Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Physical Exercise as a Diagnostic, Rehabilitation, and Preventive Tool: Influence on Neuroplasticity and Motor Recovery after Stroke Mon, 23 Nov 2015 05:50:51 +0000 Stroke remains a leading cause of adult motor disabilities in the world and accounts for the greatest number of hospitalizations for neurological disease. Stroke treatments/therapies need to promote neuroplasticity to improve motor function. Physical exercise is considered as a major candidate for ultimately promoting neural plasticity and could be used for different purposes in human and animal experiments. First, acute exercise could be used as a diagnostic tool to understand new neural mechanisms underlying stroke physiopathology. Indeed, better knowledge of stroke mechanisms that affect movements is crucial for enhancing treatment/rehabilitation effectiveness. Secondly, it is well established that physical exercise training is advised as an effective rehabilitation tool. Indeed, it reduces inflammatory processes and apoptotic marker expression, promotes brain angiogenesis and expression of some growth factors, and improves the activation of affected muscles during exercise. Nevertheless, exercise training might also aggravate sensorimotor deficits and brain injury depending on the chosen exercise parameters. For the last few years, physical training has been combined with pharmacological treatments to accentuate and/or accelerate beneficial neural and motor effects. Finally, physical exercise might also be considered as a major nonpharmacological preventive strategy that provides neuroprotective effects reducing adverse effects of brain ischemia. Therefore, prestroke regular physical activity may also decrease the motor outcome severity of stroke. Caroline Pin-Barre and Jérôme Laurin Copyright © 2015 Caroline Pin-Barre and Jérôme Laurin. All rights reserved. Distinct Functions of Endophilin Isoforms in Synaptic Vesicle Endocytosis Sun, 22 Nov 2015 09:49:54 +0000 Endophilin isoforms perform distinct characteristics in their interactions with N-type Ca2+ channels and dynamin. However, precise functional differences for the endophilin isoforms on synaptic vesicle (SV) endocytosis remain unknown. By coupling RNA interference and electrophysiological recording techniques in cultured rat hippocampal neurons, we investigated the functional differences of three isoforms of endophilin in SV endocytosis. The results showed that the amplitude of normalized evoked excitatory postsynaptic currents in endophilin1 knockdown neurons decreased significantly for both single train and multiple train stimulations. Similar results were found using endophilin2 knockdown neurons, whereas endophilin3 siRNA exhibited no change compared with control neurons. Endophilin1 and endophilin2 affected SV endocytosis, but the effect of endophilin1 and endophilin2 double knockdown was not different from that of either knockdown alone. This result suggested that endophilin1 and endophilin2 functioned together but not independently during SV endocytosis. Taken together, our results indicate that SV endocytosis is sustained by endophilin1 and endophilin2 isoforms, but not by endophilin3, in primary cultured hippocampal neurons. Jifeng Zhang, Minghui Tan, Yichen Yin, Bingyu Ren, Nannan Jiang, Guoqing Guo, and Yuan Chen Copyright © 2015 Jifeng Zhang et al. All rights reserved. Development and Structural Variety of the Chondroitin Sulfate Proteoglycans-Contained Extracellular Matrix in the Mouse Brain Mon, 16 Nov 2015 08:09:25 +0000 Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix (ECM) in the brain. In adult mammals, CSPGs form the specialized ECM structure perineuronal nets (PNNs) that surround somata and dendrites of certain types of neurons. PNNs restrict synaptic plasticity and regulate the closure of critical periods. Although previous studies have examined the starting period of PNN formation, focusing on primary sensory cortices, there are no systematic studies at the whole brain level. Here, we examined the starting period of PNN formation in male mice ranging in age from postnatal day 3 to week 11, mainly focusing on several cortical areas, limbic structures, hypothalamus, and brain stem, using lectin histochemistry with Wisteria floribunda agglutinin (WFA). Results showed that early PNN formation was observed in several reticular formations of the brain stem related to the cranial nerves and primary somatosensory cortices. In the limbic system, PNN formation in the hippocampus started earlier than that of the amygdala. Furthermore, in the medial amygdaloid nucleus and some hypothalamic regions, WFA labeling did not show typical PNN-like forms. The present study suggests spatiotemporal differences at the beginning of PNN formation and a structural variety of CSPG-contained ECM in the brain. Noriko Horii-Hayashi, Takayo Sasagawa, Wataru Matsunaga, and Mayumi Nishi Copyright © 2015 Noriko Horii-Hayashi et al. All rights reserved. Synaptic