Restorative Neurology and Neuroscience - Volume 35, issue 2

Authors: Kim, Min Sun | Koo, Ho | Han, Sang Who | Paulus, Walter | Nitsche, Michael A. | Kim, Yun-Hee | Yoon, Jin A | Shin, Yong-Il

Article Type: Research Article

Abstract: Background: Anodal transcranial direct current stimulation (A-tDCS) induces a long-lasting increase in cortical excitability that can increase gene transcription in the brain. Objective: The purpose of this study was to evaluate the expression of genes related to activity-dependent neuronal plasticity in the sensorimotor cortex and hippocampus of young Sprague-Dawley rats following A-tDCS. Methods: We applied A-tDCS over the right sensorimotor cortex epicranially with a circular electrode (3 mm diameter) at 250 μA for 20 min per day for 7 consecutive days. Levels of mRNA for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), synapsin I, Ca2+ …/calmodulin-dependent protein kinase II (CaMKII), activity-regulated cytoskeleton-associated protein (Arc), and c-Fos were analyzed using SYBR Green quantitative real-time polymerase chain reaction (PCR). Results: We found that 7 days of unilateral A-tDCS resulted in significant increases in transcription of all plasticity-related genes tested in the ipsilateral cortex. Daily A-tDCS also resulted in a significant increase in c-Fos mRNA in the ipsilateral hippocampus. Conclusion: These results indicate that altered expression of plasticity-associated genes in the cortex and hippocampus is a molecular substrate of A-tDCS-induced neural plasticity. Show more

Keywords: Anodal transcranial direct current stimulation, immediate-early genes, somatosensory cortex, synaptic plasticity-related genes

DOI: 10.3233/RNN-160689

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 137-146, 2017

Authors: Alekseichuk, Ivan | Pabel, Stefanie Corinna | Antal, Andrea | Paulus, Walter

Article Type: Research Article

Abstract: Background: There is a growing interest in large-scale connectivity as one of the crucial factors in working memory. Correlative evidence has revealed the anatomical and electrophysiological players in the working memory network, but understanding of the effective role of their connectivity remains elusive. Objective: In this double-blind, placebo-controlled study we aimed to identify the causal role of theta phase connectivity in visual-spatial working memory. Methods: The frontoparietal network was over- or de-synchronized in the anterior-posterior direction by multi-electrode, 6 Hz transcranial alternating current stimulation (tACS). Results: A decrease in memory performance and increase in …reaction time was caused by frontoparietal intrahemispheric desynchronization. According to the diffusion drift model, this originated in a lower signal-to-noise ratio, known as the drift rate index, in the memory system. The EEG analysis revealed a corresponding decrease in phase connectivity between prefrontal and parietal areas after tACS-driven desynchronization. The over-synchronization did not result in any changes in either the behavioral or electrophysiological levels in healthy participants. Conclusion: Taken together, we demonstrate the feasibility of manipulating multi-site large-scale networks in humans, and the disruptive effect of frontoparietal desynchronization on theta phase connectivity and visual-spatial working memory. Show more

Keywords: Connectivity, frontoparietal network, theta rhythm, tACS, working memory, EEG

DOI: 10.3233/RNN-160714

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 147-158, 2017

Authors: da Silva, Fabiana Tenório Gomes | Browne, Rodrigo Alberto Vieira | Pinto, Camila Bonin | Saleh Velez, Faddi Ghassan | do Egito, Eryvaldo Sócrates Tabosa | do Rêgo, Jeferson Tafarel Pereira | da Silva, Marília Rodrigues | Dantas, Paulo Moreira Silva | Fregni, Felipe

