Restorative Neurology and Neuroscience - Volume 35, issue 5

Authors: Ray, Nicholas R. | O’Connell, Margaret A. | Nashiro, Kaoru | Smith, Evan T. | Qin, Shuo | Basak, Chandramallika

Article Type: Research Article

Abstract: Background: Many studies are currently researching the effects of video games, particularly in the domain of cognitive training. Great variability exists among video games however, and few studies have attempted to compare different types of video games. Little is known, for instance, about the cognitive processes or brain structures that underlie learning of different genres of video games. Objective: To examine the cognitive and neural underpinnings of two different types of game learning in order to evaluate their common and separate correlates, with the hopes of informing future intervention research. Methods: Participants (31 younger adults and …31 older adults) completed an extensive cognitive battery and played two different genres of video games, one action game and one strategy game, for 1.5 hours each. DTI scans were acquired for each participant, and regional fractional anisotropy (FA) values were extracted using the JHU atlas. Results: Behavioral results indicated that better performance on tasks of working memory and perceptual discrimination was related to enhanced learning in both games, even after controlling for age, whereas better performance on a perceptual speed task was uniquely related with enhanced learning of the strategy game. DTI results indicated that white matter FA in the right fornix/stria terminalis was correlated with action game learning, whereas white matter FA in the left cingulum/hippocampus was correlated with strategy game learning, even after controlling for age. Conclusion: Although cognition, to a large extent, was a common predictor of both types of game learning, regional white matter FA could separately predict action and strategy game learning. Given the neural and cognitive correlates of strategy game learning, strategy games may provide a more beneficial training tool for adults suffering from memory-related disorders or declines in processing speed, particularly older adults. Show more

Keywords: Video game, DTI, white matter, learning, cognition, aging

DOI: 10.3233/RNN-160716

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 437-456, 2017

Authors: Sun, Yefei | Sun, Xiaoyu | Qu, Huiling | Zhao, Shanshan | Xiao, Ting | Zhao, Chuansheng

Article Type: Research Article

Abstract: The brain can undergo self-repair and has the ability to compensate for functions lost after a stroke. The plasticity of the ischemic brain is influenced by several factors including aging and pharmacotherapy. Fluoxetine is an antidepressant which enhances serotonergic neurotransmission through selective inhibition of neuronal reuptake of serotonin. In clinical practice, fluoxetine alleviates the symptoms of post-stroke depression (PSD), helps motor recovery in stroke patients. In animal experiments, chronic administration of fluoxetine induces increased excitability of mature granule cells (GCs), enhancing axonal and dendritic reorganization, as well as promoting neurogenesis or angiogenesis in the dentate gurus (DG), but the effect …of fluoxetine in the subventricular zone (SVZ) remains controversial. Meanwhile, chronic treatment with fluoxetine did not reverse age-dependent suppression of proliferation cells in the DG. Interestingly, although fluoxetine has been found to enhance neurogenesis in the DG in stroke rats, this property is not consistent with the behavioral recovery. More studies into this issue will be required to reveal how to translate enhanced neuronal plasticity into behavioral benefits. This review provides an update of the current knowledge about the neurogenesis and the fate of the newly generated cells after the use of fluoxetine, as well as its ability to promote a behavioral recovery after stroke in clinical and experimental results and attempts to define the therapeutic properties of fluoxetine in regenerative neuroscience. Show more

Keywords: Fluoxetine, stroke, neuroplasticity, behavioral recovery

DOI: 10.3233/RNN-170725

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 457-468, 2017

Authors: Suárez, Isabel | Bodega, Guillermo | Rubio, Miguel | Fernández, Benjamín

