Neural Plasticity The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. The Effect of Aerobic Exercise on Brain-Derived Neurotrophic Factor in People with Neurological Disorders: A Systematic Review and Meta-Analysis Tue, 19 Sep 2017 00:00:00 +0000 Objective. To determine the effect of aerobic exercise on brain-derived neurotrophic factor (BDNF) levels in people with neurological disorders. Data Sources. Six electronic databases (CINAHL, PubMed, Cochrane, PsycINFO, SportDiscus, and Web of Science) were searched until the end of December 2016. Study Selection. Experimental or observational studies of people with neurological disorders who undertook an exercise intervention with BDNF as an outcome measure. The search strategy yielded 984 articles. Data Extraction. Study data were independently extracted from each article. Methodological quality of studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. A meta-analysis was planned based on the assessment of predetermined criteria. Data Synthesis. Eleven articles were included. Studies employed either a program of aerobic exercise, a single bout of aerobic exercise, or both. A meta-analysis of studies comparing a program of aerobic exercise against usual care/nil therapy showed a large effect (SMD: 0.84, 95% CI 0.47–1.20, ) in favour of aerobic exercise to increase levels of BDNF. Findings for a single bout of aerobic exercise were mixed. Quality of studies was low (PEDro average score 4.3/10). Conclusions. A program of aerobic exercise may contribute to increased levels of BDNF in neurological populations. Christopher P. Mackay, Suzanne S. Kuys, and Sandra G. Brauer Copyright © 2017 Christopher P. Mackay et al. All rights reserved. The Effect of Electroacupuncture on PKMzeta in the ACC in Regulating Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain Mon, 18 Sep 2017 07:24:06 +0000 Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA) has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta) has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC). We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT) and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560), PKMzeta, p-PKMzeta (T560), and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560) in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC. Junying Du, Junfan Fang, Cun Wen, Xiaomei Shao, Yi Liang, and Jianqiao Fang Copyright © 2017 Junying Du et al. All rights reserved. Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness Sun, 17 Sep 2017 00:00:00 +0000 Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling. Zhilu Zou, Yin Chen, Qinqin Shen, Xiaoyan Guo, Yuxuan Zhang, and Gang Chen Copyright © 2017 Zhilu Zou et al. All rights reserved. Does the Somatosensory Temporal Discrimination Threshold Change over Time in Focal Dystonia? Thu, 14 Sep 2017 00:00:00 +0000 Background. The somatosensory temporal discrimination threshold (STDT) is defined as the shortest interval at which an individual recognizes two stimuli as asynchronous. Some evidence suggests that STDT depends on cortical inhibitory interneurons in the basal ganglia and in primary somatosensory cortex. Several studies have reported that the STDT in patients with dystonia is abnormal. No longitudinal studies have yet investigated whether STDT values in different forms of focal dystonia change during the course of the disease. Methods. We designed a follow-up study on 25 patients with dystonia (15 with blepharospasm and 10 with cervical dystonia) who were tested twice: upon enrolment and 8 years later. STDT values from dystonic patients at the baseline were also compared with those from a group of 30 age-matched healthy subjects. Results. Our findings show that the abnormally high STDT values observed in patients with focal dystonia remained unchanged at the 8-year follow-up assessment whereas disease severity worsened. Conclusions. Our observation that STDT abnormalities in dystonia remain unmodified during the course of the disease suggests that the altered activity of inhibitory interneurons—either at cortical or at subcortical level—responsible for the increased STDT does not deteriorate as the disease progresses. Antonella Conte, Gina Ferrazzano, Daniele Belvisi, Nicoletta Manzo, Antonio Suppa, Giovanni Fabbrini, and Alfredo Berardelli Copyright © 2017 Antonella Conte et al. All rights reserved. For Better or Worse: The Effect of Prismatic Adaptation on Auditory Neglect Tue, 12 Sep 2017 08:08:11 +0000 Patients with auditory neglect attend less to auditory stimuli on their left and/or make systematic directional errors when indicating sound positions. Rightward prismatic adaptation (R-PA) was repeatedly shown to alleviate symptoms of visuospatial neglect and once to restore partially spatial bias in dichotic listening. It is currently unknown whether R-PA affects only this ear-related symptom or also other aspects of auditory neglect. We have investigated