Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . 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. Neuroplasticity: Insights from Patients Harboring Gliomas Tue, 05 Jul 2016 10:49:23 +0000 Neuroplasticity is the ability of the brain to reorganize itself during normal development and in response to illness. Recent advances in neuroimaging and direct cortical stimulation in human subjects have given neuroscientists a window into the timing and functional anatomy of brain networks underlying this dynamic process. This review will discuss the current knowledge about the mechanisms underlying neuroplasticity, with a particular emphasis on reorganization following CNS pathology. First, traditional mechanisms of neuroplasticity, most relevant to learning and memory, will be addressed, followed by a review of adaptive mechanisms in response to pathology, particularly the recruitment of perilesional cortical regions and unmasking of latent connections. Next, we discuss the utility and limitations of various investigative techniques, such as direct electrocortical stimulation (DES), functional magnetic resonance imaging (fMRI), corticocortical evoked potential (CCEP), and diffusion tensor imaging (DTI). Finally, the clinical utility of these results will be highlighted as well as possible future studies aimed at better understanding of the plastic potential of the brain with the ultimate goal of improving quality of life for patients with neurologic injury. Nathan W. Kong, William R. Gibb, and Matthew C. Tate Copyright © 2016 Nathan W. Kong et al. All rights reserved. Acute Exercise and Motor Memory Consolidation: The Role of Exercise Timing Sun, 03 Jul 2016 10:10:52 +0000 High intensity aerobic exercise amplifies offline gains in procedural memory acquired during motor practice. This effect seems to be evident when exercise is placed immediately after acquisition, during the first stages of memory consolidation, but the importance of temporal proximity of the exercise bout used to stimulate improvements in procedural memory is unknown. The effects of three different temporal placements of high intensity exercise were investigated following visuomotor skill acquisition on the retention of motor memory in 48 young (24.0 ± 2.5 yrs), healthy male subjects randomly assigned to one of four groups either performing a high intensity (90% Maximal Power Output) exercise bout at 20 min (EX90), 1 h (EX90+1), 2 h (EX90+2) after acquisition or rested (CON). Retention tests were performed at 1 d (R1) and 7 d (R7). At R1 changes in performance scores after acquisition were greater for EX90 than CON () and EX90+2 (). At R7 changes in performance scores for EX90, EX90+1, and EX90+2 were higher than CON (, , and , resp.). Changes for EX90 at R7 were greater than EX90+2 (). Exercise-induced improvements in procedural memory diminish as the temporal proximity of exercise from acquisition is increased. Timing of exercise following motor practice is important for motor memory consolidation. Richard Thomas, Mikkel Malling Beck, Rune Rasmussen Lind, Line Korsgaard Johnsen, Svend Sparre Geertsen, Lasse Christiansen, Christian Ritz, Marc Roig, and Jesper Lundbye-Jensen Copyright © 2016 Richard Thomas et al. All rights reserved. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults Wed, 29 Jun 2016 10:54:24 +0000 In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans. Kirsten Hötting, Nadine Schickert, Jochen Kaiser, Brigitte Röder, and Maren Schmidt-Kassow Copyright © 2016 Kirsten Hötting et al. All rights reserved. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair Wed, 29 Jun 2016 08:17:16 +0000 Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons. Natalia Perussi Biscola, Luciana Politti Cartarozzi, Rui Seabra Ferreira Junior, Benedito Barraviera, and Alexandre Leite Rodrigues de Oliveira Copyright © 2016 Natalia Perussi Biscola et al. All rights reserved. Selective Requirement for Maintenance of Synaptic Contacts onto Motoneurons by Target-Derived trkB Receptors Tue, 28 Jun 2016 10:40:06 +0000 Synaptic contacts onto motoneurons were studied in mice in which the gene for the trkB neurotrophin receptor was knocked out selectively in a subset of spinal motoneurons. The extent of contacts by structures immunoreactive for either of two different vesicular glutamate transporters (VGLUT1 and VGLUT2), the vesicular GABA transporter, or glutamic acid decarboxylase 67 (GAD67) with the somata of motoneurons, was studied in wild type and trkB knockout cells in tamoxifen treated male and female SLICK-trkB−/− mice. Selective knockout of the trkB gene resulted in a marked reduction in contacts made by VGLUT2- and GAD67-immunoreactive structures in both sexes and a significant reduction in contacts containing only glycine in male mice. No reduction was found for glycinergic contacts in female mice or for VGLUT1 immunoreactive contacts in either