Plasticity and Neurological Disorders in Neurotropic Viral Infections Mon, 16 Nov 2015 06:37:59 +0000 Based on the type of cells or tissues they tend to harbor or attack, many of the viruses are characterized. But, in case of neurotropic viruses, it is not possible to classify them based on their tropism because many of them are not primarily neurotropic. While rabies and poliovirus are considered as strictly neurotropic, other neurotropic viruses involve nervous tissue only secondarily. Since the AIDS pandemic, the interest in neurotropic viral infections has become essential for all clinical neurologists. Although these neurotropic viruses are able to be harbored in or infect the nervous system, not all the neurotropic viruses have been reported to cause disrupted synaptic plasticity and impaired cognitive functions. In this review, we have discussed the neurotropic viruses, which play a major role in altered synaptic plasticity and neurological disorders. Venkata Subba Rao Atluri, Melissa Hidalgo, Thangavel Samikkannu, Kesava Rao Venkata Kurapati, and Madhavan Nair Copyright © 2015 Venkata Subba Rao Atluri et al. All rights reserved. Brain Plasticity following Intensive Bimanual Therapy in Children with Hemiparesis: Preliminary Evidence Tue, 10 Nov 2015 07:53:45 +0000 Neuroplasticity studies examining children with hemiparesis (CH) have focused predominantly on unilateral interventions. CH also have bimanual coordination impairments with bimanual interventions showing benefits. We explored neuroplasticity following hand-arm bimanual intensive therapy (HABIT) of 60 hours in twelve CH (6 females, mean age 11 ± 3.6 y). Serial behavioral evaluations and MR imaging including diffusion tensor (DTI) and functional (fMRI) imaging were performed before, immediately after, and at 6-week follow-up. Manual skills were assessed repeatedly with the Assisting Hand Assessment, Children’s Hand Experience Questionnaire, and Jebsen-Taylor Test of Hand Function. Beta values, indicating the level of activation, and lateralization index (LI), indicating the pattern of brain activation, were computed from fMRI. White matter integrity of major fibers was assessed using DTI. 11/12 children showed improvement after intervention in at least one measure, with 8/12 improving on two or more tests. Changes were retained in 6/8 children at follow-up. Beta activation in the affected hemisphere increased at follow-up, and LI increased both after intervention and at follow-up. Correlations between LI and motor function emerged after intervention. Increased white matter integrity was detected in the corpus callosum and corticospinal tract after intervention in about half of the participants. Results provide first evidence for neuroplasticity changes following bimanual intervention in CH. Maya Weinstein, Vicki Myers, Dido Green, Mitchell Schertz, Shelly I. Shiran, Ronny Geva, Moran Artzi, Andrew M. Gordon, Aviva Fattal-Valevski, and Dafna Ben Bashat Copyright © 2015 Maya Weinstein et al. All rights reserved. The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection Sun, 08 Nov 2015 13:38:55 +0000 Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model. Vinnitsa Buzoianu-Anguiano, Sandra Orozco-Suárez, Elisa García-Vences, Sara Caballero-Chacón, Gabriel Guizar-Sahagún, Luis Chavez-Sanchez, and Israel Grijalva Copyright © 2015 Vinnitsa Buzoianu-Anguiano et al. All rights reserved. Cortical Reorganization Is Associated with Surgical Decompression of Cervical Spondylotic Myelopathy Mon, 02 Nov 2015 06:28:22 +0000 Background. Cervical spondylotic myelopathy (CSM) results in sensorimotor limb deficits, bladder, and bowel dysfunction, but mechanisms underlying motor plasticity changes before and after surgery are unclear. Methods. We studied 24 patients who underwent decompression surgery and 15 healthy controls. Patients with mixed upper and lower limb dysfunction (Group A) and only lower limb dysfunction (Group B) were then analysed separately. Results. The sum amplitude of motor evoked potentials sMEP () and number of focal points where MEPs were elicited () () were significantly larger in CSM patients compared with controls. For Group A (16 patients), sMEP () and () showed similar findings. However, for Group B (8 patients), only () was significantly larger in patients than controls. Group A had significantly increased grip strength () and reduced sMEP () and () after surgery. Changes in sMEP (cMEP) significantly correlated inversely with improved feeding () and stacking () times as was the change in number of focal points (NDiff) with improved writing times (). Group B did not show significant reduction in sMEP or after surgery, or significant correlation of cMEP or NDiff with all hand function tests. No significant differences in reflex parameters obtained from the flexor carpi radialis, or central motor conduction time changes, were noted after surgery. Discussion. Compensatory expansion of motor cortical representation occurs largely at