated Ca˅2.1 channel is expressed at uniform levels in all Purkinje cells, its copresence with RyR1 staining suggests that a Ca˅2.1 channel dysfunction links with the expression of RyR1 in Purkinje cells of rolling mice. However, an ectopic expression of TH in the Purkinje cells is topologically related to the projection of corticotrophin-releasing factor—immunopositive climbing fibers rather than expression of the mutated Ca˅2.1 channel. On the other hand, increased levels of serotonin (5-HT) in 5-HTergic fibers were revealed immunohistochemically in Purkinje cells of the vermis of rolling cerebellum. Thus, to determine whether or not cerebellar abnormalities are related to Purkinje cell populations revealed by zebrin II expression is essential for enhancing our understanding of the pathogenesis of hereditary cerebellar ataxic mutants such as rolling mice. Kazuhiko Sawada and Yoshihiro Fukui Copyright © 2010 Kazuhiko Sawada and Yoshihiro Fukui. All rights reserved. Synthetic Peptide Corresponding to The Amino-Terminal Region of the Human Tryptophanyl-Trna Synthetase, a Component Of Alzheimer’S Disease Special Congophlic Plaques Aggregates In Vitro to Form Amyloid-Like Fibrils Mon, 01 Jan 1900 00:00:00 +0000 Elena L. Paley, Vladimir Malinovskii, and Beka Solomon Copyright © 2002 Elena L. Paley et al. All rights reserved. A Discussion of the Role of Frontoparietal Activity in Cognition Mon, 01 Jan 1900 00:00:00 +0000 A consistently observed pattern in the functional brain imaging literature is that of joint frontal and parietal activation.  Because this pattern of activation has been observed under many different experimental conditions and when different cognitive domains have been tested, it is likely that frontoparietal activity plays a very general role in cognition.  This article considers one such possible role – the representation of behaviourally relevant information. Nicholas Hon Copyright © 2007 Nicholas Hon. All rights reserved. The Role of Accumbal Hypoactivity in Cocaine Addiction. Mon, 01 Jan 1900 00:00:00 +0000 Cocaine-induced hypoactivity of the nucleus accumbens (NAC) is hypothesized to contribute to cocaine addiction. There are two important questions related to this hypothesis. First, cocaine addiction is characterized by an increase in drug-directed behavior and a simultaneous weakening of other motivated behaviors. However, the NAC contributes to both drug- and nondrug-directed behavior. Moreover, the nature of the contributions is similar and associated predominantly with excitatory phasic firing patterns. Given these observations it is not clear how hypoactivity of NAC neurons might contribute to the behaviors that characterize cocaine addiction. Second, various types of investigations have documented neurochemical and molecular adaptations that could underlie NAC hypoactivity. However, there is also evidence of other adaptations in the NAC, and in NAC afferents, which are expected to have an excitatory influence on NAC neural activity. In the present review we will briefly overview these issues. We will also describe a hypothesis, and related empirical evidence, that may contribute to answering these questions. Further investigation of the issues and the hypothesis may contribute to a better understanding of the neuroadaptations that contribute to cocaine addiction. L. L. Peoples, A. V. Kravitz, and K. Guillem Copyright © 2007 L. L. Peoples et al. All rights reserved. F-Waves – Physiology and Clinical Uses Mon, 01 Jan 1900 00:00:00 +0000 F-waves are low amplitude responses produced by antidromic activation of motoneurons. They may not appear after each stimulus and are inherently variable in latency, amplitude, and configuration. Meaningful analysis of F-waves requires an appreciation of these characteristics of F-waves as well as an understanding of their physiology. These features of F-waves as well as their physiology are reviewed. This is important since F-waves are one of the most frequently used studies in clinical neurophysiology and much of the controversies surrounding the use of F-waves relates to a failure to adequately consider the requirements of F-wave analysis. These requirements include the number of F-waves that need to be recorded, the parameters that should be evaluated, and the muscle from which the F-waves are recorded. If analyzed correctly, current reports would indicate that F-waves are the most sensitive and reliable nerve conduction study for evaluating polyneuropathies, can be abnormal in focal proximal nerve dysfunction, can be at least as sensitive as needle electromyography for defining lumbosacral radiculopathies, and can provide a meaningful physiological window into disorders of the central nervous system. Reports supporting these statements and their clinical relevance are discussed. Morris A. Fisher Copyright © 2007 Morris A. Fisher. All rights reserved. Neuromodulation for Lower Urinary Tract Dysfunction – An Update Mon, 01 Jan 1900 00:00:00 +0000 The aim of this review is to provide an update on the use of neuromodulation using sacral nerve stimulation for the treatment of disorders of the lower urinary tract. Neuromodulation using the InterStim® system (Medtronic Inc.) is now accepted as an established therapeutic option for patients with detrusor overactivity, and for women with retention or severe voiding difficulties. However, the use of nerve stimulation in modulating lower urinary tract function has to be regarded as a technique that is in its infancy. Much has yet to be learned about the mechanism by which neuromodulation exerts its effects and there is a need to better define the clinical indications for the treatment. There is also work to be done in terms of optimising stimulation delivery, both in anatomical and electronic terms. Zahid Hussain and Simon C. W. Harrison Copyright © 2007 Zahid Hussain and Simon C. W. Harrison. All rights reserved. Altered Neuroadaptation in Opiate Dependence and Neurogenic Inflammatory Nociception in αCGRP Deficient Mice Mon, 01 Jan 1900 00:00:00 +0000 A.-M. Salmon, I. M. Damaj, L. M. Marubio, M. P. Epping-Jordan, E. Merlo Pich, and J.-P. Changeux Copyright © 2001 A.-M. Salmon et al. All rights reserved. Spina Bifida Advocacy – A Case Study In Public Policy Success Mon, 01 Jan 1900 00:00:00 +0000 Cindy Brownstein, Ilisa Halpern Paul, and Anne House Quinn Copyright © 2007 Cindy Brownstein et al. All rights reserved. Neurophysiological Effects of Chronic Indoor Environmental Toxic Mold Exposure on Children Mon, 01 Jan 1900 00:00:00 +0000 The phenomenon of building-related diseases is attracting much research interest in recent years because of the extent to which it affects people with compromised immune systems, especially children. In this study, we reported the neurological findings in children who attended our Center because of chronic exposure to toxic molds. Clinical neurological and neurobehavioral questionnaires were administered with the cooperation of the children�s parents. The children then underwent a series of neurophysiological tests including electroencephalogram (EEG), brainstem evoked potential (BAEP), visual evoked potential (VEP), and somatosensory evoked potential (SSEP). The results showed high levels of abnormalities in the analysis of the subjective responses derived from the questionnaires. The EEG examination was abnormal in seven out of ten of the patients compared to the controls with only one in ten with episodes of bihemispheric sharp activity. In all the patients, there was frontotemporal theta wave ativity that seemed to indicate diffuse changes characteristic of metabolic encephalopathies. Also, there was highly marked 1 to 3 Hz delta activity that was asymmetrical in the right hemisphere of the brain in three out of ten patients. The waveforms of BAEP showed abnormalities in 90% of the patients with both 15’ and 31’ check sizes compared to none in the controls. There were significant delays in waveform V in a majority of the patients representing dysfunctional cognitive process and conductive hearing loss in both ears. VEP showed clear abnormalities in four in ten of the patients with P100 amplitudes and latencies decreased bilaterally. In all the patients, there was slowing of conduction in the right tibial at an average of 36.9 ms and there was significant decrease in amplitude of response at the proximal stimulation site. Sensory latencies obtained in the median, ulnar, and sural nerves bilaterally showed abnormalities in five out of ten compared to none in the controls. The median, ulnar, and sural sensory potentials were abnormal in six out of ten patients. There was prolongation of the median distal sensory latencies bilaterally at an average of 4.55 ms on the right and an average of 6.10 ms on the left as compared to the ulnars of 2.55 ms bilaterally. There was no abnormality in the controls. These findings represent evidence of diffuse polyneuropathy to which three patients demonstrated borderline slow motor conduction at an average of 41.1 ms. Overall, the objective neurophysiological measurements (EEG, BAEP, VEP, and SSEP) were abnormal, indicating significant neurological deficits in all the patients. Our findings revealed the extent to which toxic molds can affect the neurological and behavioral status of children. Further work should be encouraged in this regard. Ebere C. Anyanwu, Andrew W. Campbell, and Aristo Vojdani Copyright © 2003 Ebere C. Anyanwu et al. All rights reserved. The Thorny Side of Addiction: Adaptive Plasticity and Dendritic Spines Mon, 01 Jan 1900 00:00:00 +0000 Dendritic spines are morphologically specialized structures that receive the vast majority of central excitatory synaptic inputs. Studies have implicated changes in the size, shape, and number of dendritic spines in activity-dependent plasticity, and have further demonstrated that spine morphology is highly dependent on the dynamic organizational and scaffolding properties of its postsynaptic density (PSD). In vitro and in vivo models of experience-dependent plasticity have linked changes in the localization of glutamate receptors at the PSD with a molecular reorganization of the PSD and alterations in spine morphology. Chronic ethanol consumption results in adaptive changes in neuronal function that manifest as tolerance, physical dependence, and addiction. A potential mechanism supporting these adaptive changes that we recently identified is the homeostatic targeting of NR2B-containing NMDA receptors to the synapse. This increase is associated with and dependent on a corresponding increase in the localization of the scaffolding protein PSD-95 at the PSD, and with an actin-dependent increase in the size of dendritic spines. These observations led us to propose a molecular model for ethanol-induced plasticity at excitatory synapses in which increases in NR2B-containing NMDA receptors and PSD-95 at the PSD provide an expanded scaffolding platform for the recruitment and activation of signaling molecules that regulate spine actin dynamics, protein translation, and synaptic plasticity. This model is consistent with accumulating evidence that glutamatergic modulation of spine actin by the PSD plays a role in the aberrant plasticity of addiction. Patrick J. Mulholland and L. Judson Chandler Copyright © 2007 Patrick J. Mulholland and L. Judson Chandler. All rights reserved. Modulation of the Expression of Calcitonin Gene-Related Peptide and Substance P in Cultured Dorsal Root Ganglia by Opioid Receptor Agonists. Involvement of the PKC Pathway Mon, 01 Jan 1900 00:00:00 +0000 S. Bolanger, W. Ma, J.