Quality of life outcomes after globus pallidus internus deep brain stimulation in idiopathic or inherited isolated dystonia: a meta-analysis.

BACKGROUND: Several studies reported the beneficial effects of globus pallidus internus deep brain stimulation (GPi DBS) on health-related quality of life (HRQoL) in patients with inherited or idiopathic isolated dystonia. However, the impact of this intervention on physical and mental/psychological domains and the effects over time remain unclear. METHODS: We conducted a systematic literature review from January 2000 to May 2019 and performed a meta-analysis of HRQoL outcomes based on the Short Form Health Survey-36 (SF-36) after GPi DBS in patients with inherited or idiopathic isolated dystonia to evaluate the effects of DBS on physical and mental QoL. RESULTS: Seven studies comprising 144 patients with dystonia (78, generalised; 34, segmental; and 32, focal cervical) were included in this comprehensive analysis. The mean (SD) age at DBS implantation was 41.0 (11.4) years, and the follow-up period after implantation was 3.2 (3.8) years. The random effects model meta-analysis revealed that both physical and mental domains of SF-36 improved following DBS with a significantly larger effect size for the physical domains (effect size=0.781; p<0.0001) compared with the mental domains (effect size=0.533; p<0.0001). A moderator variable analysis demonstrated that effect sizes for HRQoL improvement were maintained over time. CONCLUSIONS: This is the first meta-analysis that demonstrates significant benefits in HRQoL following DBS in patients with inherited or idiopathic isolated dystonia. The benefits are greater for physical QoL domains compared with mental/psychological QoL. These findings highlight the importance of a comprehensive multidisciplinary approach to improve mental/psychological QoL.

Transient changes in paretic and non-paretic isometric force control during bimanual submaximal and maximal contractions.

PURPOSE: The purpose of this study was to investigate transient bimanual effects on the force control capabilities of the paretic and non-paretic arms in individuals post stroke across submaximal and maximal force control tasks. METHODS: Fourteen chronic stroke patients (mean age = 63.8 ± 15.9; stroke duration = 38.7 ± 45.2 months) completed two isometric force control tasks: (a) submaximal control and (b) maximal sustained force production. Participants executed both tasks with their wrist and fingers extending across unimanual (paretic and non-paretic arms) and bimanual conditions. Mean force, force variability using coefficient of variation, force regularity using sample entropy were calculated for each condition. RESULTS: During the submaximal force control tasks (i.e., 5, 25, and 50% of maximum voluntary contraction), the asymmetrical mean force between the paretic and non-paretic arms decreased from unimanual to bimanual conditions. The asymmetry of force variability and regularity between the two arms while executing unimanual force control tended to decrease in the bimanual condition because of greater increases in the force variability and regularity for the non-paretic arm than those for the paretic arm. During the maximal sustained force production tasks (i.e., 100% of maximum voluntary contraction), the paretic arm increased maximal forces and decreased force variability in the bimanual condition, whereas the non-paretic arm reduced maximal forces and elevated force variability from unimanual to bimanual conditions. CONCLUSIONS: The current findings support a proposition that repetitive bimanual isometric training with higher execution intensity may facilitate progress toward stroke motor recovery.

Age-related deficits in bilateral motor synergies and force coordination.

BACKGROUND: Ageing may cause impairments in executing bilateral movement control. This study investigated age-related changes in interlimb force coordination across multiple trials by quantifying bilateral motor synergies based on the uncontrolled manifold hypothesis. Participants completed the trials with and without visual feedback. METHODS: Twenty healthy individuals (10 older adults and 10 young adults) performed 12 isometric force control trials for the two vision conditions at 5% of maximal voluntary contraction. All dependent variables were analyzed in two-way mixed model (Group × Vision Condition; 2 × 2) ANOVAs with repeated measures on the last factor. RESULTS: The analyses revealed that older adults had greater mean force produced by two hands in both vision conditions (i.e., yes and no visual feedback). Across both vision conditions, the older adult group showed greater asymmetrical force variability (i.e., standard deviation of non-dominant hand > standard deviation of dominant hand) and revealed more positive correlation coefficients between forces produced by two hands as compared with the young adult group. Finally, an index of bilateral motor synergies was significantly greater in young adults than older adults when visual feedback was available. CONCLUSION: The current findings indicate that deficits in interlimb force coordination across multiple trials appeared in older adults.