cortical rather than spinal levels, with a tendency to normalization after surgery. These mirrored improvements in relevant tasks requiring utilization of intrinsic hand muscles. Andrew Green, Priscilia W. T. Cheong, Stephanie Fook-Chong, Rajendra Tiruchelvarayan, Chang Ming Guo, Wai Mun Yue, John Chen, and Yew Long Lo Copyright © 2015 Andrew Green et al. All rights reserved. A Novel Nitronyl Nitroxide with Salicylic Acid Framework Attenuates Pain Hypersensitivity and Ectopic Neuronal Discharges in Radicular Low Back Pain Sun, 01 Nov 2015 09:07:05 +0000 Evidence has accumulated that reactive oxygen species and inflammation play crucial roles in the development of chronic pain, including radicular low back pain. Nonsteroid anti-inflammatory drugs (NSAIDs), for example, salicylic acid, aspirin, provided analgesic effects in various types of pain. However, long-term use of these drugs causes unwanted side effects, which limits their implication. Stable nitronyl (NIT) nitroxide radicals have been extensively studied as a unique and interesting class of new antioxidants for protection against oxidative damage. The present study synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) to provide synergistic effect of both antioxidation and antiinflammation. We demonstrated for the first time that both acute and repeated SANR treatment exerted dramatic analgesic effect in radicular low back pain mimicked by chronic compression of dorsal root ganglion in rats. This analgesic potency was more potent than that produced by classical NSAIDs aspirin and traditional nitroxide radical Tempol alone. Furthermore, SANR-induced behavioral analgesia is found to be mediated, at least in partial, by a reduction of ectopic spontaneous discharges in injured DRG neurons. Therefore, the synthesized NIT nitroxide radical coupling with salicylic acid framework may represent a novel potential therapeutic candidate for treatment of chronic pain, including radicular low back pain. Wen-Juan Han, Lei Chen, Hai-Bo Wang, Xiang-Zeng Liu, San-Jue Hu, Xiao-Li Sun, and Ceng Luo Copyright © 2015 Wen-Juan Han et al. All rights reserved. Alterations of the Ceramide Metabolism in the Peri-Infarct Cortex Are Independent of the Sphingomyelinase Pathway and Not Influenced by the Acid Sphingomyelinase Inhibitor Fluoxetine Wed, 28 Oct 2015 08:36:17 +0000 Ceramides induce important intracellular signaling pathways, modulating proliferation, migration, apoptosis, and inflammation. However, the relevance of the ceramide metabolism in the reconvalescence phase after stroke is unclear. Besides its well-known property as a selective serotonin reuptake inhibitor, fluoxetine has been reported to inhibit the acid sphingomyelinase (ASM), a key regulator of ceramide levels which derives ceramide from sphingomyelin. Furthermore, fluoxetine has shown therapeutic potential in a randomized controlled rehabilitation trial in stroke patients. Our aim was to investigate and modulate ceramide concentrations in the peri-infarct cortex, whose morphological and functional properties correlate with long-term functional outcome in stroke. We show that certain ceramide species are modulated after experimental stroke and that these changes do not result from alterations of ASM activity, but rather from nontranscriptional induction of the ceramide de novo pathway. Unexpectedly, although reducing lesion size, fluoxetine did not improve functional outcome in our model and had no significant influence on ASM activity or the concentration of ceramides. The ceramide metabolism could emerge as a potential therapeutic target in the reconvalescence phase after stroke, as its accumulation in the peri-infarct cortex potentially influences membrane functions as well as signaling events in the tissue essential for neurological recovery. R. Brunkhorst, F. Friedlaender, N. Ferreirós, S. Schwalm, A. Koch, G. Grammatikos, S. Toennes, C. Foerch, J. Pfeilschifter, and W. Pfeilschifter Copyright © 2015 R. Brunkhorst et al. All rights reserved. The Plasticity of Brain Gray Matter and White Matter following Lower Limb Amputation Mon, 26 Oct 2015 06:26:42 +0000 Accumulating evidence has indicated that amputation induces functional reorganization in the sensory and motor cortices. However, the extent of structural changes after lower limb amputation in patients without phantom pain remains uncertain. We studied 17 adult patients with right lower limb amputation and 18 healthy control subjects using T1-weighted magnetic resonance imaging and diffusion tensor imaging. Cortical thickness and fractional anisotropy (FA) of white matter (WM) were investigated. In amputees, a thinning trend was seen in the left premotor cortex (PMC). Smaller clusters were also noted in the visual-to-motor regions. In addition, the amputees also exhibited a decreased FA in the right superior corona radiata and WM regions underlying the right temporal lobe and left PMC. Fiber tractography from these WM regions showed microstructural changes in the