-G. Chabot, and R. Quirion Copyright © 2001 S. Bolanger et al. All rights reserved. Human Development XI: The Structure of the Cerebral Cortex. Are There Really Modules in the Brain? Mon, 01 Jan 1900 00:00:00 +0000 The structure of human consciousness is thought to be closely connected to the structure of cerebral cortex. One of the most appreciated concepts in this regard is the Szanthagothei model of a modular building of neo-cortex. The modules are believed to organize brain activity pretty much like a computer. We looked at examples in the literature and argue that there is no significant evidence that supports Szanthagothei's model. We discuss the use of the limited genetic information, the corticocortical afferents termination and the columns in primary sensory cortex as arguments for the existence of the cortex-module. Further, we discuss the results of experiments with Luminization Microscopy (LM) colouration of myalinized fibres, in which vertical bundles of afferent/efferent fibres that could support the cortex module are identified. We conclude that sensory maps seem not to be an expression for simple specific connectivity, but rather to be functional defined. We also conclude that evidence for the existence of the postulated module or column does not exist in the discussed material. This opens up for an important discussion of the brain as functionally directed by biological information (information-directed self-organisation), and for consciousness being closely linked to the structure of the universe at large. Consciousness is thus not a local phenomena limited to the brain, but a much more global phenomena connected to the wholeness of the world. Tyge Dahl Hermansen, Søren Ventegodt, and Isack Kandel Copyright © 2007 Tyge Dahl Hermansen et al. All rights reserved. Developmental and Activity Dependent Regulation of Ionotropic Glutamate Receptors at Synapses Mon, 01 Jan 1900 00:00:00 +0000 Glutamate receptors mediate the majority of excitatory responses in the central nervous system. The establishment and refinement of glutamatergic synaptic connections depend on the concerted actions of a-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), N-methyl-D-aspartate (NMDA), and kainate (KA) type ionotropic glutamate receptors (iGluRs) and G-protein coupled metabotropic receptors. While a lot remains to be clarified, the most is known about the mechanisms by which the iGluR subtypes are targeted and how this is influenced by synaptic activity on both short and long time scales. Changes in their subunit compositions are also input specific and developmentally regulated. The identification of key molecular components of the postsynaptic density (PSD) and novel proteins that influence receptor targeting and clustering have started to reveal the underlying molecular mechanisms of the trafficking and targeting of iGluRs. Here we discuss the evidence that these basic mechanisms are used during developmental synaptic plasticity. Elek Molnar and John T.R. Isaac Copyright © 2002 Elek Molnar and John T.R. Isaac. All rights reserved. Retroperitoneal Ganglioneuroma Encasing the Celiac and Superior Mesenteric Arteries Mon, 01 Jan 1900 00:00:00 +0000 Ganglioneuroma is a rare neoplasm arising from the sympathoadrenal neuroendocrine system and has anatomic distribution paralleling the sympathetic chain ganglia and the adrenal medulla. In some cases, ganglioneuroma is the end stage maturation of less-differentiated neoplasms such as neuroblastoma or ganglioneuroblastoma, but based on age at diagnosis (over 10 years of age) and anatomic location, many of these tumors appear to arise de novo. It must be included in the differential diagnosis of posterior mediastinal and retroperitoneal mass. We report a case of retroperitoneal ganglioneuroma involving the celiac axis and superior mesenteric arteries in a 40-year-old female. Justin K. Nelms, Eric K. Diner, Ernest E. Lack, Sunil V. Patel, Seyed R. Ghasemian, and Mohan Verghese Copyright © 2004 Justin K. Nelms et al. All rights reserved. Integrated Brain Circuits: Neuron-Astrocyte Interaction in Sleep-Related Rhythmogenesis Mon, 01 Jan 1900 00:00:00 +0000 Although astrocytes are increasingly recognized as important modulators of neuronal excitability and information transfer at the synapse, whether these cells regulate neuronal network activity has only recently started to be investigated. In this article, we highlight the role of astrocytes in the modulation of circuit function with particular focus on sleep-related rhythmogenesis. We discuss recent data showing that these glial cells regulate slow oscillations, a specific thalamocortical activity that characterizes non-REM sleep, and sleep-associated behaviors. Based on these findings, we predict that our understanding of the genesis and tuning of thalamocortical rhythms will necessarily go through an integrated view of brain circuits in which non-neuronal cells can play important neuromodulatory roles. Michael M. Halassa, Marco Dal Maschio, Riccardo Beltramo, Philip G. Haydon, Fabio Benfenati, and Tommaso Fellin Copyright © 2010 Michael M. Halassa et al. All rights reserved. Human Development XII: A Theory for the Structure and Function of the Human Brain Mon, 01 Jan 1900 00:00:00 +0000 The human brain is probably the most complicated single structure in the biological universe. The cerebral cortex that is traditionally connected with consciousness is extremely complex. The brain contains approximately 1,000,000 km of nerve fibers, indicating its enormous complexity and which makes it difficult for scientists to reveal the function of the brain. In this paper, we propose a new model for brain functions, i.e., information-guided self-organization of neural patterns, where information is provided from the abstract wholeness of the biophysical system of an organism (often called the true self, or the “soul””). We present a number of arguments in favor of this model that provide self-conscious control over the thought process or cognition. Our arguments arise from analyzing experimental data from different research fields: histology, anatomy, electroencephalography (EEG), cerebral blood flow, neuropsychology, evolutionary studies, and mathematics. We criticize the popular network theories as the consequence of a simplistic, mechanical interpretation of reality (philosophical materialism) applied to the brain. We demonstrate how viewing brain functions as information-guided self-organization of neural patterns can explain the structure of conscious mentation; we seem to have a dual hierarchical representation in the cerebral cortex: one for sensation-perception and one for will-action. The model explains many of our unique mental abilities to think, memorize, associate, discriminate, and make abstractions. The presented model of the conscious brain also seems to be able to explain the function of the simpler brains, such as those of insects and hydra. Søren Ventegodt, Tyge Dahl Hermansen, Isack Kandel, and Joav Merrick Copyright © 2008 SȖren Ventegodt et al. All rights reserved. Control of Cell Survival and Proliferation in the Oligodendrocyte Cell Lineage Mon, 01 Jan 1900 00:00:00 +0000 Martin Raff, Yasu Tokumoto, and Dean Tang Copyright © 2001 Martin Raff et al. All rights reserved. A 5-Year Audit of Accidental Dural Punctures, Postdural Puncture Headaches, and Failed Regional Anesthetics at a Tertiary-Care Medical Center Mon, 01 Jan 1900 00:00:00 +0000 Obstetric anesthesia-related complications occur as a result of labor epidural or spinal placement. The purpose of this continuous quality-improvement audit was to review the occurrence of accidental dural punctures (ADPs), postdural puncture headaches (PDPHs), and failed regional anesthetics at an academic tertiary-care medical center over a 5-year period. Obstetric anesthesia complications contained in three databases consisting of ADPs, PDPHs, and failed regional anesthetics were matched to a perinatal database, with no complications serving as controls. Of the 40,894 consecutive parturients, there were 765 documented complications. Complication rates were 0.73% (95% CI: 0.65–0.82) for ADP, 0.49% (95% CI: 0.43–0.56) for PDPH, and 0.65% (95% CI: 0.57–0.73) for failed regional anesthetic. When compared to the no complication group, factors associated with obstetric anesthesia complications included increased weight and BMI (p < 0.01), epidural block (p < 0.01), and vaginal delivery (p< 0.01). Sukhdip Singh, Shagufta Y. Chaudry, Amy L. Phelps, and Manuel C Vallejo Copyright © 2009 Sukhdip Singh et al. All rights reserved. Bluish Discolouration of Urine Drainage Tube and Bag in a Female Patient with Spina Bifida, Paraplegia, and Suprapubic Cystostomy Mon, 01 Jan 1900 00:00:00 +0000 We present a female patient with spina bifida, paraplegia, suprapubic cystostomy, and chronic constipation, who became anxious when she noticed a bluish discolouration of her urine drainage system. Urine microbiology revealed growth of Providencia stuartii and Staphylococcus aureus. There were no systemic features of infection and, therefore, antibiotics were not prescribed for asymptomatic bacteriuria. This patient was advised to change the urine bag every day, and was prescribed senna to facilitate bowel evacuation. She was reassured that bluish discolouration of the urine drainage tube and bag was a transient, benign phenomenon and not indicative of any underlying pathology. Over the next 7 days, the bluish discolouration gradually faded away. Clinical characteristics of patients who are likely to develop this phenomenon and the underlying biochemical mechanism for bluish discolouration of the urine drainage system are discussed in brief. Subramanian Vaidyanathan and Bakul M. Soni Copyright © 2007 Subramanian Vaidyanathan and Bakul M Soni. All rights reserved. Anterograde and Retrograde Effects of Benzodiazepines on Memory Mon, 01 Jan 1900 00:00:00 +0000 Benzodiazepines are known as “acquisition-impairing” molecules, and their effects on anterograde memory processes are well described. In contrast, the impact of benzodiazepines on retrograde