Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2017 , Hindawi Publishing Corporation . All rights reserved. The Relative Weight of Temporal Envelope Cues in Different Frequency Regions for Mandarin Sentence Recognition Thu, 19 Jan 2017 08:01:50 +0000 Acoustic temporal envelope (E) cues containing speech information are distributed across the frequency spectrum. To investigate the relative weight of E cues in different frequency regions for Mandarin sentence recognition, E information was extracted from 30 contiguous bands across the range of 80–7,562 Hz using Hilbert decomposition and then allocated to five frequency regions. Recognition scores were obtained with acoustic E cues from 1 or 2 random regions from 40 normal-hearing listeners. While the recognition scores ranged from 8.2% to 16.3% when E information from only one region was available, the scores ranged from 57.9% to 87.7% when E information from two frequency regions was presented, suggesting a synergistic effect among the temporal E cues in different frequency regions. Next, the relative contributions of the E information from the five frequency regions to sentence perception were computed using a least-squares approach. The results demonstrated that, for Mandarin Chinese, a tonal language, the temporal E cues of Frequency Region 1 (80–502 Hz) and Region 3 (1,022–1,913 Hz) contributed more to the intelligence of sentence recognition than other regions, particularly the region of 80–502 Hz, which contained fundamental frequency () information. Yang Guo, Yuanyuan Sun, Yanmei Feng, Yujun Zhang, and Shankai Yin Copyright © 2017 Yang Guo et al. All rights reserved. Unilateral Laryngeal Pacing System and Its Functional Evaluation Thu, 19 Jan 2017 00:00:00 +0000 Goal. To establish a reliable instrumental system for synchronized reactivation of a unilaterally paralyzed vocal fold and evaluate its functional feasibility. Methods. Unilateral vocal fold paralysis model was induced by destruction of the left recurrent laryngeal nerve (RLN) in anesthetized dogs. With a micro controller-based electronic system, electromyography (EMG) signals from cricothyroid (CT) muscle on the ipsilateral side were recorded and used to trigger pacing of paralyzed vocalis muscles. The dynamic movement of vocal folds was continuously monitored using an endoscope, and the opening and closing of the glottis were quantified with customized imaging processing software. Results. The recorded video images showed that left side vocal fold was obviously paralyzed after destructing the RLN. Using the pacing system with feedback triggering EMG signals from the ipsilateral CT muscle, the paralyzed vocal fold was successfully reactivated, and its movement was shown to be synchronized with the healthy side. Significance. The developed unilateral laryngeal pacing system triggered by EMG from the ipsilateral side CT muscle could be successfully used in unilateral vocal fold paralysis with the advantage of avoiding disturbance to the healthy side muscles. Taiping Zeng, Zhiping Zhang, Weiwei Peng, Fei Zhang, Baker Y. Shi, and Fangyi Chen Copyright © 2017 Taiping Zeng et al. All rights reserved. Chronic Social Defeat Stress Modulates Dendritic Spines Structural Plasticity in Adult Mouse Frontal Association Cortex Wed, 18 Jan 2017 10:56:04 +0000 Chronic stress is associated with occurrence of many mental disorders. Previous studies have shown that dendrites and spines of pyramidal neurons of the prefrontal cortex undergo drastic reorganization following chronic stress experience. So the prefrontal cortex is believed to play a key role in response of neural system to chronic stress. However, how stress induces dynamic structural changes in neural circuit of prefrontal cortex remains unknown. In the present study, we examined the effects of chronic social defeat stress on dendritic spine structural plasticity in the mouse frontal association (FrA) cortex in vivo using two-photon microscopy. We found that chronic stress altered spine dynamics in FrA and increased the connectivity in FrA neural circuits. We also found that the changes in spine dynamics in FrA are correlated with the deficit of sucrose preference in defeated mice. Our findings suggest that chronic stress experience leads to adaptive change in neural circuits that may be important for encoding stress experience related memory and anhedonia. Yu Shu and Tonghui Xu Copyright © 2017 Yu Shu and Tonghui Xu. All rights reserved. The Function of FGFR1 Signalling in the Spinal Cord: Therapeutic Approaches Using FGFR1 Ligands after Spinal Cord Injury Wed, 18 Jan 2017 00:00:00 +0000 Extensive research is ongoing that concentrates on finding therapies to enhance CNS regeneration after spinal cord injury (SCI) and to cure paralysis. This review sheds light on the role of the FGFR pathway in the injured spinal cord and discusses various therapies that use FGFR activating ligands to promote regeneration after SCI. We discuss studies that use peripheral nerve grafts or Schwann cell grafts in combination with FGF1 or FGF2 supplementation. Most of these studies show evidence that these therapies successfully enhance axon regeneration into the graft. Further they provide evidence for partial recovery of sensory function shown by electrophysiology and motor activity evidenced by behavioural data. We also present one study that