commissural fibers connecting the bilateral premotor cortices, compatible with the hypothesis that amputation can lead to a change in interhemispheric interactions. Finally, the lower limb amputees also displayed significant FA reduction in the right inferior frontooccipital fasciculus, which is negatively correlated with the time since amputation. In conclusion, our findings indicate that the amputation of lower limb could induce changes in the cortical representation of the missing limb and the underlying WM connections. Guangyao Jiang, Xuntao Yin, Chuanming Li, Lei Li, Lu Zhao, Alan C. Evans, Tianzi Jiang, Jixiang Wu, and Jian Wang Copyright © 2015 Guangyao Jiang et al. All rights reserved. Alterations of Regional Spontaneous Brain Activity and Gray Matter Volume in the Blind Mon, 19 Oct 2015 12:36:15 +0000 Visual deprivation can induce alterations of regional spontaneous brain activity (RSBA). However, the effects of onset age of blindness on the RSBA and the association between the alterations of RSBA and brain structure are still unclear in the blind. In this study, we performed resting-state functional and structural magnetic resonance imaging on 50 sighted controls and 91 blind subjects (20 congenitally blind, 27 early blind, and 44 late blind individuals). Compared with the sighted control, we identified increased RSBA in the blind in primary and high-level visual areas and decreased RSBA in brain regions which are ascribed to sensorimotor and salience networks. In contrast, blind subjects exhibited significantly decreased gray matter volume (GMV) in the visual areas, while they exhibited significantly increased GMV in the sensorimotor areas. Moreover, the onset age of blindness was negatively correlated with the GMV of visual areas in blind subjects, whereas it exerted complex influences on the RSBA. Finally, significant negative correlations were shown between RSBA and GMV values. Our results demonstrated system-dependent, inverse alterations in RSBA and GMV after visual deprivation. Furthermore, the onset age of blindness has different effects on the reorganizations in RSBA and GMV. Aili Jiang, Jing Tian, Rui Li, Yong Liu, Tianzi Jiang, Wen Qin, and Chunshui Yu Copyright © 2015 Aili Jiang et al. All rights reserved. Postinjury Neuroplasticity in Central Neural Networks Sun, 18 Oct 2015 08:47:58 +0000 Bae Hwan Lee, Tae-Hong Lim, Young Wook Yoon, Midori A. Yenari, and Yong Jeong Copyright © 2015 Bae Hwan Lee et al. All rights reserved. Acute Putrescine Supplementation with Schwann Cell Implantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injured Rats Tue, 13 Oct 2015 07:45:47 +0000 Schwann cell (SC) transplantation exhibits significant potential for spinal cord injury (SCI) repair and its use as a therapeutic modality has now progressed to clinical trials for subacute and chronic human SCI. Although SC implants provide a receptive environment for axonal regrowth and support functional recovery in a number of experimental SCI models, axonal regeneration is largely limited to local systems and the behavioral improvements are modest without additional combinatory approaches. In the current study we investigated whether the concurrent delivery of the polyamine putrescine, started either 30 min or 1 week after SCI, could enhance the efficacy of SCs when implanted subacutely (1 week after injury) into the contused rat spinal cord. Polyamines are ubiquitous organic cations that play an important role in the regulation of the cell cycle, cell division, cytoskeletal organization, and cell differentiation. We show that the combination of putrescine with SCs provides a significant increase in implant size, an enhancement in axonal (sensory and serotonergic) sparing and/or growth, and improved open field locomotion after SCI, as compared to SC implantation alone. These findings demonstrate that polyamine supplementation can augment the effectiveness of SCs when used as a therapeutic approach for subacute SCI repair. J. Bryan Iorgulescu, Samik P. Patel, Jack Louro, Christian M. Andrade, Andre R. Sanchez, and Damien D. Pearse Copyright © 2015 J. Bryan Iorgulescu et al. All rights reserved. Clinical Trial of Human Fetal Brain-Derived Neural Stem/Progenitor Cell Transplantation in Patients with Traumatic Cervical Spinal Cord Injury Sun, 11 Oct 2015 08:18:33 +0000 In a phase I/IIa open-label and nonrandomized controlled clinical trial, we sought to assess the safety and neurological effects of human neural stem/progenitor cells (hNSPCs) transplanted into the injured cord after traumatic cervical spinal cord injury (SCI). Of 19 treated subjects, 17 were sensorimotor complete and 2 were motor complete and sensory incomplete. hNSPCs derived from the fetal telencephalon were grown as neurospheres and transplanted into the cord. In the control group, who did not receive cell implantation but were otherwise closely matched with the transplantation group, 15 patients with traumatic cervical SCI were included. At 1 year after cell