Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Progressive FastICA Peel-Off and Convolution Kernel Compensation Demonstrate High Agreement for High Density Surface EMG Decomposition Thu, 25 Aug 2016 07:37:35 +0000 Decomposition of electromyograms (EMG) is a key approach to investigating motor unit plasticity. Various signal processing techniques have been developed for high density surface EMG decomposition, among which the convolution kernel compensation (CKC) has achieved high decomposition yield with extensive validation. Very recently, a progressive FastICA peel-off (PFP) framework has also been developed for high density surface EMG decomposition. In this study, the CKC and PFP methods were independently applied to decompose the same sets of high density surface EMG signals. Across 91 trials of 64-channel surface EMG signals recorded from the first dorsal interosseous (FDI) muscle of 9 neurologically intact subjects, there were a total of 1477 motor units identified from the two methods, including 969 common motor units. On average, common motor units were identified from each trial, which showed a very high matching rate of % in their discharge instants. The high degree of agreement of common motor units from the CKC and the PFP processing provides supportive evidence of the decomposition accuracy for both methods. The different motor units obtained from each method also suggest that combination of the two methods may have the potential to further increase the decomposition yield. Maoqi Chen, Ales Holobar, Xu Zhang, and Ping Zhou Copyright © 2016 Maoqi Chen et al. All rights reserved. Mirror Visual Feedback Training Improves Intermanual Transfer in a Sport-Specific Task: A Comparison between Different Skill Levels Wed, 24 Aug 2016 17:59:52 +0000 Mirror training therapy is a promising tool to initiate neural plasticity and facilitate the recovery process of motor skills after diseases such as stroke or hemiparesis by improving the intermanual transfer of fine motor skills in healthy people as well as in patients. This study evaluated whether these augmented performance improvements by mirror visual feedback (MVF) could be used for learning a sport-specific skill and if the effects are modulated by skill level. A sample of 39 young, healthy, and experienced basketball and handball players and 41 novices performed a stationary basketball dribble task at a mirror box in a standing position and received either MVF or direct feedback. After four training days using only the right hand, performance of both hands improved from pre- to posttest measurements. Only the left hand (untrained) performance of the experienced participants receiving MVF was more pronounced than for the control group. This indicates that intermanual motor transfer can be improved by MVF in a sport-specific task. However, this effect cannot be generalized to motor learning per se since it is modulated by individuals’ skill level, a factor that might be considered in mirror therapy research. Fabian Steinberg, Nils Henrik Pixa, and Michael Doppelmayr Copyright © 2016 Fabian Steinberg et al. All rights reserved. Direct Spinal Ventral Root Repair following Avulsion: Effectiveness of a New Heterologous Fibrin Sealant on Motoneuron Survival and Regeneration Wed, 24 Aug 2016 11:43:36 +0000 Axonal injuries at the interface between central and peripheral nervous system, such as ventral root avulsion (VRA), induce important degenerative processes, mostly resulting in neuronal and motor function loss. In the present work, we have compared two different fibrin sealants, one derived from human blood and another derived from animal blood and Crotalus durissus terrificus venom, as a promising treatment for this type of injury. Lewis rats were submitted to VRA (L4–L6) and had the avulsed roots reimplanted to the surface of the spinal cord, with the aid of fibrin sealant. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity, 4 and 12 weeks after lesion. Sciatic nerves were processed to investigate Schwann cell activity by expression (4 weeks after surgery) and to count myelinated axons and morphometric evaluation (12 weeks after surgery). Walking track test was used to evaluate gait recovery, up to 12 weeks. The results indicate that both fibrin sealants are similarly efficient. However, the snake-derived fibrin glue is a potentially safer alternative for being a biological and biodegradable product which does not contain human blood derivatives. Therefore, the venom glue can be a useful tool for the scientific community due to its advantages and variety of applications. Mateus Vidigal de Castro, Roberta Barbizan, Rui Seabra Ferreira Jr., Benedito Barraviera, and Alexandre Leite Rodrigues de Oliveira Copyright © 2016 Mateus Vidigal de Castro et al. All rights reserved. Stepping in Place While Voluntarily Turning Around Produces a Long-Lasting Posteffect