Impaired Brain-Heart Relation in Patients With Methamphetamine Use Disorder During VR Induction of Drug Cue Reactivity.

Methamphetamine use disorder (MUD) is an illness associated with severe health consequences. Virtual reality (VR) is used to induce the drug-cue reactivity and significant EEG and ECG abnormalities were found in MUD patients. However, whether a link exists between EEG and ECG abnormalities in patients with MUD during exposure to drug cues remains unknown. This is important from the therapeutic viewpoint because different treatment strategies may be applied when EEG abnormalities and ECG irregularities are complications of MUD. We designed a VR system with drug cues and EEG and ECG were recorded during VR exposure. Sixteen patients with MUD and sixteen healthy subjects were recruited. Statistical tests and Pearson correlation were employed to analyze the EEG and ECG. The results showed that, during VR induction, the patients with MUD but not healthy controls showed significant [Formula: see text] and [Formula: see text] power increases when the stimulus materials were most intense. This finding indicated that the stimuli are indiscriminate to healthy controls but meaningful to patients with MUD. Five heart rate variability (HRV) indexes significantly differed between patients and controls, suggesting abnormalities in the reaction of patient's autonomic nervous system. Importantly, significant relations between EEG and HRV indexes changes were only identified in the controls, but not in MUD patients, signifying a disruption of brain-heart relations in patients. Our findings of stimulus-specific EEG changes and the impaired brain-heart relations in patients with MUD shed light on the understanding of drug-cue reactivity and may be used to design diagnostic and/or therapeutic strategies for MUD.

Right arcuate fasciculus as outcome predictor after low-frequency repetitive transcranial magnetic stimulation in nonfluent aphasic stroke.

BACKGROUND AND PURPOSE: A reliable neuroimaging biomarker to predict language improvement after neuromodulation in post-stroke aphasia is lacking. It is hypothesized that aphasic patients with stroke injuries in the left primary language circuits but with sufficient right arcuate fasciculus (AF) integrity might respond to low-frequency repetitive transcranial magnetic stimulation (LF-rTMS), leading to language improvement. This study aimed to assess the microstructural indices of the right AF before LF-rTMS treatment and further correlate with language improvement after the treatment. METHODS: Thirty-three patients with at least 3 months after stroke in the left hemisphere and nonfluent aphasia were recruited in this randomized double-blind study. All patients received real 1-Hz LF-rTMS (n = 16) or sham stimulation (n = 17) at the right pars triangularis for 10 consecutive weekdays. Fractional anisotropy, axial diffusivity, radial diffusivity and apparent diffusion coefficient of the right AF were extracted using diffusion tensor imaging before the rTMS treatment and correlated with the measured functional improvement by the Concise Chinese Aphasia Test. RESULTS: The Concise Chinese Aphasia Test change scores revealed a stronger language improvement in auditory/reading comprehension and expression in the rTMS group than in the sham group. Regression analysis showed that the pre-treatment fractional anisotropy, axial diffusivity and apparent diffusion coefficient of the right AF significantly correlated with the expression abilities (R2 > 0.700, p < 0.044) and comprehension abilities (R2 > 0.702, p < 0.039) in the rTMS group. CONCLUSIONS: It was concluded that the right AF could be a predictor in language recovery induced by LF-rTMS after the injuries of primary language circuits.

Functional Remodeling Associated With Language Recovery After Repetitive Transcranial Magnetic Stimulation in Chronic Aphasic Stroke.

