Neural Plasticity The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model Thu, 23 Feb 2017 11:20:27 +0000 Birth asphyxia also termed perinatal asphyxia is an obstetric complication that strongly affects brain structure and function. Central nervous system is highly susceptible to oxidative damage caused by perinatal asphyxia while activation and maturity of the proper pathways are relevant to avoiding abnormal neural development. Perinatal asphyxia is associated with high morbimortality in term and preterm neonates. Although several studies have demonstrated a variety of biochemical and molecular pathways involved in perinatal asphyxia physiopathology, little is known about the synaptic alterations induced by perinatal asphyxia. Nearly 25% of the newborns who survive perinatal asphyxia develop neurological disorders such as cerebral palsy and certain neurodevelopmental and learning disabilities where synaptic connectivity disturbances may be involved. Accordingly, here we review and discuss the association of possible synaptic dysfunction with perinatal asphyxia on the basis of updated evidence from an experimental model. María Inés Herrera, Matilde Otero-Losada, Lucas Daniel Udovin, Carlos Kusnier, Rodolfo Kölliker-Frers, Wanderley de Souza, and Francisco Capani Copyright © 2017 María Inés Herrera et al. All rights reserved. Predictors of Recovery from Traumatic Brain Injury-Induced Prolonged Consciousness Disorder Thu, 23 Feb 2017 11:13:20 +0000 We investigated the clinical predictors of the degree of recovery in patients with prolonged disorders of consciousness (PDC) caused by traumatic brain injury. Fourteen patients with PDC underwent two diffusion tensor imaging (DTI) studies; the first and second scans were performed at and days after the injury, respectively. In addition to the temporal changes in each of these diffusion parameters, fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity were assessed over a 1-year period. Relationship of clinical and DTI parameters with recovery from PDC (RPDC) was evaluated using Spearman’s rank-correlation and stepwise multiple linear regression analysis. The mean FA and number of voxels with FA values > 0.4 (VsFA0.4) were significantly decreased at the second scan. A significant positive correlation was observed between the degree of RPDC and mean FA () and VsFA0.4 () as well as between the difference in VsFA0.4 () and AD () between the first and second scans. On multiple linear regression analysis, initial severity of PDC and the difference in AD remained significantly associated with the degree of RPDC. The microstructural white matter changes observed in this study indicate their potential relation with the degree of RPDC over the longer term. Hiroaki Abe, Keigo Shimoji, Yoshihide Nagamine, Satoru Fujiwara, and Shin-Ichi Izumi Copyright © 2017 Hiroaki Abe et al. All rights reserved. Fatigue and Muscle Strength Involving Walking Speed in Parkinson’s Disease: Insights for Developing Rehabilitation Strategy for PD Wed, 22 Feb 2017 13:20:20 +0000 Background. Problems with gait in Parkinson’s disease (PD) are a challenge in neurorehabilitation, partly because the mechanisms causing the walking disability are unclear. Weakness and fatigue, which may significantly influence gait, are commonly reported by patients with PD. Hence, the aim of this study was to investigate the association between weakness and fatigue and walking ability in patients with PD. Methods. We recruited 25 patients with idiopathic PD and 25 age-matched healthy adults. The maximum voluntary contraction (MVC), twitch force, and voluntary activation levels were measured before and after a knee fatigue exercise. General fatigue, central fatigue, and peripheral fatigue were quantified by exercise-induced changes in MVC, twitch force, and activation level. In addition, subjective fatigue was measured using the Multidimensional Fatigue Inventory (MFI) and Fatigue Severity Scale (FSS). Results. The patients with PD had lower activation levels, more central fatigue, and more subjective fatigue than the healthy controls. There were no significant differences in twitch force or peripheral fatigue index between the two groups. The reduction in walking speed was related to the loss of peripheral strength and PD itself. Conclusion. Fatigue and weakness of central origin were related to PD, while peripheral strength was important for walking ability. The results suggest that rehabilitation programs for PD should focus on improving both central and peripheral components of force. Ying-Zu Huang, Fang-Yu Chang, Wei-Chia Liu, Yu-Fen Chuang, Li-Ling Chuang, and Ya-Ju Chang Copyright © 2017 Ying-Zu Huang et al. All rights reserved. The Impact of Feedback on the Different Time Courses of Multisensory Temporal Recalibration Tue, 21 Feb 2017 07:06:30 +0000 The capacity to rapidly adjust perceptual representations confers a fundamental advantage when confronted with a constantly changing world. Unexplored is how feedback regarding sensory judgments (top-down factors) interacts with sensory statistics (bottom-up factors) to drive long- and short-term recalibration of multisensory perceptual