Article Type: Research Article

Abstract: Purpose: The present work examines α-synuclein expression in the nigrostriatal system of a rat chronic hepatic encephalopathy model induced by portacaval anastomosis (PCA). There is evidence that dopaminergic dysfunction in disease conditions is strongly associated with such expression. Possible relationships among dopaminergic neurons, astroglial cells and α-synuclein expression were sought. Methods: Brain tissue samples from rats at 1 and 6 months post-PCA, and controls, were analysed immunohistochemically using antibodies against tyrosine hydroxylase (TH), α-synuclein, glial fibrillary acidic protein (GFAP) and ubiquitin (Ub). Results: In the control rats, TH immunoreactivity was detected in the neuronal cell bodies …and processes in the substantia nigra pars compacta (SNc). A dense TH-positive network of neurons was also seen in the striatum. In the PCA-exposed rats, however, a reduction in TH-positive neurons was seen at both 1 and 6 months in the SNc, as well as a reduction in TH-positive fibres in the striatum. This was coincident with the appearance of α-synuclein-immunoreactive neurons in the SNc; some of the TH-positive neurons also showed α-synuclein immunoreactivity. In addition, α-synuclein accumulation was seen in the SNc and striatum at both 1 and 6 months post-PCA, whereas α-synuclein was only mildly expressed in the nigrostriatal pathway of the controls. Astrogliosis was also seen following PCA, as revealed by increased GFAP expression from 1 month to 6 months post-PCA in both the SN and striatum. The astroglial activation level in the SN paralleled the reduced neuronal expression of TH throughout PCA exposure. Conclusion: α-synuclein accumulation following PCA may induce dopaminergic dysfunction via the downregulation of TH, as well as astroglial activation. Show more

Keywords: α-synuclein, GFAP, hepatic encephalopathy, hyperammonaemia, substantia nigra, tyrosine hydroxylase

DOI: 10.3233/RNN-170728

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 469-481, 2017

Authors: Barollo, Michele | Contemori, Giulio | Battaglini, Luca | Pavan, Andrea | Casco, Clara

Article Type: Research Article

Abstract: Background: Amblyopic observers present abnormal spatial interactions between a low-contrast sinusoidal target and high-contrast collinear flankers. It has been demonstrated that perceptual learning (PL) can modulate these low-level lateral interactions, resulting in improved visual acuity and contrast sensitivity. Objective: We measured the extent and duration of generalization effects to various spatial tasks (i.e., visual acuity, Vernier acuity, and foveal crowding) through PL on the target’s contrast detection. Methods: Amblyopic observers were trained on a contrast-detection task for a central target (i.e., a Gabor patch) flanked above and below by two high-contrast Gabor patches. The pre- and …post-learning tasks included lateral interactions at different target-to-flankers separations (i.e., 2, 3, 4, 8λ ) and included a range of spatial frequencies and stimulus durations as well as visual acuity, Vernier acuity, contrast-sensitivity function, and foveal crowding. Results: The results showed that perceptual training reduced the target’s contrast-detection thresholds more for the longest target-to-flanker separation (i.e., 8λ ). We also found generalization of PL to different stimuli and tasks: contrast sensitivity for both trained and untrained spatial frequencies, visual acuity for Sloan letters, and foveal crowding, and partially for Vernier acuity. Follow-ups after 5–7 months showed not only complete maintenance of PL effects on visual acuity and contrast sensitivity function but also further improvement in these tasks. Conclusion: These results suggest that PL improves facilitatory lateral interactions in amblyopic observers, which usually extend over larger separations than in typical foveal vision. The improvement in these basic visual spatial operations leads to a more efficient capability of performing spatial tasks involving high levels of visual processing, possibly due to the refinement of bottom-up and top-down networks of visual areas. Show more

Keywords: Amblyopia, perceptual learning, visual acuity, crowding, contrast sensitivity

DOI: 10.3233/RNN-170731

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 483-496, 2017

Authors: Iodice, Rosa | Manganelli, Fiore | Dubbioso, Raffaele

Article Type: Research Article

Abstract: Background: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and a leading cause of disability in young adults. Many disabling symptoms in MS, such as spasticity, pain, depression and cognitive deficits are not fully controlled by drug treatment. Non-invasive brain stimulation (NIBS) techniques can be used as tools for modulating altered cortical excitability and plasticity MS patients, providing an improvement in disabling symptoms affecting such patients. Objective: This review reported and summarized some of the most interesting and promising recent achievements regarding the therapeutic use of NIBS in MS patients. Methods: …We reviewed the clinical application of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), emphasizing their effect on clinical symptoms and signs that are commonly involved in MS patients. In addition, we shortly described new NIBS protocols, such as transcranial alternating current stimulation and transcranial focused ultrasound stimulation as potential and innovative therapeutic options to be applied in future studies in MS patients. Results: We reviewed twenty-one studies covering six main clinical domains. Most of such studies focused on fatigues (33.3%), motor performance (19%) and spasticity (19%), sparse results were about pain (9.5%), cognitive abilities (9.5%), sensory deficit (4.8%) and bladder function (4.8%). The most promising results have been published for the improvement of motor (i.e. hand dexterity) and cognitive performances (i.e. attention and working memory) by applying rTMS or tDCS alone or in association with motor/cognitive training, for pain’s treatment by using tDCS. Conclusion: There are still no official recommendations for the therapeutic use of tDCS or rTMS in MS. The huge inter-individual variability of NIBS efficacy is still a big challenge which needs to be solved. However, well-designed studies, deeper knowledge about pathomechanisms underlying MS, and the combination of such techniques with motor and cognitive rehabilitation might results in higher effectiveness of NIBS. Show more