Background: Repetitive transcranial magnetic stimulation (rTMS) has shown promising efficacy in improving the language functions in poststroke aphasia. However, randomized controlled trials were lacking to investigate the rTMS-related neuroimaging changes underlying the therapeutic effects on language improvement in chronic aphasia. Objective: In this study, we aimed to evaluate the effects of low-frequency rTMS (LF-rTMS) on chronic poststroke aphasia. We hypothesized that the deactivation of the right pars triangularis could restore the balance of interhemispheric inhibition and, hence, facilitated the functional remodeling of language networks in both the hemispheres. Furthermore, the rTMS-induced functional reorganization should underpin the language recovery after rTMS. Methods: A total of 33 patients (22 males; age: 58.70 ± 13.77 years) with chronic stroke in the left hemisphere and nonfluent aphasia were recruited in this randomized double-blinded study. The ratio of randomization between the rTMS and sham groups is 17:16. All the patients received real 1-Hz rTMS or sham stimulation (placebo coil delivered < 5% of magnetic output with similar audible click-on discharge) at the right posterior pars triangularis for 10 consecutive weekdays (stroke onset to the first stimulation: 10.97 ± 10.35 months). Functional connectivity of language networks measured by resting-state fMRI was calculated and correlated to the scores of the Concise Chinese Aphasia Test by using the stepwise regression analysis. Results: After LF-rTMS intervention, significant improvement in language functions in terms of comprehension and expression abilities was observed compared with the sham group. The rTMS group showed a significant decrease of coupling strength between right pars triangularis and pars opercularis with a strengthened connection between right pars orbitalis and angular gyrus. Furthermore, the LF-rTMS significantly enhanced the coupling strength associated with left Wernicke area. Results of regression analysis showed that the identified functional remodeling involving both the hemispheres could support and predict the language recovery after LF-rTMS treatment. Conclusion: We reported the therapeutic effects of LF-rTMS and corresponding functional remodeling in chronic poststroke aphasia. Our results provided neuroimage evidence reflecting the rebalance of interhemispheric inhibition induced by LF-rTMS, which could facilitate future research in the refinement of rTMS protocol to optimize the neuromodulation efficacy and benefit the clinical management of patients with stroke.

Neuronal Abnormalities Induced by an Intelligent Virtual Reality System for Methamphetamine Use Disorder.

Methamphetamine use disorder (MUD) is a brain disease that leads to altered regional neuronal activity. Virtual reality (VR) is used to induce the drug cue reactivity. Previous studies reported significant frequency-specific neuronal abnormalities in patients with MUD during VR induction of drug craving. However, whether those patients exhibit neuronal abnormalities after VR induction that could serve as the treatment target remains unclear. Here, we used an integrated VR system for inducing drug related changes and investigated the neuronal abnormalities after VR exposure in patients. Fifteen patients with MUD and ten healthy subjects were recruited and exposed to drug-related VR environments. Resting-state EEG were recorded for 5 minutes twice-before and after VR and transformed to obtain the frequency-specific data. Three self-reported scales for measurement of the anxiety levels and impulsivity of participants were obtained after VR task. Statistical tests and machine learning methods were employed to reveal the differences between patients and healthy subjects. The result showed that patients with MUD and healthy subjects significantly differed in Θ, α, and γ power changes after VR. These neuronal abnormalities in patients were associated with the self-reported behavioral scales, indicating impaired impulse control. Our findings of resting-state EEG abnormalities in patients with MUD after VR exposure have the translational value and can be used to develop the treatment strategies for methamphetamine use disorder.

Resting-State Network Changes Following Transcranial Magnetic Stimulation in Patients With Aphasia-A Randomized Controlled Study.