the effect of R-PA on left ear extinction in dichotic listening, space-related inattention assessed by diotic listening, and directional errors in auditory localization in patients with auditory neglect. The most striking effect of R-PA was the alleviation of left ear extinction in dichotic listening, which occurred in half of the patients with initial deficit. In contrast to nonresponders, their lesions spared the right dorsal attentional system and posterior temporal cortex. The beneficial effect of R-PA on an ear-related performance contrasted with detrimental effects on diotic listening and auditory localization. The former can be parsimoniously explained by the SHD-VAS model (shift in hemispheric dominance within the ventral attentional system; Clarke and Crottaz-Herbette 2016), which is based on the R-PA-induced shift of the right-dominant ventral attentional system to the left hemisphere. The negative effects in space-related tasks may be due to the complex nature of auditory space encoding at a cortical level. Isabel Tissieres, Mona Elamly, Stephanie Clarke, and Sonia Crottaz-Herbette Copyright © 2017 Isabel Tissieres et al. All rights reserved. Following Spinal Cord Injury Transected Reticulospinal Tract Axons Develop New Collateral Inputs to Spinal Interneurons in Parallel with Locomotor Recovery Tue, 12 Sep 2017 00:00:00 +0000 The reticulospinal tract (RtST) descends from the reticular formation and terminates in the spinal cord. The RtST drives the initiation of locomotion and postural control. RtST axons form new contacts with propriospinal interneurons (PrINs) after incomplete spinal cord injury (SCI); however, it is unclear if injured or uninjured axons make these connections. We completely transected all traced RtST axons in rats using a staggered model, where a hemisection SCI at vertebra T10 is followed by a contralateral hemisection at vertebra T7. In one group of the animals, the T7 SCI was performed 2 weeks after the T10 SCI (delayed; dSTAG), and in another group, the T10 and T7 SCIs were concomitant (cSTAG). dSTAG animals had significantly more RtST-PrIN contacts in the grey matter compared to cSTAG animals (). These results were accompanied by enhanced locomotor recovery with dSTAG animals significantly outperforming cSTAG animals (BBB test; ). This difference suggests that activity in neuronal networks below the first SCI may contribute to enhanced recovery, because dSTAG rats recovered locomotor ability before the second hemisection. In conclusion, our findings support the hypothesis that the injured RtST forms new connections and is a key player in the recovery of locomotion post-SCI. Zacnicte May, Keith K. Fenrich, Julia Dahlby, Nicholas J. Batty, Abel Torres-Espín, and Karim Fouad Copyright © 2017 Zacnicte May et al. All rights reserved. Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus Tue, 05 Sep 2017 00:00:00 +0000 Degeneration of locus coeruleus (LC) is an underappreciated hallmark of Alzheimer’s disease (AD). The LC is the main source of norepinephrine (NE) in the forebrain, and its degeneration is highly correlated with cognitive impairment and amyloid-beta (Aβ) and tangle pathology. Hyperphosphorylated tau in the LC is among the first detectable AD-like neuropathology in the brain, and while the LC/NE system impacts multiple aspects of AD (e.g., cognition, neuropathology, and neuroinflammation), the functional consequences of hyperphosphorylated tau accrual on LC neurons are not known. Recent evidence suggests that LC neurons accumulate aberrant tau species for decades before frank LC cell body degeneration occurs in AD, suggesting that a therapeutic window exists. In this review, we combine the literature on how pathogenic tau affects forebrain neurons with the known properties and degeneration patterns of LC neurons to synthesize hypotheses on hyperphosphorylated tau-induced dysfunction of LC neurons and the prion-like spread of pretangle tau from the LC to the forebrain. We also propose novel experiments using both in vitro and in vivo models to address the many questions surrounding the impact of hyperphosphorylated tau on LC neurons in AD and its role in disease progression. Termpanit Chalermpalanupap, David Weinshenker, and Jacki M. Rorabaugh Copyright © 2017 Termpanit Chalermpalanupap et al. All rights reserved. Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence Wed, 30 Aug 2017 04:12:59 +0000 The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression. Camila Lubaczeuski, Luciana Mateus Gonçalves, Jean Franciesco Vettorazzi, Mirian Ayumi Kurauti, Junia Carolina Santos-Silva, Maria Lúcia Bonfleur, Antonio Carlos Boschero, José Maria Costa-Júnior, and Everardo Magalhães Carneiro Copyright © 2017 Camila Lubaczeuski et al. All rights reserved. Neuronal-Glial Interactions Maintain Chronic Neuropathic Pain after Spinal Cord Injury Tue, 29 Aug 2017 06:52:47 +0000 The hyperactive state of sensory neurons in the spinal cord enhances pain transmission. Spinal glial cells have also been implicated in enhanced excitability of spinal dorsal horn neurons, resulting in pain amplification and distortions. Traumatic injuries of the neural system such as spinal cord injury (SCI) induce neuronal hyperactivity and glial activation, causing maladaptive synaptic plasticity in the spinal cord. Recent studies demonstrate that SCI causes persistent glial activation with concomitant neuronal hyperactivity, thus providing the substrate for central neuropathic pain. Hyperactive sensory neurons and activated glial cells increase intracellular and extracellular glutamate, neuropeptides, adenosine triphosphates, proinflammatory cytokines, and reactive oxygen species concentrations, all of which enhance pain transmission. In addition, hyperactive sensory neurons and glial cells overexpress receptors and ion channels that maintain this enhanced pain transmission. Therefore, post-SCI neuronal-glial interactions create maladaptive synaptic circuits and activate intracellular signaling events that permanently contribute to enhanced neuropathic pain. In this review, we describe how hyperactivity of sensory neurons contributes to the maintenance of chronic neuropathic pain via neuronal-glial interactions following SCI. Young S. Gwak, Claire E. Hulsebosch, and Joong Woo Leem Copyright © 2017 Young S. Gwak et al. All rights reserved. Cholinergic Potentiation of Restoration of Visual Function after Optic Nerve Damage in Rats Sun, 27 Aug 2017 00:00:00 +0000 Enhancing cortical plasticity and brain connectivity may improve residual vision following a visual impairment. Since acetylcholine plays an important role in attention and neuronal plasticity, we explored whether potentiation of the cholinergic transmission has an effect on the visual function restoration. To this end, we evaluated for 4 weeks the effect of the acetylcholinesterase inhibitor donepezil on brightness discrimination, visually evoked potentials, and visual cortex reactivity after a bilateral and partial optic nerve crush in adult rats. Donepezil administration enhanced brightness discrimination capacity after optic nerve crush compared to nontreated animals. The visually evoked activation of the primary visual cortex was not restored, as measured by evoked potentials, but the cortical neuronal activity measured by thallium autometallography was not significantly affected four weeks after the optic nerve crush. Altogether, the results suggest a role of the cholinergic system in postlesion cortical plasticity. This finding agrees with the view that restoration of visual function may involve mechanisms beyond the area of primary damage and opens a new perspective for improving visual rehabilitation in humans. Mira Chamoun, Elena G. Sergeeva, Petra Henrich-Noack, Shaobo Jia, Lisa Grigartzik, Jing Ma, Qing You, Frédéric Huppé-Gourgues, Bernhard A. Sabel, and Elvire Vaucher Copyright © 2017 Mira Chamoun et al. All rights reserved. Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus Thu, 24 Aug 2017 00:00:00 +0000 Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP. sEH inhibitor (sEHI) N-[1-(oxopropyl)-4-piperidinyl]-N’-[4-(trifluoromethoxy) phenyl)-urea (TPPU) and exogenous 14,15-EET increased HFS-LTP, which could be blocked by an N-methyl-D-aspartate (NMDA) receptor subunit NR2B antagonist. TPPU- or 14,15-EET-facilitated FSK-mediated LTP can be potentiated by an A1 adenosine receptor antagonist and a phosphodiesterase inhibitor, but is prevented by a cAMP-dependent protein kinase (PKA) inhibitor. sEHI and 14,15-EET upregulated the activation of extracellular signal-regulated kinases (ERKs) and Ca2+/calmodulin- (CaM-) dependent protein kinase II (CaMKII). Phosphorylation of synaptic receptors NR2B and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 was increased by TPPU and 14,15-EET administration. These results indicated that EETs increased NMDAR- and FSK-mediated synaptic potentiation via the AC-cAMP-PKA signaling cascade and upregulated the ERKs and CaMKII, resulting in increased phosphorylation of NR2B and GluR1 in the hippocampus. Han-Fang Wu, Yi-Ju Chen, Su-Zhen Wu, Chi-Wei Lee, I-Tuan Chen, Yi-Chao Lee, Chi-Chen Huang, Chung-Hsi Hsing, Chih-Wei Tang, and Hui-Ching Lin Copyright © 2017 Han-Fang Wu et al. All rights reserved. Maturation, Refinement, and Serotonergic Modulation of Cerebellar Cortical Circuits in Normal Development and in Murine Models of Autism Tue, 15 Aug 2017 00:00:00 +0000 The formation of the complex cerebellar cortical circuits follows different phases, with initial synaptogenesis and subsequent processes of refinement guided by a variety of mechanisms. The regularity of the cellular and synaptic organization of the cerebellar cortex allowed detailed studies of the structural plasticity mechanisms underlying the formation of new synapses and retraction of redundant ones. For the attainment