Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Relationship between the LHPP Gene Polymorphism and Resting-State Brain Activity in Major Depressive Disorder Sun, 23 Oct 2016 13:54:01 +0000 A single-nucleotide polymorphism at the LHPP gene (rs35936514) has been reported in genome-wide association studies to be associated with major depressive disorder (MDD). However, the neural system effects of rs35936514 that mediate the association are unknown. The present work explores whether the LHPP rs35936514 polymorphism moderates brain regional activity in MDD. A total of 160 subjects were studied: a CC group homozygous for the C allele (23 individuals with MDD and 57 controls) and a T-carrier group carrying the high risk T allele (CT/TT genotypes; 22 MDD and 58 controls). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Brain activity was assessed using the amplitudes of low-frequency fluctuations (ALFF). MDD patients showed a significant increased ALFF in the left middle temporal gyrus and occipital cortex. The T-carrier group showed increased ALFF in the left superior temporal gyrus. Significant diagnosis × genotype interaction was noted in the bilateral lingual gyri, bilateral dorsal lateral prefrontal cortex (dlPFC), and left medial prefrontal cortex (mPFC) (, corrected). Results demonstrated that MDD patients with LHPP rs35936514 CT/TT genotype may influence the regional brain activity. These findings implicate the effects of the rs35936514 variation on the neural system in MDD. Lingling Cui, Xiaohong Gong, Yanqing Tang, Lingtao Kong, Miao Chang, Haiyang Geng, Ke Xu, and Fei Wang Copyright © 2016 Lingling Cui et al. All rights reserved. Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota Thu, 20 Oct 2016 16:06:52 +0000 Several genetic causes of autism spectrum disorder (ASD) have been identified. However, more recent work has highlighted that certain environmental exposures early in life may also account for some cases of autism. Environmental insults during pregnancy, such as infection or malnutrition, seem to dramatically impact brain development. Maternal viral or bacterial infections have been characterized as disruptors of brain shaping, even if their underlying mechanisms are not yet fully understood. Poor nutritional diversity, as well as nutrient deficiency, is strongly associated with neurodevelopmental disorders in children. For instance, imbalanced levels of essential fatty acids, and especially polyunsaturated fatty acids (PUFAs), are observed in patients with ASD and other neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder (ADHD) and schizophrenia). Interestingly, PUFAs, and specifically n-3 PUFAs, are powerful immunomodulators that exert anti-inflammatory properties. These prenatal dietary and immunologic factors not only impact the fetal brain, but also affect the microbiota. Recent work suggests that the microbiota could be the missing link between environmental insults in prenatal life and future neurodevelopmental disorders. As both nutrition and inflammation can massively affect the microbiota, we discuss here how understanding the crosstalk between these three actors could provide a promising framework to better elucidate ASD etiology. Charlotte Madore, Quentin Leyrolle, Chloé Lacabanne, Anouk Benmamar-Badel, Corinne Joffre, Agnes Nadjar, and Sophie Layé Copyright © 2016 Charlotte Madore et al. All rights reserved. Gender-Specific Hippocampal Dysrhythmia and Aberrant Hippocampal and Cortical Excitability in the APPswePS1dE9 Model of Alzheimer’s Disease Thu, 20 Oct 2016 12:54:31 +0000 Alzheimer’s disease (AD) is a multifactorial disorder leading to progressive memory loss and eventually death. In this study an APPswePS1dE9 AD mouse model has been analyzed using implantable video-EEG radiotelemetry to perform long-term EEG recordings from the primary motor cortex M1 and the hippocampal CA1 region in both genders. Besides motor activity, EEG recordings were analyzed for electroencephalographic seizure activity and frequency characteristics using a Fast Fourier Transformation (FFT) based approach. Automatic seizure detection revealed severe electroencephalographic seizure activity in both M1 and CA1 deflection in APPswePS1dE9 mice with gender-specific characteristics. Frequency analysis of both surface and deep EEG recordings elicited complex age, gender, and activity dependent alterations in the theta and gamma range. Females displayed an antithetic decrease in theta (θ) and increase in gamma (γ) power at 18-19 weeks of age whereas related changes in males occurred earlier at 14 weeks of age. In females, theta (θ) and gamma (γ) power alterations predominated in the inactive state suggesting a reduction in atropine-sensitive type II theta in APPswePS1dE9 animals. Gender-specific