BACKGROUND: Although repetitive transcranial magnetic stimulation (rTMS) has exhibited promising efficacy in treating stroke-related aphasia, changes in neuroimaging in response to this therapy remain unclear. MATERIALS AND METHODS: By using resting-state functional magnetic resonance imaging (rsfMRI), we examined brain activations associated with language recovery in patients with poststroke nonfluent aphasia during an rTMS intervention. Twenty-six stroke patients with nonfluent aphasia were recruited in this randomized double-blinded study. The patients received real (n = 13) or sham (n = 13) 1-Hz inhibitory rTMS to the right pars triangularis (PTr) for ten consecutive weekdays. They underwent rsfMRI and completed the Concise Chinese Aphasia Test (CCAT) before and after the rTMS intervention. RESULT: The fractional amplitude of low-frequency fluctuation (fALFF) was calculated to investigate spontaneous neural activity in the brain. After treatment, the language function in the experimental group was higher than that in the sham group in terms of total CCAT score (p = 0.014) and the CCAT subscores of conversation (p = 0.012), description (p = 0.006), and expression (p = 0.003). Postintervention intergroup comparisons revealed that fALFF was significantly increased in the right superior temporal gyrus, right dorsolateral prefrontal gyrus, insular cortex, and caudate nucleus. Clusters in the right thalamus exhibited suppressed fALFF. The enhanced clusters in the frontotemporal region were significantly correlated with CCAT score improvements. CONCLUSIONS: Our findings provide empirical evidence for the vital role of the right frontotemporal and subcortical regions in language recovery after rTMS interventions in patients with aphasia. Inhibitory rTMS may improve language expression by promoting involvement of the right frontotemporal region. The results can be further used to refine rTMS protocols and optimize brain stimulation treatments. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03059225.

Functional Near-Infrared Spectroscopy as a Target Navigator for rTMS Modulation in Patients with Hemiplegia: A Randomized Control Study.

INTRODUCTION: Although repetitive transcranial magnetic stimulation (rTMS) is efficacious for motor neuromodulation in stroke survivors, high interindividual variability for responsiveness remains a concern. Target probing on the skull using a proper brain-mapping technique may help overcome this challenge. This study assessed the feasibility of functional near-infrared spectroscopy (fNIRS) as a target navigator in rTMS treatment for motor facilitation in patients with stroke. METHODS: Fifty-one patients with stroke were enrolled in this randomized controlled study. The patients were assigned to three groups: fNIRS-guided rTMS treatment (fNIRS group, n = 20), motor evoked potential (MEP)-guided rTMS treatment (MEP group, n = 16), and sham (n = 15) group. Motor assessments, including Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), and muscle strength, were conducted at baseline and after the 10-session rTMS treatment. RESULTS: The fNIRS-guided hotspot (fNIRS-HS) was obtained for each patient, even those for whom the MEP-guided hotspot was undetectable. Both intervention groups exhibited significant improvements in muscle strength, FMA, and WMFT scores (P < 0.001) compared with the sham group. The fNIRS group achieved significantly greater improvement in elbow function (P = 0.001) than the MEP group. CONCLUSION: fNIRS can be a reliable tool for hotspot navigation for motor neuromodulation in patients with stroke. With high sensitivity to cortical oxygenation changes, this navigation system achieved a superior outcome to the traditional MEP-based method in patients with stroke. fNIRS-based systems may also facilitate the integration of machine learning, thus enabling precision medicine for neuromodulation. TRIAL REGISTRATION: https://clinicaltrials.gov ; Unique identifier: NCT02006615.

Integration of Virtual Reality into Transcranial Magnetic Stimulation Improves Cognitive Function in Patients with Parkinson's Disease with Cognitive Impairment: A Proof-of-Concept Study.

BACKGROUND: Emerging evidence has indicated the positive effects of repetitive transcranial magnetic stimulation (rTMS) on patients with Parkinson's disease (PD) for the treatment of mild cognitive impairment (MCI). OBJECTIVE: Investigating whether combining virtual reality (VR) training with rTMS can further enhance cognitive improvement induced by rTMS treatment. METHODS: We randomly assigned 40 patients with PD and MCI into three groups, namely the rTMS-VR group (n = 13), rTMS group (n = 11), and sham rTMS group (n = 16). rTMS was administered as 10 consecutive sessions of intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex. In the rTMS-VR group, VR training was administered immediately after each rTMS session. Cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Montreal Cognitive Assessment (MoCA) at baseline, immediately after intervention, and at 3-month follow-up. RESULTS: Compared with the rTMS group, the rTMS-VR group exhibited significantly more improvements in total and delayed memory scores of the RBANS and the visuospatial/executive function score of the MoCA after intervention (p = 0.000∼0.046) and the delayed memory score of the RBANS at 3-month follow-up (p = 0.028). CONCLUSION: The integrated rTMS-VR protocol achieved a superior outcome in global cognitive function, more effectively enhancing working memory and visuospatial executive function than did the rTMS protocol alone. The combination of VR and rTMS can be an effective regimen for improving the cognitive function of patients with PD.