of the monoinnervation of the Purkinje cell by a single climbing fiber, several signals are involved, including electrical activity, contact signals, homosynaptic and heterosynaptic interaction, calcium transients, postsynaptic receptors, and transduction pathways. An important role in this developmental program is played by serotonergic projections that, acting on temporally and spatially regulated postsynaptic receptors, induce and modulate the phases of synaptic formation and maturation. In the adult cerebellar cortex, many developmental mechanisms persist but play different roles, such as supporting synaptic plasticity during learning and formation of cerebellar memory traces. A dysfunction at any stage of this process can lead to disorders of cerebellar origin, which include autism spectrum disorders but are not limited to motor deficits. Recent evidence in animal models links impairment of Purkinje cell function with autism-like symptoms including sociability deficits, stereotyped movements, and interspecific communication by vocalization. Eriola Hoxha, Pellegrino Lippiello, Bibiana Scelfo, Filippo Tempia, Mirella Ghirardi, and Maria Concetta Miniaci Copyright © 2017 Eriola Hoxha et al. All rights reserved. AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury Sun, 13 Aug 2017 00:00:00 +0000 DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced. In vivo, young adult C57BL/6 mice received a T10 contusion followed by an AAV-KLF7 injection at the T7–9 levels above the lesion. Five weeks later, overexpression of KLF7 was expressed in DPSN. KLF7 and KLF7 target genes (NGF, TrkA, GAP43, and P0) were detectably increased in the injured spinal cord. Myelin sparring at the lesion site, DPSN axonal regeneration and synapse formation, muscle weight, motor endplate morphology, and functional parameters were all additionally improved by KLF7 treatment. Our findings suggest that KLF7 promotes DPSN axonal plasticity and the formation of synapses with motor neurons at the caudal spinal cord, leading to improved functional recovery and further supporting the potential of AAV-KLF7 as a therapeutic agent for spinal cord injury. Wen-Yuan Li, Ying Wang, Feng-Guo Zhai, Ping Sun, Yong-Xia Cheng, Ling-Xiao Deng, and Zhen-Yu Wang Copyright © 2017 Wen-Yuan Li et al. All rights reserved. Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection Tue, 08 Aug 2017 07:51:32 +0000 Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. Cristy Phillips Copyright © 2017 Cristy Phillips. All rights reserved. The Effect of Glucocorticoid and Glucocorticoid Receptor Interactions on Brain, Spinal Cord, and Glial Cell Plasticity Tue, 08 Aug 2017 00:00:00 +0000 Stress, injury, and disease trigger glucocorticoid (GC) elevation. Elevated GCs bind to the ubiquitously expressed glucocorticoid receptor (GR). While GRs are in every cell in the nervous system, the expression level varies, suggesting that diverse cell types react differently to GR activation. Stress/GCs induce structural plasticity in neurons, Schwann cells, microglia, oligodendrocytes, and astrocytes as well as affect neurotransmission by changing the release and reuptake of glutamate. While general nervous system plasticity is essential for adaptation and learning and memory, stress-induced plasticity is often maladaptive and contributes to neuropsychiatric disorders and neuropathic pain. In this brief review, we describe the evidence that stress/GCs activate GR to promote cell type-specific changes in cellular plasticity throughout the nervous system. Kathryn M. Madalena and Jessica K. Lerch Copyright © 2017 Kathryn M. Madalena and Jessica K. Lerch. All rights reserved. Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors Sun, 06 Aug 2017 00:00:00 +0000 Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS. Eric Boué-Grabot and Yuriy Pankratov Copyright © 2017 Eric Boué-Grabot and Yuriy Pankratov. All rights reserved. White Matter Hyperintensity Load Modulates Brain Morphometry and Brain Connectivity in Healthy Adults: A Neuroplastic Mechanism? Thu, 03 Aug 2017 04:31:37 +0000 White matter hyperintensities (WMHs) are acquired lesions that accumulate and disrupt neuron-to-neuron connectivity. We tested the associations between WMH load and (1) regional grey matter volumes and (2) functional connectivity of resting-state networks, in a sample of 51 healthy adults. Specifically, we focused on the positive associations (more damage, more volume/connectivity) to investigate a potential route of adaptive plasticity. WMHs were quantified with an automated procedure. Voxel-based morphometry was carried out to model grey matter. An independent component analysis was run to extract the anterior and posterior default-mode network, the salience network, the left and right frontoparietal networks, and the visual network. Each model was corrected for age, global levels of atrophy, and indices of brain and cognitive