central dysrhythmia and network alterations in APPswePS1dE9 point to a functional role in behavioral and cognitive deficits and might serve as early biomarkers for AD in the future. Anna Papazoglou, Julien Soos, Andreas Lundt, Carola Wormuth, Varun Raj Ginde, Ralf Müller, Christina Henseler, Karl Broich, Kan Xie, Dan Ehninger, Britta Haenisch, and Marco Weiergräber Copyright © 2016 Anna Papazoglou et al. All rights reserved. Ipsilesional High Frequency Repetitive Transcranial Magnetic Stimulation Add-On Therapy Improved Diffusion Parameters of Stroke Patients with Motor Dysfunction: A Preliminary DTI Study Thu, 20 Oct 2016 11:19:10 +0000 Purpose. The aim of this study was to evaluate the effects of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stroke patients with motor dysfunction and to investigate the underlying neural mechanism. Methods. Fifteen stroke patients were assigned to the rTMS treatment (RT) group and conventional treatment (CT) group. Patients in the RT received 10 Hz rTMS stimulation on the ipsilesional primary motor cortex for 10 days plus conventional treatment of CT, which consisted of acupuncture and antiplatelet aggregation medication. Difference in fractional anisotropy (FA) between pretreatment and posttreatment and between two groups was determined. Correlations between FA values and neurological assessments were also calculated. Results. Both groups significantly improved the neurological function after treatment. rTMS-treated patients showed better improvement in Fugl-Meyer Assessment (FMA) score and increased FA value in motor-related white matter and gray matter cortices compared with CT-treated patients and pretreatment status. Besides, the increased FA value in the ipsilesional posterior limb of the internal capsule in RT group was significantly correlated with the improved FMA score. Significance. HF-rTMS could be a supplement therapy to CT in improving motor recovery in patients with stroke. And this benefit effect may be achieved through modulating the ipsilesional corticospinal tracts and motor-related gray matter cortices. Zhiwei Guo, Yu Jin, Haitao Peng, Guoqiang Xing, Xiang Liao, Yunfeng Wang, Huaping Chen, Bin He, Morgan A. McClure, and Qiwen Mu Copyright © 2016 Zhiwei Guo et al. All rights reserved. Electroacupuncture Reduces the Effects of Acute Noxious Stimulation on the Electrical Activity of Pain-Related Neurons in the Hippocampus of Control and Neuropathic Pain Rats Wed, 19 Oct 2016 11:58:33 +0000 To study the effects of acupuncture analgesia on the hippocampus, we observed the effects of electroacupuncture (EA) and mitogen-activated protein kinase (MEK) inhibitor on pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal area CA1 of sham or chronic constrictive injury (CCI) rats. The animals were randomly divided into a control, a CCI, and a U0126 (MEK1/2 inhibitor) group. In all experiments, we briefly (10-second duration) stimulated the sciatic nerve electrically and recorded the firing rates of PENs and PINs. The results showed that in both sham and CCI rats brief sciatic nerve stimulation significantly increased the electrical activity of PENs and markedly decreased the electrical activity of PINs. These effects were significantly greater in CCI rats compared to sham rats. EA treatment reduced the effects of the noxious stimulus on PENs and PINs in both sham and CCI rats. The effects of EA treatment could be inhibited by U0126 in sham-operated rats. The results suggest that EA reduces effects of acute sciatic nerve stimulation on PENs and PINs in the CA1 region of the hippocampus of both sham and CCI rats and that the ERK (extracellular regulated kinase) signaling pathway is involved in the modulation of EA analgesia. Jun-Ying Wang, Renbo Chen, Shu-Ping Chen, Yong-Hui Gao, Jian-Liang Zhang, Xiu-Mei Feng, Yaxia Yan, Jun-Ling Liu, Ingrid Gaischek, Daniela Litscher, Lu Wang, Irmgard Th. Lippe, and Gerhard Litscher Copyright © 2016 Jun-Ying Wang et al. All rights reserved. Rostral Agranular Insular Cortex Lesion with Motor Cortex Stimulation Enhances Pain Modulation Effect on Neuropathic Pain Model Wed, 19 Oct 2016 06:18:08 +0000 It is well known that the insular cortex is involved in the processing of painful input. The aim of this study was to evaluate the pain modulation role of the insular cortex during motor cortex stimulation (MCS). After inducing neuropathic pain (NP) rat models by the spared nerve injury method, we made a lesion on the rostral agranular insular cortex (RAIC) unilaterally and compared behaviorally determined pain threshold and latency in 2 groups: Group A (NP + MCS; ) and Group B (NP + RAIC lesion + MCS; ). Also, we simultaneously recorded neuronal activity (NP; ) in the thalamus of the ventral posterolateral nucleus and RAIC to