memory and, more particularly, on retrieval processes, is only marginally studied. This mini-review provides an overlook of the main studies evidencing an effect of benzodiazepines on retrograde memory, both in humans and animals, with special emphasis on retrieval processes. The conditions for the emergence of the benzodiazepine-induced retrieval impairments are also discussed. Daniel Beracochea Copyright © 2006 Daniel Beracochea. All rights reserved. Glial Cells and the Neurobiology of Addiction Mon, 01 Jan 1900 00:00:00 +0000 Diane M. P. Lawrence, David A. Thomas, and Da-Yu Wu Copyright © 2007 Diane M. P. Lawrence et al. All rights reserved. Proteins Involved in the Trafficking and Functional Synaptic Expression of AMPA and KA Receptors Mon, 01 Jan 1900 00:00:00 +0000 α-Amino-3-hydroxy-5-methylisoxazolepropionate receptors (AMPARs) mediate the majority of fast synaptic transmission in the mammalian central nervous system, play a central role in synapse stabilisation and plasticity, and their prolonged activation is potently neurotoxic. The functional roles of kainate receptors (KARs) are less well defined but they play a role in some forms of synaptic plasticity. Both receptor types have been shown to be highly developmentally and activity-dependently regulated and their functional synaptic expression is under tight cellular regulation. The molecular and cellular mechanisms that regulate the synaptic localisation and functional expression of AMPARs and KARs are objects of concerted research. There has been significant progress towards elucidating some of the processes involved with the discovery of an array of proteins that selectively interact with individual AMPAR and KAR subunits. These proteins have been implicated in, among other things, the regulation of post-translational modification, targeting and trafficking, surface expression, and anchoring. The aim of this review is to present an overview of the major interacting proteins and suggest how they may fit into the hierarchical series of events controlling the trafficking of AMPARs and KARs. Sarah A. De La Rue and Jeremy M. Henley Copyright © 2002 Sarah A. De La Rue and Jeremy M. Henley. All rights reserved. Repeat Intrathecal Triamcinolone Acetonide Application Reduces Acute Occurring Painful Dysesthesia in Patients with Relapsing Remitting Multiple Sclerosis Mon, 01 Jan 1900 00:00:00 +0000 We describe four patients with relapsing remitting multiple sclerosis (RRMS) who experienced a relapse with acute onset of painful sensations. Pain sensations disappeared in two of them and markedly reduced in the other ones after repeat application of intrathecal triamcinolone acetonide (TCA) following a prior unsuccessful treatment with intravenous steroids. TCA administration was well tolerated and no serious side effects occurred. Repeated intrathecal TCA injection may provide a substantial benefit in RRMS patients with acute onset of pain due to an inflammatory lesion within the spinal cord. Kerstin Hellwig, Carsten Lukas, Niels Brune, Volker Hoffmann, Sebastian Schimrigk, Horst Przuntek, and Thomas Müller Copyright © 2006 Kerstin Hellwig et al. All rights reserved. Rett Syndrome. Guidelines for Individual Intervention Mon, 01 Jan 1900 00:00:00 +0000 Rett syndrome (RS) is a neurological disorder affecting mainly females. RS is considered the second most frequent cause for severe and complex neurological dysfunction in females after Down syndrome. Patients with RS are characterized by an array of neurological and orthopedic difficulties that mandate an intensive therapeutic intervention program for the duration of the individual's life. Many aspects of the client’s well-being and functional status depend on the therapeutic intervention she receives and on her compliance to it. This article will briefly review common intervention approaches for individuals with RS and their present day's application. Due to the notion that individual intervention is the foundation on which progress and development of the functional gains rests, the present article will place basic guidelines for individual intervention with clients with RS. The article is mainly based on the clinical experience of the author and others working with individuals with RS. Meir Lotan Copyright © 2006 Meir Lotan. All rights reserved. From Hydra Regeneration to Human Brain Structural Plasticity: A Long Trip through Narrowing Roads Mon, 01 Jan 1900 00:00:00 +0000 Regeneration is a strategy to maintain form and function throughout life. Studies carried out on animal models throughout the phylogenetic tree have flourished in the last decades in search of mechanisms underlying the regenerative processes. The development of such studies is strictly linked with stem cell research and both are viewed as one of the most promising outcomes for regenerative medicine; yet, regeneration, stem cells, and tissue repair do not seem to follow a logical path through the different animal species and tissues. As a result, some mammalian organs, e.g., kidney and brain, have lost most of their regenerative capacity. The human nervous system, although harboring neural stem cells, is placed at the extreme of “perennial” tissues. In addition, it is affected by neurodegenerative diseases, whose heavy burden is heightened by enhanced life spans. This review, starting from the basic principles of tissue regeneration viewed in a comparative context, tries to answer this question: To which extent can regenerative medicine be figured out in a mammalian brain equipped with many anatomical/evolutionary constraints? Luca Bonfanti Copyright © 2011 Luca Bonfanti. All rights reserved. Metabolism of Mycotoxins, Intracellular Functions of Vitamin B12, and Neurological Manifestations in Patients with Chronic Toxigenic Mold Exposures. A Review Mon, 01 Jan 1900 00:00:00 +0000 This paper evaluates the possible reasons for consistent vitamin B12 deficiency in chronic toxigenic mold exposures and the synergistic relationships with the possible mycotoxic effects on one-carbon metabolism that lead to the manifestations of clinical neuropathological symptomology. Vitamins are first defined in general and the nutritional sources of vitamin B12 are evaluated in particular. Since patients with chronic exposures to toxigenic molds manifest vitamin B12 deficiencies, the role of mycotoxins in vitamin B12 metabolism is assessed, and since vitamin B12 plays important biochemical roles in one-carbon metabolism, the synergistic effects with mycotoxins on humans are reviewed. An outline of the proposed mechanism by which mycotoxins disrupt or interfere with the normal functions of vitamin B12 on one-carbon metabolism is proposed. The overall functions of vitamin B12 as a source of coenzymes, in intracellular recycling of methionine, in methionine synthase reaction, in the prevention of chromosome breakage, in methylation, and in maintaining a one-carbon metabolic balance are reviewed. Signs, symptoms, and clinical neurological indications of vitamin B12 deficiency are also cited. By implication and derivation, it is likely that the interruption of the structure and function of vitamin B12 would in turn interfere with the one-carbon metabolism leading to the neurological manifestations. This review is an attempt to formulate a basis for an ongoing research investigation on the subject. Ebere C. Anyanwu, Mohammed Morad, and Andrew W. Campbell Copyright © 2004 Ebere C. Anyanwu et al. All rights reserved. Alcohol and Suicide: Neurobiological and Clinical Aspects Mon, 01 Jan 1900 00:00:00 +0000 Alcohol, primarily in the form of ethyl alcohol (ethanol), has occupied an important place in the history of humankind for at least 8,000 years. In most Western societies, at least 90% of people consume alcohol at some time during their lives, and 30% or more of drinkers develop alcohol-related problems. Severe alcohol-related life impairment, alcohol dependence (alcoholism), is observed at some time during their lives in about 10% of men and 3—5% of women. An additional 5—10% of each sex develops persistent, but less intense, problems that are diagnosed as alcohol abuse. It this review, neurobiological aspects of suicidal behavior in alcoholism is discussed. In individuals with comorbid depression and alcoholism, greater serotonergic impairment may be associated with higher risk of completed suicide. Dopaminergic dysfunction may play an important role in the pathophysiology of suicidal behavior in alcoholism. Brain damage and neurobehavioral deficits are associated with alcohol use disorders and may contribute to suicidal behavior in persons with alcohol dependence or abuse. Aggression/impulsivity and alcoholism severity affect risk for suicide among individuals with alcoholism. Major depressive episodes and stressful life events particularly, partner-relationship disruptions, may precipitate suicidal behavior in individuals with alcohol use disorders. Alcohol misuse and psychosocial adversity can combine to increase stress on the person, and, thereby, potentially, increase the risk for suicidal behavior. The management of suicidal patients with alcohol use disorders is also discussed. It is to be hoped that the efforts of clinicians will reduce morbidity and mortality associated with alcohol misuse. Leo Sher Copyright © 2006 Leo Sher. All rights reserved. Sex-Change Chemicals and their Influence on the Brain Mon, 01 Jan 1900 00:00:00 +0000 The potential for man-made chemicals to mimic or antagonise natural hormones is a controversial issue, but one for which increasing amounts of evidence are being gathered worldwide. The controversy surrounds not so much the matter of whether these chemicals can mimic hormones in vitro — this phenomenon has been widely accepted in the scientific world — but more whether, as a result, they can disrupt reproduction in a wildlife situation. It has, nevertheless, been acknowledged that many wildlife populations are exhibiting reproductive and/or developmental abnormalities such as intersex gonads in wild roach populations in the U.K.