transplantation, there was no evidence of cord damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity. The American Spinal Injury Association Impairment Scale (AIS) grade improved in 5 of 19 transplanted patients, 2 (A → C), 1 (A → B), and 2 (B → D), whereas only one patient in the control group showed improvement (A → B). Improvements included increased motor scores, recovery of motor levels, and responses to electrophysiological studies in the transplantation group. Therefore, the transplantation of hNSPCs into cervical SCI is safe and well-tolerated and is of modest neurological benefit up to 1 year after transplants. This trial is registered with Clinical Research Information Service (CRIS), Registration Number: KCT0000879. Ji Cheol Shin, Keung Nyun Kim, Jeehyun Yoo, Il-Sun Kim, Seokhwan Yun, Hyejin Lee, Kwangsoo Jung, Kyujin Hwang, Miri Kim, Il-Shin Lee, Jeong Eun Shin, and Kook In Park Copyright © 2015 Ji Cheol Shin et al. All rights reserved. The Effects of Exercise on Cognitive Recovery after Acquired Brain Injury in Animal Models: A Systematic Review Mon, 05 Oct 2015 09:47:59 +0000 The objective of the present paper is to review the current status of exercise as a tool to promote cognitive rehabilitation after acquired brain injury (ABI) in animal model-based research. Searches were conducted on the PubMed, Scopus, and psycINFO databases in February 2014. Search strings used were: exercise (and) animal model (or) rodent (or) rat (and) traumatic brain injury (or) cerebral ischemia (or) brain irradiation. Studies were selected if they were (1) in English, (2) used adult animals subjected to acquired brain injury, (3) used exercise as an intervention tool after inflicted injury, (4) used exercise paradigms demanding movement of all extremities, (5) had exercise intervention effects that could be distinguished from other potential intervention effects, and (6) contained at least one measure of cognitive and/or emotional function. Out of 2308 hits, 22 publications fulfilled the criteria. The studies were examined relative to cognitive effects associated with three themes: exercise type (forced or voluntary), timing of exercise (early or late), and dose-related factors (intensity, duration, etc.). The studies indicate that exercise in many cases can promote cognitive recovery after brain injury. However, the optimal parameters to ensure cognitive rehabilitation efficacy still elude us, due to considerable methodological variations between studies. Elise Wogensen, Hana Malá, and Jesper Mogensen Copyright © 2015 Elise Wogensen et al. All rights reserved. Spinal Cord Hemisection Facilitates Aromatic L-Amino Acid Decarboxylase Cells to Produce Serotonin in the Subchronic but Not the Chronic Phase Sun, 04 Oct 2015 06:42:13 +0000 Neuromodulators, such as serotonin (5-hydroxytryptamine, 5-HT) and noradrenalin, play an essential role in regulating the motor and sensory functions in the spinal cord. We have previously shown that in the rat spinal cord the activity of aromatic L-amino acid decarboxylase (AADC) cells to produce 5-HT from its precursor (5-hydroxytryptophan, 5-HTP) is dramatically increased following complete spinal cord transection. In this study, we investigated whether a partial loss of 5-HT innervation could similarly increase AADC activity. Adult rats with spinal cord hemisected at thoracic level (T11/T12) were used with a postoperation interval at 5 days or 60 days. Using immunohistochemistry, first, we observed a significant reduction in the density of 5-HT-immunoreactive fibers in the spinal cord below the lesion on the injured side for both groups. Second, we found that the AADC cells were similarly expressed on both injured and uninjured sides in both groups. Third, increased production of 5-HT in AADC cells following 5-HTP was seen in 5-day but not in 60-day postinjury group. These results suggest that plastic changes of the 5-HT system might happen primarily in the subchronic phase and for longer period its function could be compensated by plastic changes of other intrinsic and/or supraspinal modulation systems. Bushra Azam, Jacob Wienecke, Dennis Bo Jensen, Aleena Azam, and Mengliang Zhang Copyright © 2015 Bushra Azam et al. All rights reserved. Contralateral Metabolic Activation Related to Plastic Changes in the Spinal Cord after Peripheral Nerve Injury in Rats Mon, 28 Sep 2015 08:43:23 +0000 We have previously reported the crossed-withdrawal reflex in which the rats with nerve injury developed behavioral pain responses of the injured paw to stimuli applied to the contralateral uninjured paw. This reflex indicates that contralateral plastic changes may occur in the spinal cord after unilateral nerve injury. The present study was performed to elucidate the mechanisms and morphological correlates underlying the crossed-withdrawal reflex by using quantitative 14C-2-deoxyglucose (2-DG) autoradiography which can examine metabolic activities and spatial patterns simultaneously. Under pentobarbital