STRUCTURE–FUNCTION COUPLING AFTER STROKE: REGIONAL SPECIFICITY AND LESION LATERALITY IN RECOVERY

Stroke disrupts the brain’s structural and functional organisation. The interaction between these systems, structure–function coupling (SFC), has been linked to performance, yet it remains underexplored in stroke. As most work has focused on the acute stage and relied on univariate measures, limiting insights into SFC–behaviour relationships, we investigated multivariate associations across recovery stages using partial least squares correlation (PLSC).
Patients were assessed at 1 week (T1; n=52) and 3 months post-stroke (T2; n=35); 30 patients contributed longitudinal data. The Structural Decoupling Index (SDI, Preti et al. 2019) quantified SFC by decomposing patients’ resting-state BOLD timeseries into structure aligned and structure divergent components, based on the harmonics of patients’ diffusion-weighted connectomes. SDI was computed for 360 cortical and 17 subcortical regions of the Glasser atlas. Based on multidomain evaluations, motor, attention, and executive functions were each described by one score obtained via non-negative matrix factorisation.
At T1, PLSC revealed distributed, lesion-side–dependent associations between SDI, attention and executive functions. Higher SDI in frontal and temporal regions related to better cognition, whereas higher SDI in cingulate regions was associated with poorer performance, particularly after right-hemispheric stroke. No significant components emerged at T2; however, acute SDI patterns were associated with outcomes at T2. Higher SDI in bilateral cingulate and lateral sulci at T1 was associated with poorer executive function at T2.
These findings suggest that SFC relates to functional outcomes in a region-, domain-, and lesion-side–specific manner, highlighting SFC as a potential marker of network reorganisation and stroke prognosis.