[1] and various reproductive disorders in alligators in Lake Apopka, Florida[2]. However, the causative agents for many of these effects are difficult to specify, due to the extensive mixtures of chemicals — each of which may act via different pathways — to which wild populations are exposed, together with the wide variability observed even in natural (uncontaminated) habitats. As a result, any information detailing fundamental mechanism of action of the so-called endocrine disrupting chemicals (EDCs) is of use in determining whether or not these chemicals, as they are present in the environment, may in fact be capable of causing some of the effects observed in wildlife over recent years. Catherine A. Harris Copyright © 2001 Catherine A. Harris. All rights reserved. Estimating Brain Load from the EEG Mon, 01 Jan 1900 00:00:00 +0000 Modern work requires cognitively demanding multitasking and the need for sustained vigilance, which may result in work-related stress and may increase the possibility of human error. Objective methods for estimating cognitive overload and mental fatigue of the brain on-line, during work performance, are needed. We present a two-channel electroencephalography (EEG)–based index, theta Fz/alpha Pz ratio, potentially implementable into a compact wearable device. The index reacts to both acute external and cumulative internal load. The index increased with the number of tasks to be performed concurrently (p = 0.004) and with increased time awake, both after normal sleep (p = 0.002) and sleep restriction (p = 0.004). Moreover, the increase of the index was more pronounced in the afternoon after sleep restriction (p = 0.006). As a measure of brain state and its dynamics, the index can be considered equivalent to the heartbeat, an indicator of the cardiovascular state, thus inspiring the name "brainbeat". Anu Holm, Kristian Lukander, Jussi Korpela, Mikael Sallinen, and Kiti M. I. Müller Copyright © 2009 Anu Holm et al. All rights reserved. Cgrp Uptake into Perivascular Capsaicin-Sensitive Nerve Terminals Mon, 01 Jan 1900 00:00:00 +0000 Specific mechanisms, providing reuptake of cathecholamine and amino acid neurotransmitters (e.g., serotonin and glutamate) into cells of the central nervous system are well known, whereas neuronal uptake of neuropeptides have not previously been reported. A. Sams-Nielsen, C. Orskov, and I. Jansen-Olesen Copyright © 2001 A. Sams-Nielsen et al. All rights reserved. Impulsivity and Addiction: A Tribute to Henri Begleiter Mon, 01 Jan 1900 00:00:00 +0000 Bernice Porjesz and Ting-Kai Li Copyright © 2007 Bernice Porjesz and Ting-Kai Li. All rights reserved. Diastematomyelia: A Case with Familial Aggregation of Neural Tube Defects Mon, 01 Jan 1900 00:00:00 +0000 Intrauterine neural tube defects, meningomyelocele, and diastematomyelia are developmental errors at different stages of the closure of the neural tube. The familial aggregation of these neural tube defects is not previously reported in the literature and should make one think about a common embryogenesis and a possible common mechanism of etiopathogenesis leading to anomalies at different stages of this embryogenesis. This paper presents a 12-year-old Turkish boy with diastematomyelia who was suspected with a demonstrative dermatologic finding without any neurologic sign and diagnosed with magnetic resonance imaging (MRI). He has a positive family history of a stillbirth with neural tube defect, an exitus with meningomyelocele, and an epileptic child in his female siblings. Nuray Öksüz Kanbur, Pınar Güner, Orhan Derman, Nejat Akalan, Ayşenur Cila, and Tezer Kutluk Copyright © 2004 Nuray Öksüz Kanbur et al. All rights reserved. Human Development XIII: The Connection Between the Structure of the Overtone System and the Tone Language of Music. Some Implications for Our Understanding of the Human Brain Mon, 01 Jan 1900 00:00:00 +0000 The functioning brain behaves like one highly-structured, coherent, informational field. It can be popularly described as a “coherent ball of energy”, making the idea of a local highly-structured quantum field that carries the consciousness very appealing. If that is so, the structure of the experience of music might be a quite unique window into a hidden quantum reality of the brain, and even of life itself. The structure of music is then a mirror of a much more complex, but similar, structure of the energetic field of the working brain. This paper discusses how the perception of music is organized in the human brain with respect to the known tone scales of major and minor. The patterns used by the brain seem to be similar to the overtones of vibrating matter, giving a positive experience of harmonies in major. However, we also like the minor scale, which can explain brain patterns as fractal-like, giving a symmetric “downward reflection” of the major scale into the minor scale. We analyze the implication of beautiful and ugly tones and harmonies for the model. We conclude that when it comes to simple perception of harmonies, the most simple is the most beautiful and the most complex is the most ugly, but in music, even the most disharmonic harmony can be beautiful, if experienced as a part of a dynamic release of musical tension. This can be taken as a general metaphor of painful, yet meaningful, and developing experiences in human life. Søren Ventegodt, Tyge Dahl Hermansen, Isack Kandel, and Joav Merrick Copyright © 2008 Søren Ventegodt et al. All rights reserved. Alterations in Neurogenic Inflammatory Responses in Mice Lacking αCGRP Mon, 01 Jan 1900 00:00:00 +0000 a-Calcitonin gene-related peptide (aCGRP) is a pleiotropic peptide neuromodulator that is widely expressed throughout the central and peripheral nervous systems. Although CGRP has been implicated in numerous physiological processes (including peripheral vasodilatation, acetylcholine receptor biosynthesis, nociception, and neurogenic inflammation), the precise physiological roles of CGRP remain to be elucidated. To provide a better understanding of the physiological role(s) mediated by this peptide neurotransmitter, we have generated aCGRP-null mice by targeted modification in embryonic stem cells. Jongho Lee and Ronald B. Emeson Copyright © 2001 Jongho Lee and Ronald B. Emeson. All rights reserved. Recent Progress in the Identification of the X-Linked Infantile Spinal Muscular Atrophy (Xl-SMA) Gene: Implications for Neuronal Apoptosis Mon, 01 Jan 1900 00:00:00 +0000 L. L. Baumbach, D. Dressman, H. Basterrechea, M. E. Ahearn, N. T. Bech-Hansen, R. D. Clark, A. Meind, and E. Hoffman Copyright © 2001 L.L. Baumbach et al. All rights reserved. Voluntary Spatial Attention has Different Effects on Voluntary and Reflexive Saccades Mon, 01 Jan 1900 00:00:00 +0000 Although numerous studies have investigated the relationship between saccadic eye movements and spatial attention, one fundamental issue remains controversial. Some studies have suggested that spatial attention facilitates saccades, whereas others have claimed that eye movements are actually inhibited when spatial attention is engaged. However, these discrepancies may be because previous research has neglected to separate and specify the effects of attention for two distinct types of saccades, namely reflexive (stimulus-directed) and voluntary (antisaccades). The present study explored the effects of voluntary spatial attention on both voluntary and reflexive saccades. Results indicate that voluntary spatial attention has different effects on the two types of saccades. Antisaccades were always greatly facilitated following the engagement of spatial attention by symbolic cues (arrows) informing the subject where the upcoming saccade should be directed. Reflexive saccades showed little or no cueing effects and exhibited significant facilitation only when these cues were randomly intermixed with uncued trials. In addition, the present study tested the effects of fixation condition (gap, step, and overlap) on attentional modulation. Cueing effects did not vary due to fixation condition. Thus, voluntary spatial attention consistently showed different effects on voluntary and reflexive saccades, and there was no evidence in these studies that voluntary cues inhibit reflexive saccades, even in a gap paradigm. Stephanie K. Seidlits, Tammie Reza, Kevin A. Briand, and Anne B. Sereno Copyright © 2003 Stephanie K. Seidlits et al. All rights reserved. Construction of Efficacious Gait and Upper Limb Functional Interventions Based on Brain Plasticity Evidence and Model-Based Measures For Stroke Patients Mon, 01 Jan 1900 00:00:00 +0000 Janis J. Daly and Robert L. Ruff Copyright © 2007 Janis J. Daly and Robert L. Ruff. All rights reserved. Delineating Neural Structures of Developmental Human Brains with Diffusion Tensor Imaging Mon, 01 Jan 1900 00:00:00 +0000 The human brain anatomy is characterized by dramatic structural changes during fetal development. It is extraordinarily complex and yet its origin is a simple tubular structure. Revealing detailed anatomy at different stages of brain development not only aids in understanding this highly ordered process, but also provides clues to detect abnormalities caused by genetic or environmental factors. However, anatomical studies of human brain development during the fetal period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor imaging (DTI) measures water diffusion to delineate the underlying neural structures. The high contrasts derived from DTI can be used to establish the brain atlas. With DTI tractography, coherent neural structures, such as white matter tracts, can be three-dimensionally reconstructed. The primary eigenvector of the diffusion tensor can be further explored to characterize microstructures in the cerebral wall of the developmental brains. In this mini-review, the application of DTI in order to reveal the structures of developmental fetal brains has been reviewed in the above-mentioned aspects. The fetal brain DTI provides a unique insight for delineating the neural structures in both macroscopic and microscopic levels. The resultant DTI database will provide structural guidance for the developmental study of human fetal brains in basic neuroscience, and reference standards for diagnostic radiology of premature newborns. Hao Huang Copyright © 2010 Hao Huang. All rights reserved. Nicotinic Receptor Activity Alters Synaptic Plasticity Mon, 01 Jan 1900 00:00:00 +0000 Studies using specific agonists, antagonists, and lesions have shown that nicotinic cholinergic systems participate in attention, learning, and memory[1,2]. The nicotinic manipulations usually have the greatest influence on difficult tasks or on cognitively impaired subjects[2]. For example, Alzheimer's disease is characterized by a loss of cholinergic projections and nicotinic acetylcholine receptors (nAChRs) in the cortex and hippocampus[3]. Nicotine skin patches can improve learning rates and attention in Alzheimer's patients[4]. John A. Dani Copyright © 2001 John A. Dani. All rights reserved. Kalirin-7 is a Key Player in the Formation of Excitatory Synapses in Hippocampal Neurons Mon, 01 Jan 1900 00:00:00 +0000 Kalirin-7 (Kal7), a major isoform of Kalirin in the adult rodent hippocampus, is exclusively localized to the postsynaptic side of mature excitatory synapses in hippocampal neurons. Kal7 interacts with multiple PDZ domain—containing proteins through its unique PDZ binding motif. Overexpression of Kal7 increases spine density and spine size, whereas reduction of endogenous Kal7 expression by small hairpin RNA (shRNA) causes a decrease in synapse number and spine density in cultured hippocampal neurons. Hippocampal CA1 pyramidal neurons of Kal7 knockout (Kal7KO) mice show decreased spine density, spine length, synapse number, and postsynaptic density (PSD) size in their apical dendrites; are deficient in long-term potentiation (LTP); and exhibit decreased frequency of spontaneous excitatory postsynaptic current (sEPSC). Kal7 plays a key role in estrogen-mediated spine/synapse formation in hippocampal neurons. Kal7 is also an essential determinant of dendritic spine formation following chronic cocaine treatment. Kal7 plays a key role in excitatory synapse formation and function. Xin-Ming Ma Copyright © 2010 Xin-Ming Ma. All rights reserved. CGRP and Adrenomedullin Modulate Synaptic Transmission in Purkinje Cells Mon, 01 Jan 1900 00:00:00 +0000 H. Cater, D. Poyner, and N. Hartell Copyright © 2001 H. Cater et al. All rights reserved. Study of Cgrp-Receptors in Human Isolated Middle Meningeal Arteries Using Bibn4096Bs, Compound 1, and HαCgrp(8-37) Mon, 01 Jan 1900 00:00:00 +0000 Calcitonin, CGRP, adrenomedullin, and amylin require both CRLR (calcitonin-gene receptor like receptor) and receptor activity modifying proteins (RAMP1, RAMP2, and RAMP3) in different combinations for expression of selective, functional receptors[1]. We investigated whether the antagonists BIBN4096BS[2], Compound 1 (WO98/11128, [3]), and CGRP(8-37) are functionally selective for CGRP receptors in human middle meningeal arteries (HMMA). Z. Razzaque, D. Shaw, M. Bock, L. Maskell, J. Pickard, D. Sirinathsinghji, and J. Longmore Copyright © 2001 Z. Razzaque et al. All rights reserved. Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct Pathway Mon, 01 Jan 1900 00:00:00 +0000 Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1 and D2 receptors, respectively. Adenosine A2A receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2 receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A2A receptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2A receptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2A receptors could provide a new target for the treatment of neuropsychiatric disorders. César Quiroz, Rafael Luján, Motokazu Uchigashima, Ana Patrícia Simoes, Talia N. Lerner, Janusz Borycz, Anil Kachroo, Paula M. Canas, Marco Orru, Michael A. Schwarzschild, Diane L. Rosin, Anatol C. Kreitzer, Rodrigo A. Cunha, Masahiko Watanabe, and Sergi Ferré Copyright © 2009 César Quiroz et al. All rights reserved. Astrocytes Control Neuronal Excitability in the Nucleus Accumbens Mon, 01 Jan 1900 00:00:00 +0000 Though accumulating evidence shows that the metabotropic glutamate receptor 5 (mGluR5) mediates some of the actions of extracellular glutamate after cocaine use, the cellular events underlying this action are poorly understood. In this review, we will discuss recent results showing that mGluR5 receptors are key regulators of astrocyte activity. Synaptic release of glutamate activates mGluR5 expressed in perisynaptic astrocytes and generates intense Ca2+ signaling in these cells. Ca2+ oscillations, in turn, trigger the release from astrocytes of the gliotransmitter glutamate, which modulates neuronal excitability by activating NMDA receptors. By integrating these results with the most recent evidence demonstrating the importance of astrocytes in the regulation of neuronal excitability, we propose that astrocytes are involved in mediating some of the mGluR5-dependent drug-induced behaviors. Tommaso Fellin, Marcello D'Ascenzo, and Philip G. Haydon Copyright © 2007 Tommaso Fellin et al. All rights reserved. Evaluating the Functional Importance of Neuroadaptions in Addiction Mon, 01 Jan 1900 00:00:00 +0000 Susan F. Volman Copyright © 2007 Susan F. Volman. All rights reserved. The Effectiveness of Intravesical Oxybutynin, Propantheline, and Capsaicin in the Management of Neuropathic Bladder following Spinal Cord Injury Mon, 01 Jan 1900 00:00:00 +0000 The objective of this study was to compare the therapeutic response of intravesical oxybutynin, propantheline, and capsaicin in the treatment of neurogenic detrusor overactivity. Carried out in the Department of Physical Medicine and Rehabilitation at a university teaching hospital in India, patients acted as their own controls. Oxybutynin 5 mg in solution or propantheline 15 mg in solution and capsaicin were instilled intravesically in each patient. Urodynamic studies were done before and after the intravesical instillation of each drug. The nonparametric tests were used for statistical analysis. The efficacy of intravesical capsaicin in the treatment of neurogenic detrusor overactivity was statistically significant for reflex volume (RV) (p = 0.018), cystometric capacity (CC) (p = 0.0440), leak volume (LV) (p = 0.000), and leak frequency (LF) (p = 0.009). The Kruskal-Wallis test for paired sample comparing pre- and post-LV and LF for intravesical capsaicin was significant at 2nd week (p = 0.002 and 0.054, respectively). There was a significant difference in therapeutic response between intravesical oxybutynin, propantheline, and capsaicin in the treatment of detrusor overactivity for LV and LF at 2nd week (p = 0.017 and 0.003, respectively). When comparing responses of oxybutynin and propantheline, more subjects demonstrated improvement with intravesical propantheline than oxybutynin for RV, detrusor leak point pressure (LPP), clean intermittent catheterization volume (CICV), and LV. This study suggests that intravesical agents may be used as effective adjuvants in the management of incontinence due to neurogenic detrusor overactivity following spinal cord injury. Jacob George, George Tharion, J. Richar, Ashish S. Macaden, Raji Thomas, and Suranjan Bhattacharji Copyright © 2007 Jacob George et al. All rights reserved. Regulation of X Chromosome-Linked Inhibitor of Apoptosis Protein (XIAP) in Kainic Acid Induced Neuronal Cell Death in the Rat Hippocampus Mon, 01 Jan 1900 00:00:00 +0000 Laura Korhonen, Natale Belluardo, and Dan Lindholm Copyright © 2001 Laura Korhonen et al. All rights reserved. Targeted Regulation Of Cgrp Gene Expression Mon, 01 Jan 1900 00:00:00 +0000 The neuropeptide calcitonin gene-related peptide (CGRP) is a potent regulator of cerebral vascular tone and contributes to neurogenic inflammation. Clinical studies have shown that CGRP levels are elevated during the painful phase of migraine headache, then restored to baseline by antimigraine 5-HT1 drugs. Conversely, CGRP is depleted in perivascular nerve terminals from patients who have suffered vasospasm following subarachnoid hemorrhage. We have investigated the mechanisms controlling CGRP expression in the trigeminal ganglia neurons, which provide virtually all of the CGRP innervation to the cerebral vasculature. We found that nerve depolarization, inflammatory compounds, and nitric oxide can increase CGRP synthesis and secretion. Using both adenoviral vectors and transfection approaches, we have shown that the increased synthesis is due to activation of a cell-specific MAP kinase-responsive enhancer upstream of the CGRP gene. Interestingly, the 5-HT1 migraine drugs are able to block this up-regulation by a mechanism that involves a very prolonged elevation of calcium. We have shown that the duration of the calcium signal is a key determinant for whether a MAP kinase responsive gene will be stimulated or repressed by calcium-activated pathways. This observation supports the importance of a finely tuned balance of calcium in the trigeminal neuron, which is intriguing in light of genetic evidence for calcium channel mutations in a rare form of inherited migraine. These studies suggest that modulation of MAP kinase control of the cell-specific CGRP gene enhancer may be a useful therapeutic strategy for neurovascular disorders. A. F. Russo and P. L. Durham Copyright © 2001 A.F. Russo and P.L. Durham. All rights reserved. Can the Spinal Cord Learn and Remember? Mon, 01 Jan 1900 00:00:00 +0000 Learning and memory traditionally have been associated with cellular processes occurring in a specialized region of the brain called the hippocampus. However, recent data have provided strong evidence to suggest that comparable processes are also expressed in the spinal cord. Experiments performed mainly in spinal cord–transected animals have reported that, indeed, spinal-mediated functions, such as the stretch or flexion reflex, pain signaling, micturition, or locomotion, may undergo plasticity changes associated with partial functional recovery that occur spontaneously or conditionally. Many of the underlying cellular mechanisms strikingly resemble those found in the hippocampus. This mini-review reports, mainly, animal data that support the idea that other areas of the central nervous system, such as the spinal cord, can also learn and remember. Pierre A. Guertin Copyright © 2008 Pierre A. Guertin. All rights reserved. Neurodegeneration in Schizophrenia: Evidence from In Vivo Neuroimaging Studies Mon, 01 Jan 1900 00:00:00 +0000 Although schizophrenia is primarily considered to be a neurodevelopmental disorder, there is a growing consensus that the disorder may also involve neurodegeneration. Recent research using non-invasive neuroimaging techniques, such as magnetic resonance imaging, suggests that some patients with schizophrenia show progressive losses of gray matter in the frontal and temporal lobes of the brain. The cellular mechanisms responsible for such gray matter losses are unknown, but have been hypothesized to involve abnormal increases in apoptosis. John G. Csernansky Copyright © 2007 John G. Csernansky. All rights reserved. Sexual Health in Adult Men with Spina Bifida Mon, 01 Jan 1900 00:00:00 +0000 Medical and surgical advances in the treatment of spina bifida (SB) have resulted in increasing numbers of patients reaching adulthood. As such, issues related to sexual maturity are being investigated to offer optimal healthcare to men with spina bifida. This report constitutes a review of the current literature relating to adults with spina bifida and issues of sexuality, erectile dysfunction and fertility. In general, adult males with spina bifida have normal sexual desires and an interest in addressing these issues with healthcare providers. Sexual education and access to intimacy are delayed compared to the general population. 