representations. Here, we examined the time course of both cumulative and rapid temporal perceptual recalibration for individuals completing an audiovisual simultaneity judgment task in which they were provided with varying degrees of feedback. We find that in the presence of feedback (as opposed to simple sensory exposure) temporal recalibration is more robust. Additionally, differential time courses are seen for cumulative and rapid recalibration dependent upon the nature of the feedback provided. Whereas cumulative recalibration effects relied more heavily on feedback that informs (i.e., negative feedback) rather than confirms (i.e., positive feedback) the judgment, rapid recalibration shows the opposite tendency. Furthermore, differential effects on rapid and cumulative recalibration were seen when the reliability of feedback was altered. Collectively, our findings illustrate that feedback signals promote and sustain audiovisual recalibration over the course of cumulative learning and enhance rapid trial-to-trial learning. Furthermore, given the differential effects seen for cumulative and rapid recalibration, these processes may function via distinct mechanisms. Matthew A. De Niear, Jean-Paul Noel, and Mark T. Wallace Copyright © 2017 Matthew A. De Niear et al. All rights reserved. Hearing Loss: Reestablish the Neural Plasticity in Regenerated Spiral Ganglion Neurons and Sensory Hair Cells Mon, 20 Feb 2017 06:32:27 +0000 Renjie Chai, Geng-Lin Li, Jian Wang, and Jing Zou Copyright © 2017 Renjie Chai et al. All rights reserved. Zinc in the Monoaminergic Theory of Depression: Its Relationship to Neural Plasticity Sun, 19 Feb 2017 06:19:21 +0000 Preclinical and clinical studies have demonstrated that zinc possesses antidepressant properties and that it may augment the therapy with conventional, that is, monoamine-based, antidepressants. In this review we aim to discuss the role of zinc in the pathophysiology and treatment of depression with regard to the monoamine hypothesis of the disease. Particular attention will be paid to the recently described zinc-sensing GPR39 receptor as well as aspects of zinc deficiency. Furthermore, an attempt will be made to give a possible explanation of the mechanisms by which zinc interacts with the monoamine system in the context of depression and neural plasticity. Urszula Doboszewska, Piotr Wlaź, Gabriel Nowak, Maria Radziwoń-Zaleska, Ranji Cui, and Katarzyna Młyniec Copyright © 2017 Urszula Doboszewska et al. All rights reserved. Sensorimotor Cortical Neuroplasticity in the Early Stage of Bell’s Palsy Sun, 19 Feb 2017 00:00:00 +0000 Neuroplasticity is a common phenomenon in the human brain following nerve injury. It is defined as the brain’s ability to reorganize by creating new neural pathways in order to adapt to change. Here, we use task-related and resting-state fMRI to investigate neuroplasticity in the primary sensory (S1) and motor cortex (M1) in patients with acute Bell’s palsy (BP). We found that the period directly following the onset of BP (less than 14 days) is associated with significant decreases in regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and intrinsic connectivity contrast (ICC) values in the contralateral S1/M1 and in ReHo and ICC values in the ipsilateral S1/M1, compared to healthy controls. The regions with decreased ReHo, fALFF, and ICC values were in both the face and hand region of S1/M1 as indicated by resting-state fMRI but not task-related fMRI. Our results suggest that the early stages of BP are associated with functional neuroplasticity in both the face and hand regions of S1/M1 and that resting-state functional fMRI may be a sensitive tool to detect these early stages of plasticity in patient populations. Wenwen Song, Minhui Dai, Lihua Xuan, Zhijian Cao, Sisi Zhou, Courtney Lang, Kun Lv, Maosheng Xu, and Jian Kong Copyright © 2017 Wenwen Song et al. All rights reserved. Neural Energy Supply-Consumption Properties Based on Hodgkin-Huxley Model Thu, 16 Feb 2017 00:00:00 +0000 Electrical activity is the foundation of the neural system. Coding theories that describe neural electrical activity by the roles of action potential timing or frequency have been thoroughly studied. However, an alternative method to study coding questions is the energy method, which is more global and economical. In this study, we clearly defined and calculated neural energy supply and consumption based on the Hodgkin-Huxley model, during firing action potentials and subthreshold activities using ion-counting and power-integral model. Furthermore, we analyzed energy properties of each ion channel and found that, under the two circumstances, power synchronization of ion channels and energy utilization ratio have significant differences. This is particularly true of the energy utilization ratio, which can rise to above 100% during subthreshold activity, revealing an overdraft property of energy use. These findings demonstrate the distinct status of the energy properties during neuronal firings and subthreshold activities. Meanwhile, after introducing a synapse energy model, this research can be generalized to energy calculation of a neural network. This is