BCI-FES With Multimodal Feedback for Motor Recovery Poststroke.

An increasing number of research teams are investigating the efficacy of brain-computer interface (BCI)-mediated interventions for promoting motor recovery following stroke. A growing body of evidence suggests that of the various BCI designs, most effective are those that deliver functional electrical stimulation (FES) of upper extremity (UE) muscles contingent on movement intent. More specifically, BCI-FES interventions utilize algorithms that isolate motor signals-user-generated intent-to-move neural activity recorded from cerebral cortical motor areas-to drive electrical stimulation of individual muscles or muscle synergies. BCI-FES interventions aim to recover sensorimotor function of an impaired extremity by facilitating and/or inducing long-term motor learning-related neuroplastic changes in appropriate control circuitry. We developed a non-invasive, electroencephalogram (EEG)-based BCI-FES system that delivers closed-loop neural activity-triggered electrical stimulation of targeted distal muscles while providing the user with multimodal sensory feedback. This BCI-FES system consists of three components: (1) EEG acquisition and signal processing to extract real-time volitional and task-dependent neural command signals from cerebral cortical motor areas, (2) FES of muscles of the impaired hand contingent on the motor cortical neural command signals, and (3) multimodal sensory feedback associated with performance of the behavioral task, including visual information, linked activation of somatosensory afferents through intact sensorimotor circuits, and electro-tactile stimulation of the tongue. In this report, we describe device parameters and intervention protocols of our BCI-FES system which, combined with standard physical rehabilitation approaches, has proven efficacious in treating UE motor impairment in stroke survivors, regardless of level of impairment and chronicity.

Ipsilesional Mu Rhythm Desynchronization Correlates With Improvements in Affected Hand Grip Strength and Functional Connectivity in Sensorimotor Cortices Following BCI-FES Intervention for Upper Extremity in Stroke Survivors.

Stroke is a leading cause of acquired long-term upper extremity motor disability. Current standard of care trajectories fail to deliver sufficient motor rehabilitation to stroke survivors. Recent research suggests that use of brain-computer interface (BCI) devices improves motor function in stroke survivors, regardless of stroke severity and chronicity, and may induce and/or facilitate neuroplastic changes associated with motor rehabilitation. The present sub analyses of ongoing crossover-controlled trial NCT02098265 examine first whether, during movements of the affected hand compared to rest, ipsilesional Mu rhythm desynchronization of cerebral cortical sensorimotor areas [Brodmann's areas (BA) 1-7] is localized and tracks with changes in grip force strength. Secondly, we test the hypothesis that BCI intervention results in changes in frequency-specific directional flow of information transmission (direct path functional connectivity) in BA 1-7 by measuring changes in isolated effective coherence (iCoh) between cerebral cortical sensorimotor areas thought to relate to electrophysiological signatures of motor actions and motor learning. A sample of 16 stroke survivors with right hemisphere lesions (left hand motor impairment), received a maximum of 18-30 h of BCI intervention. Electroencephalograms were recorded during intervention sessions while outcome measures of motor function and capacity were assessed at baseline and completion of intervention. Greater desynchronization of Mu rhythm, during movements of the impaired hand compared to rest, were primarily localized to ipsilesional sensorimotor cortices (BA 1-7). In addition, increased Mu desynchronization in the ipsilesional primary motor cortex, Post vs. Pre BCI intervention, correlated significantly with improvements in hand function as assessed by grip force measurements. Moreover, the results show a significant change in the direction of causal information flow, as measured by iCoh, toward the ipsilesional motor (BA 4) and ipsilesional premotor cortices (BA 6) during BCI intervention. Significant iCoh increases from ipsilesional BA 4 to ipsilesional BA 6 were observed in both Mu [8-12 Hz] and Beta [18-26 Hz] frequency ranges. In summary, the present results are indicative of improvements in motor capacity and behavior, and they are consistent with the view that BCI-FES intervention improves functional motor capacity of the ipsilesional hemisphere and the impaired hand.

Ipsilesional Mu Rhythm Desynchronization and Changes in Motor Behavior Following Post Stroke BCI Intervention for Motor Rehabilitation.

Loss of motor function is a common deficit following stroke insult and often manifests as persistent upper extremity (UE) disability which can affect a survivor's ability to participate in activities of daily living. Recent research suggests the use of brain-computer interface (BCI) devices might improve UE function in stroke survivors at various times since stroke. This randomized crossover-controlled trial examines whether intervention with this BCI device design attenuates the effects of hemiparesis, encourages reorganization of motor related brain signals (EEG measured sensorimotor rhythm desynchronization), and improves movement, as measured by the Action Research Arm Test (ARAT). A sample of 21 stroke survivors, presenting with varied times since stroke and levels of UE impairment, received a maximum of 18-30 h of intervention with a novel electroencephalogram-based BCI-driven functional electrical stimulator (EEG-BCI-FES) device. Driven by spectral power recordings from contralateral EEG electrodes during cued attempted grasping of the hand, the user's input to the EEG-BCI-FES device modulates horizontal movement of a virtual cursor and also facilitates concurrent stimulation of the impaired UE. Outcome measures of function and capacity were assessed at baseline, mid-therapy, and at completion of therapy while EEG was recorded only during intervention sessions. A significant increase in r-squared values [reflecting Mu rhythm (8-12 Hz) desynchronization as the result of attempted movements of the impaired hand] presented post-therapy compared to baseline. These findings suggest that intervention corresponds with greater desynchronization of Mu rhythm in the ipsilesional hemisphere during attempted movements of the impaired hand and this change is related to changes in behavior as a result of the intervention. BCI intervention may be an effective way of addressing the recovery of a stroke impaired UE and studying neuromechanical coupling with motor outputs. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02098265.