Consisting in Inadvertent Turning While Stepping Eyes Closed Mon, 22 Aug 2016 08:52:42 +0000 Training subjects to step in place on a rotating platform while maintaining a fixed body orientation in space produces a posteffect consisting in inadvertent turning around while stepping in place eyes closed (podokinetic after-rotation, PKAR). We tested the hypothesis that voluntary turning around while stepping in place also produces a posteffect similar to PKAR. Sixteen subjects performed 12 min of voluntary turning while stepping around their vertical axis eyes closed and 12 min of stepping in place eyes open on the center of a platform rotating at 60°/s (pretests). Then, subjects continued stepping in place eyes closed for at least 10 min (posteffect). We recorded the positions of markers fixed to head, shoulder, and feet. The posteffect of voluntary turning shared all features of PKAR. Time decay of angular velocity, stepping cadence, head acceleration, and ratio of angular velocity after to angular velocity before were similar between both protocols. Both postrotations took place inadvertently. The posteffects are possibly dependent on the repeated voluntary contraction of leg and foot intrarotating pelvic muscles that rotate the trunk over the stance foot, a synergy common to both protocols. We propose that stepping in place and voluntary turning can be a scheme ancillary to the rotating platform for training body segment coordination in patients with impairment of turning synergies of various origin. Stefania Sozzi and Marco Schieppati Copyright © 2016 Stefania Sozzi and Marco Schieppati. All rights reserved. Role of Spindle Oscillations across Lifespan in Health and Disease Thu, 18 Aug 2016 16:02:53 +0000 Julie Seibt, Igor Timofeev, Julie Carrier, and Adrien Peyrache Copyright © 2016 Julie Seibt et al. All rights reserved. Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies Thu, 18 Aug 2016 13:54:02 +0000 N-Methyl-D-aspartate receptors (NMDARs) have two opposing roles in the brain. On the one hand, NMDARs control critical events in the formation and development of synaptic organization and synaptic plasticity. On the other hand, the overactivation of NMDARs can promote neuronal death in neuropathological conditions. Ca2+ influx acts as a primary modulator after NMDAR channel activation. An imbalance in Ca2+ homeostasis is associated with several neurological diseases including schizophrenia, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. These chronic conditions have a lengthy progression depending on internal and external factors. External factors such as acute episodes of brain damage are associated with an earlier onset of several of these chronic mental conditions. Here, we will review some of the current evidence of how traumatic brain injury can hasten the onset of several neurological conditions, focusing on the role of NMDAR distribution and the functional consequences in calcium homeostasis associated with synaptic dysfunction and neuronal death present in this group of chronic diseases. Francisco J. Carvajal, Hayley A. Mattison, and Waldo Cerpa Copyright © 2016 Francisco J. Carvajal et al. All rights reserved. Plasticity and Awareness of Bodily Distortion Thu, 18 Aug 2016 11:55:02 +0000 Knowledge of the body is filtered by perceptual information, recalibrated through predominantly innate stored information, and neurally mediated by direct sensory motor information. Despite multiple sources, the immediate prediction, construction, and evaluation of one’s body are distorted. The origins of such distortions are unclear. In this review, we consider three possible sources of awareness that inform body distortion. First, the precision in the body metric may be based on the sight and positioning sense of a particular body segment. This view provides information on the dual nature of body representation, the reliability of a conscious body image, and implicit alterations in the metrics and positional correspondence of body parts. Second, body awareness may reflect an innate organizational experience of unity and continuity in the brain, with no strong isomorphism to body morphology. Third, body awareness may be based on efferent/afferent neural signals, suggesting that major body distortions may result from changes in neural sensorimotor experiences. All these views can be supported empirically, suggesting that body awareness is synthesized from multimodal integration and the temporal constancy of multiple body representations. For each of these views, we briefly discuss abnormalities and therapeutic strategies for correcting the bodily distortions in various clinical disorders. Mariella Pazzaglia and Marta Zantedeschi Copyright © 2016 Mariella Pazzaglia and Marta Zantedeschi. All rights reserved. Neuromuscular Plasticity: Disentangling Stable and Variable Motor Maps in the Human Sensorimotor Cortex Tue, 16 Aug 