potentially important for understanding the relationship between dynamical network activities and cognitive behaviors. Yihong Wang, Rubin Wang, and Xuying Xu Copyright © 2017 Yihong Wang et al. All rights reserved. Nonpharmacological Interventions in Targeting Pain-Related Brain Plasticity Thu, 16 Feb 2017 00:00:00 +0000 Chronic pain is a highly prevalent and debilitating condition that is frequently associated with multiple comorbid psychiatric conditions and functional, biochemical, and anatomical alterations in various brain centers. Due to its widespread and diverse manifestations, chronic pain is often resistant to classical pharmacological treatment paradigms, prompting the search for alternative treatment approaches that are safe and efficacious. The current review will focus on the following themes: attentional and cognitive interventions, the role of global environmental factors, and the effects of exercise and physical rehabilitation in both chronic pain patients and preclinical pain models. The manuscript will discuss not only the analgesic efficacy of these therapies, but also their ability to reverse pain-related brain neuroplasticity. Finally, we will discuss the potential mechanisms of action for each of the interventions. Maral Tajerian and J. David Clark Copyright © 2017 Maral Tajerian and J. David Clark. All rights reserved. Short Latency Gray Matter Changes in Voxel-Based Morphometry following High Frequent Visual Stimulation Wed, 15 Feb 2017 00:00:00 +0000 Magnetic resonance imaging studies using voxel-based morphometry (VBM) detected structural changes in the human brain within periods of months or weeks. The underlying molecular mechanisms of VBM findings remain unresolved. We showed that simple visual stimulation by an alternating checkerboard leads to instant, short-lasting alterations of the primary and secondary visual cortex detected by VBM. The rapidness of occurrence (i.e., within 10 minutes) rather excludes most of the proposed physiological mechanism such as neural or glial cell genesis/degeneration or synapse turnover. We therefore favour cerebral fluid shifts to be the underlying correlate of the here observed VBM gray matter changes. Fast onset gray matter changes might be one important explanation for the inconsistency of VBM study results that often raise concern in regard to the validity of presented data. This study shows that changes detectable by VBM may occur within a few minutes after physiological stimulation and must be considered in future VBM experiments to avoid misinterpretation of results. Steffen Naegel, Tim Hagenacker, Nina Theysohn, Hans-Christoph Diener, Zaza Katsarava, Mark Obermann, and Dagny Holle Copyright © 2017 Steffen Naegel et al. All rights reserved. Neuroplasticity Changes on Human Motor Cortex Induced by Acupuncture Therapy: A Preliminary Study Wed, 15 Feb 2017 00:00:00 +0000 While neuroplasticity changes measured by transcranial magnetic stimulation have been proved to be highly correlated to motor recovery and have been tested in various forms of interventions, it has not been applied to investigate the neurophysiologic mechanism of acupuncture therapy. The aim of this study is to investigate neuroplasticity changes induced by a single session of acupuncture therapy in healthy adults, regarding the excitability change on bilateral primary motor cortex and interhemispheric inhibition. Ten subjects took a 30-minute acupuncture therapy and the same length relaxing phase in separate days. Transcranial magnetic stimulation measures, including resting motor threshold, amplitudes of motor-evoked potential, and interhemispheric inhibition, were assessed before and 10 minutes after intervention. Acupuncture treatment showed significant changes on potential amplitude from both ipsilateral and contralateral hemispheres to acupuncture compared to baseline. Also, interhemispheric inhibition from the contralateral motor cortex to the opposite showed a significant decline. The results indicated that corticomotoneuronal excitability and interhemispheric competition could be modulated by acupuncture therapy on healthy subjects. The following question about whether these changes will be observed in the same way on stroke patients and whether they correlate with the therapeutic effect on movement need to be answered by following studies. This trial is registered with ISRCTN13074245. Yi Yang, Ines Eisner, Siqi Chen, Shaosong Wang, Fan Zhang, and Linpeng Wang Copyright © 2017 Yi Yang et al. All rights reserved. Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia Wed, 15 Feb 2017 00:00:00 +0000 HDAC3 has been shown to regulate inflammation. However, the role of HDAC3 in primary microglia is largely unknown. RGFP966 is a newly discovered selective HDAC3 inhibitor. In this study, we used protein mass spectrometry to analyze protein alterations in LPS-treated primary microglia with the application of RGFP966. Generally, about 2000 proteins were studied. 