reserve. Positive associations were found with morphometry and functional connectivity of the anterior default-mode network and salience network. Within the anterior default-mode network, an association was found in the left mediotemporal-limbic complex. Within the salience network, an association was found in the right parietal cortex. The findings support the suggestion that, even in the absence of overt disease, the brain actuates a compensatory (neuroplastic) response to the accumulation of WMH, leading to increases in regional grey matter and modified functional connectivity. Matteo De Marco, Riccardo Manca, Micaela Mitolo, and Annalena Venneri Copyright © 2017 Matteo De Marco et al. All rights reserved. The Temporal Pattern of a Lesion Modulates the Functional Network Topology of Remote Brain Regions Thu, 03 Aug 2017 04:06:52 +0000 Focal brain lesions can alter the morphology and function of remote brain areas. When the damage is inflicted more slowly, the functional compensation by and structural reshaping of these areas seem to be more effective. It remains unclear, however, whether the momentum of lesion development also modulates the functional network topology of the remote brain areas. In this study, we compared resting-state functional connectivity data of patients with a slowly growing low-grade glioma (LGG) with that of patients with a faster-growing high-grade glioma (HGG). Using graph theory, we examined whether the tumour growth velocity modulated the functional network topology of remote areas, more specifically of the hemisphere contralateral to the lesion. We observed that the contralesional network topology characteristics differed between patient groups. Based only on the connectivity of the hemisphere contralateral to the lesion, patients could be classified in the correct tumour-grade group with 70% accuracy. Additionally, LGG patients showed smaller contralesional intramodular connectivity, smaller contralesional ratio between intra- and intermodular connectivity, and larger contralesional intermodular connectivity than HGG patients. These results suggest that, in the hemisphere contralateral to the lesion, there is a lower capacity for local, specialized information processing coupled to a higher capacity for distributed information processing in LGG patients. These results underline the utility of a network perspective in evaluating effects of focal brain injury. W. De Baene, G. J. M. Rutten, and M. M. Sitskoorn Copyright © 2017 W. De Baene et al. All rights reserved. A Hypothalamic Leptin-Glutamate Interaction in the Regulation of Sympathetic Nerve Activity Thu, 03 Aug 2017 00:00:00 +0000 Accumulated evidence indicates that obesity-induced type 2 diabetes (T2D) is associated with enhanced sympathetic activation. The present study was conducted to investigate the role for leptin-glutamate signaling within the hypothalamus in regulating sympathetic nerve activity. In anesthetized rats, microinjections of leptin (5 ng ~ 100 ng) into the arcuate nucleus (ARCN) and paraventricular nucleus (PVN) induced increases in renal sympathetic nerve activity (RSNA), blood pressure (BP), and heart rate (HR). Prior microinjections of NMDA receptor antagonist AP5 (16 pmol) into the ARCN or PVN reduced leptin-induced increases in RSNA, BP, and HR in both ARCN and PVN. Knockdown of a leptin receptor with siRNA inhibited NMDA-induced increases in RSNA, BP, and HR in the ARCN but not in the PVN. Confocal calcium imaging in the neuronal NG108 and astrocytic C6 cells demonstrated that preincubation with leptin induced an increase in intracellular calcium green fluorescence when the cells were challenged with glutamate. In high-fat diet and low-dose streptozotocin-induced T2D rats, we found that leptin receptor and NMDA NR1 receptor expressions in the ARCN and PVN were significantly increased. In conclusion, these studies provide evidence that within the hypothalamic nuclei, leptin-glutamate signaling regulates the sympathetic activation. This may contribute to the sympathoexcitation commonly observed in obesity-related T2D. Hong Zheng, Xuefei Liu, Yulong Li, and Kaushik P. Patel Copyright © 2017 Hong Zheng et al. All rights reserved. Emotion Processing by ERP Combined with Development and Plasticity Mon, 31 Jul 2017 00:00:00 +0000 Emotions important for survival and social interaction have received wide and deep investigations. The application of the fMRI technique into emotion processing has obtained overwhelming achievements with respect to the localization of emotion processes. The ERP method, which possesses highly temporal resolution compared to fMRI, can be employed to investigate the time course of emotion processing. The emotional modulation of the ERP component has been verified across numerous researches. Emotions, described as dynamically developing along with the growing age, have the possibility to be enhanced through learning (or training) or