Article Type: Research Article

Abstract: Background: We hypothesized in this study that transcranial direct current stimulation (tDCS) of primary motor cortex could exert top-down modulation over subcortical systems associated with autonomic control and thus be useful to revert some of the dysfunctional changes found in the autonomic nervous system (ANS) of subjects with spinal cord injuries (SCI). Objective: To explore the acute effect of tDCS on ANS indexed by Heart Rate Variability (HRV) in individuals with SCI and analyze whether this effect depends on the gender, degree, level and time of injury. Methods: In this randomized, placebo-controlled, crossover, double-blinded study, …18 adults with SCI (32.9±7.9 years old) were included; the intervention consisted of a single 12-minute session of active tDCS (anodal, 2 mA) and a control session of sham tDCS applied over Cz (bihemispheric motor cortex). HRV was calculated using spectral analysis. Low-frequency (LF), high-frequency (HF), and LF/HF ratio variables were evaluated before, during, and post tDCS. Results: A two-way repeated measures ANOVA showed that after active (anodal) stimulation, LF/HF ratio was significantly increased (P  = 0.013). There was a trend for an interaction between time and stimulation for both LF and HF (P  = 0.052). Paired exploratory t -tests reported effects on the difference of time [post–pre] between stimulation conditions for LF (P  = 0.052), HF (P  = 0.052) and LF/HF (P  = 0.003). Conclusion: Anodal tDCS of the motor cortex modulated ANS activity in individuals with SCI independent of gender, type and time of lesion. These changes were in the direction of normalization of ANS parameters, thus confirming our initial hypothesis that an enhancement of cortical excitability by tDCS could at least partially restore some of the dysfunctional activity in the ANS system of subjects with SCI. Show more

Keywords: Transcranial direct current stimulation, autonomic nervous system, spinal cord injury, heart rate variability

DOI: 10.3233/RNN-160685

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 159-169, 2017

Authors: Robert, Maxime T. | Sambasivan, Krithika | Levin, Mindy F.

Article Type: Research Article

Abstract: Background : Improvment of upper limb motor skills occurs through motor learning that can be enhanced by providing extrinsic feedback. Different types and frequencies of feedback are discussed but specific guidelines for use of feedback for motor learning in typically-developing (TD) children and children with Cerebral Palsy (CP) are not available. Objective: Identify the most effective modalities and frequencies of feedback for improving upper limb motor skills in TD children and children with CP. Methods : Ovid MEDLINE, Cochrane, PEDro and PubMed-NCBI were searched from 1950 to December 2015 to identify English-language articles addressing the role of …extrinsic feedback on upper limb motor learning in TD children and children with CP. Nine studies were selected with a total of 243 TD children and 102 children with CP. Study quality was evaluated using the Downs and Black scale and levels of evidence were determined with Sackett’s quality ratings. Results: There was a lack of consistency in the modalities and frequencies of feedback delivery used to improve motor learning in TD children and in children with CP. Moreover, the complexity of the task to be learned influenced the degree of motor learning achieved. Conclusion: A better understanding of the influence of feedback on motor learning is needed to optimize motor skill acquisition in children with CP. Show more

Keywords: Feedback, children, motor learning, upper limb, review

DOI: 10.3233/RNN-160688

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 171-184, 2017

Authors: Manthou, Marilena | Abdulla, Diana Saad Yousif | Pavlov, Stoyan Pavlov | Jansen, Ramona | Bendella, Habib | Nohroudi, Klaus | Stein, Gregor | Meyer, Carolin | Ozsoy, Ozlem | Ozsoy, Umut | Behram Kandemir, Yasemin | Sarikcioglu, Levent | Semler, Oliver | Schoenau, Eckhard | Dunlop, Sarah | Angelov, Doychin Nikolov