Keywords: Transcranial direct current stimulation, repetitive transcranial magnetic stimulation, transcranial alternating current stimulation, transcranial focused ultrasound, rehabilitation, review, therapy

DOI: 10.3233/RNN-170735

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 497-509, 2017

Authors: Naro, Antonino | Leo, Antonino | Bruno, Rocco | Cannavò, Antonino | Buda, Antonio | Manuli, Alfredo | Bramanti, Alessia | Bramanti, Placido | Calabrò, Rocco Salvatore

Article Type: Research Article

Abstract: Background: The patients with chronic Disorders of Consciousness (DoC) mostly present with extremely challenging differential diagnosis. The advanced analysis of electroencephalographic (EEG) signals induced by brain stimulation paradigms may provide an appropriate approach to differentiate patients with DoC, besides the clinical assessment. Objective: This study was performed with an objective of identifying residual brain network perturbations following an innovative, non-invasive audiovisual stimulation protocol, which could be related to behavioral responsiveness in patients with DoC. Methods: The study comprised of ten healthy controls (HC), seven patients with Minimally Conscious State (MCS), and nine patients with Unresponsive Wakefulness …Syndrome (UWS). Both synchronous as well as asynchronous transorbital and transauricolar alternating current were employed as stimuli and their effects were measured in terms of functional and effective connectivity. Results: A more noticeable deterioration of long range connectivity patterns were found in patients with UWS than in those with MCS, with an exception of two patients with UWS, who showed connectivity values similar to those of MCS patients. Conclusion: The audiovisual stimulation paradigm used in the present study may be employed as a supportive bedside tool for improving the differential diagnosis in patients with DoC. Show more

Keywords: Audiovisual stimulation, alternating current stimulation, Minimally Conscious State, Unresponsive Wakefulness Syndrome

DOI: 10.3233/RNN-170741

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 511-526, 2017

Authors: Seo, Han Gil | Lee, Woo Hyung | Lee, Seung Hak | Yi, Youbin | Kim, Kwang Dong | Oh, Byung-Mo

Article Type: Research Article

Abstract: Background: Although robotic-assisted gait training (RAGT) is becoming a standard method in stroke rehabilitation, its effect on chronic stroke patients is uncertain. Objective: This study aimed to investigate whether anodal transcranial direct current stimulation (tDCS) enhances the effect of RAGT on functional ambulation in chronic stroke patients. Methods: Chronic hemiplegic stroke patients with a Functional Ambulatory Category (FAC) score≤4 were randomly assigned to either the RAGT with anodal tDCS (Anodal) group the sham tDCS (Sham) group. The patients were provided with RAGT for 45 min after allocated tDCS on the leg motor cortex in the impaired hemisphere …for 20 min every weekday for 2 weeks. The primary outcome measure was the FAC, and the secondary outcome measures included 10-m walking test, 6-min walking test, Berg Balance Scale, Fugl-Meyer assessment of the lower extremity, Medical Research Council Scale, and motor-evoked potential (MEP) parameters. They were evaluated before treatment (T0), immediately after treatment (T1), and 4 weeks after the end of treatment (T2). Results: Twenty-one patients were finally included. The percentage of participants who achieved improvement in the FAC score was greater in the Anodal group than in the Sham group, and the difference was significant at T2 (66.7% vs. 12.5%, p  = 0.024). In secondary outcome measures, the Anodal group showed greater improvement in the 6-min walking test than the Sham group at T2 (56.49±38.87 vs. 23.59±17.00, p  = 0.038). The changes in the MEP parameters were not significantly different between the two groups. Conclusion: This pilot study suggested that anodal tDCS on the leg motor cortex in the impaired hemisphere may facilitate the effect of RAGT on functional ambulation in chronic stroke patients. Larger clinical trials will be needed to confirm the effect of RAGT combined with tDCS in chronic stroke patients based on the present study. Show more

