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This interdisciplinary journal publishes papers relating the plasticity and response of the nervous system to accidental or experimental injuries and their interventions, transplantation, neurodegenerative disorders and experimental strategies to improve regeneration or functional recovery and rehabilitation.
Experimental and clinical research papers adopting fresh conceptual approaches are encouraged. The overriding criteria for publication are novelty, significant experimental or clinical relevance and interest to a multidisciplinary audience.
Authors: Chang, Won Hyuk | Kim, Hyun | Sun, Woong | Kim, Joo Yeon | Shin, Yong-Il | Kim, Yun-Hee
Article Type: Research Article
Abstract: Purpose: Previous studies demonstrated that administering extradural cortical stimulation (ECS) to rats during the acute phase of a photothrombotic infarct enhances motor recovery. However, the effect of ECS during the subacute phase was unknown. We aimed to evaluate the effects of ECS on motor recovery in a rat model of subacute photothrombotic stroke. Methods: Photothrombotic ischemic injury to the left sensorimotor cortex (SMC) was induced in 41 male Sprague-Dawley rats using Rose-bengal dye (20 mg/kg) and cold light. The rats were randomly divided into two groups: ECS on infarcted SMC (ECS group) and no ECS on …infarcted SMC (non-stimulated group). The ECS group received continuous ECS for 14 days starting from day 5 after the stroke onset. Behavioral training with the single-pellet reaching task (SPRT) was performed daily for all of the rats from the fifth day after stroke onset. After 19 days, brain sections were immunostained to allow the quantification of infarct volumes and the evaluation of the neuronal markers. Results: The SPRT scores showed significantly faster and greater improvement in the ECS group than in the non-stimulated group. There were no significant differences in infarct size. However, in the ECS group, significantly more doublecortin-labeled cells were identified close to the penumbra region of the cerebral cortex. Conclusions: ECS in the subacute phase improved the behavior motor function in the stroke rat model, and induced a significant axonal sprouting in the peri-infarct area. Show more
Keywords: Axonal sprouting, extradural cortical stimulation, motor recovery, stroke
DOI: 10.3233/RNN-140445
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 589-596, 2015
Authors: Bocci, Tommaso | Santarcangelo, Enrica | Vannini, Beatrice | Torzini, Antonio | Carli, Giancarlo | Ferrucci, Roberta | Priori, Alberto | Valeriani, Massimiliano | Sartucci, Ferdinando
Article Type: Research Article
Abstract: Purpose: The cerebellum is involved in a wide number of integrative functions, but its role in pain experience and in the nociceptive information processing is poorly understood. In healthy volunteers we evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying the changes in the perceptive threshold, pain intensity at given stimulation intensities (VAS:0-10) and laser evoked potentials (LEPs) variables (N1 and N2/P2 amplitudes and latencies). Methods: Fifteen subjects were studied before and after anodal, cathodal and sham tcDCS. LEPs were obtained using a neodymium:yttrium–aluminium–perovskite (Nd:YAP) laser and recorded from the dorsum of …the left hand. VAS was evaluated by delivering laser pulses at two different intensities, respectively two and three times the perceptive threshold. Results: Cathodal polarization dampened significantly the perceptive threshold and increased the VAS score, while the anodal one had opposite effects. Cathodal tcDCS increased significantly the N1 and N2/P2 amplitudes and decreased their latencies, whereas anodal tcDCS elicited opposite effects. Motor thresholds assessed through transcranial magnetic stimulation were not affected by cerebellar stimulation. Conclusions: tcDCS modulates pain perception and its cortical correlates. Since it is effective on both N1 and N2/P2 components, we speculate that the cerebellum engagement in pain processing modulates the activity of both somatosensory and cingulate cortices. Present findings prompt investigation of the cerebellar direct current polarization as a possible novel and safe therapeutic tool in chronic pain patients. Show more
Keywords: Pain cerebellum, cerebellar direct current stimulation, tDCS, laser evoked potentials, pain modulation
DOI: 10.3233/RNN-140453
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 597-609, 2015