indicates that combination with additional, synergistic factors might further drive the system towards functional regeneration. In essence, this review summarises the potential of nerve and cell grafts combined with FGF1/2 supplementation to improve outcome even after severe spinal cord injury. Barbara Haenzi and Lawrence D. F. Moon Copyright © 2017 Barbara Haenzi and Lawrence D. F. Moon. All rights reserved. Localizing Age-Related Changes in Brain Structure Using Voxel-Based Morphometry Tue, 17 Jan 2017 00:00:00 +0000 Aim. We report the dynamic anatomical sequence of human cortical gray matter development from late childhood to young adults using VBM and ROI-based methods. Method. The structural MRI of 91 normal individuals ranging in age from 6 to 26 years was obtained and the GMV for each region was measured. Results. Our results showed that the earliest loss of GMV occurred in left olfactory, right precuneus, caudate, left putamen, pallidum, and left middle temporal gyrus. In addition, the trajectory of maturational and aging showed a linear decline in GMV on both cortical lobes and subcortical regions. The most loss of gray matter was observed in the parietal lobe and basal ganglia, whereas the less loss occurred in the temporal lobe and hippocampus, especially in the left middle temporal pole, which showed no decline until 26 years old. Moreover, the volumes of GM, WM, and CSF were also assessed for linear age effects, showing a significant linear decline in GM with age and a significant linear increase in both WM and CSF with age. Interpretation. Overall, our findings lend support to previous findings of the normal brain development of regional cortex, and they may help in understanding of neurodevelopmental disorders. Shu Hua Mu, Min Xu, Jun Xiu Duan, Jian Zhang, and Li Hai Tan Copyright © 2017 Shu Hua Mu et al. All rights reserved. Alterations in Cortical Thickness and White Matter Integrity in Mild-to-Moderate Communicating Hydrocephalic School-Aged Children Measured by Whole-Brain Cortical Thickness Mapping and DTI Mon, 16 Jan 2017 00:00:00 +0000 Follow-up observation is required for mild-to-moderate hydrocephalic patients because of the potential damage to brain. However, effects of mild-to-moderate hydrocephalus on gray and white matter remain unclear in vivo. Using structural MRI and diffusion tensor imaging (DTI), current study compared the cortical thickness and white matter integrity between children with mild-to-moderate communicating hydrocephalus and healthy controls. The relationships between cortical changes and intelligence quota were also examined in patients. We found that cortical thickness in the left middle temporal and left rostral middle frontal gyrus was significantly lower in the hydrocephalus group compared with that of controls. Fractional anisotropy in the right corpus callosum body was significantly lower in the hydrocephalus group compared with that of controls. In addition, there was no association of cortical thinning or white matter fractional anisotropy with intelligence quota in either group. Thus, our findings provide clues to that mild-to-moderate hydrocephalus could lead to structural brain deficits especially in the middle temporal and middle frontal gyrus prior to the behavior changes. Siyu Zhang, Xinjian Ye, Guanghui Bai, Yuchuan Fu, Chuanwan Mao, Aiqin Wu, Xiaozheng Liu, and Zhihan Yan Copyright © 2017 Siyu Zhang et al. All rights reserved. Hybrid Assistive Neuromuscular Dynamic Stimulation Therapy: A New Strategy for Improving Upper Extremity Function in Patients with Hemiparesis following Stroke Mon, 16 Jan 2017 00:00:00 +0000 Hybrid Assistive Neuromuscular Dynamic Stimulation (HANDS) therapy is one of the neurorehabilitation therapeutic approaches that facilitates the use of the paretic upper extremity (UE) in daily life by combining closed-loop electromyography- (EMG-) controlled neuromuscular electrical stimulation (NMES) with a wrist-hand splint. This closed-loop EMG-controlled NMES can change its stimulation intensity in direct proportion to the changes in voluntary generated EMG amplitudes recorded with surface electrodes placed on the target muscle. The stimulation was applied to the paretic finger extensors. Patients wore a wrist-hand splint and carried a portable stimulator in an arm holder for 8 hours during the daytime. The system was active for 8 hours, and patients were instructed to use their paretic hand as much as possible. HANDS therapy was conducted for 3 weeks. The patients were also instructed to practice bimanual activities in their daily lives. Paretic upper extremity motor function improved after 3 weeks of HANDS therapy. Functional improvement of upper extremity motor function and spasticity with HANDS therapy is based on the disinhibition of the affected hemisphere and modulation of reciprocal inhibition. HANDS therapy may offer a promising option for the management of the paretic UE in patients with stroke. Toshiyuki Fujiwara, Michiyuki Kawakami, Kaoru Honaga, Michi Tochikura, and Kaoru Abe Copyright © 2017 Toshiyuki Fujiwara et al. All rights reserved. Neuroplastic Correlates in the mPFC Underlying the Impairment of Stress-Coping Ability and Cognitive Flexibility in Adult Rats Exposed to Chronic Mild Stress during Adolescence Sun, 15 Jan 2017 09:00:51 +0000 Using a valid chronic mild stress (CMS) model of depression, we