Reorganized Functional Networks Underlie Working Memory Deficits After Right-Hemispheric Stroke

Working memory (WM) is a core component of higher-order cognition, and its impairment is a common consequence of stroke. While traditional lesion-symptom mapping highlights focal damage, it often overlooks alterations in large-scale brain network dynamics. This study investigated WM deficits through functional connectivity (FC) analyses of frontoparietal networks in 34 patients with right hemisphere (RH) stroke and 35 healthy controls. Resting-state fMRI was used to examine region-of-interest and whole-brain seed-to-voxel FC in relation to WM performance on verbal and spatial N-back tasks. Compared to controls, stroke patients exhibited disrupted FC-WM associations, characterized by reduced intrahemispheric FC between anterior and posterior RH regions, which correlated with poorer WM performance. Notably, enhanced interhemispheric FC, particularly between the right middle and inferior frontal gyri and contralateral parietal cortices, was positively associated with WM accuracy, suggesting compensatory engagement of the intact hemisphere. No performance differences were observed between task modalities, supporting the involvement of domain-general WM mechanisms. These findings highlight the role of early network-level reorganization in shaping cognitive outcomes post-stroke. Specifically, WM deficits appear to result not solely from structural damage but from altered FC patterns, where reduced intrahemispheric connectivity may be mitigated by adaptive interhemispheric recruitment.