evaluate electrophysiological changes from MCS. The pain threshold and tolerance latency increased in Group A with “MCS on” and in Group B with or without “MCS on.” Moreover, its increase in Group B with “MCS on” was more than that of Group B without MCS or of Group A, suggesting that MCS and RAIC lesioning are involved in pain modulation. Compared with the “MCS off” condition, the “MCS on” induced significant threshold changes in an electrophysiological study. Our data suggest that the RAIC has its own pain modulation effect, which is influenced by MCS. Hyun Ho Jung, Jaewoo Shin, Jinhyung Kim, Seung-Hee Ahn, Sung Eun Lee, Chin Su Koh, Jae Sung Cho, Chanho Kong, Hyung-Cheul Shin, Sung June Kim, and Jin Woo Chang Copyright © 2016 Hyun Ho Jung et al. All rights reserved. Adaptive Plasticity in the Healthy Language Network: Implications for Language Recovery after Stroke Tue, 18 Oct 2016 15:57:57 +0000 Across the last three decades, the application of noninvasive brain stimulation (NIBS) has substantially increased the current knowledge of the brain’s potential to undergo rapid short-term reorganization on the systems level. A large number of studies applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in the healthy brain to probe the functional relevance and interaction of specific areas for different cognitive processes. NIBS is also increasingly being used to induce adaptive plasticity in motor and cognitive networks and shape cognitive functions. Recently, NIBS has been combined with electrophysiological techniques to modulate neural oscillations of specific cortical networks. In this review, we will discuss recent advances in the use of NIBS to modulate neural activity and effective connectivity in the healthy language network, with a special focus on the combination of NIBS and neuroimaging or electrophysiological approaches. Moreover, we outline how these results can be transferred to the lesioned brain to unravel the dynamics of reorganization processes in poststroke aphasia. We conclude with a critical discussion on the potential of NIBS to facilitate language recovery after stroke and propose a phase-specific model for the application of NIBS in language rehabilitation. Gesa Hartwigsen Copyright © 2016 Gesa Hartwigsen. All rights reserved. Strengthened Corticosubcortical Functional Connectivity during Muscle Fatigue Mon, 17 Oct 2016 11:57:06 +0000 The present study examined functional connectivity (FC) between functional MRI (fMRI) signals of the primary motor cortex (M1) and each of the three subcortical neural structures, cerebellum (CB), basal ganglia (BG), and thalamus (TL), during muscle fatigue using the quantile regression technique. Understanding activation relation between the subcortical structures and the M1 during prolonged motor performance should help delineate how central motor control network modulates acute perturbations at peripheral sensorimotor system such as muscle fatigue. Ten healthy subjects participated in the study and completed a 20-minute intermittent handgrip motor task at 50% of their maximal voluntary contraction (MVC) level. Quantile regression analyses were carried out to compare the FC between the contralateral (left) M1 and CB, BG, and TL in the minimal (beginning 100 s) versus significant (ending 100 s) fatigue stages. Widespread, statistically significant increases in FC were found in bilateral BG, CB, and TL with the left M1 during significant versus minimal fatigue stages. Our results imply that these subcortical nuclei are critical components in the motor control network and actively involved in modulating voluntary muscle fatigue, possibly, by working together with the M1 to strengthen the descending central command to prolong the motor performance. Zhiguo Jiang, Xiao-Feng Wang, and Guang H. Yue Copyright © 2016 Zhiguo Jiang et al. All rights reserved. Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury Thu, 13 Oct 2016 14:45:03 +0000 Spinal cord injury is a devastating disease which disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. Most injured neurons fail to regenerate in the central nervous system after injury. Multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration after injury. MicroRNAs can modulate multiple genes’ expression and are tightly controlled during nerve development or the injury process. Evidence has demonstrated that microRNAs and their signaling pathways play important roles in mediating axon regeneration and glial scar formation after spinal cord injury. This article reviews the role and mechanism of differentially expressed microRNAs in regulating axon regeneration and glial scar formation after spinal cord injury, as well as their therapeutic potential for promoting axonal regeneration and repair of the injured spinal