Evaluation of Changes in the Motor Network Following BCI Therapy Based on Graph Theory Analysis.

Despite the established effectiveness of the brain-computer interface (BCI) therapy during stroke rehabilitation (Song et al., 2014a, 2015; Young et al., 2014a,b,c, 2015; Remsik et al., 2016), little is understood about the connections between motor network reorganization and functional motor improvements. The aim of this study was to investigate changes in the network reorganization of the motor cortex during BCI therapy. Graph theoretical approaches are used on resting-state functional magnetic resonance imaging (fMRI) data acquired from stroke patients to evaluate these changes. Correlations between changes in graph measurements and behavioral measurements were also examined. Right hemisphere chronic stroke patients (average time from stroke onset = 38.23 months, standard deviation (SD) = 46.27 months, n = 13, 6 males, 10 right-handed) with upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device. Eyes-closed resting-state fMRI (rs-fMRI) scans, along with T-1 weighted anatomical scans on 3.0T MRI scanners were collected from these patients at four test points. Immediate therapeutic effects were investigated by comparing pre and post-therapy results. Results displayed that th average clustering coefficient of the motor network increased significantly from pre to post-therapy. Furthermore, increased regional centrality of ipsilesional primary motor area (p = 0.02) and decreases in regional centrality of contralesional thalamus (p = 0.05), basal ganglia (p = 0.05 in betweenness centrality analysis and p = 0.03 for degree centrality), and dentate nucleus (p = 0.03) were observed (uncorrected). These findings suggest an overall trend toward significance in terms of involvement of these regions. Increased centrality of primary motor area may indicate increased efficiency within its interactive network as an effect of BCI therapy. Notably, changes in centrality of the bilateral cerebellum regions have strong correlations with both clinical variables [the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT)].

Behavioral Outcomes Following Brain-Computer Interface Intervention for Upper Extremity Rehabilitation in Stroke: A Randomized Controlled Trial.

Stroke is a leading cause of persistent upper extremity (UE) motor disability in adults. Brain-computer interface (BCI) intervention has demonstrated potential as a motor rehabilitation strategy for stroke survivors. This sub-analysis of ongoing clinical trial (NCT02098265) examines rehabilitative efficacy of this BCI design and seeks to identify stroke participant characteristics associated with behavioral improvement. Stroke participants (n = 21) with UE impairment were assessed using Action Research Arm Test (ARAT) and measures of function. Nine participants completed three assessments during the experimental BCI intervention period and at 1-month follow-up. Twelve other participants first completed three assessments over a parallel time-matched control period and then crossed over into the BCI intervention condition 1-month later. Participants who realized positive change (≥1 point) in total ARAT performance of the stroke affected UE between the first and third assessments of the intervention period were dichotomized as "responders" (<1 = "non-responders") and similarly analyzed. Of the 14 participants with room for ARAT improvement, 64% (9/14) showed some positive change at completion and approximately 43% (6/14) of the participants had changes of minimal detectable change (MDC = 3 pts) or minimally clinical important difference (MCID = 5.7 points). Participants with room for improvement in the primary outcome measure made significant mean gains in ARATtotal score at completion (ΔARATtotal = 2, p = 0.028) and 1-month follow-up (ΔARATtotal = 3.4, p = 0.0010), controlling for severity, gender, chronicity, and concordance. Secondary outcome measures, SISmobility, SISadl, SISstrength, and 9HPTaffected, also showed significant improvement over time during intervention. Participants in intervention through follow-up showed a significantly increased improvement rate in SISstrength compared to controls (p = 0.0117), controlling for severity, chronicity, gender, as well as the individual effects of time and intervention type. Participants who best responded to BCI intervention, as evaluated by ARAT score improvement, showed significantly increased outcome values through completion and follow-up for SISmobility (p = 0.0002, p = 0.002) and SISstrength (p = 0.04995, p = 0.0483). These findings may suggest possible secondary outcome measure patterns indicative of increased improvement resulting from this BCI intervention regimen as well as demonstrating primary efficacy of this BCI design for treatment of UE impairment in stroke survivors. Clinical Trial Registration: ClinicalTrials.gov, NCT02098265.

Early Findings on Functional Connectivity Correlates of Behavioral Outcomes of Brain-Computer Interface Stroke Rehabilitation Using Machine Learning.