Increased risk of stroke in patients with diffuse idiopathic skeletal hyperostosis: a nationwide population-based cohort study.

Diffuse idiopathic skeletal hyperostosis (DISH) is frequently an incidental finding during X-ray examination. Although it has been shown to be associated with several chronic diseases, the hazard of cerebrovascular disease has seldom been explored. Our study aimed at determining the risk of stroke conferred by DISH, which is a retrospective cohort study adopting the largest medical database in Taiwan. Patients with a diagnosis of DISH at least three times from 2005 to 2010 were identified as the study group, and those in the control group were selected by matching age and gender. Patients were followed up until the end of 2015 to trace the incidence of stroke. Cox regression analysis was performed to compute the hazard ratio of stroke. Among the included 5300 patients, 1060 had a diagnosis of DISH. Significantly higher prevalence rates of stroke, hypertension, diabetes, and hyperlipidemia were noted in these patients. Overall, DISH conferred a 1.68 times higher risk of developing stroke. The significantly higher hazard ratio could be identified in both genders whether hypertension existed or not. Even in those without comorbidities, DISH still conferred a significantly higher risk of cerebrovascular disease in the future, which should never be ignored when encountered during clinical practice.

A Machine-Learning-Based Assessment Method for Early-Stage Neurocognitive Impairment by an Immersive Virtual Supermarket.

Alzheimer's disease (AD) is a neurodegenerative disorder. Though it is not yet curable or reversible, research has shown that clinical intervention or intensive cognitive training at an early stage may effectively delay the progress of the disease. As a result, screening populations with mild cognitive impairment (MCI) or early AD via efficient, effective and low-cost cognitive assessments is important. Currently, a cognitive assessment relies mostly on cognitive tests, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA), which must be performed by therapists. Also, cognitive functions can be divided into a variety of dimensions, such as memory, attention, executive function, visual spatial and so on. Executive functions (EF), also known as executive control or cognitive control, refer to a set of skills necessary to perform higher-order cognitive processes, including working memory, planning, attention, cognitive flexibility, and inhibitory control. Along with the fast progress of virtual reality (VR) and artificial intelligence (AI), this study proposes an intelligent assessment method aimed at assessing executive functions. Utilizing machine learning to develop an automatic evidence-based assessment model, behavioral information is acquired through performing executive-function tasks in a VR supermarket. Clinical trials were performed individuals with MCI or early AD and six healthy participants. Statistical analysis showed that 45 out of 46 indices derived from behavioral information were found to differ significantly between individuals with neurocognitive disorder and healthy participants. This analysis indicates these indices may be potential bio-markers. Further, machine-learning methods were applied to build classifiers that differentiate between individuals with MCI or early AD and healthy participants. The accuracy of the classifier is up to 100%, demonstrating the derived features from the VR system were highly related to diagnosis of individuals with MCI or early AD.

Theta Burst Magnetic Stimulation Improves Parkinson's-Related Cognitive Impairment: A Randomised Controlled Study.

Background. Evidence remains mixed as to the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in treating mild cognitive impairment (MCI) in patients with Parkinson's disease (PD). Objective. In this study, we examined the short- and long-term effects of patterned rTMS. Methods. We randomly assigned 35 patients with PD with MCI to two groups. One group received intermittent theta burst stimulation (iTBS; n = 20), and the other received its sham counterpart (n = 15). The stimulations were applied over the left dorsolateral prefrontal cortex for 10 consecutive weekdays. Measurements based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Montreal Cognitive Assessment (MoCA) were conducted at three time points: at baseline, immediately after the last intervention and at 3-month follow-up. Each patient received a 99mTc-TRODAT-1 single-photon emission computed tomography (SPECT) brain scan at baseline. Results. The iTBS group exhibited significantly greater improvement than the sham group did in total RBANS and MoCA scores (p < .001 for both) immediately after intervention and at the 3-month follow-up. Radiotracer uptake in the bilateral basal ganglion in baseline SPECT was positively correlated with response to iTBS conditioning with respect to improvements in MoCA scores (p = .021). Conclusion. This randomised controlled trial provides evidence that a consecutive iTBS protocol can achieve a persistent and wide-ranging therapeutic effect in patients with PD with MCI.