anesthesia, rats were subjected to unilateral nerve injury. Mechanical allodynia was tested for two weeks after nerve injury. After nerve injury, neuropathic pain behaviors developed progressively. The crossed-withdrawal reflex was observed at two weeks postoperatively. Contralateral enhancement of 2-DG uptake in the ventral horn of the spinal cord to electrical stimulation of the uninjured paw was observed. These results suggest that the facilitation of information processing from the uninjured side to the injured side may contribute to the crossed-withdrawal reflex by plastic changes in the spinal cord of nerve-injured rats. Ran Won and Bae Hwan Lee Copyright © 2015 Ran Won and Bae Hwan Lee. All rights reserved. Cortical Excitability Measured with nTMS and MEG during Stroke Recovery Sun, 27 Sep 2015 07:29:11 +0000 Objective. Stroke alters cortical excitability both in the lesioned and in the nonlesioned hemisphere. Stroke recovery has been studied using transcranial magnetic stimulation (TMS). Spontaneous brain oscillations and somatosensory evoked fields (SEFs) measured by magnetoencephalography (MEG) are modified in stroke patients during recovery. Methods. We recorded SEFs and spontaneous MEG activity and motor threshold (MT) short intracortical inhibition (SICI) and intracortical facilitation (ICF) with navigated TMS (nTMS) at one and three months after first-ever hemispheric ischemic strokes. Changes of MEG and nTMS parameters attributed to gamma-aminobutyrate and glutamate transmission were compared. Results. ICF correlated with the strength and extent of SEF source areas depicted by MEG at three months. The nTMS MT and event-related desynchronization (ERD) of beta-band MEG activity and SICI and the beta-band MEG event-related synchronization (ERS) were correlated, but less strongly. Conclusions. This first report using sequential nTMS and MEG in stroke recovery found intra- and interhemispheric correlations of nTMS and MEG estimates of cortical excitability. ICF and SEF parameters, MT and the ERD of the lesioned hemisphere, and SICI and ERS of the nonlesioned hemisphere were correlated. Covarying excitability in the lesioned and nonlesioned hemispheres emphasizes the importance of the hemispheric balance of the excitability of the sensorimotor system. Jyrki P. Mäkelä, Pantelis Lioumis, Kristina Laaksonen, Nina Forss, Turgut Tatlisumak, Markku Kaste, and Satu Mustanoja Copyright © 2015 Jyrki P. Mäkelä et al. All rights reserved. Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury Sun, 20 Sep 2015 09:50:16 +0000 The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain. Jeongsoo Han, Minjee Kwon, Myeounghoon Cha, Motomasa Tanioka, Seong-Karp Hong, Sun Joon Bai, and Bae Hwan Lee Copyright © 2015 Jeongsoo Han et al. All rights reserved. Reactive Oxygen Species Donors Increase the Responsiveness of Dorsal Horn Neurons and Induce Mechanical Hyperalgesia in Rats Sun, 20 Sep 2015 09:33:40 +0000 Our previous studies suggest that reactive oxygen species (ROS) scavengers have analgesic effect on neuropathic pain through spinal mechanisms in the rat. The studies suggest that superoxide in spinal cord is one of important mediators of persistent pain. To test the hypothesis that increase of superoxide-derived intermediates leads to central sensitization and pain, the effects of an intrathecal injection of chemical ROS donors releasing either , , or H2O2 were examined on pain behaviors. Following treatment with t-BOOH ( donor), dorsal horn neuron responses to mechanical stimuli in normal rats and the changes of neuronal excitability were explored on substantia gelatinosa (SG) neurons using whole-cell patch clamping recordings. Intrathecal administration of t-BOOH or NaOCl ( donor), but not H2O2, significantly decreased mechanical thresholds of hind paws. The responses of wide dynamic range neurons to mechanical stimuli increased after a local application of t-BOOH. The t-BOOH increased the frequency and the amplitude of excitatory postsynaptic potentials, depolarized membrane potential in SG neurons, and increased the frequency of action potentials evoked by depolarizing current pulses. These results suggest that elevated ROS, especially , in the spinal cord sensitized dorsal horn neurons and produced hyperalgesia in normal rats. Hee Young Kim, Inhyung Lee, Sang Woo Chun, and Hee Kee Kim Copyright © 2015 Hee Young Kim et al. All rights reserved. Modulation of Spinal GABAergic Inhibition and Mechanical Hypersensitivity following Chronic Compression of Dorsal Root Ganglion in the Rat Mon, 14 Sep 2015 07:56:19 +0000 Chronic compression of dorsal root ganglion (CCD) results in neuropathic pain. We investigated the role of spinal GABA in CCD-induced pain using rats with unilateral CCD. A stereological analysis revealed that the proportion of GABA-immunoreactive neurons to total neurons at L4/5 laminae I–III on the injured side decreased in the early phase of CCD (post-CCD week 1) and then returned to the sham-control level in the late