The primary goal of this work was to apply data-driven machine learning regression to assess if resting state functional connectivity (rs-FC) could estimate measures of behavioral domains in stroke subjects who completed brain-computer interface (BCI) intervention for motor rehabilitation. The study cohort consisted of 20 chronic-stage stroke subjects exhibiting persistent upper-extremity motor deficits who received the intervention using a closed-loop neurofeedback BCI device. Over the course of this intervention, resting state functional MRI scans were collected at four distinct time points: namely, pre-intervention, mid-intervention, post-intervention and 1-month after completion of intervention. Behavioral assessments were administered outside the scanner at each time-point to collect objective measures such as the Action Research Arm Test, Nine-Hole Peg Test, and Barthel Index as well as subjective measures including the Stroke Impact Scale. The present analysis focused on neuroplasticity and behavioral outcomes measured across pre-intervention, post-intervention and 1-month post-intervention to study immediate and carry-over effects. Rs-FC, changes in rs-FC within the motor network and the behavioral measures at preceding stages were used as input features and behavioral measures and associated changes at succeeding stages were used as outcomes for machine-learning-based support vector regression (SVR) models. Potential clinical confounding factors such as age, gender, lesion hemisphere, and stroke severity were included as additional features in each of the regression models. Sequential forward feature selection procedure narrowed the search for important correlates. Behavioral outcomes at preceding time-points outperformed rs-FC-based correlates. Rs-FC and changes associated with bilateral primary motor areas were found to be important correlates of across several behavioral outcomes and were stable upon inclusion of clinical variables as well. NIH Stroke Scale and motor impairment severity were the most influential clinical variables. Comparatively, linear SVR models aided in evaluation of contribution of individual correlates and seed regions while non-linear SVR models achieved higher performance in prediction of behavioral outcomes.

Machine Learning Classification to Identify the Stage of Brain-Computer Interface Therapy for Stroke Rehabilitation Using Functional Connectivity.

Interventional therapy using brain-computer interface (BCI) technology has shown promise in facilitating motor recovery in stroke survivors; however, the impact of this form of intervention on functional networks outside of the motor network specifically is not well-understood. Here, we investigated resting-state functional connectivity (rs-FC) in stroke participants undergoing BCI therapy across stages, namely pre- and post-intervention, to identify discriminative functional changes using a machine learning classifier with the goal of categorizing participants into one of the two therapy stages. Twenty chronic stroke participants with persistent upper-extremity motor impairment received neuromodulatory training using a closed-loop neurofeedback BCI device, and rs-functional MRI (rs-fMRI) scans were collected at four time points: pre-, mid-, post-, and 1 month post-therapy. To evaluate the peak effects of this intervention, rs-FC was analyzed from two specific stages, namely pre- and post-therapy. In total, 236 seeds spanning both motor and non-motor regions of the brain were computed at each stage. A univariate feature selection was applied to reduce the number of features followed by a principal component-based data transformation used by a linear binary support vector machine (SVM) classifier to classify each participant into a therapy stage. The SVM classifier achieved a cross-validation accuracy of 92.5% using a leave-one-out method. Outside of the motor network, seeds from the fronto-parietal task control, default mode, subcortical, and visual networks emerged as important contributors to the classification. Furthermore, a higher number of functional changes were observed to be strengthening from the pre- to post-therapy stage than the ones weakening, both of which involved motor and non-motor regions of the brain. These findings may provide new evidence to support the potential clinical utility of BCI therapy as a form of stroke rehabilitation that not only benefits motor recovery but also facilitates recovery in other brain networks. Moreover, delineation of stronger and weaker changes may inform more optimal designs of BCI interventional therapy so as to facilitate strengthened and suppress weakened changes in the recovery process.

Brain-Computer Interface Training after Stroke Affects Patterns of Brain-Behavior Relationships in Corticospinal Motor Fibers.

Background: Brain-computer interface (BCI) devices are being investigated for their application in stroke rehabilitation, but little is known about how structural changes in the motor system relate to behavioral measures with the use of these systems. Objective: This study examined relationships among diffusion tensor imaging (DTI)-derived metrics and with behavioral changes in stroke patients with and without BCI training. Methods: Stroke patients (n = 19) with upper extremity motor impairment were assessed using Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), Nine-Hole Peg Test (9-HPT), and DTI scans. Ten subjects completed four assessments over a control period during which no training was administered. Seventeen subjects, including eight who completed the control period, completed four assessments over an experimental period during which subjects received interventional BCI training. Fractional anisotropy (FA) values were extracted from each corticospinal tract (CST) and transcallosal motor fibers for each scan. Results: No significant group by time interactions were identified at the group level in DTI or behavioral measures. During the control period, increases in contralesional CST FA and in asymmetric FA (aFA) correlated with poorer scores on SIS and 9-HPT. During the experimental period (with BCI training), increases in contralesional CST FA were correlated with improvements in 9-HPT while increases in aFA correlated with improvements in ARAT but with worsening 9-HPT performance; changes in transcallosal motor fibers positively correlated with those in the contralesional CST. All correlations p < 0.05 corrected. Conclusion: These findings suggest that the integrity of the contralesional CST may be used to track individual behavioral changes observed with BCI training after stroke.