Authors: Tremblay, Sara | Vernet, Marine | Bashir, Shahid | Pascual-Leone, Alvaro | Théoret, Hugo
Article Type: Research Article
Abstract: Purpose: Recent studies investigating the effects of mild traumatic brain injury (mTBI) suggest the presence of unbalanced excitatory and inhibitory mechanisms within primary motor cortex (M1). Whether these abnormalities are associated with impaired synaptic plasticity remains unknown. Methods: The effects of continuous theta burst stimulation (cTBS) on transcranial magnetic stimulation-induced motor evoked potentials (MEPs) were assessed on average two weeks and six weeks following mTBI in five individuals. Results: The procedure was well-tolerated by all participants. Continuous TBS failed to induce a significant reduction of MEP amplitudes two weeks after the injury, …but response to cTBS normalized six weeks following injury, as a majority of patients became asymptomatic. Conclusions: These preliminary results suggest that cTBS can be used to assess M1 synaptic plasticity in subacute phase following mTBI and may provide insights into neurobiological substrates of symptoms and consequences of mTBI. Show more
Keywords: Traumatic brain injury, concussion, transcranial magnetic stimulation, plasticity, motor cortex
DOI: 10.3233/RNN-140459
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 611-620, 2015
Authors: Ernst, Alexandra | Blanc, Frédéric | De Seze, Jérôme | Manning, Liliann
Article Type: Research Article
Abstract: Purpose: The co-occurrence of autobiographical memory (AM) and episodic future thinking (EFT) impairment has been documented in relapsing-remitting multiple sclerosis (RR-MS) patients. On these bases, we aimed at probing the efficacy of a mental visual imagery (MVI)-based facilitation programme on AM and EFT functioning in the context of a randomised-controlled trial study in RR-MS patients. Methods: Using the Autobiographical Interview (AI), 40 patients presenting with an AM/EFT impairment were randomly assigned in three groups: (i) the experimental (n = 17), who followed the MVI programme, (ii) the verbal control (n = 10), who followed a sham verbal …programme, and (iii) the stability groups (n = 13), who underwent the AM/EFT test twice, with no intervention in between. Results: AI’s second assessment scores showed a significant improvement of AM and EFT performance only for the experimental group, with a long-term robustness of treatment benefits. Conclusions: The control and stability groups’ results ruled out nursing and test learning effects as explanations of AM/EFT improvement. These benefits were corroborated by the patients’ comments, which indicated an effective MVI strategy transfer to daily life. Our results suggest that the MVI programme tackles a common cognitive process of scene construction present in AM and EFT. Show more
Keywords: Autobiographical memory, episodic future thinking, neuropsychological rehabilitation, mental visual imagery, multiple sclerosis
DOI: 10.3233/RNN-140461
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 621-638, 2015
Authors: González-Tapia, David | Velázquez-Zamora, Dulce A. | Olvera-Cortés, María Esther | González-Burgos, Ignacio
Article Type: Research Article
Abstract: Purpose: The presynaptic stimulatory activity of parallel fibers on the dendritic spines of cerebellar Purkinje cells (PC) has a strong influence on the organization of motor learning. Motor learning has been shown to modify the synapses established on PC dendritic spines but the plastic changes of the different spine types, possibly underlying motor learning, have not been studied. Methods: Adult male Sprague-Dawley rats were trained daily for 26 days using an acrobatic paradigm (AC), at the end of which dendritic spine density and the proportion of the different types of spines was assessed. …Results: The learning curves of AC rats reflected a robust decrease in the latency for resolution and in the errors committed during the first week of training, which subsequently stabilized until the end of training. Dendritic spine density was greater in these AC rats, reflected in a larger proportion of thin, mushroom and stubby spines. Conclusions: Since thin spines are associated with acquiring novel information whilst mushroom spines are associated with long-term information storage, there appears to be a strong relationship between AC motor learning and consolidation. The increase in stubby spines could be related to the regulation of excitatory stimulation underlying motor overactivity. Show more