75% of men achieve erections, but maintaining erections is a problem and some may be merely reflexive in nature. The many of these men show marked improvement with sildenafil. In SB erectile dysfunction and infertility are related to the level of neurological lesion with the best performance status in those with sacral lesions and intact reflexes. Men with lesions higher than T10 are at risk for azoospermia. There is an increased risk of neural tube defects in the children of men with spina bifida, but the current incidence with modern folic acid therapy is unknown. As the number of males with spina bifida reaching sexual maturity increases, further investigation into sexuality, sex education, intimacy, and treatments for erectile dysfunction and infertility will be needed. Gary W. Bong and Eric S. Rovner Copyright © 2007 Gary W. Bong and Eric S. Rovner. All rights reserved. Organophosphate Nerve Agent Detection with Europium Complexes Mon, 01 Jan 1900 00:00:00 +0000 We explore the detection of paraoxon, a model compound for nonvolatile organophosphate nerve agents such as VX. The detection utilizes europium complexes with 1,10 phenanthroline and thenoyltrifluoroacetone as sensitizing ligands. Both europium luminescence quenching and luminescence enhancement modalities are involved in the detection, which is simple, rapid, and sensitive. It is adaptable as well to the more volatile fluorophosphate nerve agents. It involves nothing more than visual luminescence observation under sample illumination by an ordinary hand-held ultraviolet lamp. Jake R. Schwierking, Laird W. Menzel, and E. Roland Menzel Copyright © 2004 Jake R. Schwierking et al. All rights reserved. Penile Rehabilitation and Neuromodulation Mon, 01 Jan 1900 00:00:00 +0000 Erectile dysfunction (ED) following treatment for clinically localized prostate cancer, particularly radical prostatectomy (RP), is a major quality of life issue that remains unsatisfactorily addressed. With the introduction and use of cavernous nerve–sparing procedures over the past 25 years, many men recover erections postoperatively that enable sexual intercourse unlike in the prior surgical era, when permanent ED postoperatively was certain. Despite this advance, 26–100% of these patients may never recover normal erectile function (EF). Recent advances in the understanding of ED after RP have stimulated great attention to develop penile rehabilitation programs and neuromodulation. The purpose of penile rehabilitation is to prevent adverse corpus cavernosal tissue structural alterations and thereby maximize the chances of recovering functional erections. Rehabilitation programs are common in clinical practice, but there is no definitive evidence to support their efficacy. Neuromodulation represents another strategy for promoting erection recovery postoperatively. This therapy involves the application of neuroprotective interventions, conceivably targeting biological elements involved in the erection response that are affected by neuropathic injury. Well-conducted, controlled trials with adequate follow-up are required in order to determine the erection preservative benefits of these therapeutic strategies. The purpose of this essay is to describe the mechanisms related to post-RP ED, assess the need for penile rehabilitation and neuromodulation following surgery, and analyze the basic science and clinical trial evidence associated with these applications for preserving EF following prostate cancer treatment. Fernando Facio Jr. and Arthur L. Burnett Copyright © 2009 Fernando Facio and Arthur L Burnett. All rights reserved. An Emerging Role for the Delta Opioid Receptor in the Regulation of Mu Opioid Receptor Function Mon, 01 Jan 1900 00:00:00 +0000 Morphine and related opiates are commonly used in the clinical management of various types of pain. However, the antinociceptive properties of morphine are often overshadowed by the development of tolerance and dependence following its chronic use. The mechanisms underlying opiate tolerance are not fully understood, but appear to involve numerous and complex physiological adaptations. Recently, a role for the heterodimerization of mu and delta opioid receptors in the development of morphine tolerance has been proposed. This novel mechanism could help us to understand several observations, such as the critical role of delta opioid receptor regulation, the impact of delta opioid receptor binding site occupancy, and the participation of beta-arrestin2, in the development of morphine tolerance. Raphael Rozenfeld, Noura S. Abul-Husn, Ivone Gomez, and Lakshmi A. Devi Copyright © 2007 Raphael Rozenfeld et al. All rights reserved. Sponsor's Foreword Mon, 01 Jan 1900 00:00:00 +0000 David Shurtleff and Sergi Ferré Copyright © 2007 David Shurtleff and Sergi Ferré. All rights reserved. Speed-Accuracy Tradeoff Operator Characteristics of Endogenous and Exogenous Covert Orienting of Attention Mon, 01 Jan 1900 00:00:00 +0000 There is debate over the mechanisms that govern the orienting of attention. Some argue that the enhanced performance observed at a cued location is the result of increased perceptual sensitivity or preferential access to decision-making processes. It has also been suggested that these effects may be the result of trades in speed for accuracy on the part of the observers. In the present study, observers performed either an exogenous or an endogenous orienting of attention task under both normal instructions (respond as quickly and as accurately as possible) and speeded instructions that used a deadline procedure to limit the amount of time observers had to complete a choice reaction time (CRT) task. An examination of the speed-accuracy operating characteristics (SAOCs) yielded evidence against the notion that CRT precuing effects are due primarily to a tradeoff of accuracy for speed. Peter A. McCormick and Lori Francis Copyright © 2005 Peter A. McCormick and Lori Francis. All rights reserved. Hepatocyte Growth Factor in Synaptic Plasticity and Alzheimer's Disease Mon, 01 Jan 1900 00:00:00 +0000 The hepatocyte growth factor (HGF) was initially identified as a protein that promoted growth of hepatocytes. It regulates proliferation and survival of different types of cells. HGF signaling, which is initiated by its binding to a receptor tyrosine kinase, plays critical roles during development. HGF and its receptor are also present in brain cells. This review describes the role of HGF in hippocampal neurons, synaptic plasticity, and the memory impairment condition, Alzheimer's disease. Shiv K. Sharma Copyright © 2010 Shiv K. Sharma. All rights reserved. Dissociating Sensory and Motor Components of Inhibition of Return Mon, 01 Jan 1900 00:00:00 +0000 Two explanations for inhibition of return (IOR) have been proposed. The first is that IOR reflects inhibition of attentional processing at previously cued locations, resulting in altered sensory analysis. The second is that IOR reflects the inhibition of responses directed towards those previously cued locations. We used a variant of a double-saccade paradigm to dissociate these two proposed effects of IOR and attempted to reveal both effects within the context of a single experimental task. Subjects viewed a series of exogenous cues and then made a localization response to subsequent targets with either a target-directed saccade or a pointing response. Results were similar for both response modes. An important finding was that the pattern of IOR depended critically on how subjects reacted to the exogenous cues. Subjects either oriented to the cued locations (via saccades or pointing) prior to responding to the target (Respond), or passively viewed the cues before responding (Ignore). In the Respond condition, IOR was observed at the most recently cued position. Although this could be consistent with an altered sensory interpretation, it would also be consistent with a spatiotopic representation. In the Ignore condition, the sole inhibited location was not the most recently cued position, but the first cued position. This finding is surprising and in conflict with previous work with multiple exogenous cues. The data are discussed in relation to a number of prominent issues in the area of IOR and suggest important new constraints and boundary conditions. Anne B. Sereno, Cameron B. Jeter, Vani Pariyadath, and Kevin A. Briand Copyright © 2006 Anne B. Sereno et al. All rights reserved. Mirror-Like Mechanisms and Music Mon, 01 Jan 1900 00:00:00 +0000 The neural processes underlying sensory-motor integration have always attracted strong interest. The classic view is that action and perception are two extremes of mental operations. In the past 2 decades, though, a large number of discoveries have indeed refuted such an interpretation in favor of a more integrated view. Specifically, the discovery of mirror neurons in monkey premotor cortex is a rather strong demonstration that sensory and motor processes share the same neural substrates. In fact, these cells show complex sensory-motor properties, such that observed, heard, or executed goal-directed actions could equally activate these neurons. On the other hand, the neuroscience of music has similarly emerged as an active and productive field of research. In fact, music-related behaviors are a useful model of action-perception mechanisms and how they develop through training. More recently, these two lines of research have begun to intersect into a novel branch of research. As a consequence, it has been proposed recently that mirror-like mechanisms might be at the basis of human music perception-production abilities. The scope of the present short review is to set the scientific background for mirror-like mechanisms in music by examining recent published data. Alessandro D'Ausilio Copyright © 2009 Alessandro D'Ausilio. All rights reserved. Founding Editorial: Cognition Mon, 01 Jan 1900 00:00:00 +0000 Michael Posner Copyright © 2002 Michael Posner. All rights reserved. The Role of CGRPin Nociception? Mon, 01 Jan 1900 00:00:00 +0000 The failure of NK1 receptor antagonists to show analgesic activity in clinical trials in spite of abundant preclinical evidence for a role of this neuropeptide in nociception, makes it somewhat dangerous to speculate on the nociceptive role of other neuropeptides, especially with respect to therapeutic utility of receptor antagonists! However, CGRP is the primary afferent peptide with the strongest evidence of a role in pain perception. It is found in a greater proportion of sensory neurones than other peptides and is a constituent of A[delta ] as well as C-fibres. Inflammation of peripheral tissues upregulates production of CGRP in sensory ganglia, coincident with the development of hyperalgesia, and CGRP knockout mice have attenuated hyperalgesic responses. CGRP is released into the dorsal horn of the spinal cord (DHSC) by noxious peripheral stimuli and excites nociceptive DHSC neurones on local application. The peptide antagonist CGRP8-37 blocks the response to exogenous CGRP and can reduce the response of DHSC neurones to noxious peripheral stimuli. CGRP8-37 has also been shown to have behavioural antinociceptive properties when given intrathecally. Conversely, injection of CGRP itself to the PAG or n. accumbens has been reported to have antinociceptive effects that are reversed by CGRP8-37. With the advent of potent non-peptide antagonists such as BIBN4096BS we