cord. Ping Li, Zhao-Qian Teng, and Chang-Mei Liu Copyright © 2016 Ping Li et al. All rights reserved. Neuroscience of Exercise: Neuroplasticity and Its Behavioral Consequences Thu, 13 Oct 2016 07:58:17 +0000 Henning Budde, Mirko Wegner, Hideaki Soya, Claudia Voelcker-Rehage, and Terry McMorris Copyright © 2016 Henning Budde et al. All rights reserved. EEG Source Imaging Guided by Spatiotemporal Specific fMRI: Toward an Understanding of Dynamic Cognitive Processes Mon, 10 Oct 2016 09:22:14 +0000 Understanding the mechanism of neuroplasticity is the first step in treating neuromuscular system impairments with cognitive rehabilitation approaches. To characterize the dynamics of the neural networks and the underlying neuroplasticity of the central motor system, neuroimaging tools with high spatial and temporal accuracy are desirable. EEG and fMRI stand among the most popular noninvasive neuroimaging modalities with complementary features, yet achieving both high spatial and temporal accuracy remains a challenge. A novel multimodal EEG/fMRI integration method was developed in this study to achieve high spatiotemporal accuracy by employing the most probable fMRI spatial subsets to guide EEG source localization in a time-variant fashion. In comparison with the traditional fMRI constrained EEG source imaging method in a visual/motor activation task study, the proposed method demonstrated superior localization accuracy with lower variation and identified neural activity patterns that agreed well with previous studies. This spatiotemporal fMRI constrained source imaging method was then implemented in a “sequential multievent-related potential” paradigm where motor activation is evoked by emotion-related visual stimuli. Results demonstrate that the proposed method can be used as a powerful neuroimaging tool to unveil the dynamics and neural networks associated with the central motor system, providing insights into neuroplasticity modulation mechanism. Thinh Nguyen, Thomas Potter, Trac Nguyen, Christof Karmonik, Robert Grossman, and Yingchun Zhang Copyright © 2016 Thinh Nguyen et al. All rights reserved. Paired Stimulation to Promote Lasting Augmentation of Corticospinal Circuits Sun, 09 Oct 2016 09:56:04 +0000 After injury, electrical stimulation of the nervous system can augment plasticity of spared or latent circuits through focal modulation. Pairing stimulation of two parts of a spared circuit can target modulation more specifically to the intended circuit. We discuss 3 kinds of paired stimulation in the context of the corticospinal system, because of its importance in clinical neurorehabilitation. The first uses principles of Hebbian plasticity: by altering the stimulation timing of presynaptic neurons and their postsynaptic targets, synapse function can be modulated up or down. The second form uses synchronized presynaptic inputs onto a common synaptic target. We dub this a “convergent” mechanism, because stimuli have to converge on a common target with coordinated timing. The third form induces focal modulation by tonic excitation of one region (e.g., the spinal cord) during phasic stimulation of another (e.g., motor cortex). Additionally, endogenous neural activity may be paired with exogenous electrical stimulation. This review addresses what is known about paired stimulation of the corticospinal system of both humans and animal models, emphasizes how it qualitatively differs from single-site stimulation, and discusses the gaps in knowledge that must be addressed to maximize its use and efficacy in neurorehabilitation. Noam Y. Harel and Jason B. Carmel Copyright © 2016 Noam Y. Harel and Jason B. Carmel. All rights reserved. Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies Tue, 04 Oct 2016 14:25:05 +0000 Shank proteins (Shank1, Shank2, and Shank3) act as scaffolding molecules in the postsynaptic density of many excitatory neurons. Mutations in SHANK genes, in particular SHANK2 and SHANK3, lead to autism spectrum disorders (ASD) in both human and mouse models. Shank3 proteins are made of several domains—the Shank/ProSAP N-terminal (SPN) domain, ankyrin repeats, SH3 domain, PDZ domain, a proline-rich region, and the sterile alpha motif (SAM) domain. Via various binding partners of these domains, Shank3 is able to bind and interact with a wide range of proteins including modulators of small GTPases such as RICH2, a RhoGAP protein, and βPIX, a RhoGEF protein for Rac1 and Cdc42, actin binding proteins and actin modulators. Dysregulation of all isoforms of Shank proteins, but especially Shank3, leads to alterations in spine morphogenesis, shape, and activity of the synapse via altering actin dynamics. Therefore, here, we highlight the role of Shank proteins as modulators of small GTPases and, ultimately, actin