In this paper we demonstrate the application of new effective connectivity analyses to characterize changing patterns of task-related directed interaction in large (25–55 node) cortical networks following the onset of aphasia. The subject was a left-handed woman who became aphasic following a right-hemisphere stroke. She was tested on an auditory word-picture verification task administered one and seven months after the onset of aphasia. MEG/EEG and anatomical MRI data were used to create high spatiotemporal resolution estimates of task-related cortical activity. Effective connectivity analyses of those data showed a reduction of bilateral network influences on preserved right-hemisphere structures, and an increase in intra-hemispheric left-hemisphere influences. She developed a connectivity pattern that was more left lateralized than that of right-handed control subjects. Her emergent left hemisphere network showed a combination of increased functional subdivision of perisylvian language areas and recruitment of medial structures.