Ultrasound-Guided Hydrodilatation With Triamcinolone Acetonide for Adhesive Capsulitis: A Randomized Controlled Trial Comparing the Posterior Glenohumeral Recess and the Rotator Cuff Interval Approaches.

For patients with adhesive capsulitis, hydrodilatation is typically performed using corticosteroids with ultrasound guidance via the posterior glenohumeral recess. Recently, a new intervention technique via the rotator cuff interval has been described. This study aimed to compare the efficacy of hydrodilatation with triamcinolone acetonide via the posterior glenohumeral recess and the rotator cuff interval in patients with adhesive capsulitis. This prospective randomized controlled trial was conducted in a tertiary care center with a follow-up period of 12 weeks. We enrolled 64 patients diagnosed with shoulder adhesive capsulitis. The subjects were randomly assigned to two groups that received hydrodilatation with corticosteroids either through the posterior glenohumeral recess or though the rotator cuff interval. The injection contained 4 ml of triamcinolone acetonide (40 mg) mixed with 4 ml of 2% lidocaine hydrochloride and 12 ml of normal saline. The shoulder pain and disability index, visual analog scale for pain, and range of motion were analyzed before and at 6 and 12 weeks after the treatment. Both groups experienced improvements in the visual analog scale scores, shoulder pain and disability index scores, and range of motion throughout the study period. A significant group-time interaction was observed in terms of the visual analog scale for pain during motion (p = 0.019), favoring hydrodilatation through the rotator cuff interval. Thus, hydrodilatation through the rotator cuff interval might be a better treatment option than that through the posterior glenohumeral recess for patients with adhesive capsulitis, considering its superior effect in alleviating pain during shoulder movement.

Low-Frequency vs. Theta Burst Transcranial Magnetic Stimulation for the Treatment of Chronic Non-fluent Aphasia in Stroke: A Proof-of-Concept Study.

BACKGROUND: Although low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise in the treatment of poststroke aphasia, the efficacy of high-frequency rTMS (HF-rTMS) has yet to be determined. PURPOSE: We investigated the efficacy of intermittent theta burst stimulation (iTBS) in ameliorating chronic non-fluent aphasia and compared it with that of LF-rTMS. METHODS: We randomly assigned patients with poststroke non-fluent aphasia to an ipsilesional iTBS (n = 29), contralesional 1-Hz rTMS (n = 27), or sham (n = 29) group. Each group received the rTMS protocol executed in 10 daily sessions over 2 weeks. We evaluated language function before and after the intervention by using the Concise Chinese Aphasia Test (CCAT). RESULTS: Compared with the sham group, the iTBS group exhibited significant improvements in conversation, description, and expression scores (P = 0.0004-0.031), which characterize verbal production, as well as in auditory comprehension, reading comprehension, and matching scores (P < 0.01), which characterize language perception. The 1-Hz group exhibited superior improvements in expression, reading comprehension, and imitation writing scores compared with the sham group (P < 0.05). The iTBS group had significantly superior results in CCAT total score, matching and auditory comprehension (P < 0.05) relative to the 1-Hz group. CONCLUSION: Our study findings contribute to a growing body of evidence that ipsilesional iTBS enhances the language recovery of patients with non-fluent aphasia after a chronic stroke. Auditory comprehension was more preferentially enhanced by iTBS compared with the 1-Hz protocol. Our findings highlight the importance of ipsilesional modulation through excitatory rTMS for the recovery of non-fluent aphasia in patients with chronic stroke. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [NCT03059225].