168 of 444 (37.8%) LPS-induced proteins were significantly reduced with the treatment of RGFP966, which mainly concentrated on Toll-like receptor signaling pathway. In this regard, we selected Toll-like receptor 2 (TLR2), TLR3, TLR6, MAPK p38, CD36, and spleen tyrosine kinase (SYK) for further validation and found that they were all significantly upregulated after LPS stimulation and downregulated in the presence of RGFP966. Additionally, RGFP966 inhibited supernatant tumor necrosis factor (TNF)-α and Interleukin 6 (IL-6) concentrations. Activation of STAT3 and STAT5 was partially blocked by RGFP966 at 2 h after LPS-stimulation. The fluorescence intensity of CD16/32 was significantly decreased in LPS + RGFP966-treated group. In conclusion, our data provided a hint that RGFP966 may be a potential therapeutic medication combating microglia activation and inflammatory response in central nervous system, which was probably related to its repressive impacts on TLR signaling pathways and STAT3/STAT5 pathways. Mingxu Xia, Qiuchen Zhao, He Zhang, Yanting Chen, Zengqiang Yuan, Yun Xu, and Meijuan Zhang Copyright © 2017 Mingxu Xia et al. All rights reserved. Motor Recovery of the Affected Hand in Subacute Stroke Correlates with Changes of Contralesional Cortical Hand Motor Representation Tue, 14 Feb 2017 10:24:06 +0000 Objective. To investigate the relationship between changes of cortical hand motor representation and motor recovery of the affected hand in subacute stroke. Methods. 17 patients with motor impairment of the affected hand were enrolled in an in-patient neurological rehabilitation program. Hand motor function tests (Wolf Motor Function Test, Action Research Arm Test) and neurophysiological evaluations (resting motor threshold, motor evoked potentials, motor map area size, motor map area volume, and motor map area location) were obtained from both hands and hemispheres at baseline and two, four, and six weeks of in-patient rehabilitation. Results. There was a wide spectrum of hand motor impairment at baseline and hand motor recovery over time. Hand motor function and recovery correlated significantly with (i) reduction of cortical excitability, (ii) reduction in size and volume of cortical hand motor representation, and (iii) a medial and anterior shift of the center of gravity of cortical hand motor representation within the contralesional hemisphere. Conclusion. Recovery of motor function of the affected hand after stroke is accompanied by definite changes in excitability, size, volume, and location of hand motor representation over the contralesional primary motor cortex. These measures may serve as surrogate markers for the outcome of hand motor rehabilitation after stroke. Jitka Veldema, Kathrin Bösl, and Dennis Alexander Nowak Copyright © 2017 Jitka Veldema et al. All rights reserved. Cerebellar Cathodal Transcranial Direct Stimulation and Performance on a Verb Generation Task: A Replication Study Tue, 14 Feb 2017 00:00:00 +0000 The role of the cerebellum in cognitive processing is increasingly recognized but still poorly understood. A recent study in this field applied cerebellar Transcranial Direct Current Stimulation (c-tDCS) to the right cerebellum to investigate the role of prefrontal-cerebellar loops in language aspects of cognition. Results showed that the improvement in participants’ verbal response times on a verb generation task was facilitated immediately after cathodal c-tDCS, compared to anodal or sham c-tDCS. The primary aim of the present study is to replicate these findings and additionally to investigate possible longer term effects. A crossover within-subject design was used, comparing cathodal and sham c-tDCS. The experiment consisted of two visits with an interval of one week. Our results show no direct contribution of cathodal c-tDCS over the cerebellum to language task performance. However, one week later, the group receiving cathodal c-tDCS in the first visit show less improvement and increased variability in their verbal response times during the second visit, compared to the group receiving sham c-tDCS in the first visit. These findings suggest a potential negative effect of c-tDCS and warrant further investigation into long term effects of c-tDCS before undertaking clinical studies with poststroke patients with aphasia. K. Spielmann, R. van der Vliet, W. M. E. van de Sandt-Koenderman, M. A. Frens, G. M. Ribbers, R. W. Selles, S. van Vugt, J. N. van der Geest, and P. Holland Copyright © 2017 K. Spielmann et al. All rights reserved. The Cognitive Neuroplasticity of Reading Recovery following Chronic Stroke: A Representational Similarity Analysis Approach Wed, 08 Feb 2017 00:00:00 +0000 Damage to certain left hemisphere regions leads to reading impairments, at least acutely, though some individuals eventually recover reading. Previous neuroimaging studies have shown a relationship between reading recovery and increases in contralesional and perilesional activation during word reading tasks, relative to controls. Questions remain about how to interpret these changes in activation. Do these changes reflect functional take-over, a reorganization of functions in the damaged brain? Or do they reveal compensatory masquerade or the use of alternative neural pathways to reading that are available in both patients and controls? We address these questions by studying a single