dynamics, as found in multiple in vitro and in vivo models. The failure to mediate this regulatory role might present a shared mechanism in the pathophysiology of autism-associated mutations, which leads to dysregulation of spine morphogenesis and synaptic signaling. Tasnuva Sarowar and Andreas M. Grabrucker Copyright © 2016 Tasnuva Sarowar and Andreas M. Grabrucker. All rights reserved. ATP Induces Disruption of Tight Junction Proteins via IL-1 Beta-Dependent MMP-9 Activation of Human Blood-Brain Barrier In Vitro Tue, 04 Oct 2016 09:14:12 +0000 Disruption of blood-brain barrier (BBB) follows brain trauma or central nervous system (CNS) stress. However, the mechanisms leading to this process or the underlying neural plasticity are not clearly known. We hypothesized that ATP/P2X7R signaling regulates the integrity of BBB. Activation of P2X7 receptor (P2X7R) by ATP induces the release of interleukin-1β (IL-1β), which in turn enhances the activity of matrix metalloproteinase-9 (MMP-9). Degradation of tight junction proteins (TJPs) such as ZO-1 and occludin occurs, which finally contributes to disruption of BBB. A contact coculture system using human astrocytes and hCMEC/D3, an immortalized human brain endothelial cell line, was used to mimic BBB in vitro. Permeability was used to evaluate changes in the integrity of TJPs. ELISA, Western blot, and immunofluorescent staining procedures were used. Our data demonstrated that exposure to the photoreactive ATP analog, 3′-O-(4-benzoyl)benzoyl adenosine 5′-triphosphate (BzATP), induced a significant decrease in ZO-1 and occludin expression. Meanwhile, the decrease of ZO-1 and occludin was significantly attenuated by P2X7R inhibitors, as well as IL-1R and MMP antagonists. Further, the induction of IL-1β and MMP-9 was closely linked to ATP/P2X7R-associated BBB leakage. In conclusion, our study explored the mechanism of ATP/P2X7R signaling in the disruption of BBB following brain trauma/stress injury, especially focusing on the relationship with IL-1β and MMP-9. Fuxing Yang, Kai Zhao, Xiufeng Zhang, Jun Zhang, and Bainan Xu Copyright © 2016 Fuxing Yang et al. All rights reserved. Neural Plasticity on Body Representations: Advancing Translational Rehabilitation Thu, 29 Sep 2016 08:28:57 +0000 Naoyuki Takeuchi, Shin-Ichi Izumi, Jun Ota, and Jun Ueda Copyright © 2016 Naoyuki Takeuchi et al. All rights reserved. Adaptation and Plasticity of Breathing during Behavioral and Cognitive Tasks Thu, 29 Sep 2016 06:06:09 +0000 Nathalie Buonviso, Mathias Dutschmann, Anne-Marie Mouly, and Daniel W. Wesson Copyright © 2016 Nathalie Buonviso et al. All rights reserved. Traumatic Brain Injury and Substance Related Disorder: A 10-Year Nationwide Cohort Study in Taiwan Tue, 27 Sep 2016 13:17:10 +0000 Whether traumatic brain injury (TBI) is causally related to substance related disorder (SRD) is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio) were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events. Chieh-Hsin Wu, Tai-Hsin Tsai, Yu-Feng Su, Zi-Hao Zhang, Wei Liu, Ming-Kung Wu, Chih-Hui Chang, Keng-Liang Kuo, Ying-Yi Lu, and Chih-Lung Lin Copyright © 2016 Chieh-Hsin Wu et al. All rights reserved. Electroacupuncture Treatment Alleviates Central Poststroke Pain by Inhibiting Brain Neuronal Apoptosis and Aberrant Astrocyte Activation Tue, 27 Sep 2016 06:36:03 +0000 Electroacupuncture (EA) is reported to effectively relieve the central poststroke pain (CPSP). However, the underlying mechanism remains unclear. The present study investigated the detailed mechanisms of action of EA treatment at different frequencies for CPSP. A CPSP model was established with a single collagenase injection to the left ventral posterolateral nucleus of the thalamus. The EA-treated groups then received EA treatment at frequency of 2, 2/15, or 15 Hz for 30 min daily for five days. The pain-related behavioral responses, neuronal apoptosis, glial activation, and the expression of pain signal transmission-related factors (β-catenin, COX-2, and NK-1R) were assessed using behavioral tests, Nissl staining, TUNEL staining, and immunohistochemical staining, respectively. The low-frequency EA treatment significantly (1) reduced brain tissue damage and hematoma sizes and (2) inhibited neuronal apoptosis, thereby exerting abirritative effects. Meanwhile, the high-frequency EA treatment induced a greater inhibition of the aberrant astrocyte activation, accompanied by the downregulation of the expressions of COX-2, β-catenin, and subsequently NK-1R, thereby alleviating inflammation and producing strong analgesic effects. Together, these findings suggest that CPSP is closely related to pathological changes of the neocortex and hippocampus. EA treatments at different frequencies may exert abirritative effects by inhibiting brain neuronal apoptosis and aberrant astrocyte activation in the brain. Gui-Hua Tian, Shan-Shan Tao, Man-Tang Chen, Yu-Sang Li, You-Ping Li, Hong-Cai Shang, Xiao-Yi Tang, Jian-Xin Chen, and He-Bin Tang Copyright © 2016 Gui-Hua Tian et al. All rights reserved. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson’s Disease Mon, 26 Sep 2016 16:42:24 +0000 In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or 2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. Lei-Fang Cao, Xiao-Yan Peng, Ya Huang, Bing Wang, Feng-Ming Zhou, Ruo-Xiao Cheng, Li-Hua Chen, Wei-Feng Luo, and Tong Liu Copyright © 2016 Lei-Fang Cao et al. All rights reserved. MRI Biomarkers for Hand-Motor Outcome Prediction and Therapy Monitoring following Stroke Mon, 26 Sep 2016 12:50:40 +0000 Several biomarkers have been identified which enable a considerable prediction of hand-motor outcome after cerebral damage already in the subacute stage after stroke. We here review the value of MRI biomarkers in the evaluation of corticospinal integrity and functional recruitment of motor resources. Many of the functional imaging parameters are not feasible early after stroke or for patients with high impairment and low compliance. Whereas functional connectivity parameters have demonstrated varying results on their predictive value for hand-motor outcome, corticospinal integrity evaluation using structural imaging showed robust and high predictive power for patients with different levels of impairment. Although this is indicative of an overall higher value of structural imaging for prediction, we suggest that this variation be explained by structure and function relationships. To gain more insight into the recovering brain, not only one biomarker is needed. We rather argue for a combination of different measures in an algorithm to classify fine-graded subgroups of patients. Approaches to determining biomarkers have to take into account the established markers to provide further information on certain subgroups. Assessing the best therapy approaches for individual patients will become more feasible as these subgroups become specified in more detail. This procedure will help to considerably save resources and optimize neurorehabilitative therapy. U. Horn, M. Grothe, and M. Lotze Copyright © 2016 U. Horn et al. All rights reserved. Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function Mon, 26 Sep 2016 11:44:34 +0000 The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function. Carola Stockburger, Davide Miano, Thea Pallas, Kristina Friedland, and Walter E. Müller Copyright © 2016 Carola Stockburger et al. All rights reserved. Sniff-Like Patterned Input Results in Long-Term Plasticity at the Rat Olfactory Bulb Mitral and Tufted Cell to Granule Cell Synapse Mon, 26 Sep 2016 07:39:30 +0000 During odor sensing the activity of principal neurons of the mammalian olfactory bulb, the mitral and tufted cells (MTCs), occurs in repetitive bursts that are synchronized to respiration, reminiscent of hippocampal theta-gamma coupling. Axonless granule cells (GCs) mediate self- and lateral inhibitory interactions between the excitatory MTCs via reciprocal dendrodendritic synapses. We have explored long-term plasticity at this synapse by using a theta burst stimulation (TBS) protocol and variations thereof. GCs were excited via glomerular stimulation in acute brain slices. We find that TBS induces exclusively long-term depression in the majority of experiments, whereas single bursts (“single-sniff paradigm”) can elicit both long-term potentiation and depression. Statistical analysis predicts that the mechanism underlying this bidirectional plasticity involves the proportional addition or removal of presynaptic release sites. Gamma stimulation with the same number of APs as in TBS was less efficient in inducing plasticity. Both TBS- and “single-sniff paradigm”-induced plasticity depend on NMDA receptor activation. Since the onset of plasticity is very rapid and requires little extra activity, we propose that these forms of plasticity might play a role already during an ongoing search for odor sources. Our results imply that components of both short-term and long-term olfactory memory may be encoded at this synapse. Mahua Chatterjee, Fernando Perez de los Cobos Pallares, Alex Loebel, Michael Lukas, and Veronica Egger Copyright © 2016 Mahua Chatterjee et al. All rights reserved. Effects of a Single Session of High Intensity Interval Treadmill Training on Corticomotor Excitability following Stroke: Implications for Therapy Sun, 25 Sep 2016 14:03:39 +0000 Objective. High intensity interval treadmill training (HIITT) has been gaining popularity for gait rehabilitation after stroke. In this study, we examined the changes in excitability of the lower limb motor cortical