Article Type: Research Article

Abstract: Background: Following spinal cord injury (SCI), exercise training provides a wide range of benefits and promotes activity-dependent synaptic plasticity. Whole body vibration (WBV) in SCI patients improves walking and spasticity as well as bone and muscle mass. However, little is known about the effects of timing or frequency of intervention. Objective: To determine which WBV-onset improves locomotor and bladder functions and influences synaptic plasticity beneficially. Methods: SCI was followed by WBV starting 1, 7, 14, 28 days after injury (WBV1, WBV7, etc.) and continued for 12 weeks. Intact animals and those receiving SCI but no …WBV (No WBV), SCI plus WBV twice daily (2×WBV) and SCI followed by passive hindlimb flexion-extension (PFE) served as controls. Locomotor [BBB rating, foot stepping angle (FSA) and rump-height index (RHI)] as well as bladder function were determined at 1, 3, 6, 9, and 12 weeks. Following perfusion fixation at 12 weeks, lesion volume and immunofluorescence for astrogliosis (GFAP), microglia (IBA1) and synaptic vesicles (synaptophysin, SYN) were determined. Results: Compared to the No WBV group, the WB7 and WBV14 groups showed significantly faster speeds of BBB score recovery though this effect was temporary. Considering RHI we detected a sustained improvement in the WBV14 and PFE groups. Bladder function was better in the WBV14, WBV28, 2×WBV and PFE groups. Synaptophysin levels improved in response to WBV7 and WBV14, but worsened after WBV28 in parallel to an increased IBA1 expression. Correlation- and principal components analysis revealed complex relationships between behavioural (BBB, FSA, RHI) and morphological (GFAP, IBA1, SYN) measurements. Conclusions: WBV started 14 days after SCI provides the most benefit (RHI, bladder); starting at 1day after SCI provides no benefit and starting at 28 days may be detrimental. Increasing the intensity of WBV to twice daily did not provide additional benefit. Show more

Keywords: Spinal cord injury, whole body vibration, synaptic plasticity, locomotor and bladder function recovery, astroglia, microglia, immunofluorescence

DOI: 10.3233/RNN-160691

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 185-216, 2017

Authors: Chen, Wei | Guo, Yijun | Yang, Wenjin | Zheng, Ping | Zeng, Jinsong | Tong, Wusong

Article Type: Research Article

Abstract: Background: Oxidative stress is an important factor in the pathophysiologic changes after traumatic brain injury (TBI). Connexin43 (Cx43) was reported to contribute to cerebral damage. However, the impacts of Cx40 have not been investigated in detail. Objective: In the present study, we hypothesized that Cx40 was involved in oxidative stress-induced brain injury after TBI. Methods : The controlled cortical impact (CCI) model was introduced to Wistar rats as a TBI model. Neurological deficits, oxidative stress and Cx40 were evaluated in TBI rats and N-acetylcysteine (NAC)-treated TBI rats. Neurological severity score (NSS) was used to assess neurological …deficits. Brain infarction was measured by histo-staining. Brain edema was evaluated by measuring the brain water content. Cortex samples were collected to measure the tissue levels of malonyldialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) and NADPH oxidase activity. Cx40 expression was determined by Western-blot. Results: TBI-induced brain injuries gradually increased from 6 h to 24 h post CCI, and the severity remained till 72 h. The level of oxidative stress was consistent with the extent of neurological deficits. Cx40 was upregulated after TBI in a linear correlated manner with increased oxidative stress. With NAC intervention, both neurological deficits and oxidative stress were significantly attenuated. Meanwhile, elevated Cx40 expression in cortex was also prevented by NAC treatment. Conclusion : These studies revealed the relationship between levels of Cx40 and oxidative stress after TBI. The cortex Cx40 expression was positively correlated with the cerebral oxidative stress, indicating the involvement of Cx40 in the progress of brain damage. Show more