found that adolescent (postnatal days [PND] 28–41) CMS induced transient alterations in anhedonia that did not persist into adulthood after a 3-week recovery period. Previously stressed adult rats exhibited more immobility/despair behaviors in the forced swimming test and a greater number of trials to reach criterion in the set-shifting task, suggesting the impaired ability to cope with stressors and the cognitive flexibility that allows adaptation to dynamic environments during adulthood. In addition, adult rat exposure to adolescent CMS had a relatively inhibited activation in ERK signaling and downstream protein expression of phosphorylated cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex. Further correlation analysis demonstrated that immobility and set-shifting performance were positively correlated with the inhibition of ERK signaling. These results indicated adolescent CMS can be used as an effective stressor to model an increased predisposition to adult depression. Yu Zhang, Feng Shao, Qiong Wang, Xi Xie, and Weiwen Wang Copyright © 2017 Yu Zhang et al. All rights reserved. Right Hemisphere Remapping of Naming Functions Depends on Lesion Size and Location in Poststroke Aphasia Thu, 12 Jan 2017 09:05:22 +0000 The study of language network plasticity following left hemisphere stroke is foundational to the understanding of aphasia recovery and neural plasticity in general. Damage in different language nodes may influence whether local plasticity is possible and whether right hemisphere recruitment is beneficial. However, the relationships of both lesion size and location to patterns of remapping are poorly understood. In the context of a picture naming fMRI task, we tested whether lesion size and location relate to activity in surviving left hemisphere language nodes, as well as homotopic activity in the right hemisphere during covert name retrieval and overt name production. We found that lesion size was positively associated with greater right hemisphere activity during both phases of naming, a pattern that has frequently been suggested but has not previously been clearly demonstrated. During overt naming, lesions in the inferior frontal gyrus led to deactivation of contralateral frontal areas, while lesions in motor cortex led to increased right motor cortex activity. Furthermore, increased right motor activity related to better naming performance only when left motor cortex was lesioned, suggesting compensatory takeover of speech or language function by the homotopic node. These findings demonstrate that reorganization of language function, and the degree to which reorganization facilitates aphasia recovery, is dependent on the size and site of the lesion. Laura M. Skipper-Kallal, Elizabeth H. Lacey, Shihui Xing, and Peter E. Turkeltaub Copyright © 2017 Laura M. Skipper-Kallal et al. All rights reserved. Short-Term Monocular Deprivation Enhances Physiological Pupillary Oscillations Mon, 09 Jan 2017 06:57:54 +0000 Short-term monocular deprivation alters visual perception in adult humans, increasing the dominance of the deprived eye, for example, as measured with binocular rivalry. This form of plasticity may depend upon the inhibition/excitation balance in the visual cortex. Recent work suggests that cortical excitability is reliably tracked by dilations and constrictions of the pupils of the eyes. Here, we ask whether monocular deprivation produces a systematic change of pupil behavior, as measured at rest, that is independent of the change of visual perception. During periods of minimal sensory stimulation (in the dark) and task requirements (minimizing body and gaze movements), slow pupil oscillations, “hippus,” spontaneously appear. We find that hippus amplitude increases after monocular deprivation, with larger hippus changes in participants showing larger ocular dominance changes (measured by binocular rivalry). This tight correlation suggests that a single latent variable explains both the change of ocular dominance and hippus. We speculate that the neurotransmitter norepinephrine may be implicated in this phenomenon, given its important role in both plasticity and pupil control. On the practical side, our results indicate that measuring the pupil hippus (a simple and short procedure) provides a sensitive index of the change of ocular dominance induced by short-term monocular deprivation, hence a proxy for plasticity. Paola Binda and Claudia Lunghi Copyright © 2017 Paola Binda and Claudia Lunghi. All rights reserved. Enhancing NMDA Receptor Function: Recent Progress on Allosteric Modulators Mon, 09 Jan 2017 00:00:00 +0000 The N-methyl-D-aspartate receptors (NMDARs) are subtype glutamate receptors that play important roles in excitatory neurotransmission and synaptic plasticity. Their hypo- or hyperactivation are proposed to contribute to the genesis or progression of various brain diseases, including stroke, schizophrenia, depression, and Alzheimer’s disease. Past efforts in targeting NMDARs for therapeutic intervention have largely been on inhibitors of NMDARs. In light of the discovery of NMDAR hypofunction in psychiatric disorders and perhaps Alzheimer’s disease, efforts in boosting NMDAR activity/functions have surged in recent years. In this review, we will focus on enhancing NMDAR functions, especially on the recent progress in the generation of