Does transcranial direct current stimulation improve functional locomotion in people with Parkinson's disease? A systematic review and meta-analysis.

PURPOSE: The purpose of this meta-analysis was to investigate the treatment effects of transcranial direct current stimulation (tDCS) on functional locomotion in people with Parkinson's disease (PD). METHODS: A systematic literature search identified 18 qualified studies that used tDCS protocols as functional locomotion rehabilitation interventions for people with PD. All included studies used either a randomized control trial or crossover designs with a sham control group. Meta-analysis quantified both (a) short-term treatment effects: change in functional locomotion between baseline and immediate posttests on 18 comparisons and (b) long-term treatment effects: change in functional locomotion between baseline and delayed retention tests on six comparisons. Moreover, we performed moderator variable analyses for comparing effect sizes between tDCS targeting multiple brain regions and tDCS targeting a single brain region. RESULTS: Random effects model meta-analyses revealed a significant short-term treatment effect (effect size = 0.359; P = 0.001), whereas no significant long-term treatment effects were identified (effect size = 0.164; P = 0.314). In addition, tDCS protocols that targeted multiple brain regions showed relatively more positive effects on functional locomotion than protocols that targeted a single brain region. CONCLUSIONS: These meta-analytic findings indicate that tDCS protocols may show immediate positive effects on functional locomotion in people with PD. However, given the relatively low effect size, exploring more appropriate tDCS protocols (i.e., targeting multiple motor and prefrontal regions and medication condition) should be a focus in future studies.

Correction to: Does transcranial direct current stimulation improve functional locomotion in people with Parkinson's disease? A systematic review and meta-analysis.

In the original article [1], we mentioned that some study characteristics of the article by Dagan and colleagues [2] were unavailable.

Transcranial direct current stimulation and suppression of contralesional primary motor cortex post-stroke: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis was to investigate the therapeutic effects of cathodal tDCS (ctDCS) that suppresses the contralesional primary motor cortex (cM1) activity for individuals with stroke in different recovery phases. METHODS: Fifteen studies that used ctDCS for suppressing the cM1 activity were included in this meta-analysis. Twenty total comparisons from the qualified studies identified motor function changes between ctDCS and sham protocols. We divided recovery stages into two categories: (a) acute and subacute phases (time since stroke ≤6 months): eight comparisons and (b) chronic phase (time since stroke >6 months): 12 comparisons. RESULTS: Random-effects meta-analysis models revealed motor improvements after applying ctDCS on the cM1 as indicated by a significant standardized effect size (ES = 0.61; P < 0.001). The moderator variable analysis showed that acute and subacute patients revealed no significant effect size of ctDCS (ES = 0.46; P = 0.07), whereas the ctDCS protocol significantly improved motor functions in chronic patients (ES = 0.71; P < 0.001). CONCLUSION: This comprehensive meta-analysis indicates that the treatment effects of ctDCS on the cM1 are different between patients in the acute and subacute phases and patients in the chronic phase post-stroke.

Right Hemisphere Contributions to Bilateral Force Control in Chronic Stroke: A Preliminary Report.

BACKGROUND: Bilateral motor control deficits poststroke may be lateralized by hemisphere damage. This preliminary study investigated bilateral force control between left and right hemisphere-damaged groups at baseline and after coupled bilateral movement training with neuromuscular stimulation. METHODS: Stroke participants (8 left hemisphere and 6 right hemisphere cerebrovascular accidents) performed a bilateral isometric force control task at 3 submaximal force levels (5%, 25%, and 50% of maximum voluntary contraction [MVC]) before and after training. Force accuracy, force variability, and interlimb force coordination were analyzed in 3-way mixed design ANOVAs (2 × 2 × 3; Group × Test Session × Force Level) with repeated measures on test session and force level. RESULTS: The findings indicated that force accuracy and variability at 50% of MVC in the right hemisphere-damaged group were more impaired than lower targeted force levels at baseline, and the impairment at the highest target level was improved after coupled bilateral movement training. However, these patterns were not observed in the left hemisphere-damaged group. CONCLUSIONS: Current findings support a proposition that the right hemisphere presumably contributes to controlling bilateral force production.