High-frequency versus theta burst transcranial magnetic stimulation for the treatment of poststroke cognitive impairment in humans

Background: Because the reliability of repetitive transcranial magnetic stimulation (rTMS) in treating poststroke cognitive impairment has not been convincingly demonstrated, we systematically examined the effectiveness of this regimen with 2 protocols. Methods: We randomly allocated 41 patients with poststroke cognitive impairment to receive 5 Hz rTMS (n = 11), intermittent theta burst stimulation (iTBS; n = 15) or sham stimulation (n = 15). Each group received 10 stimulation sessions over the left dorsolateral prefrontal cortex. We performed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Beck Depression Inventory at baseline and after the intervention. Results: The 5 Hz rTMS group showed significantly greater improvement than the sham group in RBANS total score (p = 0.006), attention (p = 0.001) and delayed memory (p < 0.001). The iTBS group showed significantly greater improvement than the sham group in RBANS total score (p = 0.005) and delayed memory (p = 0.007). The 5 Hz rTMS group exhibited a superior modulating effect in attention compared to the iTBS group (p = 0.016). Patients without comorbid hypertension (p = 0.008) were predisposed to favourable therapeutic outcomes. Limitations: Although we included only patients with left hemispheric stroke, heterogeneity associated with cortical and subcortical implications existed. We did not investigate the remote effects of rTMS. Conclusion: Our results demonstrated that both 5 Hz rTMS and iTBS were effective for poststroke cognitive impairment in terms of global cognition, attention and memory function; the domain of attention was susceptible to 5 Hz modulation. Treatment with 5 Hz rTMS may slow cognitive decline, representing both a pivotal process in poststroke cognitive impairment and an aspect of neuroplasticity that contributes to disease-modifying strategies. Clinical trial registration: NCT02006615; clinicaltrials.gov/ct2/show/NCT02006615.

Vagus nerve magnetic modulation facilitates dysphagia recovery in patients with stroke involving the brainstem - A proof of concept study.

BACKGROUND & AIMS: Stroke involving the brainstem (SBS) causes severe oropharyngeal dysphagia (OD). Research on the therapeutic efficacy of vagus nerve modulation (VNM) by using repetitive transcranial magnetic stimulation (rTMS) in SBS patients with OD has been limited thus far. We aimed to assess the effect of VNM by using rTMS in improving swallowing function after SBS. METHOD: We conducted a sham-controlled, double-blinded, parallel pilot study in 28 SBS patients with OD randomly allocated to a real rTMS group (n = 13; TMSreal) or a sham group (n = 15; TMSsham). For VNM, 5-Hz rTMS was applied to the left mastoid in 10 sessions. We evaluated all patients for swallowing function before and after rTMS conditioning, assessed on the 8-point Penetration-Aspiration Scale (PAS) through videofluoroscopy and the Australian Therapy Outcome Measures-Swallowing scale (AusTOMs). We measured the amplitude and latency of cricopharyngeal motor evoked potentials (CP-MEPs) as the neurophysiological parameters. RESULTS: TMSreal exhibited significant improvement in all swallowing outcomes-neurophysiological, radiological, and functional-compared with TMSsham: We noted higher CP-MEP amplitude (p = 0.004), shorter CP-MEP latency (p = 0.004), a lower PAS score (p = 0.001), and a higher AusTOMs score (p < 0.001) following rTMS in TMSreal. Moreover, the neurophysiological improvements were significantly correlated with the functional outcomes (p < 0.05). CONCLUSIONS: Our results encourage the application of VNM by using rTMS for improving swallowing function after SBS. The immediate therapeutic effects suggest that this novel intervention can be an effective complementary therapy to traditional oropharyngeal rehabilitation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02893033.