2016 16:16:38 +0000 Motor maps acquired with transcranial magnetic stimulation (TMS) are evolving as a biomarker for monitoring disease progression or the effects of therapeutic interventions. High test-retest reliability of this technique for long observation periods is therefore required to differentiate daily or weekly fluctuations from stable plastic reorganization of corticospinal connectivity. In this study, a novel projection, interpolation, and coregistration technique, which considers the individual gyral anatomy, was applied in healthy subjects for biweekly acquired TMS motor maps over a period of twelve weeks. The intraclass correlation coefficient revealed long-term reliability of motor maps with relevant interhemispheric differences. The sensorimotor cortex and nonprimary motor areas of the dominant hemisphere showed more extended and more stable corticospinal connectivity. Long-term correlations of the MEP amplitudes at each stimulation site revealed mosaic-like clusters of consistent corticospinal excitability. The resting motor threshold, centre of gravity, and mean MEPs across all TMS sites, as highly reliable cortical map parameters, could be disentangled from more variable parameters such as MEP area and volume. Cortical TMS motor maps provide high test-retest reliability for long-term monitoring when analyzed with refined techniques. They may guide restorative interventions which target dormant corticospinal connectivity for neurorehabilitation. Dominic Kraus and Alireza Gharabaghi Copyright © 2016 Dominic Kraus and Alireza Gharabaghi. All rights reserved. Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury Thu, 11 Aug 2016 12:36:33 +0000 In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI), this study investigated the effects of electroacupuncture (EA) for SCI rat models. SCI was induced by a modified Allen’s weight-drop method. We investigated the response of EA at Dazhui (GV 14) and Mingmen (GV 4) acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats’ hind limbs among groups, and EA was shown to promote the recovery of SCI rats’ motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3) in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3. Yu-ping Mo, Hai-jiang Yao, Wei Lv, Liang-yu Song, Hong-tao Song, Xiao-chen Yuan, Ying-qiu Mao, Quan-kai Jing, Su-hua Shi, and Zhi-gang Li Copyright © 2016 Yu-ping Mo et al. All rights reserved. MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process Mon, 08 Aug 2016 11:04:43 +0000 Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (miR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether miR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model. Silencing miR-132 inhibited the electrical excitability level of cultured epileptic neurons, whereas silencing p250GAP had an opposite effect. In addition, we verified the effect of miR-132 in vivo and found that silencing miR-132 inhibited the aberrant formation of dendritic spines and chronic spontaneous seizure in a lithium-pilocarpine-induced epileptic mouse model. Finally, we confirmed that silencing miR-132 has a neuroprotective effect on cultured epileptic neurons; however, this effect did not occur through the p250GAP pathway. Generally, silencing miR-132 may suppress spontaneous seizure activity through the miR-132/p250GAP/Cdc42 pathway by regulating the morphology and electrophysiology of dendritic spines; therefore, miR-132 may serve as a potential target for the development of antiepileptic drugs. Jinxian Yuan, Hao Huang, Xin Zhou, Xi Liu, Shu Ou, Tao Xu, Ruohan Li, Limin Ma, and Yangmei Chen Copyright © 2016 Jinxian Yuan et al. All rights reserved. Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus Sun, 07 Aug 2016 13:53:39 +0000 Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (−23%) and dentate gyrus (−48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression. Daniel Reyes-Haro, Francisco Emmanuel Labrada-Moncada, Durairaj Ragu Varman, Janina Krüger, Teresa Morales, Ricardo Miledi, and Ataúlfo Martínez-Torres Copyright © 2016 Daniel Reyes-Haro et al. All rights reserved. Neuroprotective and Neurorestorative Processes after Spinal Cord Injury: The Case of the Bulbospinal Respiratory Neurons Wed, 03 Aug 2016 12:13:36 +0000 High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways. Since part of this recovery is dependent on the damaged side of the spinal cord, the present review highlights our current understanding of the anatomical neuroplasticity processes that are developed by the surviving damaged bulbospinal neurons, notably axonal sprouting and rerouting. Such anatomical neuroplasticity relies also on coordinated molecular mechanisms at the level of the axotomized bulbospinal neurons that will promote both neuroprotection and axon growth. Anne Kastner and Valéry Matarazzo Copyright © 2016 Anne Kastner and Valéry Matarazzo. All rights reserved. Mirror