Keywords: Stroke, transcranial direct current stimulation, gait, robotics, stroke rehabilitation

DOI: 10.3233/RNN-170745

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 527-536, 2017

Authors: Marquardt, Michael K. | Cohen, Anna-Lisa | Gollwitzer, Peter M. | Gilbert, Sam J. | Dettmers, Christian

Article Type: Research Article

Abstract: Background: After stroke, the learned non-use of a paretic arm is a major obstacle to the improvement of hand function. Objective: We examined whether patients with a central paresis could profit from applying the self-regulation strategy of making if-then plans that specify situational triggers to using the paretic arm. Method: Seventeen stroke patients with a mild to moderate hand paresis were asked to perform a Simon task which is commonly used to study the enhanced executive control needed when there is a mismatch between stimulus (e.g., color) and response (e.g., location) features. We examined whether patients …with hemiparesis would be able to reduce the Simon effect (i.e., responding slower to mismatched as compared to matched stimulus and response features) by creating new stimulus-response associations via if-then plans. Results: A significant Simon effect was observed in both the affected and the non-affected arm for control trials. However, there was no longer a significant Simon effect for the critical trials prepared by forming if-then plans. This led to a significant stimulus×compatibility interaction effect for the affected arm and a marginally significant interaction effect for the non-affected arm. Making if-then plans was effective for eliminating or at least reducing the Simon effect for the affected and the non-affected arm, respectively. Conclusion: This observation opens a potential new route to improving stroke rehabilitation. If-then plans may qualify as a viable strategy to overcome the learned non-use of the affected arm. Further research is now required to develop and test therapeutic measures based on this proof-of-principle. Show more

Keywords: Implementation intentions, rehabilitation, hemiparesis, stroke, learned nonuse

DOI: 10.3233/RNN-170748

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 537-545, 2017

Authors: Gomes-Osman, Joyce | Cabral, Danylo F. | Hinchman, Carrie | Jannati, Ali | Morris, Timothy P. | Pascual-Leone, Alvaro

Article Type: Research Article

Abstract: Background: Exercise-mediated cognitive improvements can be at least partly attributed to neuroplastic changes in the nervous system, and may be influenced by the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene. Transcranial magnetic stimulation (TMS) can be used to assess mechanisms of plasticity in humans noninvasively. Objectives: To assess the feasibility of evaluating the effects of short-term regular exercise on cognitive performance, and to evaluate the relationship between these effects, TMS measures of plasticity, and BDNF Met carrier status in young healthy sedentary adults. Methods: Of the 19 participants who enrolled in the study, 14 …sedentary adults (12 females, age mean±SD , 27±12.3 yr), with less than two sessions of physical exercise in the preceding 2 months, completed an aerobic exercise regimen including four 30-min daily sessions per week for 4 weeks (for a total of 16 sessions) delivered at 55–64% of age-predicted maximal heart rate. Prior to and following the exercise regimen, participants performed a neuropsychological test battery and an intermittent theta-burst TMS plasticity protocol. Results: All participants completed the various measures and adhered to the exercise regimen. There were no complications and the results obtained were reliable. The feasibility of the approach is thus well established. Between-group comparisons of pre-post change revealed trends toward increased performance on the Stroop and faster reaction times in the CPT detectability in the Val66Val subgroup (p  = 0.07 and p  = 0.08), and a reduction in TBS-induced modulation of TMS responses in Met carriers (p  = 0.07). Conclusion: Acute exercise interventions in sedentary adults can be meaningfully conducted along with cognitive and neurophysiologic measures to assess behavioral and neurobiological effects and assessment of BDNF polymorphism. TMS measures of plasticity can be used to evaluate the effects of exercise on brain plasticity, and relate them to neuropsychological measures of cognition. Show more

Keywords: Aerobic exercise, transcranial magnetic stimulation, cognition, iTBS, plasticity, BDNF

DOI: 10.3233/RNN-170758

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 547-556, 2017