Bilateral synergy as an index of force coordination in chronic stroke.

Dysfunction in bilateral coordination post-stroke is responsible for impaired bilateral movements. This study examined bilateral synergies using the uncontrolled manifold (UCM) approach while individuals in a chronic stage after stroke executed bilateral isometric force control at three submaximal force levels. Nine patients with stroke and nine age-matched healthy controls performed 24 trials of wrist and fingers extension at 5, 25, and 50% of MVC. The UCM findings revealed: (a) decreased bilateral synergies in patients with stroke as compared to controls at 50% of MVC and (b) reduced good variability and increased bad variability components in patients with stroke at 50% of MVC. Moreover, correlation analyses across both groups showed that a reduction of bilateral synergies was related to increased force error at 50% of MVC and an inconsistent force ratio between the two hands across multiple trials correlated with increased good and bad variability at 5% of MVC. Current findings indicate that quantifying bilateral synergies may provide meaningful profiles for estimating impairments as well as improvements of cooperative behaviors between two hands post-stroke.

Transcranial direct current stimulation facilitates motor learning post-stroke: a systematic review and meta-analysis.

Transcranial direct current stimulation (tDCS) is an attractive protocol for stroke motor recovery. The current systematic review and meta-analysis investigated the effects of tDCS on motor learning post-stroke. Specifically, we determined long-term learning effects by examining motor improvements from baseline to at least 5 days after tDCS intervention and motor practise. 17 studies reported long-term retention testing (mean retention interval=43.8 days; SD=56.6 days) and qualified for inclusion in our meta-analysis. Assessing primary outcome measures for groups that received tDCS and motor practise versus sham control groups created 21 valid comparisons: (1) 16 clinical assessments and (2) 5 motor skill acquisition tests. A random effects model meta-analysis showed a significant overall effect size=0.59 (p<0.0001; low heterogeneity, T(2)=0.04; I(2)=22.75%; and high classic fail-safe N=240). 4 moderator variable analyses revealed beneficial effects of tDCS on long-term motor learning: (1) stimulation protocols: anodal on the ipsilesional hemisphere, cathodal on the contralesional hemisphere, or bilateral; (2) recovery stage: subacute or chronic stroke; (3) stimulation timing: tDCS before or during motor practise; and (4) task-specific training or conventional rehabilitation protocols. This robust meta-analysis identified novel long-term motor learning effects with tDCS and motor practise post-stroke.

Force control improvements in chronic stroke: bimanual coordination and motor synergy evidence after coupled bimanual movement training.

Bimanual movement disorders are common dysfunctions post stroke. This stroke study investigated bimanual force control capabilities to determine the effect of coupled bimanual movement training on bimanual coordination and motor synergy. Stroke participants (N = 11) completed three bimanual force control tasks at 5, 25, and 50 % of maximum voluntary contraction before and after coupled bimanual movement training. Root mean square error (RMSE), approximate entropy, correlation, and bimanual motor synergy were analyzed in two-way completely within-subjects ANOVAs (Test Session × Force Level: 2 × 3). Multiple linear regression analysis determined the relationship between RMSE and other force control measures. The analyses revealed three important findings: (1) RMSE decreased from baseline to posttest (2) negative correlation (e.g., error compensation) and bimanual motor synergy increased at 25 and 50 % after rehabilitation, and (3) increased bimanual motor synergy was strongly associated with decreased RMSE after training. The findings indicate that coupled bimanual movement training improved force control performance, bimanual coordination, and motor synergies. Indeed, the present findings extend bimanual motor synergies as a meaningful indicator for estimating task performance improvements. Finally, bimanual force control is a valid outcome measure in quantifying progress toward motor recovery post stroke.

Motor recovery patterns in arm muscles: coupled bilateral training and neuromuscular stimulation.