representation (M1) in chronic stroke survivors following a single session of HIITT. We also determined whether exercise-induced changes in excitability could be modulated by transcranial direct current stimulation (tDCS) enhanced with a paretic ankle skill acquisition task. Methods. Eleven individuals with chronic stroke participated in two 40-minute treadmill-training sessions: HIITT alone and HITT preceded by anodal tDCS enhanced with a skill acquisition task (e-tDCS+HIITT). Transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability of paretic and nonparetic tibialis anterior (TA) muscles. Results. HIIT alone reduced paretic TA M1 excitability in 7 of 11 participants by ≥ 10%. e-tDCS+HIITT increased paretic TA M1 excitability and decreased nonparetic TA M1 excitability. Conclusions. HIITT suppresses corticomotor excitability in some people with chronic stroke. When HIITT is preceded by tDCS in combination with a skill acquisition task, the asymmetry of between-hemisphere corticomotor excitability is reduced. Significance. This study provides preliminary data indicating that the cardiovascular benefits of HIITT may be achieved without suppressing motor excitability in some stroke survivors. Sangeetha Madhavan, James W. Stinear, and Neeta Kanekar Copyright © 2016 Sangeetha Madhavan et al. All rights reserved. Senior Dance Experience, Cognitive Performance, and Brain Volume in Older Women Sun, 25 Sep 2016 08:56:03 +0000 Physical activity is positively related to cognitive functioning and brain volume in older adults. Interestingly, different types of physical activity vary in their effects on cognition and on the brain. For example, dancing has become an interesting topic in aging research, as it is a popular leisure activity among older adults, involving cardiovascular and motor fitness dimensions that can be positively related to cognition. However, studies on brain structure are missing. In this study, we tested the association of long-term senior dance experience with cognitive performance and gray matter brain volume in older women aged 65 to 82 years. We compared nonprofessional senior dancers () with nonsedentary control group participants without any dancing experience (), who were similar in age, education, IQ score, lifestyle and health factors, and fitness level. Differences neither in the four tested cognitive domains (executive control, perceptual speed, episodic memory, and long-term memory) nor in brain volume (VBM whole-brain analysis, region-of-interest analysis of the hippocampus) were observed. Results indicate that moderate dancing activity (1-2 times per week, on average) has no additional effects on gray matter volume and cognitive functioning when a certain lifestyle or physical activity and fitness level are reached. Claudia Niemann, Ben Godde, and Claudia Voelcker-Rehage Copyright © 2016 Claudia Niemann et al. All rights reserved. Neurostimulation Thu, 22 Sep 2016 06:34:11 +0000 Helena Knotkova, Michael A. Nitsche, and Volker Tronnier Copyright © 2016 Helena Knotkova et al. All rights reserved. Cochlear Synaptopathy and Noise-Induced Hidden Hearing Loss Wed, 21 Sep 2016 12:24:47 +0000 Recent studies on animal models have shown that noise exposure that does not lead to permanent threshold shift (PTS) can cause considerable damage around the synapses between inner hair cells (IHCs) and type-I afferent auditory nerve fibers (ANFs). Disruption of these synapses not only disables the innervated ANFs but also results in the slow degeneration of spiral ganglion neurons if the synapses are not reestablished. Such a loss of ANFs should result in signal coding deficits, which are exacerbated by the bias of the damage toward synapses connecting low-spontaneous-rate (SR) ANFs, which are known to be vital for signal coding in noisy background. As there is no PTS, these functional deficits cannot be detected using routine audiological evaluations and may be unknown to subjects who have them. Such functional deficits in hearing without changes in sensitivity are generally called “noise-induced hidden hearing loss (NIHHL).” Here, we provide a brief review to address several critical issues related to NIHHL: (1) the mechanism of noise induced synaptic damage, (2) reversibility of the synaptic damage, (3) the functional deficits as the nature of NIHHL in animal studies, (4) evidence of NIHHL in human subjects, and (5) peripheral and central contribution of NIHHL. Lijuan Shi, Ying Chang, Xiaowei Li, Steve Aiken, Lijie Liu, and Jian Wang Copyright © 2016 Lijuan Shi et al. All rights reserved. Safety Needs Mediate Stressful Events Induced Mental Disorders Wed, 21 Sep 2016 11:28:48 +0000 “Safety first,” we say these words almost every day, but we all take this for granted for what Maslow proposed