Keywords: Traumatic brain injury (TBI), connexin40, oxidative stress

DOI: 10.3233/RNN-160705

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 217-224, 2017

Authors: Buchs, Galit | Simon, Noa | Maidenbaum, Shachar | Amedi, Amir

Article Type: Research Article

Abstract: Background: One of the most stirring statistics in relation to the mobility of blind individuals is the high rate of upper body injuries, even when using the white-cane. Objective: We here addressed a rehabilitation- oriented challenge of providing a reliable tool for blind people to avoid waist-up obstacles, namely one of the impediments to their successful mobility using currently available methods (e.g., white-cane). Methods: We used the EyeCane, a device we developed which translates distances from several angles to haptic and auditory cues in an intuitive and unobtrusive manner, serving both as a primary and …secondary mobility aid. We investigated the rehabilitation potential of such a device in facilitating visionless waist-up body protection. Results: After ∼5 minutes of training with the EyeCane blind participants were able to successfully detect and avoid obstacles waist-high and up. This was significantly higher than their success when using the white-cane alone. As avoidance of obstacles required participants to perform an additional cognitive process after their detection, the avoidance rate was significantly lower than the detection rate. Conclusion: Our work has demonstrated that the EyeCane has the potential to extend the sensory world of blind individuals by expanding their currently accessible inputs, and has offered them a new practical rehabilitation tool. Show more

Keywords: Blind, assistive technology, mobility aid, active sensing, multisensory, mobility

DOI: 10.3233/RNN-160686

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 225-235, 2017

Authors: Lussier, Maxime | Bugaiska, Aurélia | Bherer, Louis

Article Type: Research Article

Abstract: Purpose: Past divided attention training studies in older adults have suggested that variable priority training (VPT) tends to show larger improvement than fixed priority training (FPT). However, it remains unclear whether VPT leads to larger transfer effects. Methods: In this study, eighty-three older adults aged between 55 and 65 received five 1-hour sessions of VPT, FPT or of an active placebo. VPT and FPT subjects trained on a complex dual-task condition with variable stimulus timings in order to promote more flexible and self-guided strategies with regard to attentional priority devoted to the concurrent tasks. Real-time individualized feedback …was provided to encourage improvement. The active placebo group attended computer classes. Near and far modality transfer tasks were used to assess the generalization of transfer effects. Results: Results showed that VPT induced significantly larger transfer effects than FPT on a near modality transfer task. Evidence for larger transfer effects in VPT than FPT on a far modality transfer task was also observed. Furthermore, the superiority of VPT on FPT in transfer effects was specific to the ability to coordinate two concurrent tasks. Conclusions: Results of this study help better understand the benefits of VPT attentional training on transfer effects, which is an essential outcome for cognitive training effectiveness and relevancy. Show more

Keywords: Cognitive training, transfer, divided attention, variable priority training, older adults

DOI: 10.3233/RNN-150581

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 237-250, 2017

Authors: Flygt, Johanna | Clausen, Fredrik | Marklund, Niklas

Article Type: Research Article

Abstract: Background: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI. Objective: We hypothesized that central fluid percussion injury (cFPI) in mice, a TBI model causing wide-spread axonal injury, results in OPC proliferation. Methods: Proliferation of OPCs was evaluated …in 27 cFPI mice using 5-ethynyl-2′-deoxyuridine (EdU) labeling and a cell proliferation assay at 2 (n  = 9), 7 (n  = 8) and 21 (n  = 10) days post injury (dpi). Sham-injured mice (n  = 14) were used as controls. OPC proliferation was quantified by immunohistochemistry using the OPC markers NG2 and Olig2 in several white matter loci including the corpus callosum, external capsule, fimbriae, the internal capsule and cerebral peduncle. Results: The number of EdU/DAPI/Olig2-positive cells were increased in the cFPI group compared to sham-injured animals at 7 days post-injury (dpi; p ≤0.05) in the majority of white matter regions. The OPC proliferation had subsided by 21 dpi. The number of EdU/DAPI/NG2 cells was also increase at 7 dpi in the external capsule and fimbriae. Conclusion: These results suggest that traumatic axonal injury in the mouse induces a transient proliferative response of residing OPCs. These proliferating OPCs may replace dead oligodendrocytes and contribute to remyelination, which needs evaluation in future studies. Show more

Keywords: Traumatic brain injury, axonal injury, proliferation, EdU, oligodendrocyte progenitor cells, white matter, myelin, fluid percussion

DOI: 10.3233/RNN-160675

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 251-263, 2017