Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Sativex in the Management of Multiple Sclerosis-Related Spasticity: Role of the Corticospinal Modulation Thu, 29 Jan 2015 08:51:32 +0000 Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability. Margherita Russo, Rocco Salvatore Calabrò, Antonino Naro, Edoardo Sessa, Carmela Rifici, Giangaetano D’Aleo, Antonino Leo, Rosaria De Luca, Angelo Quartarone, and Placido Bramanti Copyright © 2015 Margherita Russo et al. All rights reserved. Odorant Receptors Signaling Instructs the Development and Plasticity of the Glomerular Map Tue, 20 Jan 2015 13:56:52 +0000 The olfactory system provides a great opportunity to explore the mechanisms that underlie the formation and function of neural circuits because of the simplicity of its structure. Olfactory sensory neurons (OSNs) located in the peripheral olfactory epithelium (OE) take part in the initial formation and function of glomeruli in the olfactory bulb (OB) inside the central nervous system. Glomeruli are key in the process of transduction of olfactory information, as they constitute a map in the OB that sorts the different types of odorant inputs. This odorant categorization allows proper olfactory perception, and it is achieved through the anatomical organization and function of the different glomerular circuits. Once formed, glomeruli keep the capacity to undergo diverse plasticity processes, which is unique among the different neural circuits of the central nervous system. In this context, through the expression and function of the odorant receptors (ORs), OSNs perform two of the most important roles in the olfactory system: transducing odorant information to the nervous system and initiating the development of the glomerular map to organize olfactory information. This review addresses essential information that has emerged in recent years about the molecular basis of these processes. Pablo Valle-Leija Copyright © 2015 Pablo Valle-Leija. All rights reserved. Auditory Cortex tACS and tRNS for Tinnitus: Single versus Multiple Sessions Mon, 22 Dec 2014 00:10:14 +0000 Tinnitus is the perception of a sound in the absence of an external acoustic source, which often exerts a significant impact on the quality of life. Currently there is evidence that neuroplastic changes in both neural pathways are involved in the generation and maintaining of tinnitus. Neuromodulation has been suggested to interfere with these neuroplastic alterations. In this study we aimed to compare the effect of two upcoming forms of transcranial electrical neuromodulation: alternating current stimulation (tACS) and random noise stimulation (tRNS), both applied on the auditory cortex. A database with 228 patients with chronic tinnitus who underwent noninvasive neuromodulation was retrospectively analyzed. The results of this study show that a single session of tRNS induces a significant suppressive effect on tinnitus loudness and distress, in contrast to tACS. Multiple sessions of tRNS augment the suppressive effect on tinnitus loudness but have no effect on tinnitus distress. In conclusion this preliminary study shows a possibly beneficial effect of tRNS on tinnitus and can be a motivation for future randomized placebo-controlled clinical studies with auditory tRNS for tinnitus. Auditory alpha-modulated tACS does not seem to be contributing to the treatment of tinnitus. Laura Claes, Hannah Stamberger, Paul Van de Heyning, Dirk De Ridder, and Sven Vanneste Copyright © 2014 Laura Claes et al. All rights reserved. Environmental Control of Adult Neurogenesis: From Hippocampal Homeostasis to Behavior and Disease Thu, 18 Dec 2014 09:56:21 +0000 Sjoukje D. Kuipers, Clive R. Bramham, Heather A. Cameron, Carlos P. Fitzsimons, Aniko Korosi, and Paul J. Lucassen Copyright © 2014 Sjoukje D. Kuipers et al. All rights reserved. Recovery of Olfactory Function Induces Neuroplasticity Effects in Patients with Smell Loss Wed, 03 Dec 2014 00:10:14 +0000 The plasticity of brain function, especially reorganization after stroke or sensory loss, has been investigated extensively. Based upon its special characteristics, the olfactory system allows the investigation of functional networks in patients with smell loss, as it holds the unique ability to be activated by the sensorimotor act of sniffing, without the presentation of an odor. In the present study, subjects with chronic peripheral smell loss and healthy controls were investigated using functional magnetic resonance imaging (fMRI) to compare functional networks in one of the major olfactory areas before and after an olfactory training program. Data analysis revealed that olfactory training induced alterations in