BACKGROUND: Neuromuscular stimulation coupled with bilateral movements facilitates functional motor recovery of the upper extremities post stroke. This study investigated electromyography activation patterns during training. The leading question asked: Do EMG activation patterns show rehabilitative effects of coupled bilateral movement training on wrist and fingers extension, elbow extension, and shoulder abduction? METHODS: Twelve stroke volunteers completed nine hours of coupled bilateral movement training on three sets of joints in their arms. Neuromuscular stimulation on the impaired limb assisted wrist and fingers extension, elbow extension, and shoulder abduction. Mean activation level data were analyzed in a three-way completely within-subjects ANOVA (Training Day × Movement Type × Trial Block: 3 × 3 × 3). RESULTS: The analysis revealed three important findings: (a) activation levels in Days 5 and 6 were significantly higher than Days 1 and 2, (b) muscle activation patterns increased across trial blocks, and (c) movements for the shoulder joint/girdle as well as wrist and fingers demonstrated higher activation than the elbow joint. Further analysis indicated that the muscle activation patterns for shoulder abduction were positively associated with force stabilization (ratio of good variability relative to bad variability) during bilateral force production. CONCLUSIONS: The findings indicate that capability to increase muscle activity during the three joint movements was improved after training. There appears to be higher muscle activation in the primary proximal and distal muscles necessary for motor control improvement.

Bimanual motor impairments in older adults: an updated systematic review and meta-analysis.

This updated systematic review and meta-analysis further examined potential effects of aging on bimanual movements. Forty-seven qualified studies that compared bimanual motor performances between elderly and younger adults were included in this meta-analysis. Moderator variable analyses additionally determined whether altered bimanual motor performances in older adults were different based on the task types (i.e., symmetry vs. asymmetry vs. complex) or outcome measures (i.e., accuracy vs. variability vs. movement time). The random effects model meta-analysis on 80 comparisons from 47 included studies revealed significant negative overall effects indicating more bimanual movement impairments in the elderly adults than younger adults. Moderator variable analyses found that older adults showed more deficits in asymmetrical bimanual movement tasks than symmetrical and complex tasks, and the bimanual movement impairments in the elderly adults included less accurate, more variable, and greater movement execution time than younger adults. These findings suggest that rehabilitation programs for improving motor actions in older adults are necessary to focus on functional recovery of interlimb motor control including advanced motor performances as well coordination.

Higher visual gain contributions to bilateral motor synergies and force control.

This study investigated the effects of altered visual gain levels on bilateral motor synergies determined by the uncontrolled manifold (UCM) hypothesis and force control. Twelve healthy participants performed bimanual index finger abduction force control tasks at 20% of their maximal voluntary contraction across four different visual gain conditions: 8, 80, 256, and 512 pixels/N. Quantifying force accuracy and variability within a trial provided a bimanual force control outcome. The UCM analysis measured bilateral motor synergies, a proportion of good variance to bad variance across multiple trials. Correlation analyses determined whether changes in the UCM variables were related to changes in force control variables from the lowest to highest visual gain conditions, respectively. Multiple analyses indicated that the three highest visual gain conditions in comparison to the lowest visual gain increased values of bilateral motor synergies and target force accuracy. The correlation findings showed that a reduction of bad variance from the lowest to three highest visual gain conditions was related to increased force accuracy. These findings reveal that visual gain greater than 8 pixels/N facilitates bimanual force control.

Force control deficits in chronic stroke: grip formation and release phases.

The aim of the study was to develop a novel approach for quantifying stair-stepping in a trajectory tracking task with the goal of understanding how age and stroke-related differences in motor control contribute to force control deficits. Nine stroke participants, nine age-matched controls, and nine young healthy adults performed an isometric gripping task while squeezing, holding, and releasing a cylindrical device. The visual tracking task involved three different rates of force production (5, 10, and 20% maximal force/s). Four outcome measures determined force control deficits: (a) root mean square error, (b) standard deviation, (c) step number, and (d) mean pause duration. Our findings indicate that step number, and especially mean pause duration, differentiated force control deficits in the three groups more effectively than the traditional root mean square error. Moreover, stroke participants showed the largest force control deficits during the grip release phase compared to age-matched and young healthy controls. Importantly, step number and mean pause duration quantified stair-stepping while measuring different constructs than root mean square error. Distinct step and duration interruptions in force modulation by persons post-stroke during the grip release phase provide new information with implications for motor recovery during rehabilitation.