Visual Feedback to Improve Bradykinesia in Parkinson’s Disease Mon, 01 Aug 2016 14:30:52 +0000 Mirror visual feedback (MVF) therapy has been applied to improve upper limb function in stroke. When combined with motor training, MVF improves the performance of the trained and untrained hand by enhancing the excitability of both primary motor cortices (M1s). Bradykinesia is a typical feature of Parkinson’s disease (PD), characterized by slowness in the execution of movement. This condition is often asymmetrical and possibly supported by a volitional hypoactivation of M1. MVF therapy could tentatively treat bradykinesia since the untrained hand, which benefits from the exercise, is generally more severely impaired in undertaking sequential movements. Aim of the study was to evaluate whether MVF therapy may improve bradykinesia of the more affected hand in PD patients. Twelve PD patients and twelve healthy controls performed for 10 minutes a finger sequence, receiving MVF of the more affected/nondominant hand. Before and after MVF training, participants performed a finger sequence at their spontaneous pace with both hands. M1 excitability was assessed in the trained and untrained hemispheres by means of transcranial magnetic stimulation. Movement speed increased after MVF training in either hand of both groups. MVF therapy enhanced cortical excitability of M1s in both groups. Our preliminary data support the use of MVF therapy to improve bradykinesia in PD patients. Gaia Bonassi, Elisa Pelosin, Carla Ogliastro, Cecilia Cerulli, Giovanni Abbruzzese, and Laura Avanzino Copyright © 2016 Gaia Bonassi et al. All rights reserved. Synchrotron Radiation X-Ray Phase-Contrast Tomography Visualizes Microvasculature Changes in Mice Brains after Ischemic Injury Sun, 31 Jul 2016 13:39:56 +0000 Imaging brain microvasculature is important in plasticity studies of cerebrovascular diseases. Applying contrast agents, traditional μCT and μMRI methods gain imaging contrast for vasculature. The aim of this study is to develop a synchrotron radiation X-ray inline phase-contrast tomography (SRXPCT) method for imaging the intact mouse brain (micro)vasculature in high resolution (~3.7 μm) without contrast agent. A specific preparation protocol was proposed to enhance the phase contrast of brain vasculature by using density difference over gas-tissue interface. The CT imaging system was developed and optimized to obtain 3D brain vasculature of adult male C57BL/6 mice. The SRXPCT method was further applied to investigate the microvasculature changes in mouse brains () after 14-day reperfusion from transient middle cerebral artery occlusion (tMCAO). 3D reconstructions of brain microvasculature demonstrated that the branching radius ratio (post- to preinjury) of small vessels (radius < 7.4 μm) in the injury group was significantly smaller than that in the sham group (). This result revealed the active angiogenesis in the recovery brain after stroke. As a high-resolution and contrast-agent-free method, the SRXPCT method demonstrates higher potential in investigations of functional plasticity in cerebrovascular diseases. Peng Miao, Zhixia Wu, Miao Li, Yuanyuan Ji, Bohua Xie, Xiaojie Lin, and Guo-Yuan Yang Copyright © 2016 Peng Miao et al. All rights reserved. Short-Term Effect of Prosthesis Transforming Sensory Modalities on Walking in Stroke Patients with Hemiparesis Sun, 31 Jul 2016 09:55:03 +0000 Sensory impairments caused by neurological or physical disorders hamper kinesthesia, making rehabilitation difficult. In order to overcome this problem, we proposed and developed a novel biofeedback prosthesis called Auditory Foot for transforming sensory modalities, in which the sensor prosthesis transforms plantar sensations to auditory feedback signals. This study investigated the short-term effect of the auditory feedback prosthesis on walking in stroke patients with hemiparesis. To evaluate the effect, we compared four conditions of auditory feedback from plantar sensors at the heel and fifth metatarsal. We found significant differences in the maximum hip extension angle and ankle plantar flexor moment on the affected side during the stance phase, between conditions with and without auditory feedback signals. These results indicate that our sensory prosthesis could enhance walking performance in stroke patients with hemiparesis, resulting in effective short-term rehabilitation. Dai Owaki, Yusuke Sekiguchi, Keita Honda, Akio Ishiguro, and Shin-ichi Izumi Copyright © 2016 Dai Owaki et al. All rights reserved. Corrigendum to “Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait” Thu, 28 Jul 2016 15:11:18 +0000 M. Rodríguez-Arias, C. Roger-Sánchez, I. Villanova, N. Revert, C. Manzanedo, J. Miñarro, and M. A. Aguilar Copyright © 2016 M. Rodríguez-Arias et al. All rights reserved. Where Environment Meets Cognition: A Focus on Two Developmental Intellectual