should soon be able to determine whether systemic blockade of all CGRP receptors produces antinociception without limiting side effects. R. G. Hill Copyright © 2001 R. G. Hill. All rights reserved. Nonsurgical Management of the Neurogenic Bladder in Children Mon, 01 Jan 1900 00:00:00 +0000 The neurogenic bladder can have many serious consequences. However, with proper understanding of the disease spectrum, and with proper awareness of the surveillance and management tools, adverse outcomes can be minimized. The incidence of renal failure is uncommon. With proper medical therapy, one can achieve continence and minimize the risk of symptomatic urinary tract infections. There are a number of nonsurgical strategies described that can help in the management of the neurogenic bladder. John Kryger Copyright © 2008 John Kryger. All rights reserved. Theta Oscillations and Reactivity of Hippocampal Stratum Oriens Neurons Mon, 01 Jan 1900 00:00:00 +0000 The supposition was advanced that the neuronal theta rhythmicity is the key mode of signal selection at the hippocampal level. To address this hypothesis, the experimental data on the responses of putative hippocampal interneurons of the stratum oriens CA1-CA3 to stimulation during enhanced theta rhythm and after its blockade are reviewed. Both a strong increase and a decrease of the natural theta rhythm disturbed the reactions of hippocampal neurons; during theta augmentation, the responses were masked or disappeared, and after theta blockade, they lost the ability to habituate. In both cases, two important events were broken: the resetting of the background activity and the phase-locking of theta cycles to stimulus. These data allow one to suppose that only important stimuli are normally capable to evoke these events and these stimuli are selected for recording. When the response to a significant stimulus occurs, the following theta prevents the responses to other stimuli. This probably protects the hippocampal activity from interference from irrelevant signals. Presumably, the absence of the theta deprives the hippocampus of this protection. During enhanced and persistent theta oscillations, the reset disappeared and theta bursts were generated without stimulus locking. In this state, the system is probably closed and the information cannot be recorded. During the theta blockade, the reset was too long and did not habituate. In this case, the system is open for any signals and the hippocampus loses the ability to select signal. This analysis suggests that information selection in the hippocampus may be performed with the participation of nonpyramidal neurons. Valentina F. Kitchigina Copyright © 2010 Valentina F. Kitchigina. All rights reserved. Founding Editorial: Higher Level Brain Function Mon, 01 Jan 1900 00:00:00 +0000 Michael Posner Copyright © 2002 Michael Posner. All rights reserved. Capsaicin-Mediated Neurogenic Vasodilatation in Neurokinin-1, NK1, Receptor Knockout Mice Mon, 01 Jan 1900 00:00:00 +0000 A. D. Grant and S. D. Brain Copyright © 2001 A.D. Grant and S.D. Brain. All rights reserved. Human Empathy Through the Lens of Social Neuroscience Mon, 01 Jan 1900 00:00:00 +0000 Empathy is the ability to experience and understand what others feel without confusion between oneself and others. Knowing what someone else is feeling plays a fundamental role in interpersonal interactions. In this paper, we articulate evidence from social psychology and cognitive neuroscience, and argue that empathy involves both emotion sharing (bottom-up information processing) and executive control to regulate and modulate this experience (top-down information processing), underpinned by specific and interacting neural systems. Furthermore, awareness of a distinction between the experiences of the self and others constitutes a crucial aspect of empathy. We discuss data from recent behavioral and functional neuroimaging studies with an emphasis on the perception of pain in others, and highlight the role of different neural mechanisms that underpin the experience of empathy, including emotion sharing, perspective taking, and emotion regulation. Jean Decety and Claus Lamm Copyright © 2006 Jean Decety and Claus Lamm. All rights reserved. The Neurological Significance of Abnormal Natural Killer Cell Activity in Chronic Toxigenic Mold Exposures Mon, 01 Jan 1900 00:00:00 +0000 Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40�C (104�F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures. Ebere Anyanwu, Andrew W. Campbell, Joseph Jones, John E. Ehiri, and Akpan I. Akpan Copyright © 2003 Ebere Anyanwu et al. All rights reserved. Brachial Plexus Anatomy: Normal and Variant Mon, 01 Jan 1900 00:00:00 +0000 Effective brachial plexus blockade requires a thorough understanding of the anatomy of the plexus, as well as an appreciation of anatomic variations that may occur. This review summarizes relevant anatomy of the plexus, along with variations and anomalies that may affect nerve blocks conducted at these levels. The Medline, Cochrane Library, and PubMed electronic databases were searched in order to compile reports related to the anatomy of the brachial plexus using the following free terms: "brachial plexus", "median nerve", "ulnar nerve", "radial nerve", "axillary nerve", and "musculocutanous nerve". Each of these was then paired with the MESH terms "anatomy", "nerve block", "anomaly", "variation", and "ultrasound". Resulting articles were hand searched for additional relevant literature. A total of 68 searches were conducted, with a total of 377 possible articles for inclusion. Of these, 57 were found to provide substantive information for this review. The normal anatomy of the brachial plexus is briefly reviewed, with an emphasis on those features revealed by use of imaging technologies. Anomalies of the anatomy that might affect the conduct of the various brachial plexus blocks are noted. Brachial plexus blockade has been effectively utilized as a component of anesthesia for upper extremity surgery for a century. Over that period, our understanding of anatomy and its variations has improved significantly. The ability to explore anatomy at the bedside, with real-time ultrasonography, has improved our appreciation of brachial plexus anatomy as well. Steven L. Orebaugh and Brian A. Williams Copyright © 2009 Steven L. Orebaugh and Brian A. Williams. All rights reserved. The Assimilation of Assistive Technology in Residential Care Centers for People with Intellectual Disabilities Mon, 01 Jan 1900 00:00:00 +0000 People with intellectual disability (ID) require special support in order to achieve independence in their daily life. Persons with ID are less exposed to assistive technology, although studies have shown that the availability of aids afford an opportunity to reach independence and cooperation. The aim of this study was to examine the nature of the relationship between involvement of the physiotherapy (PT) team and the degree to which assistive technology was used. A questionnaire was sent to all PTs employed at all 54 residential care centers for persons with ID of the Division for Mental Retardation at the Ministry of Social Affairs in Israel. A significantly positive correlation was found between the degree of involvement of the PT and the utilization of assistive technology. The study results may be summarized by stating that PTs demonstrated a great deal of involvement, particularly in relation to the extent of their work in the residential care centers. PT's awareness of the importance was indicated as the major reason to use assistive technology. Eli Carmeli, Carmit Cahana, and Joav Merrick Copyright © 2004 Eli Carmeli et al. All rights reserved. Altered Short-Term Synaptic Plasticity in Mice Lacking the Metabotropic Glutamate Receptor mGlu7 Mon, 01 Jan 1900 00:00:00 +0000 Eight subtypes of metabotropic glutamate (mGlu) receptors have been identified of which two, mGlu5 and mGlu7, are highly expressed at synapses made between CA3 and CA1 pyramidal neurons in the hippocampus. This input, the Schaffer collateral-commissural pathway, displays robust long-term potentiation (LTP), a process believed to utilise molecular mechanisms that are key processes involved in the synaptic basis of learning and memory. To investigate the possible function in LTP of mGlu7 receptors, a subtype for which no specific antagonists exist, we generated a mouse lacking this receptor, by homologous recombination. We found that LTP could be induced in mGlu7-/- mice and that once the potentiation had reached a stable level there was no difference in the magnitude of LTP between mGlu7-/- mice and their littermate controls. However, the initial decremental phase of LTP, known as short-term potentiation (STP), was greatly attenuated in the mGlu7-/- mouse. In addition, there was less frequency facilitation during, and less post-tetanic potentiation following, a high frequency train in the mGlu7-/- mouse. These results show that the absence of mGlu7 receptors results in alterations in short-term synaptic plasticity in the hippocampus. Trevor J. Bushell, Gilles Sansig, Valerie J. Collett, Herman van der Putten, and Graham L. Collingridge Copyright © 2002 Trevor J. Bushell et al. All rights reserved. Volume Transmission and Pain Perception Mon, 01 Jan 1900 00:00:00 +0000 Volume transmission (VT) is the diffusion through the brain extracellular fluid of neurotransmitters released at points that may be remote from the target cells with the resulting activation of extrasynaptic receptors. VT appears to play multiple roles in the brain in normal and abnormal activity, brain plasticity and drug actions. The relevance of VT to pain perception has been explored in this review. Gilberto C. Castañeda-Hernàndez and Paul Bach-y-Rita Copyright © 2003 Gilberto C. Castaneda-Hernandez and Paul Bach-y-Rita. All rights reserved. Human development III: Bridging Brain-Mind and Body-Mind. Introduction to “Deep” (Fractal, Poly-Ray) Cosmology Mon, 01 Jan 1900 00:00:00 +0000 Reality can be interpreted in many ways, but two distinctly different ways are the mental and the emotional interpretation. The traditional way of thinking in science today is the first: an often simple and mechanical interpretation of reality that empowers us to handle the outer physical world with great, often brutal efficiency. The development of a mind that enables us to handle the outer physical world and survive makes a lot of sense from an evolutionary perspective; the problem is that the mental reason and linear logic reduces all phenomena to well-defined interacting objects, which might not exist from a deeper perspective of reality. A more intuitive way to interpret the world makes much more sense, when it comes to our human relations. So to function as a human being, we need both these two ways of seeing the world, and two