Brain-Computer Interface Training With Functional Electrical Stimulation: Facilitating Changes in Interhemispheric Functional Connectivity and Motor Outcomes Post-stroke.

While most survivors of stroke experience some spontaneous recovery and receive treatment in the subacute setting, they are often left with persistent impairments in upper limb sensorimotor function which impact autonomy in daily life. Brain-Computer Interface (BCI) technology has shown promise as a form of rehabilitation that can facilitate motor recovery after stroke, however, we have a limited understanding of the changes in functional connectivity and behavioral outcomes associated with its use. Here, we investigate the effects of EEG-based BCI intervention with functional electrical stimulation (FES) on resting-state functional connectivity (rsFC) and motor outcomes in stroke recovery. 23 patients post-stroke with upper limb motor impairment completed BCI intervention with FES. Resting-state functional magnetic resonance imaging (rs-fMRI) scans and behavioral data were collected prior to intervention, post- and 1-month post-intervention. Changes in rsFC within the motor network and behavioral measures were investigated to identify brain-behavior correlations. At the group-level, there were significant increases in interhemispheric and network rsFC in the motor network after BCI intervention, and patients significantly improved on the Action Research Arm Test (ARAT) and SIS domains. Notably, changes in interhemispheric rsFC from pre- to both post- and 1 month post-intervention correlated with behavioral improvements across several motor-related domains. These findings suggest that BCI intervention with FES can facilitate interhemispheric connectivity changes and upper limb motor recovery in patients after stroke.

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.