functional connectivity networks. Thus, olfactory training is capable of inducing neural reorganization processes. Furthermore, these findings provide evidence for the underlying neural mechanisms of olfactory training. Kathrin Kollndorfer, Ksenia Kowalczyk, Elisabeth Hoche, Christian A. Mueller, Michael Pollak, Siegfried Trattnig, and Veronika Schöpf Copyright © 2014 Kathrin Kollndorfer et al. All rights reserved. Glucagon-Like Peptide-1 as Predictor of Body Mass Index and Dentate Gyrus Neurogenesis: Neuroplasticity and the Metabolic Milieu Sun, 23 Nov 2014 12:00:38 +0000 Glucagon-like peptide-1 (GLP-1) regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1), and body mass index (BMI) in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues. Jeremy D. Coplan, Shariful Syed, Tarique D. Perera, Sasha L. Fulton, Mary Ann Banerji, Andrew J. Dwork, and John G. Kral Copyright © 2014 Jeremy D. Coplan et al. All rights reserved. Functional Near-Infrared Spectroscopy to Probe State- and Trait-Like Conditions in Chronic Tinnitus: A Proof-of-Principle Study Sun, 16 Nov 2014 00:00:00 +0000 Objective. Several neuroscience tools showed the involvement of auditory cortex in chronic tinnitus. In this proof-of-principle study we probed the capability of functional near-infrared spectroscopy (fNIRS) for the measurement of brain oxygenation in auditory cortex in dependence from chronic tinnitus and from intervention with transcranial magnetic stimulation. Methods. Twenty-three patients received continuous theta burst stimulation over the left primary auditory cortex in a randomized sham-controlled neuronavigated trial (verum = 12; placebo = 11). Before and after treatment, sound-evoked brain oxygenation in temporal areas was measured with fNIRS. Brain oxygenation was measured once in healthy controls . Results. Sound-evoked activity in right temporal areas was increased in the patients in contrast to healthy controls. Left-sided temporal activity under the stimulated area changed over the course of the trial; high baseline oxygenation was reduced and vice versa. Conclusions. By demonstrating that rTMS interacts with auditory evoked brain activity, our results confirm earlier electrophysiological findings and indicate the sensitivity of fNIRS for detecting rTMS induced changes in brain activity. Moreover, our findings of trait- and state-related oxygenation changes indicate the potential of fNIRS for the investigation of tinnitus pathophysiology and treatment response. Martin Schecklmann, Anette Giani, Sara Tupak, Berthold Langguth, Vincent Raab, Thomas Polak, Csanád Várallyay, Wilma Harnisch, Martin J. Herrmann, and Andreas J. Fallgatter Copyright © 2014 Martin Schecklmann et al. All rights reserved. Long-Term Effects of Musical Training and Functional Plasticity in Salience System Thu, 13 Nov 2014 00:00:00 +0000 Musicians undergoing long-term musical training show improved emotional and cognitive function, which suggests the presence of neuroplasticity. The structural and functional impacts of the human brain have been observed in musicians. In this study, we used data-driven functional connectivity analysis to map local and distant functional connectivity in resting-state functional magnetic resonance imaging data from 28 professional musicians and 28 nonmusicians. Compared with nonmusicians, musicians exhibited significantly greater local functional connectivity density in 10 regions, including the bilateral dorsal anterior cingulate cortex, anterior insula, and anterior temporoparietal junction. A distant functional connectivity analysis demonstrated that most of these regions were included in salience system, which is associated with high-level cognitive control and fundamental attentional process. Additionally, musicians had significantly greater functional integration in this system, especially for connections to the left insula. Increased functional connectivity between the left insula and right temporoparietal junction may be a response to long-term musical training. Our findings indicate that the improvement of salience network is involved in musical training. The salience system may represent a new avenue for exploration regarding the underlying foundations of enhanced higher-level cognitive processes in musicians. Cheng Luo, Shipeng Tu, Yueheng Peng, Shan Gao, Jianfu Li, Li Dong, Gujing Li, Yongxiu Lai, Hong Li, and Dezhong Yao Copyright © 2014 Cheng Luo et al. All rights reserved. Activation of the Prefrontal Cortex While Performing a Task at Preferred Slow Pace and Metronome Slow Pace: A Functional Near-Infrared Spectroscopy Study Mon, 10 Nov 2014 06:52:25 +0000 Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions. Kaori