different modi operandi. In many patients, we find an internalized conflict between logical and mental reasoning on one hand, and emotional and sexual approach to reality and human needs on the other. We speculate that this conflict causes the deep emotional problems that really are the basis of most human diseases. Only by merging brain-mind and body-mind will we be whole and free and truly ourselves. We need to develop our mental understanding, deepen our cosmology, and develop our sexuality and body-mind in order to make them meet and merge. To facilitate this existential healing, we propose a third integrative way of looking at our human nature, which we call “the energetic-informational interpretation of reality”. What it does is allows us to look at both brain-mind and body-mind as a highly structured field of “energy and information”. Energy and information are actually the same from a scientific point of view; when the world is seen through the body-mind, it looks more like energy; when seen though the brain-mind, it looks more like information. Søren Ventegodt, Tyge Dahl Hermansen, Erik Rald, Trine Flensborg-Madsen, Maj Lyck Nielsen, Birgitte Clausen, and Joav Merrick Copyright © 2006 Søren Ventegodt et al. All rights reserved. Botulinum Toxin-A Therapy in Pediatric Urology: Indications for the Neurogenic and Non-Neurogenic Neurogenic Bladder Mon, 01 Jan 1900 00:00:00 +0000 Although, the role of Botulinum Toxin-A in the treatment of the neurogenic and non-neurogenic neurogenic bladder is becoming more defined, this is the first review article to characterize the emerging role of Botulinum Toxin-A in the pediatric urologic population. Injection of Botulinum Toxin-A at the level of the bladder works by inhibiting uninhibited bladder contractions and, possibly, by blocking some of the sensory nerve fibers. In children with sphincter dyssynergy, injection at the level of the urethral sphincter works by inhibiting the involuntary guarding reflex and blocking dyssynergic voiding. Lori Dyer and Israel Franco Copyright © 2009 Lori Dyer and Israel Franco. All rights reserved. Long-Term Neuropsychological Outcome in Preterm Twins Mon, 01 Jan 1900 00:00:00 +0000 Few long-term studies have yet described neuropsychological outcome in preterm twins. Our aim was to assess, by long-term evaluation, neuropsychological outcome in preterm twins in order to define a correct follow-up program. Our study was a cohort one, with an index and a comparison group. Neonatal medical records of all preterm newborns admitted to our centre between 1991 and 1997 were reviewed and selected patients were recalled. The sample population included two matched groups of children aged 6—12 years, 86 twins and 86 singletons, submitted to paediatric, neurological, psychological, and ophthalmological examinations. Inclusion criteria were twin pregnancy and gestational age 27—36 weeks for index group; same gestational age, but single pregnancy, for the comparison group. All children underwent paediatric and neuropsychiatric examinations, cognitive assessment, and psychological evaluation by standardized tests for screening of learning specific disorders and language difficulties, and finally, ophthalmological examination. In order to study their role in predicting neuropsychological outcome, we examined some perinatal prognostic factors by statistical analysis. Unfavourable neuropsychological outcome was observed in 55/172 (32%) children, with different prevalence in the two groups, 42/172 (24%) in twins and 13/172 (8%) in singletons. Statistical analysis performed for examined prognostic factors showed significant differences in neuropsychological outcome with regard only to gestational age < 32 weeks, low birth weight, intraventricular haemorrhage, and periventricular leukomalacia. The incidence of neuropsychological diseases in the two groups showed significant difference about language and learning difficulties. Our data suggest that preterm twins represent a particular high-risk category of premature babies, mostly regarding the risk of so-called “minimal brain dysfunction”, so a careful follow-up is recommended. Giovanni Iannone, Clelia Tripaldi, Antonino Chindemi, Lorenzo Piscitelli, Antonio Mastrorocco, Silvano Palazzo, and Luigi Esposito Copyright © 2006 Giovanni Iannone et al. All rights reserved. Non-Traditional Management of the Neurogenic Bladder: Tissue Engineering and Neuromodulation Mon, 01 Jan 1900 00:00:00 +0000 Patients with spina bifida and a neurogenic bladder have traditionally been managed with clean intermittent catheterization and pharmacotherapy in order to treat abnormal bladder wall dynamics, protect the upper urinary tract from damage, and achieve urinary continence. However, some patients will fail this therapy and require surgical reconstruction in the form of bladder augmentation surgery using reconfigured intestine or stomach to increase the bladder capacity while reducing the internal storage pressure. Despite functional success of bladder augmentation in achieving a low pressure reservoir, there are several associated complications of this operation and patients do not have the ability to volitionally void. For these reasons, alternative treatments have been sought. Two exciting alternative approaches that are currently being investigated are tissue engineering and neuromodulation. Tissue engineering aims to create new bladder tissue for replacement purposes with both “seeded” and “unseeded” technology. Advances in the fields of nanotechnology and stem cell biology have further enhanced these tissue engineering technologies. Neuromodulation therapies directly address the root of the problem in patients with spina bifida and a neurogenic bladder, namely the abnormal relationship between the nerves and the bladder wall. These therapies include transurethral bladder electrostimulation, sacral neuromodulation, and neurosurgical techniques such as selective sacral rhizotomy and artificial somatic-autonomic reflex pathway construction. This review will discuss both tissue engineering techniques and neuromodulation therapies in more detail including rationale, experimental data, current status of clinical application, and future direction. Jane M. Lewis and Earl Y. Cheng Copyright © 2007 Jane M. Lewis and Earl Y. Cheng. All rights reserved. Snoezelen or Controlled Multisensory Stimulation. Treatment Aspects from Israel Mon, 01 Jan 1900 00:00:00 +0000 In Israel today, with a total population of over 6 million persons, the Division for Mental Retardation (DMR) provides services to 23,000 persons with intellectual disability (ID). Of the 23,000, residential services are provided to more than 6,000 in close to 60 residential centers, another 2,000 are provided residential care in hostels or group homes in the community in about 50 locations, while the rest are served with day-care kindergarten, day-treatment centers, sheltered workshops, or integrated care in the community. The first Snoezelen room (controlled multisensory stimulation) in the DMR was established at the Bnei Zion residential care center in 1995. The Snoezelen method is now used in Israel in more than 30 residential care centers and 3 community settings. Since the year 2000, a physiotherapist has been employed in order to supervise the treatment and development of the method nationally. Professional staff meetings take place every 4 months. A certification course has been established on a national basis for individuals from different professions (occupational therapists, physiotherapists, teachers, music therapists, nurses, speech therapists, or caregivers). Snoezelen has proved to be an important instrument and a powerful therapeutic tool among the various treatment modules employed in Israel for persons with ID. This paper presents the concept illustrated with two case stories. Joav Merrick, Carmit Cahana, Meir Lotan, Isack Kandel, and Eli Carmeli Copyright © 2004 Joav Merrick et al. All rights reserved. Microglia and Astrocytes in Neuro-Aids, Alzheimers Disease, and Multiple Sclerosis Mon, 01 Jan 1900 00:00:00 +0000 Alireza Minagar, Paul Shapshak, Melvin Heyes, William A. Sheremata, Robert Fujimara, Ray Ownby, Karl Goodkin, and Karl Eisdorfer Copyright © 2001 Alireza Minagar et al. All rights reserved. The Digestive System and Nutritional Considerations for Individuals with Rett Syndrome Mon, 01 Jan 1900 00:00:00 +0000 Rett syndrome (RS) is a neurodevelopmental syndrome of genetic origin that mainly affects females. Individuals diagnosed with RS exhibit a variety of functional difficulties that impair their quality of life. One of the affected systems is the digestive system, where 74% of persons with RS have abnormal functioning. The affected digestive system causes this population to present an array of problems, such as gastroesophageal reflux (GER), constipation, and malnutrition, leading to failure to thrive (FTT), which resolves in reduced functional ability. Due to the severe effects of the dysfunctional digestive system of individuals with RS, this article will describe the problems common to this population, as well as propose some clinical suggestions for intervention. . Meir Lotan and Lilit Zysman Copyright © 2006 Meir Lotan and Lilit Zysman. All rights reserved. Challenges of Analysing Gene-Environment Interactions in Mouse Models of Schizophrenia Mon, 01 Jan 1900 00:00:00 +0000 The modelling of neuropsychiatric disease using the mouse has provided a wealth of information regarding the relationship between specific genetic lesions and behavioural endophenotypes. However, it is becoming increasingly apparent that synergy between genetic and nongenetic factors is a key feature of these disorders that must also be taken into account. With the inherent limitations of retrospective human studies, experiments in mice have begun to tackle this complex association, combining well-established behavioural paradigms and quantitative neuropathology with a range of environmental insults. The conclusions from this work have been varied, due in part to a lack of standardised methodology, although most have illustrated that phenotypes related to disorders such as schizophrenia are consistently modified. Far fewer studies, however, have attempted to generate a “two-hit” model, whereby the consequences of a pathogenic mutation are analysed in combination with environmental manipulation such as prenatal stress. This significant, yet relatively new, approach is beginning to produce valuable new models of neuropsychiatric disease. Focussing on prenatal and perinatal stress models of schizophrenia, this review discusses the current progress in this field, and highlights important issues regarding the interpretation and comparative analysis of such complex behavioural data. Peter L. Oliver Copyright © 2011 Peter L Oliver. All rights reserved.