A consistent white-matter lesion is associated with network-level structural and functional disconnection in chronic...

Broca's aphasia has traditionally been attributed to cortical damage in Broca's area; however, emerging evidence suggests broader network-level dysfunction. This study investigated whether a consistent white-matter lesion underlies Broca's aphasia and how its structural dysconnectivity (SDC) relates to functional network disruption and severity. We analyzed multimodal MRI data from patients with chronic Broca's aphasia (n = 58). Voxel-based lesion overlap mapping (VLOM) revealed a focal white-matter lesion beneath the left central sulcus in 90% of patients with Broca's aphasia. Logistic regression analysis showed that it distinguishes Broca's aphasia from other aphasia types (Odds ratio = 149.2, p < 0.001), suggesting a specific association rather than general anatomical vulnerability. Voxel-based lesion-symptom mapping (VLSM) identified perisylvian regions associated with aphasia severity. Notably, the core lesion was centrally embedded within these regions predictive of severity. Approximately 40% of the streamlines passing through the core lesion were connected to the predictor regions. Diffusion tractography revealed that the core lesion disrupted key pathways, including the arcuate fasciculus (AF) and frontal aslant tract (FAT). Network modeling indicated SDC extended to large-scale networks, including salience, default mode, and frontoparietal networks. Functional connectivity analyses revealed that the SDC arising from the core lesion was significantly correlated with the extent of widespread network-level functional dysconnectivity and overall language function (r > 0.4, p < 0.05), thereby linking the structural pathology to the functional network abnormalities. These findings suggest Broca's aphasia reflects a consistent focal lesion associated with distributed structural and functional disconnection, underscoring network-level pathology beyond Broca's area.