Energy Homeostasis and Abnormal RNA Metabolism in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is clinically characterized by progressive muscle weakness and impaired voluntary movement due to the loss of motor neurons in the brain, brain stem and spinal cord. To date, no effective treatment is available. Ample evidence suggests that impaired RNA homeostasis and abnormal energy status are two major pathogenesis pathways in ALS. In the present review article, we focus on recent studies that report molecular insights of both pathways, and discuss the possibility that energy dysfunction might negatively regulate RNA homeostasis via the impairment of cytoplasmic-nuclear shuttling in motor neurons and subsequently contribute to the development of ALS.

Effects of Computer-Aided Interlimb Force Coupling Training on Paretic Hand and Arm Motor Control following Chronic Stroke: A Randomized Controlled Trial.

OBJECTIVE: We investigated the training effects of interlimb force coupling training on paretic upper extremity outcomes in patients with chronic stroke and analyzed the relationship between motor recovery of the paretic hand, arm and functional performances on paretic upper limb. DESIGN: A randomized controlled trial with outcome assessment at baseline and after 4 weeks of intervention. SETTING: Taipei Veterans General Hospital, National Yang-Ming University. PARTICIPANTS: Thirty-three subjects with chronic stroke were recruited and randomly assigned to training (n = 16) and control groups (n = 17). INTERVENTIONS: The computer-aided interlimb force coupling training task with visual feedback included different grip force generation methods on both hands. MAIN OUTCOME MEASURES: The Barthel Index (BI), the upper extremity motor control Fugl-Meyer Assessment (FMA-UE), the Motor Assessment Score (MAS), and the Wolf Motor Function Test (WMFT). All assessments were executed by a blinded evaluator, and data management and statistical analysis were also conducted by a blinded researcher. RESULTS: The training group demonstrated greater improvement on the FMA-UE (p<.001), WMFT (p<.001), MAS (p = .004) and BI (p = .037) than the control group after 4 weeks of intervention. In addition, a moderate correlation was found between the improvement of scores for hand scales of the FMA and other portions of the FMA UE (r = .528, p = .018) or MAS (r = .596, p = .015) in the training group. CONCLUSION: Computer-aided interlimb force coupling training improves the motor recovery of a paretic hand, and facilitates motor control and enhances functional performance in the paretic upper extremity of people with chronic stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT02247674.

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study.

OBJECTIVE: To identify the effective predictors for therapeutic outcomes based on intermittent theta-burst stimulation (iTBS). DESIGN: A sham-controlled, double-blind parallel study design. SETTING: A tertiary hospital. PARTICIPANTS: People with stroke (N=72) who presented with unilateral hemiplegia. INTERVENTIONS: Ten consecutive sessions of real or sham iTBS were implemented with the aim of enhancing hand function. Patients were categorized into 4 groups according to the presence (MEP+) or absence (MEP-) of motor-evoked potentials (MEPs) and grip strength according to the Medical Research Council (MRC) scale. MAIN OUTCOME MEASURES: Cortical excitability, Wolf Motor Function Test (WMFT), finger-tapping task (FT), and simple reaction time were performed before and after the sessions. RESULTS: MEPs and the MRC scale were predictive of iTBS therapeutic outcomes. Group A (MEP+, MRC>1) exhibited the greatest WMFT change (7.6±2.3, P<.001), followed by group B (MEP-, MRC>1; 5.2±2.2 score change) and group C (MEP-, MRC=0; 2.3±1.5 score change). These improvements were correlated significantly with baseline motor function and ipsilesional maximum MEP amplitude. CONCLUSIONS: The effectiveness of iTBS modulation for poststroke motor enhancement depends on baseline hand grip strength and the presence of MEPs. Our findings indicate that establishing neurostimulation strategies based on the proposed electrophysiological and clinical criteria can allow iTBS to be executed with substantial precision. Effective neuromodulatory strategies can be formulated by using electrophysiological features and clinical presentation information as guidelines.

Efficacy of synchronous verbal training during repetitive transcranial magnetic stimulation in patients with chronic aphasia.