subunit-selective, allosteric positive modulators (PAMs) of NMDARs. We shall also discuss the usefulness of these newly developed NMDAR-PAMs. Lulu Yao and Qiang Zhou Copyright © 2017 Lulu Yao and Qiang Zhou. All rights reserved. Pilocarpine-Induced Status Epilepticus Is Associated with Changes in the Actin-Modulating Protein Synaptopodin and Alterations in Long-Term Potentiation in the Mouse Hippocampus Thu, 05 Jan 2017 00:00:00 +0000 Epilepsy is a complex neurological disorder which can severely affect neuronal function. Some patients may experience status epilepticus, a life-threatening state of ongoing seizure activity associated with postictal cognitive dysfunction. However, the molecular mechanisms by which status epilepticus influences brain function beyond seizure activity remain not well understood. Here, we addressed the question of whether pilocarpine-induced status epilepticus affects synaptopodin (SP), an actin-binding protein, which regulates the ability of neurons to express synaptic plasticity. This makes SP an interesting marker for epilepsy-associated alterations in synaptic function. Indeed, single dose intraperitoneal pilocarpine injection (250 mg/kg) in three-month-old male C57BL/6J mice leads to a rapid reduction in hippocampal SP-cluster sizes and numbers (in CA1 stratum radiatum of the dorsal hippocampus; 90 min after injection). In line with this observation (and previous work using SP-deficient mice), a defect in the ability to induce long-term potentiation (LTP) of Schaffer collateral-CA1 synapses is observed. Based on these findings we propose that status epilepticus could exert its aftereffects on cognition at least in part by perturbing SP-dependent mechanisms of synaptic plasticity. Maximilian Lenz, Marina Ben Shimon, Thomas Deller, Andreas Vlachos, and Nicola Maggio Copyright © 2017 Maximilian Lenz et al. All rights reserved. The Contribution of α-Synuclein Spreading to Parkinson’s Disease Synaptopathy Tue, 03 Jan 2017 12:01:22 +0000 Synaptopathies are diseases with synapse defects as shared pathogenic features, encompassing neurodegenerative disorders such as Parkinson’s disease (PD). In sporadic PD, the most common age-related neurodegenerative movement disorder, nigrostriatal dopaminergic deficits are responsible for the onset of motor symptoms that have been related to α-synuclein deposition at synaptic sites. Indeed, α-synuclein accumulation can impair synaptic dopamine release and induces the death of nigrostriatal neurons. While in physiological conditions the protein can interact with and modulate synaptic vesicle proteins and membranes, numerous experimental evidences have confirmed that its pathological aggregation can compromise correct neuronal functioning. In addition, recent findings indicate that α-synuclein pathology spreads into the brain and can affect the peripheral autonomic and somatic nervous system. Indeed, monomeric, oligomeric, and fibrillary α-synuclein can move from cell to cell and can trigger the aggregation of the endogenous protein in recipient neurons. This novel “prion-like” behavior could further contribute to synaptic failure in PD and other synucleinopathies. This review describes the major findings supporting the occurrence of α-synuclein pathology propagation in PD and discusses how this phenomenon could induce or contribute to synaptic injury and degeneration. Francesca Longhena, Gaia Faustini, Cristina Missale, Marina Pizzi, PierFranco Spano, and Arianna Bellucci Copyright © 2017 Francesca Longhena et al. All rights reserved. Electroacupuncture Regulates Hippocampal Synaptic Plasticity via miR-134-Mediated LIMK1 Function in Rats with Ischemic Stroke Mon, 02 Jan 2017 13:13:56 +0000 MircoRNAs (miRs) have been implicated in learning and memory, by regulating LIM domain kinase (LIMK1) to induce synaptic-dendritic plasticity. The study aimed to investigate whether miRNAs/LIMK1 signaling was involved in electroacupuncture- (EA-) mediated synaptic-dendritic plasticity in a rat model of middle cerebral artery occlusion induced cognitive deficit (MICD). Compared to untreatment or non-acupoint-EA treatment, EA at DU20 and DU24 acupoints could shorten escape latency and increase the frequency of crossing platform in Morris water maze test. T2-weighted imaging showed that the MICD rat brain lesions were located in cortex, hippocampus, corpus striatum, and thalamus regions and injured volumes were reduced after EA. Furthermore, we found that the density of dendritic spine and the number of synapses in the hippocampal CA1 pyramidal cells were obviously reduced at Day 14 after MICD. However, synaptic-dendritic loss could be rescued after EA. Moreover, the synaptic-dendritic plasticity was associated with increases of the total LIMK1 and phospho-LIMK1 levels in hippocampal CA1 region, wherein EA decreased the expression of miR-134, negatively regulating LIMK1 to enhance synaptic-dendritic plasticity. Therefore, miR-134-mediated LIMK1 was involved in EA-induced hippocampal synaptic plasticity, which served as a contributor to improving learning and memory during the recovery stage of ischemic stroke. Weilin Liu, Jie Wu, Jia Huang, Peiyuan Zhuo, Yunjiao Lin, Lulu Wang, Ruhui Lin, Lidian Chen, and Jing Tao Copyright © 2017 Weilin Liu et al. All rights reserved. Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach Thu, 29 Dec 2016 14:28:42 +0000 Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied. Ben Holmes, Seung Ho Jung, Jing Lu, Jessica A. Wagner, Liudmilla Rubbi, Matteo Pellegrini, and Ryan Jankord Copyright © 2016 Ben Holmes et al. All rights reserved. Mammalian Cochlear Hair Cell Regeneration and Ribbon Synapse Reformation Thu, 29 Dec 2016 12:49:49 +0000 Hair cells (HCs) are the sensory preceptor cells in the inner ear, which play an important role in hearing and balance. The HCs of organ of Corti are susceptible to noise, ototoxic drugs, and infections, thus resulting in permanent hearing loss. Recent approaches of HCs regeneration provide new directions for finding the treatment of sensor neural deafness. To have normal hearing function, the regenerated HCs must be reinnervated by nerve fibers and reform ribbon synapse with the dendrite of spiral ganglion neuron through nerve regeneration. In this review, we discuss the research progress in HC regeneration, the synaptic plasticity, and the reinnervation of new regenerated HCs in mammalian inner ear. Xiaoling Lu, Yilai Shu, Mingliang Tang, and Huawei Li Copyright © 2016 Xiaoling Lu et al. All rights reserved. Cortical Reorganization in Patients Recovered from Bell’s Palsy: An Orofacial and Finger Movements Task-State fMRI Study Wed, 28 Dec 2016 09:26:20 +0000 Objective. To explore cortical reorganization of patients recovered from Bell’s palsy (BP) by task-state functional magnetic resonance imaging (fMRI) during finger and orofacial movements and provide more evidence for acupuncture clinical treatment of BP. Methods. We collected 17 BP patients with complete clinical recovery (BP group) and 20 healthy volunteers (control group) accepted the task-state fMRI scans with lip pursing movements and finger movements, respectively. Results. It was found that there were significant differences of brain functional status between the two groups. Conclusions. The results showed that there was cortical reorganization in the brain of patients recovered from BP after acupuncture treatment, which also suggested the relationship between the hand motor areas and facial motor areas of BP patients. Jaeyoun Lee, Jun Yang, Chuanfu Li, Aihong Yuan, Hongli Wu, Anqin Wang, Qiuju Xue, Tao Wang, Linying Wang, and Ting Gao Copyright © 2016 Jaeyoun Lee et al. All rights reserved. Adenovirus Vectors Target Several Cell Subtypes of Mammalian Inner Ear In Vivo Wed, 28 Dec 2016 06:17:30 +0000 Mammalian inner ear harbors diverse cell types that are essential for hearing and balance. Adenovirus is one of the major vectors to deliver genes into the inner ear for functional studies and hair cell regeneration. To identify adenovirus vectors that target specific cell subtypes in the inner ear, we studied three adenovirus vectors, carrying a reporter gene encoding green fluorescent protein (GFP) from two vendors or with a genome editing gene Cre recombinase (Cre), by injection into postnatal days 0 (P0) and 4 (P4) mouse cochlea through scala media by cochleostomy in vivo. We found three adenovirus vectors transduced mouse inner ear cells with different specificities and expression levels, depending on the type of adenoviral vectors and the age of mice. The most frequently targeted region was the cochlear sensory epithelium, including auditory hair cells and supporting cells. Adenovirus with GFP transduced utricular supporting cells as well. This study shows that adenovirus vectors are capable of efficiently and specifically transducing different cell types in the mammalian inner ear and provides useful tools to study inner ear gene function and to evaluate gene therapy to treat hearing loss and vestibular dysfunction. Yilai Shu, Yong Tao, Wenyan Li, Jun Shen, Zhengmin Wang, and Zheng-Yi Chen Copyright © 2016 Yilai Shu et al. All rights reserved. A Randomised Controlled Trial of Efficacy of Cognitive Rehabilitation in Multiple Sclerosis: A Cognitive, Behavioural, and MRI Study Tue, 27 Dec 2016 14:30:35 +0000 Aim. To explore the efficacy of home-based, computerised, cognitive rehabilitation in patients with multiple sclerosis using neuropsychological assessment and advanced structural and functional magnetic resonance imaging (fMRI). Methods. 38 patients with MS and cognitive impairment on the Brief International Cognitive Assessment for MS (BICAMS) were enrolled. Patients were randomised to undergo 45 minutes of computerised cognitive rehabilitation using RehaCom software () three times weekly for six weeks or to a control condition (). Neuropsychological and MRI data were obtained at baseline (time 1), following the 6-week intervention (time 2), and after a further twelve weeks (time 3). Cortical activations were explored using fMRI and microstructural changes were explored using quantitative magnetisation transfer (QMT) imaging. Results. The treatment group showed a greater improvement in SDMT gain scores between baseline and time 2 compared to the control group (). The treatment group exhibited increased activation in the bilateral prefrontal cortex and right temporoparietal regions relative to control group at time 3 (). No significant changes were observed on QMT. Conclusion. This study supports the hypothesis that home-based, computerised, cognitive rehabilitation may be effective in improving cognitive performance in patients with MS. Clinical trials registration is ISRCTN54901925. J. Campbell, D. Langdon, M. Cercignani, and W. Rashid Copyright © 2016 J. Campbell et al. All rights reserved. Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons Tue, 27 Dec 2016 13:49:32 +0000 Wnt/β-catenin signaling modulates brain development and function and its deregulation underlies pathological changes occurring in neurodegenerative and neurodevelopmental disorders. Since one of the main effects of Wnt/β-catenin signaling is the modulation of target genes, in the present work we examined global transcriptional changes induced by short-term Wnt3a treatment (4 h) in primary cultures of rat hippocampal neurons. RNAseq experiments allowed the identification of 170 differentially expressed genes, including known Wnt/β-catenin target genes such as Notum, Axin2, and Lef1, as well as novel potential candidates Fam84a, Stk32a, and Itga9. Main biological processes enriched with differentially expressed genes included neural precursor (GO:0061364, -adjusted = 2.5 × 10−7), forebrain development (GO:0030900, -adjusted = 7.3 × 10−7), and stem cell differentiation (GO:0048863 -adjusted = 7.3 × 10−7). Likewise, following activation of the signaling cascade, the expression of a significant number of genes with transcription factor activity (GO:0043565, -adjusted = 4.1 × 10−6) was induced. We also studied molecular networks enriched upon Wnt3a activation and detected three highly significant expression modules involved in glycerolipid metabolic process (GO:0046486, -adjusted = 4.5 × 10−19), learning or memory (GO:0007611, -adjusted = 4.0 × 10−5), and neurotransmitter secretion (GO:0007269, -adjusted = 5.3 × 10−12). Our results indicate that Wnt/β-catenin mediated transcription controls multiple biological processes related to neuronal structure and activity that are affected in synaptic dysfunction disorders. Eduardo Pérez-Palma, Víctor Andrade, Mario O. Caracci, Bernabé I. Bustos, Camilo Villaman, Matías A. Medina, Miguel E. Ávila, Giorgia D. Ugarte, and Giancarlo V. De Ferrari Copyright © 2016 Eduardo Pérez-Palma et al. All rights reserved. Neural Network Underlying Recovery from Disowned Bodily States Induced by the Rubber Hand Illusion Tue, 27 Dec 2016 10:23:11 +0000 We used functional magnetic resonance imaging to investigate how causal influences between brain regions during the rubber hand illusion (RHI) are modulated by tactile and visual stimuli. We applied needle rotations during the RHI in two different ways: one was with the real hand (reinstantiation by tactile stimuli, R-TS) and the other was with the rubber hand (reinstantiation by visual stimuli, R-VS). We used dynamic causal modeling to investigate interactions among four relevant brain regions: the ventral premotor cortex (PMv), the intraparietal sulcus (IPS), the secondary somatosensory cortex (SII), and the lateral occipitotemporal cortex (LOC). The tactile aspects of needle rotations changed the effective connectivity by directly influencing activity in the SII, whereas visual aspects of needle rotation changed the effective connectivity by influencing both the SII and the LOC. The endogenous connectivity parameters between the IPS and the PMv were reduced significantly in the R-TS condition. The modulatory parameters between the IPS and the PMv were enhanced significantly in the R-TS condition. The connectivity patterns driven by disowned bodily states could be differentially modulated by tactile and visual afferent inputs. Effective connectivity between the parietal and frontal multimodal areas may play important roles in the reinstantiation of body ownership. In-Seon Lee and Younbyoung Chae Copyright © 2016 In-Seon Lee and Younbyoung Chae. All rights reserved. Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH Tue, 27 Dec 2016 09:29:36 +0000 DFNA9 is a late-onset, progressive, autosomal dominantly inherited sensorineural hearing loss with vestibular dysfunction, which is caused by mutations in the COCH (coagulation factor C homology) gene. In this study, we investigated a Chinese family segregating autosomal dominant nonsyndromic sensorineural hearing loss. We identified a missense mutation c.T275A p.V92D in the LCCL domain of COCH cosegregating with the disease and absent in 100 normal hearing controls. This mutation leads to substitution of the hydrophobic valine to an acidic amino acid aspartic acid. Our data enriched the mutation spectrum of DFNA9 and implied the importance for mutation screening of COCH in age related hearing loss with vestibular dysfunctions. Xiaodong Gu, Wenling Su, Mingliang Tang, Luo Guo, Liping Zhao, and Huawei Li Copyright © 2016 Xiaodong Gu et al. All rights reserved. Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome Mon, 26 Dec 2016 13:10:26 +0000 The patients with DiGeorge syndrome (DGS), caused by deletion containing dozens of genes in chromosome 22, often carry cardiovascular problem and hearing loss associated with chronic otitis media. Inside the deletion region, a transcription factor TBX1 was highly suspected. Furthermore, similar DGS phenotypes were found in the Tbx1 heterozygous knockout mice. Using ENU-induced mutagenesis and G1 dominant screening strategy, here we identified a nonsynonymous mutation p.W118R in T-box of TBX1, the DNA binding domain for transcription activity. The mutant mice showed deficiency of inner ear functions, including head tossing and circling, plus increased hearing threshold determined by audiometry. Therefore, our result further confirms the pathogenic basis of Tbx1 in DGS, points out the crucial role of DNA binding activity of TBX1 for the ear function, and provides additional animal model for studying the DGS disease mechanisms. Jiaofeng Chen, Xue Zhang, Jie Li, Chenmeng Song, Yichang Jia, and Wei Xiong Copyright © 2016 Jiaofeng Chen et al. All rights reserved. Loss of Myh14 Increases Susceptibility to Noise-Induced Hearing Loss in CBA/CaJ Mice Thu, 22 Dec 2016 11:52:08 +0000 MYH14 is a member of the myosin family, which has been implicated in many motile processes such as ion-channel gating, organelle translocation, and the cytoskeleton rearrangement. Mutations in MYH14 lead to a DFNA4-type hearing impairment. Further evidence also shows that MYH14 is a candidate noise-induced hearing loss (NIHL) susceptible gene. However, the specific roles of MYH14 in auditory function and NIHL are not fully understood. In the present study, we used CRISPR/Cas9 technology to establish a Myh14 knockout mice line in CBA/CaJ background (now referred to as Myh14−/− mice) and clarify the role of MYH14 in the cochlea and NIHL. We found that Myh14−/− mice did not exhibit significant hearing loss until five months of age. In addition, Myh14−/− mice were more vulnerable to high intensity noise compared to control mice. More significant outer hair cell loss was observed in Myh14−/− mice than in wild type controls after acoustic trauma. Our findings suggest that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice. Xiaolong Fu, Linqing Zhang, Yecheng Jin, Xiaoyang Sun, Aizhen Zhang, Zongzhuang Wen, Yichen Zhou, Ming Xia, and Jiangang Gao Copyright © 2016 Xiaolong Fu et al. All rights reserved. Synchronized Progression of Prestin Expression and Auditory Brainstem Response during Postnatal Development in Rats Wed, 21 Dec 2016 14:13:10 +0000 Prestin is the motor protein expressed in the cochlear outer hair cells (OHCs) of mammalian inner ear. The electromotility of OHCs driven by prestin is responsible for the cochlear amplification which is required for normal hearing in adult animals. Postnatal expression of prestin and activity of OHCs may contribute to the maturation of hearing in rodents. However, the temporal and spatial expression of prestin in cochlea during the development is not well characterized. In the present study, we examined the expression and function of prestin from the OHCs in apical, middle, and basal turns of the cochleae of postnatal rats. Prestin first appeared at postnatal day 6 (P6) for basal turn, P7 in middle turn, and P9 for apical turn of cochlea. The expression level increased progressively over the next few days and by P14 reached the mature level for all three segments. By comparison with the time course of the development of auditory brainstem response for different frequencies, our data reveal that prestin expression synchronized with the hearing development. The present study suggests that the onset time of hearing may require the expression of prestin and is determined by the mature function of OHCs. Jianfeng Hang, Wenlu Pan, Aoshuang Chang, Shun Li, Cuixian Li, Mingyu Fu, and Jie Tang Copyright © 2016 Jianfeng Hang et al. All rights reserved. Effects of a Home-Based Family-Centred Early Habilitation Program on Neurobehavioural Outcomes of Very Preterm Born Infants: A Retrospective Cohort Study Tue, 20 Dec 2016 14:07:39 +0000 Preterm children have an increased risk of neurodevelopmental impairments which include psychomotor and language retardation. The objectives of the present retrospective cohort study were to examine the effects of an individually adapted, home-based, and family-centred early developmental habilitation program on neurodevelopmental and behavioural outcomes of very preterm children compared with a standard follow-up at 2 years’ corrected age. Enrolled infants were retrospectively assigned to the intervention group (61 subjects) or to the control group (62 subjects) depending on whether they had or had not carried out a home-based family-centred early developmental habilitation program focused on environmental enrichment, parent-guided environmental interaction, and infant development. Developmental outcome was assessed for both groups at 24 months’ corrected age using the Bayley Scales of Infant Development 2nd Edition. Intervention significantly improved both cognitive and behavioural outcomes. In addition, males had significantly lower scores than females either before or after treatment. However, the treatment was effective in both genders to the same extent. In conclusion, a timely updated environment suitable to the infant’s developmental needs could provide the best substrate where the parent-infant relationship can be practised with the ultimate goal of achieving further developmental steps. Michela Poggioli, Fabrizio Minichilli, Tiziana Bononi, Pasquina Meghi, Paolo Andre, Alessandra Crecchi, Bruno Rossi, Maria Chiara Carboncini, Alberto Ottolini, and Luca Bonfiglio Copyright © 2016 Michela Poggioli et al. All rights reserved. Neurosteroids Involvement in the Epigenetic Control of Memory Formation and Storage Tue, 20 Dec 2016 09:44:04 +0000 Memory is our ability to store and remember past experiences; it is the result of changes in neuronal circuits of specific brain areas as the hippocampus. During memory