individual, CH, who has made a partial recovery of reading familiar words following stroke. We use an fMRI analysis technique, representational similarity analysis (RSA), which allows us to decode cognitive function from distributed patterns of neural activity. Relative to controls, we find that CH shows a shift from visual to orthographic processing in contralesional regions, with a marginally significant result in perilesional regions as well. This pattern supports a contralesional reorganization of orthographic processing following stroke. More generally, these analyses demonstrate how powerful RSA can be for mapping the neural plasticity of language function. Simon Fischer-Baum, Ava Jang, and David Kajander Copyright © 2017 Simon Fischer-Baum et al. All rights reserved. Acupuncture Attenuates Renal Sympathetic Activity and Blood Pressure via Beta-Adrenergic Receptors in Spontaneously Hypertensive Rats Wed, 08 Feb 2017 00:00:00 +0000 The sympathetic nervous system, via epinephrine and norepinephrine, regulates β-adrenergic receptor (β-AR) expression, and renal sympathetic activation causes sustained increases in blood pressure by enhanced renin release. In this study, we aim to investigate the effect and underlying mechanism of acupuncture at Taichong (LR3) on renal sympathetic activity in spontaneously hypertensive rats. Unanesthetized rats were subject to daily acupuncture for 2 weeks. Mean blood pressure (MBP) and heart rate variability (HRV) were monitored at days 0, 7, and 14 by radiotelemetry. After euthanasia on the 14th day, blood and the kidneys were collected and subject to the following analyses. Epinephrine and norepinephrine were detected by ELISA. The expression of β-ARs was studied by western blotting and PCR. The renin content was analyzed by radioimmunoassay. 14-day acupuncture significantly attenuates the increase of MBP. The HRV indices, the standard deviation of all normal NN intervals (SDNN), and the ratio of the low-frequency component to the high-frequency component (LF/HF) were improved following acupuncture. Renal sympathetic activation induced upregulation of epinephrine, norepinephrine, and renin content were attenuated by acupuncture. In addition, acupuncture decreased β1-AR expression and improved β2-AR expression. These results indicated that acupuncture relieves the increased MBP via the regulation of renal sympathetic activity and β-ARs. Jing-Wen Yang, Yang Ye, Xue-Rui Wang, Fang Li, Ling-Yong Xiao, Guang-Xia Shi, and Cun-Zhi Liu Copyright © 2017 Jing-Wen Yang et al. All rights reserved. Thalamo-Sensorimotor Functional Connectivity Correlates with World Ranking of Olympic, Elite, and High Performance Athletes Thu, 02 Feb 2017 00:00:00 +0000 Brain plasticity studies have shown functional reorganization in participants with outstanding motor expertise. Little is known about neural plasticity associated with exceptionally long motor training or of its predictive value for motor performance excellence. The present study utilised resting-state functional magnetic resonance imaging (rs-fMRI) in a unique sample of world-class athletes: Olympic, elite, and internationally ranked swimmers (). Their world ranking ranged from 1st to 250th: each had prepared for participation in the Olympic Games. Combining rs-fMRI graph-theoretical and seed-based functional connectivity analyses, it was discovered that the thalamus has its strongest connections with the sensorimotor network in elite swimmers with the highest world rankings (career best rank: 1–35). Strikingly, thalamo-sensorimotor functional connections were highly correlated with the swimmers’ motor performance excellence, that is, accounting for 41% of the individual variance in best world ranking. Our findings shed light on neural correlates of long-term athletic performance involving thalamo-sensorimotor functional circuits. Zirui Huang, Henry (Hap) Davis IV, Annemarie Wolff, and Georg Northoff Copyright © 2017 Zirui Huang et al. All rights reserved. Impairments in Brain Perfusion, Metabolites, Functional Connectivity, and Cognition in Severe Asymptomatic Carotid Stenosis Patients: An Integrated MRI Study Wed, 01 Feb 2017 12:52:52 +0000 Carotid artery stenosis without transient ischemic attack (TIA) or stroke is considered as “asymptomatic.” However, recent studies have demonstrated that these asymptomatic carotid artery stenosis (aCAS) patients had cognitive impairment in tests of executive function, psychomotor speed, and memory, indicating that “asymptomatic” carotid stenosis may not be truly asymptomatic. In this study, when 19 aCAS patients compared with 24 healthy controls, aCAS patients showed significantly poorer performance on global cognition, memory, and executive function. By utilizing an integrated MRI including pulsed arterial spin labeling (pASL) MRI, Proton MR Spectroscopy (MRS), and resting-state functional MRI (R-fMRI), we also found that aCAS patients suffered decreased cerebral blood flow (CBF) mainly in the Left Frontal Gyrus and had decreased NAA/Cr ratio in the left hippocampus and decreased connectivity to the posterior cingulate cortex (PCC) in the anterior part of default mode network (DMN). Tao