Long-term rehabilitation for chronic stroke arm movements: a randomized controlled trial.

OBJECTIVE: We investigated the effect of long-term practice on motor improvements in chronic stroke patients. DESIGN: Randomized parallel group controlled study. SETTING: Motor Behavior Laboratory, University of Florida. SUBJECTS: Eighteen individuals who experienced a stroke more than nine months prior to enrolling. INTERVENTIONS: The treatment interventions were bilateral arm movements coupled with active neuromuscular stimulation on the impaired arm for both practice duration groups. The short-term group received one treatment protocol, whereas, over 16 months, the long-term practice group completed 10 treatment protocols. All protocol sessions were 6 hours long (90 minutes 1 day/week/4 weeks) and were separated by 22 days. MAIN OUTCOME MEASURES: Repeated data collection on three primary outcome measures (i.e. Box and Block test, fractionated reaction times, and sustained force production) evaluated motor capabilities across rehabilitation times. RESULTS: Mixed design ANOVAs (Group × Retention Test: 2 × 4; Group × Retention Test × Arm Condition: 2 × 4 × 2) revealed improved motor capabilities for the long-term practice duration group on each primary measure. At the 16-month delayed retention test, when compared to the short-term group, the long-term group demonstrated: (a) more blocks moved (43 v 32), (b) faster premotor reaction times (158 v 208 ms), and (c) higher force production (75 v 45 N). CONCLUSION: Sixty hours of rehabilitation over 16 months provided by various bilateral arm movements and coupled active stimulation improved motor capabilities in chronic stroke.

Visual feedback improves bimanual force control performances at planning and execution levels.

The purpose of this study was to determine the effect of different visual conditions and targeted force levels on bilateral motor synergies and bimanual force control performances. Fourteen healthy young participants performed bimanual isometric force control tasks by extending their wrists and fingers under two visual feedback conditions (i.e., vision and no-vision) and three targeted force levels (i.e., 5%, 25%, and 50% of maximum voluntary contraction: MVC). To estimate bilateral motor synergies across multiple trials, we calculated the proportion of good variability relative to bad variability using an uncontrolled manifold analysis. To assess bimanual force control performances within a trial, we used the accuracy, variability, and regularity of total forces produced by two hands. Further, analysis included correlation coefficients between forces from the left and right hands. In addition, we examined the correlations between altered bilateral motor synergies and force control performances from no-vision to vision conditions for each targeted force level. Importantly, our findings revealed that the presence of visual feedback increased bilateral motor synergies across multiple trials significantly with a reduction of bad variability as well as improved bimanual force control performances within a trial based on higher force accuracy, lower force variability, less force regularity, and decreased correlation coefficients between hands. Further, we found two significant correlations in (a) increased bilateral motor synergy versus higher force accuracy at 5% of MVC and (b) increased bilateral motor synergy versus lower force variability at 50% of MVC. Together, these results suggested that visual feedback effectively improved both synergetic coordination behaviors across multiple trials and stability of task performance within a trial across various submaximal force levels.

Children with cerebral palsy: a systematic review and meta-analysis on gait and electrical stimulation.

OBJECTIVE: To conduct a systematic review and meta-analysis using the International Classification of Functioning to determine the summary effect of electrical stimulation on impairment and activity limitations relevant to gait problems of children with cerebral palsy. METHODS: We identified 40 cerebral palsy and electrical stimulation studies, and 17 gait studies qualified for inclusion. Applying enablement classification methods to walking abnormalities created two subgroups: impairment (N = 14) and activity limitations (N = 15). Overall, 238 participants experienced electrical stimulation treatments and 224 served as a no stimulation control group. Calculations followed conventional data extraction and meta-analysis techniques: (a) individual standardized mean differences, (b) summary effect size, (c) I² heterogeneity test, (d) fail-safe N analysis and (e) moderator variable analyses. RESULTS: Common outcome measures associated with impairment (n = 3) and activity limitations (n = 6) were submitted to separate random effects models meta-analyses, and revealed significant cumulative effect sizes: (a) impairment = 0.616 (SE = 0.10) and (b) activity limitations = 0.635 (SE = 0.14). I² indicated low and medium amounts of dispersion, whereas fail-safe analyses revealed high N-values for both disablement categories. Moderator variable analyses further confirmed the positive treatment effects from both functional and neuromuscular stimulation. CONCLUSIONS: The present systematic review and meta-analyses determined medium effect sizes for electrical stimulation on walking impairment and activity limitations of children with cerebral palsy.

