A lesion and connectivity-based hierarchical model of chronic aphasia recovery dissociates patients and healthy controls.

Traditional models of left hemisphere stroke recovery propose that reactivation of remaining ipsilesional tissue is optimal for language processing whereas reliance on contralesional right hemisphere homologues is less beneficial or possibly maladaptive in the chronic recovery stage. However, neuroimaging evidence for this proposal is mixed. This study aimed to elucidate patterns of effective connectivity in patients with chronic aphasia in light of healthy control connectivity patterns and in relation to damaged tissue within left hemisphere regions of interest and according to performance on a semantic decision task. Using fMRI and dynamic causal modeling, biologically-plausible models within four model families were created to correspond to potential neural recovery patterns, including Family A: Left-lateralized connectivity (i.e., no/minimal damage), Family B: Bilateral anterior-weighted connectivity (i.e., posterior damage), Family C: Bilateral posterior-weighted connectivity (i.e., anterior damage) and Family D: Right-lateralized connectivity (i.e., extensive damage). Controls exhibited a strong preference for left-lateralized network models (Family A) whereas patients demonstrated a split preference for Families A and C. At the level of connections, controls exhibited stronger left intrahemispheric task-modulated connections than did patients. Within the patient group, damage to left superior frontal structures resulted in greater right intrahemispheric connectivity whereas damage to left ventral structures resulted in heightened modulation of left frontal regions. Lesion metrics best predicted accuracy on the fMRI task and aphasia severity whereas left intrahemispheric connectivity predicted fMRI task reaction times. These results are discussed within the context of the hierarchical recovery model of chronic aphasia.