Lesion-dependent Cingulo-opercular Network and Language Network Integration in Post-stroke Aphasia

This study explores differential impairment patterns in resting-state functional connectivity (rs-FC) between the cingulo-opercular network (CON) and canonical language networks (LN) in post-stroke aphasia (PSA), emphasizing structure-function relationships mediated by white matter integrity. It specifically investigates how LN lesion topography modulates CON-LN connectivity and behavioral correlates. Sixty-three first-time PSA patients were divided into LN lesion-positive (LNL+, n = 31) and negative (LNL-, n = 32) groups based on lesion volume (>1 cm3) within the canonical LN. Using lesion-based individualized ROIs and group-based template rs-FC, the CON-LN rs-FC was correlated with verbal fluency and white matter integrity metrics, with particular focus on arcuate fasciculus (AF) and superior longitudinal fasciculus (SLF) subdivisions in the LNL+ and LNL- groups, respectively. Although no intergroup differences in CON-LN rs-FC were observed at baseline, distinct lesion-dependent patterns emerged. In LNL+ patients, individualized CON-LN rs-FC was positively correlated with verbal fluency (r = .504, p = .009) and negative correlation with the damage severity of the AF subdivisions (anterior: r = -.601, p < .001; long: r = -.426, p = .024) and SLF subdivisions (SLF II: r = -.483, p = .011; III: r = -.664, p < .001). However, the LNL- patients lacked significant structure-function-behavior associations. The group-based template analysis also detected no significant correlations in either group. Our findings implicate the critical role of CON-LN functional integration for language recovery in PSA patients with direct LN damage. The anterior/long AF segments and SLF II/III are key white matter substrates supporting this functional integration.