Keywords: Cerebellum, Purkinje, motor learning, plasticity, dendritic spines
DOI: 10.3233/RNN-140462
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 639-645, 2015
Authors: Làdavas, Elisabetta | Giulietti, Sara | Avenanti, Alessio | Bertini, Caterina | Lorenzini, Eleonora | Quinquinio, Cristina | Serino, Andrea
Article Type: Research Article
Abstract: Background and objective: The aim of the study is to compare the effects of multiple sessions of cathodal (c-tDCS) or anodal tDCS (a-tDCS) in modulating the beneficial effects of prism adaptation (PA) treatment in neglect patients. Methods: 30 neglect patients were submitted to 10 daily sessions of PA treatment. Patients were pseudo-randomly divided into 3 groups. In the c-tDCS-group, each PA session was coupled with 20 minutes of cathodal stimulation of the left, intact PPC; in the a-tDCS-group, anodal stimulation was applied to PPC of the damaged hemisphere; in the Sham group, sham stimulation was …applied. Neglect was evaluated before and after treatment with the Behavioral Inattention Test. Results: Combined tDCS-PA treatment induced stronger neglect improvement in the a-tDCS group as compared to the Sham group. No improvement was found in the c-tDCSgroup, with respect to that normally induced by PA and found in the Sham group. Conclusions: c-tDCS abolished neglect amelioration after PA, possibly because stimulation affected the sensorimotor network controlling prism adaptation. Instead, a-tDCS PPC boosted neglect amelioration after PA probably thanks to increased excitability of residual tissue in the lesioned hemisphere, which in turn might reduce dysfunctional over-excitability of the intact hemisphere. Show more
Keywords: Neglect, Prism Adaptation, tDCS
DOI: 10.3233/RNN-140464
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 647-662, 2015
Authors: Dutta, Anirban | Krishnan, Chandramouli | Kantak, Shailesh S. | Ranganathan, Rajiv | Nitsche, Michael A.
Article Type: Research Article
Abstract: Purpose: Recent evidence indicates that anodal transcranial direct current stimulation (tDCS) can selectively alter the EMG/force relationship of agonist arm muscles; however, the mechanisms mediating those changes are less clear. The purpose of this study was to evaluate the effect of anodal tDCS on motor unit synchronization by using a sophisticated non-linear EMG analysis called recurrence quantification analysis (RQA). Methods: Surface EMG signals were collected from the biceps brachii muscle of eighteen healthy young adults (9 tDCS and 9 control) at various force levels (12.5%, 25%, 37.5%, and 50% maximum) before and after the application …of anodal tDCS over the primary motor cortex. RQA was employed to quantify the changes in percentage of determinism (% DET) and laminarity (% LAM) of the surface EMG signals, which are surrogate measures of motor unit synchronization. Results: RQA analyses indicated that the changes in % DET and % LAM scores were significantly higher in the tDCS group than in the control group (p < 0.05) and this effect was particularly pronounced at higher force levels. Conclusion: The results of this study provide novel evidence supporting that anodal tDCS significantly alters motor unit firing strategies (i.e., the degree of synchronization) of the biceps brachii muscle. Show more
Keywords: Recurrence analysis, electromyography, nonlinear analysis, brain stimulation, motor unit, synchronization
DOI: 10.3233/RNN-140469
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 663-669, 2015
Authors: Calabrò, Rocco Salvatore | Naro, Antonino | Russo, Margherita | Leo, Antonino | Balletta, Tina | Saccá, Ileana | De Luca, Rosaria | Bramanti, Placido
Article Type: Research Article
Abstract: Background: Tilt-table equipped with the dynamic foot-support (ERIGO) and the functional electric stimulation could be a safe and suitable device for stabilization of vital signs, increasing patient’s motivation for further recovery, decreasing the duration of hospitalization, and accelerating the adaptation to vertical posture in bedridden patients with brain-injury. Moreover, it is conceivable that verticalization may improve cognitive functions, and induce plastic changes at sensory motor and vestibular system level that may in turn facilitate motor functional recovery. Objective: To test the safety and effectiveness of ERIGO treatment on motor and cognitive functions, cortical plasticity within …vestibular and sensory-motor systems in a bedridden post-stroke sample. Methods: 20 patients were randomly divided in two groups that performed ERIGO training (30 