in his famous theory of Hierarchy of Needs: safety needs come second to physiological needs. Here we propose that safety needs come before physiological needs. Safety needs are personal security, financial security, and health and well-being, which are more fundamental than physiological needs. Safety worrying is the major reason for mental disorders, such as anxiety, phobia, depression, and PTSD. The neural basis for safety is amygdala, LC/NE system, and corticotrophin-releasing hormone system, which can be regarded as a “safety circuitry,” whose major behavior function is “fight or flight” and “fear and anger” emotions. This is similar to the Appraisal theory for emotions: fear is due to the primary appraisal, which is related to safety of individual, while anger is due to secondary appraisal, which is related to coping with the unsafe situations. If coping is good, the individual will be happy; if coping failed, the individual will be sad or depressed. Zheng Zheng, Simeng Gu, Yu Lei, Shanshan Lu, Wei Wang, Yang Li, and Fushun Wang Copyright © 2016 Zheng Zheng et al. All rights reserved. Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats Tue, 20 Sep 2016 16:47:22 +0000 Spontaneous intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20) exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa’s scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH (). In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. Hui-Qin Li, Yan Li, Zi-Xian Chen, Xiao-Guang Zhang, Xia-wei Zheng, Wen-ting Yang, Shuang Chen, and Guo-Qing Zheng Copyright © 2016 Hui-Qin Li et al. All rights reserved. Training-Specific Neural Plasticity in Spinal Reflexes after Incomplete Spinal Cord Injury Tue, 20 Sep 2016 16:46:40 +0000 The neural plasticity of spinal reflexes after two contrasting forms of walking training was determined in individuals with chronic, motor-incomplete spinal cord injury (SCI). Endurance Training involved treadmill walking for as long as possible, and Precision Training involved walking precisely over obstacles and onto targets overground. Twenty participants started either Endurance or Precision Training for 2 months and then crossed over after a 2-month rest period to the other form of training for 2 months. Measures were taken before and after each phase of training and rest. The cutaneomuscular reflex (CMR) during walking was evoked in the soleus (SOL) and tibialis anterior muscles by stimulating the posterior tibial nerve at the ankle. Clonus was estimated from the EMG power in the SOL during unperturbed walking. The inhibitory component of the SOL CMR was enhanced after Endurance but not Precision Training. Clonus did not change after either form of training. Participants with lower reflex excitability tended to be better walkers (i.e., faster walking speeds) prior to training, and the reduction in clonus was significantly correlated with the improvement in walking speed and distance. Thus, reflex excitability responded in a training-specific way, with the reduction in reflex excitability related to improvements in walking function. Trial registration number is NCT01765153. Atif S. Khan, Susan K. Patrick, Francois D. Roy, Monica A. Gorassini, and Jaynie F. Yang Copyright © 2016 Atif S. Khan et al. All rights reserved. Shuyu Capsules Relieve Premenstrual Syndrome Depression by Reducing and Expression in the Rat Brain Tue, 20 Sep 2016 13:36:27 +0000 The effects of the Shuyu capsule on and expression in a rat model of premenstrual syndrome (PMS) depression and on and expression and hippocampal neuron 5-HT3 channel current were investigated, to elucidate its mechanism of action against PMS depression. PMS depression model rats were divided into depression and Shuyu- and fluoxetine-treated groups, which were compared to control rats for frontal lobe and hippocampal and expression and behavior. The depressed model rats displayed symptoms of depression, which were reduced in treated and normal control rats. Frontal lobe and hippocampal and levels were significantly higher in the model versus the control group and were significantly lower in the Shuyu group. As compared to control rats, the 5-HT3R channel current in the model group was significantly higher; the 5-HT3R channel current in hippocampal neurons treated with serum from Shuyu group rats was significantly lower than that in those treated with model group serum. Thus, PMS depression may be related to and expression and increased 5-HT3 channel current. Shuyu capsules rectified abnormal and expression and 5-HT3 channel current changes in a rat model; this finding may provide insight into treating PMS depression. Fang Li, Jizhen Feng, Dongmei Gao, Jieqiong Wang, Chunhong Song, Sheng Wei, and Mingqi Qiao Copyright © 2016 Fang Li et al. All rights reserved.