to be damaged due to disturbances in growth, which is underlain by the neural plasticity of emotion-relevant nervous systems. And mood disorders with typical symptoms of emotion discordance probably have been caused by the dysfunctional neural plasticity. Rui Ding, Ping Li, Wei Wang, and Wenbo Luo Copyright © 2017 Rui Ding et al. All rights reserved. Exercise Promotes Neuroplasticity in Both Healthy and Depressed Brains: An fMRI Pilot Study Sun, 30 Jul 2017 00:00:00 +0000 Memory impairments are a frequently reported cognitive symptom in people suffering from major depressive disorder (MDD) and often persist despite antidepressant therapy. Neuroimaging studies have identified abnormal hippocampal activity during memory processes in MDD. Exercise as an ad-on treatment for MDD is a promising therapeutic strategy shown to improve mood, cognitive function, and neural structure and function. To advance our understanding of how exercise impacts neural function in MDD, we must also understand how exercise impacts healthy individuals without MDD. This pilot study used a subsequent memory paradigm to investigate the effects of an eight-week exercise intervention on hippocampal function in low-active healthy () and low-active MDD () individuals. Results showed a marked improvement in depression scores for the MDD group () and no change in memory performance for either group (). Functional imaging results showed a marginally significant decrease in hippocampal activity in both groups following the exercise intervention. Our whole brain analysis collapsed across groups revealed a similar deactivation pattern across several memory-associated regions. These results suggest that exercise may enhance neural efficiency in low-fit individuals while still resulting in a substantially greater mood effect for those suffering from MDD. This trial is registered with clinical NCT03191994. Joanne Gourgouvelis, Paul Yielder, and Bernadette Murphy Copyright © 2017 Joanne Gourgouvelis et al. All rights reserved. Learning “How to Learn”: Super Declarative Motor Learning Is Impaired in Parkinson’s Disease Sun, 30 Jul 2017 00:00:00 +0000 Learning new information is crucial in daily activities and occurs continuously during a subject’s lifetime. Retention of learned material is required for later recall and reuse, although learning capacity is limited and interference between consecutively learned information may occur. Learning processes are impaired in Parkinson’s disease (PD); however, little is known about the processes related to retention and interference. The aim of this study is to investigate the retention and anterograde interference using a declarative sequence learning task in drug-naive patients in the disease’s early stages. Eleven patients with PD and eleven age-matched controls learned a visuomotor sequence, SEQ1, during Day1; the following day, retention of SEQ1 was assessed and, immediately after, a new sequence of comparable complexity, SEQ2, was learned. The comparison of the learning rates of SEQ1 on Day1 and SEQ2 on Day2 assessed the anterograde interference of SEQ1 on SEQ2. We found that SEQ1 performance improved in both patients and controls on Day2. Surprisingly, controls learned SEQ2 better than SEQ1, suggesting the absence of anterograde interference and the occurrence of learning optimization, a process that we defined as “learning how to learn.” Patients with PD lacked such improvement, suggesting defective performance optimization processes. Lucio Marinelli, Carlo Trompetto, Stefania Canneva, Laura Mori, Flavio Nobili, Francesco Fattapposta, Antonio Currà, Giovanni Abbruzzese, and Maria Felice Ghilardi Copyright © 2017 Lucio Marinelli et al. All rights reserved. Genesis and Maintenance of Attentional Biases: The Role of the Locus Coeruleus-Noradrenaline System Thu, 20 Jul 2017 00:00:00 +0000 Emotionally arousing events are typically better remembered than mundane ones, in part because emotionally relevant aspects of our environment are prioritized in attention. Such biased attentional tuning is itself the result of associative processes through which we learn affective and motivational relevance of cues. We propose that the locus coeruleus-noradrenaline (LC-NA) system plays an important role in the genesis of attentional biases through associative learning processes as well as their maintenance. We further propose that individual differences in and disruptions of the LC-NA system underlie the development of maladaptive biases linked to psychopathology. We provide support for the proposed role of the LC-NA system by first reviewing work on attentional biases in development and its link to psychopathology in relation to alterations and individual differences in NA availability. We focus on pharmacological manipulations to demonstrate the effect of a disrupted system as well as the ADRA2b polymorphism as a tool to investigate naturally occurring differences