sex. Signaling through postsynaptic trkB receptors is considered to be an essential part of a cellular mechanism for maintaining the contacts of some, but not all, synaptic contacts onto motoneurons. Xiya Zhu, Patricia J. Ward, and Arthur W. English Copyright © 2016 Xiya Zhu et al. All rights reserved. Maladaptive Plasticity in Aphasia: Brain Activation Maps Underlying Verb Retrieval Errors Mon, 27 Jun 2016 14:17:29 +0000 Anomia, or impaired word retrieval, is the most widespread symptom of aphasia, an acquired language impairment secondary to brain damage. In the last decades, functional neuroimaging techniques have enabled studying the neural basis underlying anomia and its recovery. The present study aimed to explore maladaptive plasticity in persistent verb anomia, in three male participants with chronic nonfluent aphasia. Brain activation maps associated with semantic verb paraphasia occurring within an oral picture-naming task were identified with an event-related fMRI paradigm. These maps were compared with those obtained in our previous study examining adaptive plasticity (i.e., successful verb naming) in the same participants. The results show that activation patterns related to semantic verb paraphasia and successful verb naming comprise a number of common areas, contributing to both maladaptive and adaptive neuroplasticity mechanisms. This finding suggests that the segregation of brain areas provides only a partial view of the neural basis of verb anomia and successful verb naming. Therefore, it indicates the importance of network approaches which may better capture the complexity of maladaptive and adaptive neuroplasticity mechanisms in anomia recovery. Kerstin Spielmann, Edith Durand, Karine Marcotte, and Ana Inés Ansaldo Copyright © 2016 Kerstin Spielmann et al. All rights reserved. Interventions to Enhance Adaptive Plasticity after Stroke: From Mechanisms to Therapeutic Perspectives Wed, 22 Jun 2016 12:31:51 +0000 Adriana Conforto, Annette Sterr, Ela Plow, and Leonardo Cohen Copyright © 2016 Adriana Conforto et al. All rights reserved. Paired-Pulse Parietal-Motor Stimulation Differentially Modulates Corticospinal Excitability across Hemispheres When Combined with Prism Adaptation Wed, 22 Jun 2016 09:59:43 +0000 Rightward prism adaptation ameliorates neglect symptoms while leftward prism adaptation (LPA) induces neglect-like biases in healthy individuals. Similarly, inhibitory repetitive transcranial magnetic stimulation (rTMS) on the right posterior parietal cortex (PPC) induces neglect-like behavior, whereas on the left PPC it ameliorates neglect symptoms and normalizes hyperexcitability of left hemisphere parietal-motor (PPC-M1) connectivity. Based on this analogy we hypothesized that LPA increases PPC-M1 excitability in the left hemisphere and decreases it in the right one. In an attempt to shed some light on the mechanisms underlying LPA’s effects on cognition, we investigated this hypothesis in healthy individuals measuring PPC-M1 excitability with dual-site paired-pulse TMS (ppTMS). We found a left hemisphere increase and a right hemisphere decrease in the amplitude of motor evoked potentials elicited by paired as well as single pulses on M1. While this could indicate that LPA biases interhemispheric connectivity, it contradicts previous evidence that M1-only MEPs are unchanged after LPA. A control experiment showed that input-output curves were not affected by LPA per se. We conclude that LPA combined with ppTMS on PPC-M1 differentially alters the excitability of the left and right M1. Selene Schintu, Elisa Martín-Arévalo, Michael Vesia, Yves Rossetti, Romeo Salemme, Laure Pisella, Alessandro Farnè, and Karen T. Reilly Copyright © 2016 Selene Schintu et al. All rights reserved. Functional Connectivity Analysis of NIRS Data under Rubber Hand Illusion to Find a Biomarker of Sense of Ownership Mon, 20 Jun 2016 08:43:11 +0000 The self-identification, which is called sense of ownership, has been researched through methodology of rubber hand illusion (RHI) because of its simple setup. Although studies with neuroimaging technique, such as fMRI, revealed that several brain areas are associated with the sense of ownership, near-infrared spectroscopy (NIRS) has not yet been utilized. Here we introduced an automated setup to induce RHI, measured the brain activity during the RHI with NIRS, and analyzed the functional connectivity so as to understand dynamical brain relationship regarding the sense of ownership. The connectivity was evaluated by multivariate Granger causality. In this experiment, the peaks of oxy-Hb on right frontal and right motor related areas during the illusion were significantly higher compared with those during the nonillusion. Furthermore, by analyzing the NIRS recordings, we found a reliable connectivity from the frontal to the motor related areas during the illusion. This finding suggests that frontal