BACKGROUND AND PURPOSE: Although multiple studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may facilitate recovery after stroke, the efficacy of synchronous speech therapy integrated with an rTMS protocol has yet to be determined. We investigated language responses to this strategy and determined the longevity of the resulting therapeutic outcomes. METHODS: Forty-five patients with stroke who presented with nonfluent aphasia were randomly assigned to the TMSsyn group and underwent synchronous picture-naming training together with contralesional 1 Hz-rTMS for 10 daily sessions. The TMSsub group underwent subsequent picture-naming activity after the primed 1 Hz-rTMS, and the TMSsham group received concurrent naming task along with the sham 1 Hz-rTMS. The Concise Chinese Aphasia test and the picture-naming test were performed before, immediately, and after 3 months of the intervention. RESULTS: TMSsyn showed significantly superior results in Concise Chinese Aphasia test score (P<0.001), expression and description subtests (P<0.001), and action (P=0.02) and object naming activity (P=0.008); the superior results lasted for 3 months (P=0.005), in comparison with the TMSsub and TMSsham groups. CONCLUSIONS: We established a real-time model that involved implementing verbal tasks together with the rTMS protocol. Our results confirmed that the strategy yielded favorable outcomes that were of considerable longevity. The results also indicated that the rTMS protocol and language training can be combined to achieve outcomes superior to those obtained when used separately. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02120508.

Inhibitory repetitive transcranial magnetic stimulation of the contralesional premotor and primary motor cortices facilitate poststroke motor recovery.

PURPOSE: The premotor cortex plays a major role in motor planning and control, exhibiting hierarchical importance comparable to that of the primary motor cortex (M1). In this study, we compared the effects of cPMd modulation, which was achieved using inhibitory repetitive transcranial magnetic stimulation (rTMS), with those of contralesional M1 (cM1) modulation, to elucidate the roles of both regions on longitudinal motor recovery following a stroke. METHODS: Forty-four patients who had sustained hemiplegia for 3 to 12 months were randomly allocated to a cPMd group, cM1 group, or sham group and received 10 sessions of 1-Hz rTMS. The Medical Research Council (MRC) Scale, Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), and a cortical excitability test were administered pre- and post- rTMS intervention. RESULTS: cPMd modulation yielded significant improvements in MRC, FMA, and WMFT scores compared with sham stimulation and a significant effect on cortical excitability suppression equivalent to that of cM1 modulation, but engendered effects on motor improvement inferior to those of cM1 modulation. CONCLUSIONS: In patients with chronic stroke, the cPMd can fulfill a role similar to that of the cM1 in interhemispheric imbalance, which can be ameliorated by applying inhibitory rTMS to achieve substantial motor restoration.

Interactive 3-dimensional virtual reality rehabilitation for patients with chronic imbalance and vestibular dysfunction.

BACKGROUND: Chronic imbalance is common in patients with vestibular dysfunction. Vestibular rehabilitation is effective in improving upright balance control. Vestibular rehabilitation exercises, such as Cawthorne-Cooksey exercises, include simple repetitive movements and have limited feedback and adaptive training protocols. Interactive systems based on virtual reality (VR) technology may improve vestibular rehabilitation. OBJECTIVE: The objective of this study was to examine the effectiveness of an interactive 3-dimensional VR system for vestibular rehabilitation. METHODS: In 49 subjects with vestibular dysfunction, VR rehabilitation exercises were performed in 6 sessions. Before and after rehabilitation, subjects were evaluated for performance of the training exercises; the center of pressure was measured for 20 seconds and balance indices were determined. RESULTS: Five training scores (total 6) showed a significant improvement. For balance indices in condition of non-stimulation, all of them (total 5) showed a trend of improvement, in which there was a significant improvement in mean mediolateral. For balance indices in condition of post-stimulation, there was a significant improvement in statokinesigram and maximum mediolateral. CONCLUSIONS: The VR rehabilitation exercises were effective in improving upright balance control in patients with vestibular dysfunction.