Disability Disorders Thu, 28 Jul 2016 08:50:07 +0000 One of the most challenging questions in neuroscience is to dissect how learning and memory, the foundational pillars of cognition, are grounded in stable, yet plastic, gene expression states. All known epigenetic mechanisms such as DNA methylation and hydroxymethylation, histone modifications, chromatin remodelling, and noncoding RNAs regulate brain gene expression, both during neurodevelopment and in the adult brain in processes related to cognition. On the other hand, alterations in the various components of the epigenetic machinery have been linked to well-known causes of intellectual disability disorders (IDDs). Two examples are Down Syndrome (DS) and Fragile X Syndrome (FXS), where global and local epigenetic alterations lead to impairments in synaptic plasticity, memory, and learning. Since epigenetic modifications are reversible, it is theoretically possible to use epigenetic drugs as cognitive enhancers for the treatment of IDDs. Epigenetic treatments act in a context specific manner, targeting different regions based on cell and state specific chromatin accessibility, facilitating the establishment of the lost balance. Here, we discuss epigenetic studies of IDDs, focusing on DS and FXS, and the use of epidrugs in combinatorial therapies for IDDs. I. De Toma, L. Manubens Gil, S. Ossowski, and M. Dierssen Copyright © 2016 I. De Toma et al. All rights reserved. Hypothalamic AMPK as a Regulator of Energy Homeostasis Thu, 28 Jul 2016 08:08:56 +0000 Activated in energy depletion conditions, AMP-activated protein kinase (AMPK) acts as a cellular energy sensor and regulator in both central nervous system and peripheral organs. Hypothalamic AMPK restores energy balance by promoting feeding behavior to increase energy intake, increasing glucose production, and reducing thermogenesis to decrease energy output. Besides energy state, many hormones have been shown to act in concert with AMPK to mediate their anorexigenic and orexigenic central effects as well as thermogenic influences. Here we explore the factors that affect hypothalamic AMPK activity and give the underlying mechanisms for the role of central AMPK in energy homeostasis together with the physiological effects of hypothalamic AMPK on energy balance restoration. My Khanh Q. Huynh, Ann W. Kinyua, Dong Joo Yang, and Ki Woo Kim Copyright © 2016 My Khanh Q. Huynh et al. All rights reserved. Flexible Coupling of Respiration and Vocalizations with Locomotion and Head Movements in the Freely Behaving Rat Mon, 25 Jul 2016 07:10:21 +0000 Quadrupedal mammals typically synchronize their respiration with body movements during rhythmic locomotion. In the rat, fast respiration is coupled to head movements during sniffing behavior, but whether respiration is entrained by stride dynamics is not known. We recorded intranasal pressure, head acceleration, instantaneous speed, and ultrasonic vocalizations from male and female adult rats while freely behaving in a social environment. We used high-speed video recordings of stride to understand how head acceleration signals relate to locomotion and developed techniques to identify episodes of sniffing, walking, trotting, and galloping from the recorded variables. Quantitative analysis of synchrony between respiration and head acceleration rhythms revealed that respiration and locomotion movements were coordinated but with a weaker coupling than expected from previous work in other mammals. We have recently shown that rats behaving in social settings produce high rates of ultrasonic vocalizations during locomotion bouts. Accordingly, rats emitted vocalizations in over half of the respiratory cycles during fast displacements. We present evidence suggesting that emission of these calls disrupts the entrainment of respiration by stride. The coupling between these two variables is thus flexible, such that it can be overridden by other behavioral demands. Joseph Andrews Alves, Barbara Ciralli Boerner, and Diego Andrés Laplagne Copyright © 2016 Joseph Andrews Alves et al. All rights reserved. Correlation between Motor Cortex Excitability Changes and Cognitive Impairment in Vascular Depression: Pathophysiological Insights from a Longitudinal TMS Study Wed, 20 Jul 2016 14:31:26 +0000 Background. Transcranial magnetic stimulation (TMS) highlighted functional changes in dementia, whereas there are few data in patients with vascular cognitive impairment-no dementia (VCI-ND). Similarly, little is known about the neurophysiological impact of vascular depression (VD) on deterioration of cognitive functions. We test whether depression might affect not only cognition but also specific cortical circuits in subcortical vascular disease. Methods. Sixteen VCI-ND and 11 VD patients, age-matched with 15 controls, underwent a clinical-cognitive, neuroimaging, and TMS assessment. After approximately two years, all