Shimoda, Yoshiya Moriguchi, Kenji Tsuchiya, Shiori Katsuyama, and Fusae Tozato Copyright © 2014 Kaori Shimoda et al. All rights reserved. Gastrodin Suppresses the Amyloid β-Induced Increase of Spontaneous Discharge in the Entorhinal Cortex of Rats Thu, 30 Oct 2014 07:32:38 +0000 Accumulated soluble amyloid beta- (Aβ-) induced aberrant neuronal network activity may directly contribute to cognitive deficits, which are the most outstanding characteristics of Alzheimer’s disease (AD). The entorhinal cortex (EC) is one of the earliest affected brain regions in AD. Impairments of EC neurons are responsible for the cognitive deficits in AD. However, little effort has been made to investigate the effects of soluble Aβ on the discharge properties of EC neurons in vivo. The present study was designed to examine the effects of soluble Aβ1−42 on the discharge properties of EC neurons, using in vivo extracellular single unit recordings. The protective effects of gastrodin (GAS) were also investigated against Aβ1−42-induced alterations in EC neuronal activities. The results showed that the spontaneous discharge of EC neurons was increased by local application of soluble Aβ1−42 and that GAS can effectively reverse Aβ1−42-induced facilitation of spontaneous discharge in a concentration-dependent manner. Moreover, whole-cell patch clamp results indicated that the protective function of GAS on abnormal hyperexcitability may be partially mediated by its inhibitory action on Aβ1−42-elicited inward currents in EC neurons. Our study suggested that GAS may provide neuroprotective effects on Aβ1−42-induced hyperactivity in EC neurons of rats. Peng-zhi Chen, Hui-hui Jiang, Bo Wen, Shuan-cheng Ren, Yang Chen, Wei-gang Ji, Bo Hu, Jun Zhang, Fenglian Xu, and Zhi-ru Zhu Copyright © 2014 Peng-zhi Chen et al. All rights reserved. NMDA Receptor-Dependent Metaplasticity by High-Frequency Magnetic Stimulation Tue, 28 Oct 2014 00:00:00 +0000 High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-priming was diminished when applied in the presence of the metabotropic glutamate receptor antagonists (RS)-α-methylserine-O-phosphate (MSOP) and (RS)-α-methyl-4-carboxyphenylglycine (MCPG). Moreover, when HFMS was delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 µM), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity. Tursonjan Tokay, Timo Kirschstein, Marco Rohde, Volker Zschorlich, and Rüdiger Köhling Copyright © 2014 Tursonjan Tokay et al. All rights reserved. Cytokines in Bipolar Disorder: Paving the Way for Neuroprogression Tue, 09 Sep 2014 00:00:00 +0000 Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with high prevalence of medical comorbidities and cognitive impairment. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Cytokines are proteins involved in the regulation and the orchestration of the immune response. We performed a review on the involvement of cytokines in BD. We also discuss the cytokines involvement in the neuroprogression of BD. It has been demonstrated that increased expression of cytokines in the central nervous system in postmortem studies is in line with the elevated circulating levels of proinflammatory cytokines in BD patients. The proinflammatory profile and the immune imbalance in BD might be regarded as potential targets to the development of new therapeutic strategies. Izabela Guimarães Barbosa, Moisés Evandro Bauer, Rodrigo Machado-Vieira, and Antonio Lucio Teixeira Copyright © 2014 Izabela Guimarães Barbosa et al. All rights reserved. Plasticity of Neural Systems in Tinnitus Mon, 08 Sep 2014 09:07:31 +0000 Martin Meyer, Berthold Langguth, Tobias Kleinjung, and Aage R. Møller Copyright © 2014 Martin Meyer et al. All rights reserved. Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices Mon, 08 Sep 2014 05:23:30 +0000 The lysosomal acid ceramidase, an enzyme known to limit intracellular ceramide accumulation, has been reported to be defective in neurodegenerative disorders. We show here that rat hippocampal slices, preincubated with the acid ceramidase inhibitor (ACI) d-NMAPPD, exhibit increased N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory postsynaptic potentials (fEPSPs) in CA1 synapses. The ACI by itself did not interfere with either paired pulse facilitation or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated fEPSPs, indicating that its influence on synaptic transmission is postsynaptic in origin and specific to the NMDA subtype of glutamate receptors. From a biochemical perspective, we observed that Tau phosphorylation at the Ser262 epitope was highly increased in hippocampal slices preincubated with the ACI, an effect totally prevented by the global NMDA receptor