formation, neurons integrate their functions and increase the strength of their connections, so that synaptic plasticity is improved and consolidated. All these processes recruit several proteins at the synapses, whose expression is highly regulated by DNA methylation and histone tails posttranslational modifications. Steroids are known to influence memory process, and, among them, neurosteroids are implicated in neurodegenerative disease related to memory loss and cognitive impairment. The epigenetic control of neurosteroids involvement in memory formation and maintenance could represent the basis for neuroregenerative therapies. Alessandra Colciago and Valerio Magnaghi Copyright © 2016 Alessandra Colciago and Valerio Magnaghi. All rights reserved. Inhibition of the cAMP/PKA/CREB Pathway Contributes to the Analgesic Effects of Electroacupuncture in the Anterior Cingulate Cortex in a Rat Pain Memory Model Tue, 20 Dec 2016 06:28:24 +0000 Pain memory is considered as endopathic factor underlying stubborn chronic pain. Our previous study demonstrated that electroacupuncture (EA) can alleviate retrieval of pain memory. This study was designed to observe the different effects between EA and indomethacin (a kind of nonsteroid anti-inflammatory drugs, NSAIDs) in a rat pain memory model. To explore the critical role of protein kinase A (PKA) in pain memory, a PKA inhibitor was microinjected into anterior cingulate cortex (ACC) in model rats. We further investigated the roles of the cyclic adenosine monophosphate (cAMP), PKA, cAMP response element-binding protein (CREB), and cAMP/PKA/CREB pathway in pain memory to explore the potential molecular mechanism. The results showed that EA alleviates the retrieval of pain memory while indomethacin failed. Intra-ACC microinjection of a PKA inhibitor blocked the occurrence of pain memory. EA reduced the activation of cAMP, PKA, and CREB and the coexpression levels of cAMP/PKA and PKA/CREB in the ACC of pain memory model rats, but indomethacin failed. The present findings identified a critical role of PKA in ACC in retrieval of pain memory. We propose that the proper mechanism of EA on pain memory is possibly due to the partial inhibition of cAMP/PKA/CREB signaling pathway by EA. Xiao-Mei Shao, Jing Sun, Yong-Liang Jiang, Bo-Yi Liu, Zui Shen, Fang Fang, Jun-Ying Du, Yuan-Yuan Wu, Jia-Ling Wang, and Jian-Qiao Fang Copyright © 2016 Xiao-Mei Shao et al. All rights reserved. Progress of Research on Diffuse Axonal Injury after Traumatic Brain Injury Mon, 19 Dec 2016 14:05:04 +0000 The current work reviews the concept, pathological mechanism, and process of diagnosing of DAI. The pathological mechanism underlying DAI is complicated, including axonal breakage caused by axonal retraction balls, discontinued protein transport along the axonal axis, calcium influx, and calpain-mediated hydrolysis of structural protein, degradation of axonal cytoskeleton network, the changes of transport proteins such as amyloid precursor protein, and changes of glia cells. Based on the above pathological mechanism, the diagnosis of DAI is usually made using methods such as CT, traditional and new MRI, biochemical markers, and neuropsychological assessment. This review provides a basis in literature for further investigation and discusses the pathological mechanism. It may also facilitate improvement of the accuracy of diagnosis for DAI, which may come to play a critical role in breaking through the bottleneck of the clinical treatment of DAI and improving the survival and quality of life of patients through clear understanding of pathological mechanisms and accurate diagnosis. Junwei Ma, Kai Zhang, Zhimin Wang, and Gang Chen Copyright © 2016 Junwei Ma et al. All rights reserved. Merging and Fractionation of Muscle Synergy Indicate the Recovery Process in Patients with Hemiplegia: The First Study of Patients after Subacute Stroke Mon, 19 Dec 2016 14:03:00 +0000 Loss of motor coordination is one of the main problems for patients after stroke. Muscle synergy is widely accepted as an indicator of motor coordination. Recently, the characteristics of muscle synergy were quantitatively evaluated using nonnegative matrix factorization (NNMF) with surface electromyography. Previous studies have identified that the number and structure of synergies were associated with motor function in patients after stroke. However, most of these studies had a cross-sectional design, and the changes in muscle synergy during recovery process are not clear. In present study, two consecutive measurements were conducted for subacute patients after stroke and the change of number and structure of muscle synergies during gait were determined using NNMF. Results showed that functional change did not rely on number of synergies in patients after subacute stroke. However, the extent of merging of the synergies was negatively associated with an increase in muscle strength and the range of angle at ankle joint. Our results suggest that the neural changes represented by NNMF were related to the longitudinal change of function and gait pattern and that the merging of synergy is an important marker in patients after subacute stroke. Yu Hashiguchi, Koji Ohata, Ryosuke Kitatani, Natsuki Yamakami, Kaoru Sakuma, Sayuri Osako, Yumi Aga, Aki Watanabe, and Shigehito Yamada Copyright © 2016 Yu Hashiguchi et al. All rights reserved.