participants were prospectively reevaluated. Results. At baseline, a significant more pronounced intracortical facilitation (ICF) was found in VCI-ND patients. Reevaluation revealed an increase of the global excitability in both VCI-ND and VD subjects. At follow-up, the ICF of VCI-ND becomes similar to the other groups. Only VD patients showed cognitive deterioration. Conclusions. Unlike VD, the hyperfacilitation found at baseline in VCI-ND patients suggests enhanced glutamatergic neurotransmission that might contribute to the preservation of cognitive functioning. The hyperexcitability observed at follow-up in both groups of patients also indicates functional changes in glutamatergic neurotransmission. The mechanisms enhancing the risk of dementia in VD might be related either to subcortical vascular lesions or to the lack of compensatory functional cortical changes. Manuela Pennisi, Giuseppe Lanza, Mariagiovanna Cantone, Riccardo Ricceri, Concetto Spampinato, Giovanni Pennisi, Vincenzo Di Lazzaro, and Rita Bella Copyright © 2016 Manuela Pennisi et al. All rights reserved. The Habituation/Cross-Habituation Test Revisited: Guidance from Sniffing and Video Tracking Tue, 19 Jul 2016 11:09:31 +0000 The habituation/cross-habituation test (HaXha) is a spontaneous odor discrimination task that has been used for many decades to evaluate olfactory function in animals. Animals are presented repeatedly with the same odorant after which a new odorant is introduced. The time the animal explores the odor object is measured. An animal is considered to cross-habituate during the novel stimulus trial when the exploration time is higher than the prior trial and indicates the degree of olfactory patency. On the other hand, habituation across the repeated trials involves decreased exploration time and is related to memory patency, especially at long intervals. Classically exploration is timed using a stopwatch when the animal is within 2 cm of the object and aimed toward it. These criteria are intuitive, but it is unclear how they relate to olfactory exploration, that is, sniffing. We used video tracking combined with plethysmography to improve accuracy, avoid observer bias, and propose more robust criteria for exploratory scoring when sniff measures are not available. We also demonstrate that sniff rate combined with proximity is the most direct measure of odorant exploration and provide a robust and sensitive criterion. G. Coronas-Samano, A. V. Ivanova, and J. V. Verhagen Copyright © 2016 G. Coronas-Samano et al. All rights reserved. Neuronal Substrates Underlying Performance Variability in Well-Trained Skillful Motor Task in Humans Tue, 19 Jul 2016 09:55:09 +0000 Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance. Nobuaki Mizuguchi, Shintaro Uehara, Satoshi Hirose, Shinji Yamamoto, and Eiichi Naito Copyright © 2016 Nobuaki Mizuguchi et al. All rights reserved. Altered Cerebellar Circuitry following Thoracic Spinal Cord Injury in Adult Rats Mon, 18 Jul 2016 17:06:22 +0000 Cerebellar function is critical for coordinating movement and motor learning. However, events occurring in the cerebellum following spinal cord injury (SCI) have not been investigated in detail. We provide evidence of SCI-induced cerebellar synaptic changes involving a loss of granule cell parallel fiber input to distal regions of the Purkinje cell dendritic tree. This is accompanied by an apparent increase in synaptic contacts to Purkinje cell proximal dendrites, presumably from climbing fibers originating in the inferior olive. We also observed an early stage injury-induced decrease in the levels of cerebellin-1, a synaptic organizing molecule that is critical for establishing and maintaining parallel fiber-Purkinje cell synaptic integrity. Interestingly, this transsynaptic reorganizational pattern is consistent with that reported during development and in certain transgenic mouse models. To our knowledge, such a reorganizational event has not been described in response to SCI in adult rats. Regardless, the novel results of this study are important for understanding SCI-induced synaptic changes in the cerebellum, which may prove critical for strategies focusing on promoting functional recovery. Nishant P. Visavadiya and Joe E. Springer Copyright © 2016 Nishant P. Visavadiya and Joe E. Springer. All rights reserved. Axon Initial Segment Cytoskeleton: Architecture, Development, and Role in Neuron Polarity Sun, 17 Jul 2016 06:55:17 +0000 The axon initial segment (AIS) is a specialized structure in neurons that resides in between axonal and somatodendritic domains. The localization of the AIS in neurons is ideal for its two major functions: it serves as the site of action potential firing and helps to maintain neuron polarity. It has become increasingly clear that the AIS cytoskeleton is fundamental to AIS functions. In this review, we discuss current understanding