antagonist D/L(−)-2-amino-5-phosphonovaleric acid (AP-5), the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), and the GluN2B (but not the GluN2A) receptor antagonist RO25-6981. On the other hand, preincubation of hippocampal slices with the compound KN-62, an inhibitor known to interfere with calcium/calmodulin-dependent protein kinase II (CaMKII), totally abolished the effect of ACI on Tau phosphorylation at Ser262 epitopes. Collectively, these results provide experimental evidence that ceramides play an important role in regulating Tau phosphorylation in the hippocampus via a mechanism dependent on GluN2B receptor subunits and CaMKII activation. Marie-Elaine Laurier-Laurin, Audrée De Montigny, Suzanne Attiori Essis, Michel Cyr, and Guy Massicotte Copyright © 2014 Marie-Elaine Laurier-Laurin et al. All rights reserved. Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors Wed, 03 Sep 2014 11:39:33 +0000 Neuronal hyperexcitability is a phenomenon associated with early Alzheimer’s disease. The underlying mechanism is considered to involve excessive activation of glutamate receptors; however, the exact molecular pathway remains to be determined. Extracellular recording from the CA1 of hippocampal slices is a long-standing standard for a range of studies both in basic research and in neuropharmacology. Evoked field potentials (fEPSPs) are regarded as the input, while spiking rate is regarded as the output of the neuronal network; however, the relationship between these two phenomena is not fully clear. We investigated the relationship between spontaneous spiking and evoked fEPSPs using mouse hippocampal slices. Blocking AMPA receptors (AMPARs) with CNQX abolished fEPSPs, but left firing rate unchanged. NMDA receptor (NMDAR) blockade with MK801 decreased neuronal spiking dose dependently without altering fEPSPs. Activating NMDARs by small concentration of NMDA induced a trend of increased firing. These results suggest that fEPSPs are mediated by synaptic activation of AMPARs, while spontaneous firing is regulated by the activation of extrasynaptic NMDARs. Synaptotoxic Abeta(1-42) increased firing activity without modifying evoked fEPSPs. This hyperexcitation was prevented by ifenprodil, an antagonist of the NR2B NMDARs. Overall, these results suggest that Abeta(1-42) induced neuronal overactivity is not dependent on AMPARs but requires NR2B. Edina Varga, Gábor Juhász, Zsolt Bozsó, Botond Penke, Lívia Fülöp, and Viktor Szegedi Copyright © 2014 Edina Varga et al. All rights reserved. Disentangling Tinnitus Distress and Tinnitus Presence by Means of EEG Power Analysis Wed, 03 Sep 2014 09:27:05 +0000 The present study investigated 24 individuals suffering from chronic tinnitus (TI) and 24 nonaffected controls (CO). We recorded resting-state EEG and collected psychometric data to obtain information about how chronic tinnitus experience affects the cognitive and emotional state of TI. The study was meant to disentangle TI with high distress from those who suffer less from persistent tinnitus based on both neurophysiological and behavioral data. A principal component analysis of psychometric data uncovers two distinct independent dimensions characterizing the individual tinnitus experience. These independent states are distress and presence, the latter is described as the perceived intensity of sound experience that increases with tinnitus duration devoid of any considerable emotional burden. Neuroplastic changes correlate with the two independent components. TI with high distress display increased EEG activity in the oscillatory range around 25 Hz (upper β-band) that agglomerates over frontal recording sites. TI with high presence show enhanced EEG signal strength in the δ-, α-, and lower γ-bands (30–40 Hz) over bilateral temporal and left perisylvian electrodes. Based on these differential patterns we suggest that the two dimensions, namely, distress and presence, should be considered as independent dimensions of chronic subjective tinnitus. Martin Meyer, Matthias S. Luethi, Patrick Neff, Nicolas Langer, and Stefan Büchi Copyright © 2014 Martin Meyer et al. All rights reserved. Proliferation in the Alzheimer Hippocampus Is due to Microglia, Not Astroglia, and Occurs at Sites of Amyloid Deposition Tue, 19 Aug 2014 09:11:07 +0000 Microglia and astrocytes contribute to Alzheimer’s disease (AD) etiology and may mediate early neuroinflammatory responses. Despite their possible role in disease progression and despite the fact that they can respond to amyloid deposition in model systems, little is known about whether astro- or microglia can undergo proliferation in AD and whether this is related to the clinical symptoms or to