Connectivity measures are robust biomarkers of cortical function and plasticity after stroke

Valid biomarkers of motor system function after stroke could improve clinical decision-making. Electroencephalography-based measures are safe, inexpensive, and accessible in complex medical settings and so are attractive candidates. This study examined specific electroencephalography cortical connectivity measures as biomarkers by assessing their relationship with motor deficits across 28 days of intensive therapy. Resting-state connectivity measures were acquired four times using dense array (256 leads) electroencephalography in 12 hemiparetic patients (7.3 ± 4.0 months post-stroke, age 26-75 years, six male/six female) across 28 days of intensive therapy targeting arm motor deficits. Structural magnetic resonance imaging measured corticospinal tract injury and infarct volume. At baseline, connectivity with leads overlying ipsilesional primary motor cortex (M1) was a robust and specific marker of motor status, accounting for 78% of variance in impairment; ipsilesional M1 connectivity with leads overlying ipsilesional frontal-premotor (PM) regions accounted for most of this (R(2) = 0.51) and remained significant after controlling for injury. Baseline impairment also correlated with corticospinal tract injury (R(2) = 0.52), though not infarct volume. A model that combined a functional measure of connectivity with a structural measure of injury (corticospinal tract injury) performed better than either measure alone (R(2) = 0.93). Across the 28 days of therapy, change in connectivity with ipsilesional M1 was a good biomarker of motor gains (R(2) = 0.61). Ipsilesional M1-PM connectivity increased in parallel with motor gains, with greater gains associated with larger increases in ipsilesional M1-PM connectivity (R(2) = 0.34); greater gains were also associated with larger decreases in M1-parietal connectivity (R(2) = 0.36). In sum, electroencephalography measures of motor cortical connectivity-particularly between ipsilesional M1 and ipsilesional premotor-are strongly related to motor deficits and their improvement with therapy after stroke and so may be useful biomarkers of cortical function and plasticity. Such measures might provide a biological approach to distinguishing patient subgroups after stroke.