sessions) (G1) or physiotherapist-assisted verticalization training (same duration) (G2), beyond conventional neurorehabilitation treatment. Motor and cognitive functions as well as sensory-motor and vestibular system plasticity were investigated either before (T0 ) or after (T1 ) the rehabilitative protocols. Results: Both the verticalization treatments were well-tolerated. Notably, the G1 patients had a significant improvement in cognitive function (p = 0.03), global motor function (p = 0.006), sensory-motor (p < 0.001) and vestibular system plasticity (p = 0.02) as compared to G2. Conclusions: ERIGO training could be a valuable tool for the adaptation to the vertical position with a better global function improvement, as also suggested by the sensory-motor and vestibular system plasticity induction. Show more
Keywords: ERIGO, verticalization, stroke, vestibular system, sensory-motor plasticity, bedridden condition
DOI: 10.3233/RNN-140475
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 671-681, 2015
Authors: Gálvez, Javier | Estrada-Reyes, Rosa | Benítez-King, Gloria | Araujo, Gabriela | Orozco, Sandra | Fernández-Mas, Rodrigo | Almazán, Salvador | Calixto, Eduardo
Article Type: Research Article
Abstract: Purpose: Characterization of sedative, possible anticonvulsant, and protective effects of Acacetin-7-O -glucoside (7-ACAG). Methods: 7-ACAG was separated and its purity was analyzed. Its sedative and anti-seizure effects (1, 10, 20, and 40 mg/kg) were evaluated in male mice. Synaptic responses were acquired from area CA1 of hippocampal slices obtained from male Wistar rats. Rats were subjected to stereotaxic surgeries to allow Electroencephalographic (EEG) recordings. Functional recovery was evaluated by measuring the time rats spent in completing the motor task. Then the rats were subjected to right hemiplegia and administered 7-ACAG (40 mg/kg) 1 h or 24 h after surgery. …Brains of each group of rats were prepared for histological analysis. Results: Effective sedative doses of 7-ACAG comprised those between 20 and 40 mg/kg. Latency and duration of the epileptiform crisis were delayed by this flavonoid. 7-ACAG decreased the synaptic response in vitro , similar to Gamma-aminobutyric acid (GABA) effects. The flavonoid facilitated functional recovery. This data was associated with preserved cytoarchitecture in brain cortex and hippocampus. Conclusions: 7-ACAG possesses anticonvulsive and sedative effects. Results suggest that GABAergic activity and neuroprotection are involved in the mechanism of action of 7-ACAG and support this compound’s being a potential drug for treatment of anxiety or post-operative conditions caused by neurosurgeries. Show more
Keywords: Flavonoids, GABAA, hemiplegia, functional recovery
DOI: 10.3233/RNN-140486
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 683-700, 2015
Authors: Dettmers, Christian | Nedelko, Violetta | Ariel Schoenfeld, Mircea
Article Type: Research Article
Abstract: Purpose: Mental training appears to be an attractive tool in stroke rehabilitation. The objective of this study was to investigate whether any differences in the processing of action observation and imagery might exist between patients with left and right hemisphere subcortical strokes. Methods: Eighteen patients with strictly subcortical stroke (nine right-hemispheric) underwent a functional magnetic resonance imaging (fMRI) study with an experimental paradigm in which motor acts had to be observed and/or imagined from a first person perspective. Changes in hemodynamic activity were measured using fMRI. Results: The activity level was found …to be higher in the non-lesioned compared to the lesioned hemisphere. Patients with lesions in the left hemisphere had a higher activation level in visual (fusiform and lingual gyri), superior temporal areas and dorsal premotor regions across all performed comparisons than those with right hemisphere lesions. Furthermore they had more vivid imagery experiences and lower scores on the Stroke Impact Scale. Conclusions: Patients with left hemisphere subcortical lesions recruit more cortical regions in the processing of action pictures and videos. This recruitment was further enhanced during imagery. This is most likely related to the fact that the lesion touched the dominant hemisphere. Show more
Keywords: Motor observation, motor imagery, subcortical strokes, handedness, functional imaging
DOI: 10.3233/RNN-140487
Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 701-712, 2015
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