Secondary Worsening Following DYT1 Dystonia Deep Brain Stimulation: A Multi-country Cohort.

Objective: To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort. Methods: In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as <30% improvement in dystonia scales at the last follow-up compared with baseline. We used a literature-driven historical cohort of 112 DYT1 patients for comparison. Results: Approximately 8% of our study cohort (11 out of 132) experienced suboptimal responses to DBS. Compared with the historical cohort, the multi-country cohort with suboptimal responses had a significantly younger age at onset (mean, 7.0 vs. 8.4 years; p = 0.025) and younger age at DBS (mean, 12.0 vs. 18.6 years; p = 0.019). Additionally, cranial involvement was more common in the multi-country cohort (before DBS, 64% vs. 45%, p = 0.074; before or after DBS, 91% vs. 47%, p = 0.001). Mean motor improvement at the last follow-up from baseline were 0% and 66% for the multi-country and historical cohorts, respectively. All 11 patients of the multi-country cohort had generalization of dystonia within 2.5 years after disease onset. All patients experienced dystonia improvement of >30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline. Conclusion: Approximately 8% of patients represent a more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression, and cranial involvement, which seems to be associated with long-term suboptimal responses to DBS (e.g., secondary worsening). This information could be useful for both clinicians and patients in clinical decision making and patient counseling before and following DBS implantations. Patients with this phenotype may have different neuroplasticity, neurogenetics, or possibly distinct neurophysiology.

Emotion and motor preparation: A transcranial magnetic stimulation study of corticospinal motor tract excitability.

In the present study, we examined whether preparing motor responses under different emotional conditions alters motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation delivered to the motor cortex. Analyses revealed three findings: (1) Reaction times were expedited during exposure to unpleasant images, as compared with pleasant and neutral images; (2) force amplitude was greater during exposure to unpleasant images, as compared with pleasant and neutral images; and (3) MEPs were larger while participants viewed unpleasant images, as compared with neutral images. Hence, coupling the preparation of motor responses with the viewing of emotional images led to arousal-driven changes in corticospinal motor tract excitability, whereas movement speed and force production varied as a function of emotional valence. These findings demonstrate that the effects of emotion on the motor system manifest at varying sensitivity levels across behavioral and neurophysiological measures. Moreover, they validate the action readiness component of emotional experience by demonstrating that emotional states influence the execution of future movements but, alone, do not lead to overt movement.

Upper extremity improvements in chronic stroke: coupled bilateral load training.

BACKGROUND: The current treatment intervention study determined the effect of coupled bilateral training (i.e., bilateral movements and EMG-triggered neuromuscular stimulation) and resistive load (mass) on upper extremity motor recovery in chronic stroke. METHODS: Thirty chronic stroke subjects were randomly assigned to one of three behavioral treatment groups and completed 6 hours of rehabilitation in 4 days: (1) coupled bilateral training with a load on the unimpaired hand, (2) coupled bilateral training with no load on the unimpaired hand, and (3) control (no stimulation assistance or load). RESULTS: Separate mixed design ANOVAs revealed improved motor capabilities by the coupled bilateral groups. From the pretest to the posttest, both the coupled bilateral no load and load groups moved a higher number of blocks and demonstrated more regularity in the sustained contraction task. Faster motor reaction times across test sessions for the coupled bilateral load group provided additional evidence for improved motor capabilities. CONCLUSIONS: Together these behavioral findings lend support to the contribution of coupled bilateral training with a load on the unimpaired arm to improved motor capabilities on the impaired arm. This evidence supports a neural explanation in that simultaneously moving both limbs during stroke rehabilitation training appears to activate balanced interhemispheric interactions while an extra load on the unimpaired limb provides stability to the system.