of the AIS cytoskeleton with particular interest in its unique architecture and role in maintenance of neuron polarity. The AIS cytoskeleton is divided into two parts, submembrane and cytoplasmic, based on localization, function, and molecular composition. Recent studies using electron and subdiffraction fluorescence microscopy indicate that submembrane cytoskeletal components (ankyrin G, βIV-spectrin, and actin filaments) form a sophisticated network in the AIS that is conceptually similar to the polygonal/triangular network of erythrocytes, with some important differences. Components of the AIS cytoplasmic cytoskeleton (microtubules, actin filaments, and neurofilaments) reside deeper within the AIS shaft and display structural features distinct from other neuronal domains. We discuss how the AIS submembrane and cytoplasmic cytoskeletons contribute to different aspects of AIS polarity function and highlight recent advances in understanding their AIS cytoskeletal assembly and stability. Steven L. Jones and Tatyana M. Svitkina Copyright © 2016 Steven L. Jones and Tatyana M. Svitkina. All rights reserved. Emotion Dysregulation and Inflammation in African-American Women with Type 2 Diabetes Sun, 17 Jul 2016 06:18:23 +0000 C-reactive protein (CRP), a marker of systemic inflammation, has been associated with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Emotion dysregulation is a transdiagnostic risk factor for many psychological disorders associated with chronic inflammatory state. The objective of this study was to determine whether inflammation is associated with emotion dysregulation in women with type 2 diabetes mellitus (T2DM). We examined associations between trauma exposure, MDD, PTSD, emotion dysregulation, and CRP among 40 African-American women with T2DM recruited from an urban hospital. Emotion dysregulation was measured using the Difficulties in Emotion Regulation Scale. PTSD and MDD were measured with structured clinical interviews. Child abuse and lifetime trauma load were also assessed. Analyses showed that both emotion dysregulation and current MDD were significantly associated with higher levels of CRP (). Current PTSD was not significantly related to CRP. In a regression model, emotion dysregulation was significantly associated with higher CRP () independent of body mass index, trauma exposure, and MDD diagnosis. These findings suggest that emotion dysregulation may be an important risk factor for chronic inflammation beyond already known risk factors among women with T2DM, though a causal relationship cannot be determined from this study. Abigail Powers, Vasiliki Michopoulos, Karen Conneely, Rachel Gluck, Hayley Dixon, Joseph Wilson, Tanja Jovanovic, Thaddeus W. W. Pace, Guillermo E. Umpierrez, Kerry J. Ressler, Bekh Bradley, and Charles F. Gillespie Copyright © 2016 Abigail Powers et al. All rights reserved. Inhibition of DNA Methylation Impairs Synaptic Plasticity during an Early Time Window in Rats Thu, 14 Jul 2016 10:35:40 +0000 Although the importance of DNA methylation-dependent gene expression to neuronal plasticity is well established, the dynamics of methylation and demethylation during the induction and expression of synaptic plasticity have not been explored. Here, we combined electrophysiological, pharmacological, molecular, and immunohistochemical approaches to examine the contribution of DNA methylation and the phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) to synaptic plasticity. We found that, at twenty minutes after theta burst stimulation (TBS), the DNA methylation inhibitor 5-aza-2-deoxycytidine (5AZA) impaired hippocampal long-term potentiation (LTP). Surprisingly, after two hours of TBS, when LTP had become a transcription-dependent process, 5AZA treatment had no effect. By comparing these results to those in naive slices, we found that, at two hours after TBS, an intergenic region of the RLN gene was hypomethylated and that the phosphorylation of residue S80 of MeCP2 was decreased, while the phosphorylation of residue S421 was increased. As expected, 5AZA affected only the methylation of the RLN gene and exerted no effect on MeCP2 phosphorylation patterns. In summary, our data suggest that tetanic stimulation induces critical changes in synaptic plasticity that affects both DNA methylation and the phosphorylation of MeCP2. These data also suggest that early alterations in DNA methylation are sufficient to impair the full expression of LTP. Pablo Muñoz, Carolina Estay, Paula Díaz, Claudio Elgueta, Álvaro O. Ardiles, and Pablo A. Lizana Copyright © 2016 Pablo Muñoz et al. All rights reserved. Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition Mon, 11 Jul 2016 14:04:00 +0000 Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs) exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population. Reut Gruber and Merrill S. Wise Copyright © 2016 Reut Gruber and Merrill S. Wise. All rights reserved. Sleep Spindles as an Electrographic Element: Description and Automatic Detection Methods Mon, 11 Jul 2016 08:44:15 +0000 Sleep spindle is a peculiar oscillatory brain pattern which has been associated with a number of sleep (isolation from exteroceptive stimuli, memory consolidation) and individual characteristics (intellectual quotient). Oddly enough, the definition of a spindle is both incomplete and restrictive. In consequence, there is no consensus about how to detect spindles. Visual scoring is cumbersome and user dependent. To analyze spindle activity in a more robust way, automatic sleep spindle detection methods are essential. Various algorithms were developed, depending on individual research interest, which hampers direct comparisons and meta-analyses. In this review, sleep spindle is first defined physically and topographically. From this general description, we tentatively extract the main characteristics to be detected and analyzed. A nonexhaustive list of automatic spindle detection methods is provided along with a description of their main processing principles. Finally, we propose a technique to assess the detection methods in a robust and comparable way. Dorothée Coppieters ’t Wallant, Pierre Maquet, and Christophe Phillips Copyright © 2016 Dorothée Coppieters ’t Wallant et al. All rights reserved. Sleep Spindles Characteristics in Insomnia Sufferers and Their Relationship with Sleep Misperception Mon, 11 Jul 2016 08:10:13 +0000 Cortical hyperarousal is higher in insomnia sufferers (INS) than in good sleepers (GS) and could be related to an alteration in sleep protection mechanisms, like reduced density or altered characteristics in sleep spindles. The deficient sleep protection mechanisms might in turn enhance underestimation of sleep. This study’s objective was to document sleep spindles characteristics in INS compared with GS and to investigate their potential role in sleep consolidation and misperception. Seventeen individuals with paradoxical insomnia (PARA-I), 24 individuals with psychophysiological insomnia (PSY-I), and 29 GS completed four consecutive polysomnographic nights in laboratory. Sleep spindles were detected automatically during stage 2 and SWS (3-4) on night 3. Number, density, duration, frequency, and amplitude of sleep spindles were calculated. A misperception index was used to determine the degree of discrepancy between subjective and objective total sleep times. Kruskal-Wallis tests and post hoc tests revealed that PARA-I had significantly shorter sleep spindles than GS but that PSY-I and GS did not differ on spindles length. A standard multiple regression model revealed that neither sleep spindles characteristics nor objective sleep measures were predictive of sleep misperception. A longer duration of spindles could reflect a higher gating process but this hypothesis still needs to be confirmed in replication studies. Marie-Pier Normand, Patrick St-Hilaire, and Célyne H. Bastien Copyright © 2016 Marie-Pier Normand et al. All rights reserved. Individual Differences in Behavioural Despair Predict Brain GSK-3beta Expression in Mice: The Power of a Modified Swim Test Tue, 05 Jul 2016 15:02:00 +0000 While deficient brain plasticity is a well-established pathophysiologic feature of depression, little is known about disorder-associated enhanced cognitive processing. Here, we studied a novel mouse paradigm that potentially models augmented learning of adverse memories during development of a depressive-like state. We used a modification of the classic two-day protocol of a mouse Porsolt test with an additional session occurring on Day 5 following the initial exposure. Unexpectedly, floating behaviour and brain glycogen synthase kinase-3 beta (GSK-3beta) mRNA levels, a factor of synaptic plasticity as well as a marker of distress and depression, were increased during the additional swimming session that was prevented by imipramine. Observed increases of GSK-3beta mRNA in prefrontal cortex during delayed testing session correlated with individual parameters of behavioural despair that was not found in the classic Porsolt test. Repeated swim exposure was accompanied by a lower pGSK-3beta/GSK-3beta ratio. A replacement of the second or the final swim sessions with exposure to the context of testing resulted in increased GSK-3beta mRNA level similar to the effects of swimming, while exclusion of the second testing prevented these changes. Together, our findings implicate the activation of brain GSK-3beta expression in enhanced contextual conditioning of adverse memories, which is associated with an individual susceptibility to a depressive syndrome. Tatyana Strekalova, Nataliia Markova, Elena Shevtsova, Olga Zubareva, Anastassia Bakhmet, Harry M. Steinbusch, Sergey Bachurin, and Klaus-Peter Lesch Copyright © 2016 Tatyana Strekalova et al. All rights reserved.