phase (post-CCD week 18). In the early phase, the rats showed an increase in both mechanical sensitivity of the hind paw and spinal WDR neuronal excitability on the injured side, and such increase was suppressed by spinally applied muscimol (GABA-A agonist, 5 nmol) and baclofen (GABA-B agonist, 25 nmol), indicating the reduced spinal GABAergic inhibition involved. In the late phase, the CCD-induced increase in mechanical sensitivity and neuronal excitability returned to pre-CCD levels, and such recovered responses were enhanced by spinally applied bicuculline (GABA-A antagonist, 15 nmol) and CGP52432 (GABA-B antagonist, 15 nmol), indicating the regained spinal GABAergic inhibition involved. In conclusion, the alteration of spinal GABAergic inhibition following CCD and leading to a gradual reduction over time of CCD-induced mechanical hypersensitivity is most likely due to changes in GABA content in spinal GABA neurons. Moon Chul Lee, Taick Sang Nam, Se Jung Jung, Young S. Gwak, and Joong Woo Leem Copyright © 2015 Moon Chul Lee et al. All rights reserved. PKA Inhibitor H89 (N-[2-p-bromocinnamylamino-ethyl]-5-isoquinolinesulfonamide) Attenuates Synaptic Dysfunction and Neuronal Cell Death following Ischemic Injury Sun, 13 Sep 2015 12:59:09 +0000 The cyclic AMP-dependent protein kinase (PKA), which activates prosurvival signaling proteins, has been implicated in the expression of long-term potentiation and hippocampal long-term memory. It has come to light that H89 commonly known as the PKA inhibitor have diverse roles in the nervous system that are unrelated to its role as a PKA inhibitor. We have investigated the role of H89 in ischemic and reperfusion injury. First, we examined the expression of postsynaptic density protein 95 (PSD95), microtubule-associated protein 2 (MAP2), and synaptophysin in mouse brain after middle cerebral artery occlusion injury. Next, we examined the role of H89 pretreatment on the expression of brain-derived neurotrophic factor (BDNF), PSD95, MAP2, and the apoptosis regulators Bcl2 and cleaved caspase-3 in cultured neuroblastoma cells exposed to hypoxia and reperfusion injury. In addition, we investigated the alteration of AKT activation in H89 pretreated neuroblastoma cells under hypoxia and reperfusion injury. The data suggest that H89 may contribute to brain recovery after ischemic stroke by regulating neuronal death and proteins related to synaptic plasticity. Juhyun Song, So Yeong Cheon, Won Taek Lee, Kyung Ah Park, and Jong Eun Lee Copyright © 2015 Juhyun Song et al. All rights reserved. Statins Promote Long-Term Recovery after Ischemic Stroke by Reconnecting Noradrenergic Neuronal Circuitry Thu, 10 Sep 2015 14:33:40 +0000 Inhibitors of HMG-CoA reductase (statins), widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term. After ischemic stroke, cardiac autonomic dysfunction and psychological problems are common complications related to deficits in the noradrenergic (NA) system. This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI). Using the wheat germ agglutinin (WGA) transgene technique combined with the recombinant adenoviral vector system, NA-specific neuronal pathways were labeled, and were identified in the locus coeruleus (LC), where NA neurons originate. NA circuitry in the atorvastatin-treated group recovered faster than in the vehicle-treated group. The damaged NA circuitry was partly reorganized with the gradual recovery of autonomic dysfunction and neurobehavioral deficit. Newly proliferated cells might contribute to reorganizing NA neurons and lead anatomic and functional recovery of NA neurons. Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function. Kyoung Joo Cho, So Young Cheon, and Gyung Whan Kim Copyright © 2015 Kyoung Joo Cho et al. All rights reserved. Altered Recruitment of the Attention Network Is Associated with Disability and Cognitive Impairment in Pediatric Patients with Acquired Brain Injury Thu, 10 Sep 2015 09:50:35 +0000 We assessed abnormalities of brain functional magnetic resonance imaging (fMRI) activity during a sustained attention task (Conners’ Continuous Performance Test (CCPT)) in 20 right-handed pediatric acquired brain injury (ABI) patients versus 7 right-handed age-matched healthy controls, and we estimated the correlation of such abnormalities with clinical and cognitive deficits. Patients underwent the Wechsler Intelligence Scale for Children (WISC), Wisconsin Card Sorting Test, and Functional Independence Measure (FIM) evaluations. During fMRI, patients and controls activated regions of the attention network. Compared to controls, ABI patients experienced a decreased average fMRI recruitment of the left cerebellum and a decreased deactivation of the left anterior cingulate cortex. With increasing task demand, compared to controls, ABI patients had an impaired ability to increase the recruitment of several posterior regions of the attention network. They also experienced a greater activation of frontal regions, which was correlated