in NA availability. We next review associative learning processes that—modulated by the LC-NA system—result in such implicit attentional biases. Further, we demonstrate how NA may influence aversive and appetitive conditioning linked to anxiety disorders as well as addiction and depression. Mana R. Ehlers and Rebecca M. Todd Copyright © 2017 Mana R. Ehlers and Rebecca M. Todd. All rights reserved. Developmental Changes in Sleep Oscillations during Early Childhood Sun, 16 Jul 2017 00:00:00 +0000 Although quantitative analysis of the sleep electroencephalogram (EEG) has uncovered important aspects of brain activity during sleep in adolescents and adults, similar findings from preschool-age children remain scarce. This study utilized our time-frequency method to examine sleep oscillations as characteristic features of human sleep EEG. Data were collected from a longitudinal sample of young children (; 3 males) at ages 2, 3, and 5 years. Following sleep stage scoring, we detected and characterized oscillatory events across age and examined how their features corresponded to spectral changes in the sleep EEG. Results indicated a developmental decrease in the incidence of delta and theta oscillations. Spindle oscillations, however, were almost absent at 2 years but pronounced at 5 years. All oscillatory event changes were stronger during light sleep than slow-wave sleep. Large interindividual differences in sleep oscillations and their characteristics (e.g., “ultrafast” spindle-like oscillations, theta oscillation incidence/frequency) also existed. Changes in delta and spindle oscillations across early childhood may indicate early maturation of the thalamocortical system. Our analytic approach holds promise for revealing novel types of sleep oscillatory events that are specific to periods of rapid normal development across the lifespan and during other times of aberrant changes in neurobehavioral function. Eckehard Olbrich, Thomas Rusterholz, Monique K. LeBourgeois, and Peter Achermann Copyright © 2017 Eckehard Olbrich et al. All rights reserved. Stress Induced Neuroplasticity and Mental Disorders Thu, 13 Jul 2017 00:00:00 +0000 Fushun Wang, Fang Pan, Lee A. Shapiro, and Jason H. Huang Copyright © 2017 Fushun Wang et al. All rights reserved. Study on Lesion Assessment of Cerebello-Thalamo-Cortical Network in Wilson’s Disease with Diffusion Tensor Imaging Tue, 11 Jul 2017 05:37:16 +0000 Wilson’s disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in the brain and any other tissues. This article aimed to assess lesions in cerebello-thalamo-cortical network with an advanced technique of diffusion tensor imaging (DTI) in WD. 35 WD patients and 30 age- and sex-matched healthy volunteers were recruited to accept diffusion-weighted images with 15 gradient vectors and conventional magnetic resonance imaging (MRI). The DTI parameters, including fractional anisotropy (FA) and mean diffusion (MD), were calculated by diffusion kurtosis estimator software. After registration, patient groups with FA mappings and MD mappings and normal groups were compared with 3dttest and receiver-operating characteristic (ROC) curve analysis, corrected with FDR simulations (, , cluster size = 326). We found that the degree of FA increased in the bilateral head of the caudate nucleus (HCN), lenticular nucleus (LN), ventral thalamus, substantia nigra (SN), red nucleus (RN), right dentate nucleus (DN), and decreased in the mediodorsal thalamus and extensive white matter. The value of MD increased in HCN, LN, SN, RN, and extensive white matter. The technique of DTI provides higher sensitivity and specificity than conventional MRI to detect Wilson’s disease. Besides, lesions in the basal ganglia, thalamus, and cerebellum might disconnect the basal ganglia-thalamo-cortical circuits or dentato-rubro-thalamic (DRT) track and disrupt cerebello-thalamo-cortical network finally, which may cause clinical extrapyramidal symptoms. Anqin Wang, Hongli Wu, Chunsheng Xu, Lanfeng Tang, Jaeyoun Lee, Min Wang, Man Jiang, Chuanfu Li, Qi Lu, and Chunyun Zhang Copyright © 2017 Anqin Wang et al. All rights reserved. Enkephalins: Endogenous Analgesics with an Emerging Role in Stress Resilience Tue, 11 Jul 2017 00:00:00 +0000 Psychological stress is a state of mental or emotional strain or tension that results from adverse or demanding circumstances. Chronic stress is well known to induce anxiety disorders and major depression; it is also considered a risk factor for Alzheimer’s disease. Stress resilience is a positive outcome that is associated with preserved cognition and healthy aging. Resilience presents psychological and biological characteristics intrinsic to an individual conferring protection against the development of psychopathologies in the face of adversity. How can we promote or improve resilience to chronic stress? Numerous studies have proposed mechanisms that could trigger this desirable process. The