cortex and motor related areas communicate with each other when the sense of ownership is induced. The result suggests that the sense of ownership is related to neural mechanism underlying human motor control, and it would be determining whether motor learning (i.e., neural plasticity) will occur. Thus RHI with the functional connectivity analysis will become an appropriate biomarker for neurorehabilitation. Naoki Arizono, Yuji Ohmura, Shiro Yano, and Toshiyuki Kondo Copyright © 2016 Naoki Arizono et al. All rights reserved. Frequency-Dependent Neural Activity in Patients with Unilateral Vascular Pulsatile Tinnitus Mon, 20 Jun 2016 07:30:54 +0000 Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies have shown that neurological changes are important findings in vascular pulsatile tinnitus (PT) patients. Here, we utilized rs-fMRI to measure the amplitude of low-frequency fluctuations (ALFF) in forty patients with unilateral PT and forty age-, gender-, and education-matched normal control subjects. Two different frequency bands (slow-4, 0.027–0.073 Hz, and slow-5, 0.010–0.027 Hz, which are more sensitive to subcortical and cortical neurological signal changes, resp.) were analyzed to examine the intrinsic brain activity in detail. Compared to controls, PT patients had increased ALFF values mainly in the PCu, bilateral IPL (inferior parietal lobule), left IFG (inferior frontal gyrus), and right IFG/anterior insula and decreased ALFF values in the multiple occipital areas including bilateral middle-inferior occipital lobe. For the differences of the two frequency bands, widespread ALFF differences were observed. The ALFF abnormalities in aMPFC/ACC, PCu, right IPL, and some regions of occipital and parietal cortices were greater in the slow-5 band compared to the slow-4 band. Additionally, the THI score of PT patients was positively correlated with changes in slow-5 and slow-4 band in PCu. Pulsatile tinnitus is a disease affecting the neurological activities of multiple brain regions. Slow-5 band is more sensitive in detecting the alternations. Our results also indicated the importance of pathophysiological investigations in patients with pulsatile tinnitus in the future. Han Lv, Pengfei Zhao, Zhaohui Liu, Guopeng Wang, Rong Zeng, Fei Yan, Cheng Dong, Ling Zhang, Rui Li, Peng Wang, Ting Li, Shusheng Gong, and Zhenchang Wang Copyright © 2016 Han Lv et al. All rights reserved. Hemodynamic Response of the Supplementary Motor Area during Locomotor Tasks with Upright versus Horizontal Postures in Humans Sun, 19 Jun 2016 09:36:14 +0000 To understand cortical mechanisms related to truncal posture control during human locomotion, we investigated hemodynamic responses in the supplementary motor area (SMA) with quadrupedal and bipedal gaits using functional near-infrared spectroscopy in 10 healthy adults. The subjects performed three locomotor tasks where the degree of postural instability varied biomechanically, namely, hand-knee quadrupedal crawling (HKQuad task), upright quadrupedalism using bilateral Lofstrand crutches (UpQuad task), and typical upright bipedalism (UpBi task), on a treadmill. We measured the concentration of oxygenated hemoglobin (oxy-Hb) during the tasks. The oxy-Hb significantly decreased in the SMA during the HKQuad task, whereas it increased during the UpQuad task. No significant responses were observed during the UpBi task. Based on the degree of oxy-Hb responses, we ranked these locomotor tasks as UpQuad > UpBi > HKQuad. The order of the different tasks did not correspond with postural instability of the tasks. However, qualitative inspection of oxy-Hb time courses showed that oxy-Hb waveform patterns differed between upright posture tasks (peak-plateau-trough pattern for the UpQuad and UpBi tasks) and horizontal posture task (downhill pattern for the HKQuad task). Thus, the SMA may contribute to the control of truncal posture accompanying locomotor movements in humans. Arito Yozu, Shigeru Obayashi, Katsumi Nakajima, and Yukihiro Hara Copyright © 2016 Arito Yozu et al. All rights reserved. A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD Thu, 16 Jun 2016 09:09:57 +0000 Posttraumatic stress disorder (PTSD) is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF) is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met), has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans () screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (). A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future. Dagmar Bruenig, Janine Lurie, Charles P. Morris, Wendy Harvey, Bruce Lawford, Ross McD Young, and Joanne Voisey Copyright © 2016 Dagmar Bruenig et al. All rights reserved. Training-Induced Functional Gains following SCI Wed, 15 Jun 2016 11:01:12 +0000 We previously demonstrated that daily, hour-long training sessions significantly improved both locomotor (limb kinematics, gait, and hindlimb flexor-extensor