local neuropathological changes. Previously, proliferation was found to be increased in glia-rich regions of the presenile hippocampus. Since their phenotype was unknown, we here used two novel triple-immunohistochemical protocols to study proliferation in astro- or microglia in relation to amyloid pathology. We selected different age-matched cohorts to study whether proliferative changes relate to clinical severity or to neuropathological changes. Proliferating cells were found across the hippocampus but never in mature neurons or astrocytes. Almost all proliferating cells were colabeled with Iba1+, indicating that particularly microglia contribute to proliferation in AD. Proliferating Iba1+ cells was specifically seen within the borders of amyloid plaques, indicative of an active involvement in, or response to, plaque accumulation. Thus, consistent with animal studies, proliferation in the AD hippocampus is due to microglia, occurs in close proximity of plaque pathology, and may contribute to the neuroinflammation common in AD. Michael W. Marlatt, Jan Bauer, Eleonora Aronica, Elise S. van Haastert, Jeroen J. M. Hoozemans, Marian Joels, and Paul J. Lucassen Copyright © 2014 Michael W. Marlatt et al. All rights reserved. Hippocampal Proliferation Is Increased in Presymptomatic Parkinson’s Disease and due to Microglia Thu, 14 Aug 2014 00:00:00 +0000 Besides dopamine-deficiency related motor symptoms, nonmotor symptoms, including cognitive changes occur in Parkinson's disease (PD) patients, that may relate to accumulation of α-synuclein in the hippocampus (HC). This brain region also contains stem cells that can proliferate. This is a well-regulated process that can, for example, be altered by neurodegenerative conditions. In contrast to proliferation in the substantia nigra and subventricular zone, little is known about the HC in PD. In addition, glial cells contribute to neurodegenerative processes and may proliferate in response to PD pathology. In the present study, we questioned whether microglial cells proliferate in the HC of established PD patients versus control subjects or incidental Lewy body disease (iLBD) cases as a prodromal state of PD. To this end, proliferation was assessed using the immunocytochemical marker minichromosome maintenance protein 2 (MCM2). Colocalization with Iba1 was performed to determine microglial proliferation. MCM2-positive cells were present in the HC of controls and were significantly increased in the presymptomatic iLBD cases, but not in established PD patients. Microglia represented the majority of the proliferating cells in the HC. This suggests an early microglial response to developing PD pathology in the HC and further indicates that neuroinflammatory processes play an important role in the development of PD pathology. Karlijn J. Doorn, Benjamin Drukarch, Anne-Marie van Dam, and Paul J. Lucassen Copyright © 2014 Karlijn J. Doorn et al. All rights reserved. Neurological Disorders Related Neuronal Network Impairment: Function and Mechanism Wed, 23 Jul 2014 08:37:36 +0000 Sheng-tian Li, Yun Wang, and Masayuki Matsushita Copyright © 2014 Sheng-tian Li et al. All rights reserved. The Interplay between Reproductive Social Stimuli and Adult Olfactory Bulb Neurogenesis Tue, 22 Jul 2014 00:00:00 +0000 Adult neurogenesis is a striking form of structural plasticity that adapts the brain to the changing world. Accordingly, new neuron production is involved in cognitive functions, such as memory, learning, and pattern separation. Recent data in rodents indicate a close link between adult neurogenesis and reproductive social behavior. This provides a key to unravel the functional meaning of adult neurogenesis in biological relevant contexts and, in parallel, opens new perspectives to explore the way the brain is processing social stimuli. In this paper we will summarize some of the major achievements on cues and mechanisms modulating adult neurogenesis during social behaviors related to reproduction and possible role/s played by olfactory newborn neurons in this context. We will point out that newborn interneurons in the accessory olfactory bulb (AOB) represent a privileged cellular target for social stimuli that elicit reproductive behaviors and that such cues modulate adult neurogenesis at two different levels increasing both proliferation of neuronal progenitors in the germinative regions and integration of newborn neurons into functional circuits. This dual mechanism provides fresh neurons that can be involved in critical activities for the individual fitness, that is, the processing of social stimuli driving the parental behavior and partner recognition. Paolo Peretto, Roberta Schellino, Silvia De Marchis, and Aldo Fasolo Copyright © 2014 Paolo Peretto et al. All rights reserved. Combination of Acellular Nerve Graft and Schwann Cells-Like Cells for Rat Sciatic Nerve Regeneration Wed, 09 Jul 2014 11:07:08 +0000 Objective. To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. Methods. Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. Results. After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (), and the difference between groups B and C was not statistically significant (). Conclusion. The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts. Songtao Gao, Yan Zheng, Qiqing Cai, Zhansheng Deng, Weitao Yao, Jiaqiang Wang, Xin Wang, and Peng Zhang Copyright © 2014 Songtao Gao et al. All rights reserved. Tinnitus-Related Distress and the Personality Characteristic Resilience Tue, 08 Jul 2014 00:00:00 +0000 It has been suggested that personality traits may be prognostic for the severity of suffering from tinnitus. Resilience as measured with the Wagnild and Young resilience scale represents a positive personality characteristic that promotes adaptation to adverse life conditions including chronic health conditions. Aim of the study was to explore the relation between resilience and tinnitus severity. In a cross-sectional study with a self-report questionnaire, information on tinnitus-related distress and subjective tinnitus loudness was recorded together with the personality characteristic resilience and emotional health, a measure generated from depression, anxiety, and somatic symptom severity scales. Data from 4705 individuals with tinnitus indicate that tinnitus-related distress and to a lesser extent the experienced loudness of the tinnitus show an inverse correlation with resilience. A mediation analysis revealed that the relationship between resilience and tinnitus-related distress is mediated by emotional health. This indirect effect indicates that high resilience is associated with better emotional health or less depression, anxiety, and somatic symptom severity, which in turn is associated with a less distressing tinnitus. Validity of resilience as a predictor for tinnitus-related distress is supported but needs to be explored further in longitudinal studies including acute tinnitus patients. Elisabeth Wallhäusser-Franke, Wolfgang Delb, Tobias Balkenhol, Wolfgang Hiller, and Karl Hörmann Copyright © 2014 Elisabeth Wallhäusser-Franke et al. All rights reserved. The Enigma of the Tinnitus-Free Dream State in a Bayesian World Sun, 06 Jul 2014 07:37:56 +0000 There are pathophysiological, clinical, and treatment analogies between phantom limb pain and phantom sound (i.e., tinnitus). Phantom limb pain commonly is absent in dreams, and the question arises whether this is also the case for tinnitus. A questionnaire was given to 78 consecutive tinnitus patients seen at a specialized tinnitus clinic. Seventy-six patients remembered their dreams and of these 74 claim not to perceive tinnitus during their dreams (97%). This can be most easily explained by a predictive Bayesian brain model. That is, during the awake state the brain constantly makes predictions about the environment. Tinnitus is hypothesized to be the result of a prediction error due to deafferentation, and missing input is filled in by the brain. The heuristic explanation then is that in the dream state there is no interaction with the environment and therefore no updating of the prediction error, resulting in the absence of tinnitus. Dirk De Ridder, Kathleen Joos, and Sven Vanneste Copyright © 2014 Dirk De Ridder et al. All rights reserved. Behavioral Improvement and Regulation of Molecules Related to Neuroplasticity in Ischemic Rat Spinal Cord Treated with PEDF Thu, 03 Jul 2014 14:17:00 +0000 Pigment epithelium derived factor (PEDF) exerts trophic actions to motoneurons and modulates nonneuronal restorative events, but its effects on neuroplasticity responses after spinal cord (SC) injury are unknown. Rats received a low thoracic SC photothrombotic ischemia and local injection of PEDF and were evaluated behaviorally six weeks later. PEDF actions were detailed in SC ventral horn (motor) in the levels of the lumbar central pattern generator (CPG), far from the injury site. Molecules related to neuroplasticity (MAP-2), those that are able to modulate such event, for instance, neurotrophic factors (NT-3, GDNF, BDNF, and FGF-2), chondroitin sulfate proteoglycans (CSPG), and those associated with angiogenesis and antiapoptosis (laminin and Bcl-2) and Eph (receptor)/ephrin system were evaluated at cellular or molecular levels. PEDF injection improved motor behavioral performance and increased MAP-2 levels and dendritic processes