with worse performance on FIM, WISC, and fMRI CCPT. Such abnormal brain recruitment was significantly influenced by the type of lesion (focal versus diffuse axonal injury) and time elapsed from the event. Pediatric ABI patients experienced an inability to optimize attention network recruitment, especially when task difficulty was increased, which likely contributes to their clinical and cognitive deficits. Sandra Strazzer, Maria A. Rocca, Erika Molteni, Ermelinda De Meo, Monica Recla, Paola Valsasina, Filippo Arrigoni, Susanna Galbiati, Alessandra Bardoni, and Massimo Filippi Copyright © 2015 Sandra Strazzer et al. All rights reserved. Audiomotor Integration in Minimally Conscious State: Proof of Concept! Thu, 03 Sep 2015 06:36:41 +0000 Patients suffering from chronic disorders of consciousness (DOC) are characterized by profound unawareness and an impairment of large-scale cortical and subcortical connectivity. In this study, we applied an electrophysiological approach aimed at identifying the residual audiomotor connectivity patterns that are thought to be linked to awareness. We measured some markers of audiomotor integration (AMI) in 20 patients affected by DOC, before and after the application of a repetitive transcranial magnetic stimulation protocol (rTMS) delivered over the left primary motor area (M1), paired to a transauricular alternating current stimulation. Our protocol induced potentiating of the electrophysiological markers of AMI and M1 excitability, paired to a clinical improvement, in all of the patients with minimally conscious state (MCS) but in none of those suffering from unresponsive wakefulness syndrome (UWS). Our protocol could be a promising approach to potentiate the functional connectivity within large-scale audiomotor networks, thus allowing clinicians to differentiate patients affected by MCS from UWS, besides the clinical assessment. Antonino Naro, Antonino Leo, Antonino Cannavò, Antonio Buda, Rocco Bruno, Carlo Salviera, Placido Bramanti, and Rocco Salvatore Calabrò Copyright © 2015 Antonino Naro et al. All rights reserved. Corrigendum to “Efficacy and Interindividual Variability in Motor-Cortex Plasticity following Anodal tDCS and Paired-Associative Stimulation” Wed, 02 Sep 2015 10:11:04 +0000 Wolfgang Strube, Tilmann Bunse, Berend Malchow, and Alkomiet Hasan Copyright © 2015 Wolfgang Strube et al. All rights reserved. Brain and Behavior Plasticity: From Fundamental Science to Health Outcomes Tue, 01 Sep 2015 07:54:43 +0000 Keh-chung Lin, Steven L. Wolf, Chetwyn Chan, Ching-yi Wu, and Ching-Po Lin Copyright © 2015 Keh-chung Lin et al. All rights reserved. Neural Plastic Effects of Cognitive Training on Aging Brain Mon, 31 Aug 2015 09:39:16 +0000 Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group () and the Active Control Group (). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age. Natalie T. Y. Leung, Helena M. K. Tam, Leung W. Chu, Timothy C. Y. Kwok, Felix Chan, Linda C. W. Lam, Jean Woo, and Tatia M. C. Lee Copyright © 2015 Natalie T. Y. Leung et al. All rights reserved. Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy Mon, 31 Aug 2015 09:28:14 +0000 Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ES-assisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.) Ying-Zu Huang, Yao-Shun Chang, Miao-Ju Hsu, Alice M. K. Wong, and Ya-Ju Chang Copyright © 2015 Ying-Zu Huang et al. All rights reserved. Coincidence Anticipation Timing Performance during an Acute Bout of Brisk Walking in Older Adults: Effect of Stimulus Speed Mon, 31 Aug 2015 09:15:45 +0000 This study examined coincidence anticipation timing (CAT) performance at slow and fast stimulus speeds before, during, and after an acute bout of walking in adults aged 60–76 years. Results from a series of repeated measures ANOVAs indicated significant rest versus exercise × stimulus speed × time interactions for absolute and variable errors (both ) whereby absolute and variable error scores, when stimulus speed was slow, improved as the duration of exercise increased. When stimulus speed was fast there were significantly greater absolute and variable errors at 18 minutes of the walking bout. There was also greater error at 18 minutes during walking compared to rest. These results suggest that, in a task involving walking and CAT, stimulus speeds plays an important role; specifically walking (exercise) enhances CAT performance at slow stimulus speeds but reduces CAT performance at fast stimulus speeds. The implications are that in everyday situations, where events require dual-task responses to be made at different speeds, for example, walking on the pavement whilst avoiding a crowd, compared to crossing a busy road, an understanding of how different stimulus speeds influence dual-task performance is extremely important, particularly in the older adult population. Michael J. Duncan, Michelle Stanley, Mike Smith, Michael J. Price, and Sheila Leddington Wright Copyright © 2015 Michael J. Duncan et al. All rights reserved.