bursting patterns) and nonlocomotor (bladder function and at-level mechanical allodynia) functions following a moderate contusive spinal cord injury. The amount of training needed to achieve this recovery is unknown. Furthermore, whether this recovery is induced primarily by neuronal activity below the lesion or other aspects related to general exercise is unclear. Therefore, the current study objectives were to (1) test the efficacy of 30 minutes of step training for recovery following a clinically relevant contusion injury in male Wistar rats and (2) test the efficacy of training without hindlimb engagement. The results indicate that as little as 30 minutes of step training six days per week enhances overground locomotion in male rats with contusive spinal cord injury but does not alter allodynia or bladder function. Thirty minutes of forelimb-only exercise did not alter locomotion, allodynia, or bladder function, and neither training protocol altered the amount of in-cage activity. Taken together, locomotor improvements were facilitated by hindlimb step training for 30 minutes, but longer durations of training are required to affect nonlocomotor systems. P. J. Ward, A. N. Herrity, S. J. Harkema, and C. H. Hubscher Copyright © 2016 P. J. Ward et al. All rights reserved. Electrical Stimulation of the Ear, Head, Cranial Nerve, or Cortex for the Treatment of Tinnitus: A Scoping Review Wed, 15 Jun 2016 08:30:29 +0000 Tinnitus is defined as the perception of sound in the absence of an external source. It is often associated with hearing loss and is thought to result from abnormal neural activity at some point or points in the auditory pathway, which is incorrectly interpreted by the brain as an actual sound. Neurostimulation therapies therefore, which interfere on some level with that abnormal activity, are a logical approach to treatment. For tinnitus, where the pathological neuronal activity might be associated with auditory and other areas of the brain, interventions using electromagnetic, electrical, or acoustic stimuli separately, or paired electrical and acoustic stimuli, have been proposed as treatments. Neurostimulation therapies should modulate neural activity to deliver a permanent reduction in tinnitus percept by driving the neuroplastic changes necessary to interrupt abnormal levels of oscillatory cortical activity and restore typical levels of activity. This change in activity should alter or interrupt the tinnitus percept (reduction or extinction) making it less bothersome. Here we review developments in therapies involving electrical stimulation of the ear, head, cranial nerve, or cortex in the treatment of tinnitus which demonstrably, or are hypothesised to, interrupt pathological neuronal activity in the cortex associated with tinnitus. Derek J. Hoare, Peyman Adjamian, and Magdalena Sereda Copyright © 2016 Derek J. Hoare et al. All rights reserved. Exploiting Interlimb Arm and Leg Connections for Walking Rehabilitation: A Training Intervention in Stroke Wed, 15 Jun 2016 06:59:54 +0000 Rhythmic arm and leg (A&L) movements share common elements of neural control. The extent to which A&L cycling training can lead to training adaptations which transfer to improved walking function remains untested. The purpose of this study was to test the efficacy of A&L cycling training as a modality to improve locomotor function after stroke. Nineteen chronic stroke (>six months) participants were recruited and performed 30 minutes of A&L cycling training three times a week for five weeks. Changes in walking function were assessed with (1) clinical tests; (2) strength during isometric contractions; and (3) treadmill walking performance and cutaneous reflex modulation. A multiple baseline (3 pretests) within-subject control design was used. Data show that A&L cycling training improved clinical walking status increased strength by ~25%, improved modulation of muscle activity by ~25%, increased range of motion by ~20%, decreased stride duration, increased frequency, and improved modulation of cutaneous reflexes during treadmill walking. On most variables, the majority of participants showed a significant improvement in walking ability. These results suggest that exploiting arm and leg connections with A&L cycling training, an accessible and cost-effective training modality, could be used to improve walking ability after stroke. Taryn Klarner, Trevor S. Barss, Yao Sun, Chelsea Kaupp, Pamela M. Loadman, and E. Paul Zehr Copyright © 2016 Taryn Klarner et al. All rights reserved. Respiratory Changes in Response to Cognitive Load: A Systematic Review Tue, 14 Jun 2016 11:39:40 +0000 When people focus attention or carry out a demanding task, their breathing changes. But which parameters of respiration vary exactly and can respiration reliably be used as an index of cognitive load? These questions are addressed in the present systematic review