in the region of lumbar CPG. Treatment also elevated GDNF and decreased NT-3, laminin, and CSPG. Injury elevated EphA4 and ephrin-B1 levels, and PEDF treatment increased ephrin A2 and ephrins B1, B2, and B3. Eph receptors and ephrins were found in specific populations of neurons and astrocytes. PEDF treatment to SC injury triggered neuroplasticity in lumbar CPG and regulation of neurotrophic factors, extracellular matrix molecules, and ephrins. Chary Marquez Batista, Leonardo Luis Torres Bianqui, Bruno Bonganha Zanon, Mauricio Menezes Aben Athar Ivo, Gabriela Pintar de Oliveira, Jessica Ruivo Maximino, and Gerson Chadi Copyright © 2014 Chary Marquez Batista et al. All rights reserved. Adult Hippocampal Neurogenesis in Parkinson’s Disease: Impact on Neuronal Survival and Plasticity Thu, 03 Jul 2014 12:01:40 +0000 In Parkinson’s disease (PD) and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research. Martin Regensburger, Iryna Prots, and Beate Winner Copyright © 2014 Martin Regensburger et al. All rights reserved. Diffusion Imaging of Auditory and Auditory-Limbic Connectivity in Tinnitus: Preliminary Evidence and Methodological Challenges Sun, 22 Jun 2014 09:39:05 +0000 Subjective tinnitus, or “ringing in the ears,” is perceived by 10 to 15 percent of the adult population and causes significant suffering in a subset of patients. While it was originally thought of as a purely auditory phenomenon, there is increasing evidence that the limbic system influences whether and how tinnitus is perceived, far beyond merely determining the patient’s emotional reaction to the phantom sound. Based on functional imaging and electrophysiological data, recent articles frame tinnitus as a “network problem” arising from abnormalities in auditory-limbic interactions. Diffusion-weighted magnetic resonance imaging is a noninvasive method for investigating anatomical connections in vivo. It thus has the potential to provide anatomical evidence for the proposed changes in auditory-limbic connectivity. However, the few diffusion imaging studies of tinnitus performed to date have inconsistent results. In the present paper, we briefly summarize the results of previous studies, aiming to reconcile their results. After detailing analysis methods, we then report findings from a new dataset. We conclude that while there is some evidence for tinnitus-related increases in auditory and auditory-limbic connectivity that counteract hearing-loss related decreases in auditory connectivity, these results should be considered preliminary until several technical challenges have been overcome. Anna Seydell-Greenwald, Erika P. Raven, Amber M. Leaver, Ted K. Turesky, and Josef P. Rauschecker Copyright © 2014 Anna Seydell-Greenwald et al. All rights reserved. Spinal fMRI of Interoceptive Attention/Awareness in Experts and Novices Tue, 17 Jun 2014 06:03:43 +0000 Many disciplines/traditions that promote interoceptive (inner sensation of body parts) attention/awareness (IAA) train practitioners to both attend to and be aware of interoceptive sensory experiences in body parts. The effect of such practices has been investigated in previous imaging studies but limited to cerebral neural activity. Here, for the first time, we studied the impact of these practices on the spinal neural activity of experts and novices. We also attempted to clarify the effect of constant and deep breathing, a paradigm utilized in concentration practices to avoid mind wandering, on IAA-related spinal neural activity. Subjects performed IAA tasks with and without a deep and constant breathing pattern in two sessions. Results showed that neural activity in the spinal segment innervating the attended-to body area increased in experts () when they performed IAA and that this increase was significantly larger for experts versus novices in each of the sessions (). The significant effects of IAA and expertise on spinal neural activity are consistent with and elaborate on previous reports showing similar effects on cerebral neural activity. As the spinal cord directly innervates body parts, the results might indicate that IAA has an instantaneous (possibly beneficial) effect on the physical body after extended training. Keyvan Kashkouli Nejad, Motoaki Sugiura, Benjamin Thyreau, Takayuki Nozawa, Yuka Kotozaki, Yoshihito Furusawa, Kozo Nishino, Toshohiro Nukiwa, and Ryuta Kawashima Copyright © 2014 Keyvan Kashkouli Nejad et al. All rights reserved. Protective Effects of Ginkgo biloba Extract EGb 761 against Noise Trauma-Induced Hearing Loss and Tinnitus Development Tue, 17 Jun 2014 00:00:00 +0000 Noise-induced hearing loss (NIHL) and resulting comorbidities like subjective tinnitus are common