EEG-based motor network biomarkers for identifying target patients with stroke for upper limb rehabilitation and its construct validity

Rehabilitation is the main therapeutic approach for reducing poststroke functional deficits in the affected upper limb; however, significant between-patient variability in rehabilitation efficacy indicates the need to target patients who are likely to have clinically significant improvement after treatment. Many studies have determined robust predictors of recovery and treatment gains and yielded many great results using linear approachs. Evidence has emerged that the nonlinearity is a crucial aspect to study the inter-areal communication in human brains and abnormality of oscillatory activities in the motor system is linked to the pathological states. In this study, we hypothesized that combinations of linear and nonlinear (cross-frequency) network connectivity parameters are favourable biomarkers for stratifying patients for upper limb rehabilitation with increased accuracy. We identified the biomarkers by using 37 prerehabilitation electroencephalogram (EEG) datasets during a movement task through effective connectivity and logistic regression analyses. The predictive power of these biomarkers was then tested by using 16 independent datasets (i.e. construct validation). In addition, 14 right handed healthy subjects were also enrolled for comparisons. The result shows that the beta plus gamma or theta network features provided the best classification accuracy of 92%. The predictive value and the sensitivity of these biomarkers were 81.3% and 90.9%, respectively. Subcortical lesion, the time poststroke and initial Wolf Motor Function Test (WMFT) score were identified as the most significant clinical variables affecting the classification accuracy of this predictive model. Moreover, 12 of 14 normal controls were classified as having favourable recovery. In conclusion, EEG-based linear and nonlinear motor network biomarkers are robust and can help clinical decision making.