of empirical studies investigating respiratory behavior in response to cognitive load. Most reviewed studies were restricted to time and volume parameters while less established, yet meaningful parameters such as respiratory variability have rarely been investigated. The available results show that respiratory behavior generally reflects cognitive processing and that distinct parameters differ in sensitivity: While mentally demanding episodes are clearly marked by faster breathing and higher minute ventilation, respiratory amplitude appears to remain rather stable. The present findings further indicate that total variability in respiratory rate is not systematically affected by cognitive load whereas the correlated fraction decreases. In addition, we found that cognitive load may lead to overbreathing as indicated by decreased end-tidal CO2 but is also accompanied by elevated oxygen consumption and CO2 release. However, additional research is needed to validate the findings on respiratory variability and gas exchange measures. We conclude by outlining recommendations for future research to increase the current understanding of respiration under cognitive load. Mariel Grassmann, Elke Vlemincx, Andreas von Leupoldt, Justin M. Mittelstädt, and Omer Van den Bergh Copyright © 2016 Mariel Grassmann et al. All rights reserved. The Current Status of Somatostatin-Interneurons in Inhibitory Control of Brain Function and Plasticity Tue, 14 Jun 2016 11:33:09 +0000 The mammalian neocortex contains many distinct inhibitory neuronal populations to balance excitatory neurotransmission. A correct excitation/inhibition equilibrium is crucial for normal brain development, functioning, and controlling lifelong cortical plasticity. Knowledge about how the inhibitory network contributes to brain plasticity however remains incomplete. Somatostatin- (SST-) interneurons constitute a large neocortical subpopulation of interneurons, next to parvalbumin- (PV-) and vasoactive intestinal peptide- (VIP-) interneurons. Unlike the extensively studied PV-interneurons, acknowledged as key components in guiding ocular dominance plasticity, the contribution of SST-interneurons is less understood. Nevertheless, SST-interneurons are ideally situated within cortical networks to integrate unimodal or cross-modal sensory information processing and therefore likely to be important mediators of experience-dependent plasticity. The lack of knowledge on SST-interneurons partially relates to the wide variety of distinct subpopulations present in the sensory neocortex. This review informs on those SST-subpopulations hitherto described based on anatomical, molecular, or electrophysiological characteristics and whose functional roles can be attributed based on specific cortical wiring patterns. A possible role for these subpopulations in experience-dependent plasticity will be discussed, emphasizing on learning-induced plasticity and on unimodal and cross-modal plasticity upon sensory loss. This knowledge will ultimately contribute to guide brain plasticity into well-defined directions to restore sensory function and promote lifelong learning. Isabelle Scheyltjens and Lutgarde Arckens Copyright © 2016 Isabelle Scheyltjens and Lutgarde Arckens. All rights reserved. Regeneration of Zebrafish CNS: Adult Neurogenesis Mon, 13 Jun 2016 07:50:47 +0000 Regeneration in the animal kingdom is one of the most fascinating problems that have allowed scientists to address many issues of fundamental importance in basic biology. However, we came to know that the regenerative capability may vary across different species. Among vertebrates, fish and amphibians are capable of regenerating a variety of complex organs through epimorphosis. Zebrafish is an excellent animal model, which can repair several organs like damaged retina, severed spinal cord, injured brain and heart, and amputated fins. The focus of the present paper is on spinal cord regeneration in adult zebrafish. We intend to discuss our current understanding of the cellular and molecular mechanism(s) that allows formation of proliferating progenitors and controls neurogenesis, which involve changes in epigenetic and transcription programs. Unlike mammals, zebrafish retains radial glia, a nonneuronal cell type in their adult central nervous system. Injury induced proliferation involves radial glia which proliferate, transcribe embryonic genes, and can give rise to new neurons. Recent technological development of exquisite molecular tools in zebrafish, such as cell ablation, lineage analysis, and novel and substantial microarray, together with advancement in stem cell biology, allowed us to investigate how progenitor cells contribute to the generation of appropriate structures and various underlying mechanisms like reprogramming. Sukla Ghosh and Subhra Prakash Hui Copyright © 2016 Sukla Ghosh and Subhra Prakash Hui. All rights reserved.