diseases in modern societies. A substance shown to be effective against NIHL in an animal model is the Ginkgo biloba extract EGb 761. Further effects of the extract on the cellular and systemic levels of the nervous system make it a promising candidate not only for protection against NIHL but also for its secondary comorbidities like tinnitus. Following an earlier study we here tested the potential effectiveness of prophylactic EGb 761 treatment against NIHL and tinnitus development in the Mongolian gerbil. We monitored the effects of EGb 761 and noise trauma-induced changes on signal processing within the auditory system by means of behavioral and electrophysiological approaches. We found significantly reduced NIHL and tinnitus development upon EGb 761 application, compared to vehicle treated animals. These protective effects of EGb 761 were correlated with changes in auditory processing, both at peripheral and central levels. We propose a model with two main effects of EGb 761 on auditory processing, first, an increase of auditory brainstem activity leading to an increased thalamic input to the primary auditory cortex (AI) and second, an asymmetric effect on lateral inhibition in AI. Konstantin Tziridis, Sabine Korn, Sönke Ahlf, and Holger Schulze Copyright © 2014 Konstantin Tziridis et al. All rights reserved. Modulation of Electrocortical Brain Activity by Attention in Individuals with and without Tinnitus Thu, 12 Jun 2014 08:11:42 +0000 Age and hearing-level matched tinnitus and control groups were presented with a 40 Hz AM sound using a carrier frequency of either 5 kHz (in the tinnitus frequency region of the tinnitus subjects) or 500 Hz (below this region). On attended blocks subjects pressed a button after each sound indicating whether a single 40 Hz AM pulse of variable increased amplitude (target, probability 0.67) had or had not occurred. On passive blocks subjects rested and ignored the sounds. The amplitude of the 40 Hz auditory steady-state response (ASSR) localizing to primary auditory cortex (A1) increased with attention in control groups probed at 500 Hz and 5 kHz and in the tinnitus group probed at 500 Hz, but not in the tinnitus group probed at 5 kHz (128 channel EEG). N1 amplitude (this response localizing to nonprimary cortex, A2) increased with attention at both sound frequencies in controls but at neither frequency in tinnitus. We suggest that tinnitus-related neural activity occurring in the 5 kHz but not the 500 Hz region of tonotopic A1 disrupted attentional modulation of the 5 kHz ASSR in tinnitus subjects, while tinnitus-related activity in A1 distributing nontonotopically in A2 impaired modulation of N1 at both sound frequencies. Brandon T. Paul, Ian C. Bruce, Daniel J. Bosnyak, David C. Thompson, and Larry E. Roberts Copyright © 2014 Brandon T. Paul et al. All rights reserved. A Brain Centred View of Psychiatric Comorbidity in Tinnitus: From Otology to Hodology Wed, 11 Jun 2014 07:50:22 +0000 Introduction. Comorbid psychiatric disorders are frequent among patients affected by tinnitus. There are mutual clinical influences between tinnitus and psychiatric disorders, as well as neurobiological relations based on partially overlapping hodological and neuroplastic phenomena. The aim of the present paper is to review the evidence of alterations in brain networks underlying tinnitus physiopathology and to discuss them in light of the current knowledge of the neurobiology of psychiatric disorders. Methods. Relevant literature was identified through a search on Medline and PubMed; search terms included tinnitus, brain, plasticity, cortex, network, and pathways. Results. Tinnitus phenomenon results from systemic-neurootological triggers followed by neuronal remapping within several auditory and nonauditory pathways. Plastic reorganization and white matter alterations within limbic system, arcuate fasciculus, insula, salience network, dorsolateral prefrontal cortex, auditory pathways, ffrontocortical, and thalamocortical networks are discussed. Discussion. Several overlapping brain network alterations do exist between tinnitus and psychiatric disorders. Tinnitus, initially related to a clinicoanatomical approach based on a cortical localizationism, could be better explained by an holistic or associationist approach considering psychic functions and tinnitus as emergent properties of partially overlapping large-scale neural networks. Massimo Salviati, Francesco Saverio Bersani, Giuseppe Valeriani, Amedeo Minichino, Roberta Panico, Graziella Francesca Romano, Filippo Mazzei, Valeria Testugini, Giancarlo Altissimi, and Giancarlo Cianfrone Copyright © 2014 Massimo Salviati et al. All rights reserved.