Wang, Feng Xiao, Guangyao Wu, Jian Fang, Zhenmeng Sun, Hongliang Feng, Junjian Zhang, and Haibo Xu Copyright © 2017 Tao Wang et al. All rights reserved. Brain White Matter Impairment in Patients with Spinal Cord Injury Wed, 01 Feb 2017 08:07:14 +0000 It remains unknown whether spinal cord injury (SCI) could indirectly impair or reshape the white matter (WM) of human brain and whether these changes are correlated with injury severity, duration, or clinical performance. We choose tract-based spatial statistics (TBSS) to investigate the possible changes in whole-brain white matter integrity and their associations with clinical variables in fifteen patients with SCI. Compared with the healthy controls, the patients exhibited significant decreases in WM fractional anisotropy (FA) in the left angular gyrus (AG), right cerebellum (CB), left precentral gyrus (PreCG), left lateral occipital region (LOC), left superior longitudinal fasciculus (SLF), left supramarginal gyrus (SMG), and left postcentral gyrus (PostCG) (, TFCE corrected). No significant differences were found in all diffusion indices between the complete and incomplete SCI. However, significantly negative correlation was shown between the increased radial diffusivity (RD) of left AG and total motor scores (uncorrected ). Our findings provide evidence that SCI can cause not only direct degeneration but also transneuronal degeneration of brain WM, and these changes may be irrespective of the injury severity. The affection of left AG on rehabilitation therapies need to be further researched in the future. Weimin Zheng, Qian Chen, Xin Chen, Lu Wan, Wen Qin, Zhigang Qi, Nan Chen, and Kuncheng Li Copyright © 2017 Weimin Zheng et al. All rights reserved. Altered Brain Functional Activity in Infants with Congenital Bilateral Severe Sensorineural Hearing Loss: A Resting-State Functional MRI Study under Sedation Wed, 01 Feb 2017 00:00:00 +0000 Early hearing deprivation could affect the development of auditory, language, and vision ability. Insufficient or no stimulation of the auditory cortex during the sensitive periods of plasticity could affect the function of hearing, language, and vision development. Twenty-three infants with congenital severe sensorineural hearing loss (CSSHL) and 17 age and sex matched normal hearing subjects were recruited. The amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo) of the auditory, language, and vision related brain areas were compared between deaf infants and normal subjects. Compared with normal hearing subjects, decreased ALFF and ReHo were observed in auditory and language-related cortex. Increased ALFF and ReHo were observed in vision related cortex, which suggest that hearing and language function were impaired and vision function was enhanced due to the loss of hearing. ALFF of left Brodmann area 45 (BA45) was negatively correlated with deaf duration in infants with CSSHL. ALFF of right BA39 was positively correlated with deaf duration in infants with CSSHL. In conclusion, ALFF and ReHo can reflect the abnormal brain function in language, auditory, and visual information processing in infants with CSSHL. This demonstrates that the development of auditory, language, and vision processing function has been affected by congenital severe sensorineural hearing loss before 4 years of age. Shuang Xia, TianBin Song, Jing Che, Qiang Li, Chao Chai, Meizhu Zheng, and Wen Shen Copyright © 2017 Shuang Xia et al. All rights reserved. The Polarization States of Microglia in TBI: A New Paradigm for Pharmacological Intervention Wed, 01 Feb 2017 00:00:00 +0000 Traumatic brain injury (TBI) is a serious medical and social problem worldwide. Because of the complex pathophysiological mechanisms of TBI, effective pharmacotherapy is still lacking. The microglial cells are resident tissue macrophages located in the brain and have two major polarization states, M1 phenotype and M2 phenotype, when activated. The M1 phenotype is related to the release of proinflammatory cytokines and secondary brain injury, while the M2 phenotype has been proved to be responsible for the release of anti-inflammation cytokines and for central nervous system (CNS) repair. In animal models, pharmacological strategies inhibiting the M1 phenotype and promoting the M2 phenotype of microglial cells could alleviate cerebral damage and improve neurological function recovery after TBI. In this review, we aimed to summarize the current knowledge about the pathological significance of microglial M1/M2 polarization in the pathophysiology of TBI. In addition, we reviewed several drugs that have provided neuroprotective effects against brain injury following TBI by altering the polarization states of the microglia. We emphasized that future investigation of the regulation mechanisms of microglial M1/M2 polarization in TBI is anticipated, which could contribute to the development of new targets of pharmacological intervention in TBI. Hangzhe Xu, Zhijiang Wang, Jianru Li, Haijian Wu, Yucong Peng, Linfeng Fan, Jingyin Chen, Chi Gu, Feng Yan, Lin Wang, and Gao Chen Copyright © 2017 Hangzhe Xu et al. All rights reserved. Gene-Environment Interactions in Neurodevelopmental Disorders Tue, 31 Jan 2017 11:25:45 +0000 Susanna Pietropaolo, Wim E. Crusio, and Joram Feldon Copyright © 2017 Susanna Pietropaolo et al. All rights reserved. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity Tue, 31 Jan 2017 10:44:04 +0000 Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, forming trans-complexes spanning the synaptic cleft or cis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics. Gabby Rudenko Copyright © 2017 Gabby Rudenko. All rights reserved. Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism Tue, 31 Jan 2017 07:07:17 +0000 Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male and WT mice. Mice were housed in social and isolation conditions to test for isolation-induced increases in social interaction. Tests were repeated to investigate potential differences in interaction in naïve and experienced mice. We identified heightened interest in mating and atypical aggressive behavior in mice. mice exhibited normal social interaction with WT females, indicating that abnormal aggressive behavior towards females is not due to altered motivation to engage. Social isolation rearing heightened interest in social behavior in all mice. Isolation housing selectively modulated the response to female pheromones in mice. This study is the first to show altered mating behavior in the mouse and has provided new insights into the aggressive phenotype in this model. E. L. Burrows, A. F. Eastwood, C. May, S. C. Kolbe, T. Hill, N. M. McLachlan, L. Churilov, and A. J. Hannan Copyright © 2017 E. L. Burrows et al. All rights reserved. Profiling Proteins in the Hypothalamus and Hippocampus of a Rat Model of Premenstrual Syndrome Irritability Tue, 31 Jan 2017 07:06:50 +0000 Premenstrual syndrome (PMS) refers to several physical and mental symptoms (such as irritability) commonly encountered in clinical gynaecology. The incidence of PMS has been increasing, attracting greater attention from medical fields. However, PMS pathogenesis remains unclear. This study employed two-dimensional gel electrophoresis (2DE) for proteomic map analysis of the hypothalamus and hippocampus of rat models of premenstrual syndrome (PMS) irritability. Matrix-assisted laser desorption/ionisation time of flight mass spectroscopy (MALDI-TOF-MS) was used to identify proteins possibly related with PMS irritability. Baixiangdan, a traditional Chinese medicine effective against PMS irritability, was used in the rat model to study putative target proteins of this medicine. The hypothalamus and hippocampus of each group modelling PMS displayed the following features: decreased expression of Ulip2, tubulin beta chain 15, α actin, and interleukin 1 receptor accessory protein; increased expression of kappa-B motif-binding phosphoprotein; decreased expression of hydrolase at the end of ubiquitin carboxy, albumin, and aldolase protein; and increased expression of M2 pyruvate kinase, panthenol-cytochrome C reductase core protein I, and calcium-binding protein. Contrasting with previous studies, the current study identified new proteins related to PMS irritability. Our findings contribute to understanding the pathogenesis of PMS irritability and could provide a reference point for further studies. Mingqi Qiao, Peng Sun, Yang Wang, Sheng Wei, Xia Wei, Chunhong Song, Fushun Wang, and Jibiao Wu Copyright © 2017 Mingqi Qiao et al. All rights reserved. The Rapid Effect of Bisphenol-A on Long-Term Potentiation in Hippocampus Involves Estrogen Receptors and ERK Activation Tue, 31 Jan 2017 00:00:00 +0000 Bisphenol-A (BPA), a widely used synthetic compound in plastics, disrupts endocrine function and interferes with physiological actions of endogenous gonadal hormones. Chronic effects of BPA on reproductive function, learning and memory, brain structure, and social behavior have been intensively investigated. However, less is known about the influence of BPA on long-term potentiation (LTP), one of the major cellular mechanisms that underlie learning and memory. In the present study, for the first time we investigated the effect of different doses of BPA on hippocampal LTP in rat brain slices. We found a biphasic effect of BPA on LTP in the dentate gyrus: exposure to BPA at a low dose (100 nM) enhanced LTP and exposure to BPA at a high dose (1000 nM) inhibited LTP compared with vehicle controls. The rapid facilitatory effect of low-dose BPA on hippocampal LTP required membrane-associated estrogen receptor (ER) and involved activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Coadministration of 17β-estradiol (E2, the primary estrogen hormone) and BPA (100 nM) abolished both the BPA-induced enhancement of LTP and the E2-induced enhancement of baseline fEPSP, suggesting a complex interaction between BPA- and E2-mediated signaling pathways. Our investigation implies that even nanomolar levels of endocrine disrupters (e.g., BPA) can induce significant effects on hippocampal LTP. Xiaowei Chen, Yu Wang, Fang Xu, Xiaofei Wei, Junfang Zhang, Chuang Wang, Hua Wei, Shujun Xu, Peiyun Yan, Wenhua Zhou, Istvan Mody, Xiaohong Xu, and Qinwen Wang Copyright © 2017 Xiaowei Chen et al. All rights reserved. Evaluation of the Hair Cell