roles of enkephalin transmission in the control of pain, physiological functions, like respiration, and affective disorders have been studied for more than 30 years. However, their role in the resilience to chronic stress has received much less attention. This review presents the evidence for an emerging involvement of enkephalin signaling through its two associated opioid receptors, μ opioid peptide receptor and δ opioid peptide receptor, in the natural adaptation to stressful lifestyles. Mathilde S. Henry, Louis Gendron, Marie-Eve Tremblay, and Guy Drolet Copyright © 2017 Mathilde S. Henry et al. All rights reserved. Anodal Transcranial Direct Current Stimulation Provokes Neuroplasticity in Repetitive Mild Traumatic Brain Injury in Rats Sun, 09 Jul 2017 00:00:00 +0000 Repetitive mild traumatic brain injury (rmTBI) provokes behavioral and cognitive changes. But the study about electrophysiologic findings and managements of rmTBI is limited. In this study, we investigate the effects of anodal transcranial direct current stimulation (tDCS) on rmTBI. Thirty-one Sprague Dawley rats were divided into the following groups: sham, rmTBI, and rmTBI treated by tDCS. Animals received closed head mTBI three consecutive times a day. Anodal tDCS was applied to the left motor cortex. We evaluated the motor-evoked potential (MEP) and the somatosensory-evoked potential (SEP). T2-weighted magnetic resonance imaging was performed 12 days after rmTBI. After rmTBI, the latency of MEP was prolonged and the amplitude in the right hind limb was reduced in the rmTBI group. The latency of SEP was delayed and the amplitude was decreased after rmTBI in the rmTBI group. In the tDCS group, the amplitude in both hind limbs was increased after tDCS in comparison with the values before rmTBI. Anodal tDCS after rmTBI seems to be a useful tool for promoting transient motor recovery through increasing the synchronicity of cortical firing, and it induces early recovery of consciousness. It can contribute to management of concussion in humans if further study is performed. Ho Jeong Kim and Soo Jeong Han Copyright © 2017 Ho Jeong Kim and Soo Jeong Han. All rights reserved. Potential Roles of Exosomal MicroRNAs as Diagnostic Biomarkers and Therapeutic Application in Alzheimer’s Disease Sun, 09 Jul 2017 00:00:00 +0000 Exosomes are bilipid layer-enclosed vesicles derived from endosomes and are released from neural cells. They contain a diversity of proteins, mRNAs, and microRNAs (miRNAs) that are delivered to neighboring cells and/or are transported to distant sites. miRNAs released from exosomes appear to be associated with multiple neurodegenerative conditions linking to Alzheimer’s disease (AD) which is marked by hyperphosphorylated tau proteins and accumulation of Aβ plaques. Exciting findings reveal that miRNAs released from exosomes modulate the expression and function of amyloid precursor proteins (APP) and tau proteins. These open up the possibility that dysfunctional exosomal miRNAs may influence AD progression. In addition, it has been confirmed that the interaction between miRNAs released by exosomes and Toll-like receptors (TLR) initiates inflammation. In exosome support-deprived neurons, exosomal miRNAs may regulate neuroplasticity to relieve neurological damage. In this review, we summarize the literature on the function of exosomal miRNAs in AD pathology, the potential of these miRNAs as diagnostic biomarkers in AD, and the use of exosomes in the delivery of miRNAs which may lead to major advances in the field of macromolecular drug delivery. Jian-jiao Chen, Bin Zhao, Jie Zhao, and Shao Li Copyright © 2017 Jian-jiao Chen et al. All rights reserved. Human APP Gene Expression Alters Active Zone Distribution and Spontaneous Neurotransmitter Release at the Drosophila Larval Neuromuscular Junction Sun, 09 Jul 2017 00:00:00 +0000 This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased. These disturbances were accompanied by a decrease in frequency of miniature excitatory junction potentials without alteration in random nature of spontaneous quantal release. Similar structural and functional changes were observed with co-overexpression of human APP and β-secretase genes. In Drosophila line with expression of human amyloid-β42 peptide itself, parameters analyzed did not differ from controls, suggesting the specificity of APP effects. These results confirm the involvement of APP in synaptogenesis and provide evidence to suggest that human APP overexpression specifically disturbs the structural and functional organization of active zone and results in altered Bruchpilot distribution and lowered probability of spontaneous neurotransmitter release. Ekaterina A. Saburova, Alexander N. Vasiliev, Violetta V. Kravtsova, Elena V. Ryabova, Andrey L. Zefirov, Olga I. Bolshakova, Svetlana V. Sarantseva, and Igor I. Krivoi Copyright © 2017 Ekaterina A. Saburova et al. All rights reserved.