Regeneration in Zebrafish Larvae by Measuring and Quantifying the Startle Responses Sun, 29 Jan 2017 09:09:42 +0000 The zebrafish has become an established model organism for the study of hearing and balance systems in the past two decades. The classical approach to examine hair cells is to use dye to conduct selective staining, which shows the number and morphology of hair cells but does not reveal their function. Startle response is a behavior closely related to the auditory function of hair cells; therefore it can be used to measure the function of hair cells. In this study, we developed a device to measure the startle response of zebrafish larvae. By applying various levels of stimulus, it showed that the system can discern a 10 dB difference. The hair cell in zebrafish can regenerate after damage due to noise exposure or drug treatment. With this device, we measured the startle response of zebrafish larvae during and after drug treatment. The results show a similar trend to the classical hair cell staining method. The startle response was reduced with drug treatment and recovered after removal of the drug. Together it demonstrated the capability of this behavioral assay in evaluating the hair cell functions of fish larvae and its potential as a high-throughput screening tool for auditory-related gene and drug discovery. Changquan Wang, Zhenmin Zhong, Peng Sun, Hanbing Zhong, Hongzhe Li, and Fangyi Chen Copyright © 2017 Changquan Wang et al. All rights reserved. The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex Thu, 26 Jan 2017 11:07:13 +0000 Neural plasticity, a fundamental mechanism of neuronal adaptation, is disrupted in depression. The changes in neural plasticity induced by stress and other negative stimuli play a significant role in the onset and development of depression. Antidepressant treatments have also been found to exert their antidepressant effects through regulatory effects on neural plasticity. However, the detailed mechanisms of neural plasticity in depression still remain unclear. Therefore, in this review, we summarize the recent literature to elaborate the possible mechanistic role of neural plasticity in depression. Taken together, these findings may pave the way for future progress in neural plasticity studies. Wei Liu, Tongtong Ge, Yashu Leng, Zhenxiang Pan, Jie Fan, Wei Yang, and Ranji Cui Copyright © 2017 Wei Liu et al. All rights reserved. Navigated Transcranial Magnetic Stimulation: A Biologically Based Assay of Lower Extremity Impairment and Gait Velocity Tue, 24 Jan 2017 06:07:19 +0000 Objectives. (a) To determine associations among motor evoked potential (MEP) amplitude, MEP latency, lower extremity (LE) impairment, and gait velocity and (b) determine the association between the presence of a detectable MEP signal with LE impairment and with gait velocity. Method. 35 subjects with chronic, stable LE hemiparesis were undergone TMS, the LE section of the Fugl-Meyer Impairment Scale (LE FM), and 10-meter walk test. We recorded presence, amplitude, and latency of MEPs in the affected tibialis anterior (TA) and soleus (SO). Results. MEP presence was associated with higher LEFM scores in both the TA and SO. MEP latency was larger in subjects with lower LEFM and difficulty walking. Conclusion. MEP latency appears to be an indicator of LE impairment and gait. Significance. Our results support the precept of using TMS, particularly MEP latency, as an adjunctive LE outcome measurement and prognostic technique. Heather T. Peters, Kari Dunning, Samir Belagaje, Brett M. Kissela, Jun Ying, Jarmo Laine, and Stephen J. Page Copyright © 2017 Heather T. Peters et al. All rights reserved. Cognitive Pragmatic Rehabilitation Program in Schizophrenia: A Single Case fMRI Study Mon, 23 Jan 2017 00:00:00 +0000 Introduction. The present study was intended to evaluate the effects of a rehabilitative training, the Cognitive Pragmatic Treatment (CPT), aimed at improving communicative-pragmatic abilities and the related cognitive components, on the cerebral modifications of a single case patient diagnosed with schizophrenia. Methods. The patient underwent two functional magnetic resonance imaging (fMRI) sessions, before and after the treatment. In order to assess brain changes, we calculated the Amplitude of Low Frequency Fluctuation (ALFF) index of the resting-state fMRI signal, which is interpreted as reflecting the intensity of the spontaneous regional activity of the brain. Behavioural measures of the patient’s communicative performance were also gathered before and after training and at follow-up. Results. The patient improved his communicative performance in almost all tests. Posttraining stronger ALFF signal emerged in the superior, inferior, and medial frontal gyri, as well as the superior temporal gyri. Conclusions. Even if based on a single case study, these preliminary results show functional changes at the cerebral level that seem to support the patient’s behavioural improvements. Ilaria Gabbatore, Francesca M. Bosco, Elisabetta Geda, Luigi Gastaldo, Sergio Duca, Tommaso Costa, Bruno G. Bara, and Katiuscia Sacco Copyright © 2017 Ilaria Gabbatore et al. All rights reserved.