The Wernicke conundrum revisited: evidence from connectome-based lesion-symptom mapping in post-stroke aphasia

The classical assumption that word and sentence comprehension deficits in stroke aphasia follow from damage to Wernicke9s area has been questioned following discrepant results in primary progressive aphasia. We tested the hypothesis of Mesulam et al. (2015; 2019) that word and sentence comprehension deficits in stroke aphasia result from 9double disconnection9 due to white matter damage: word comprehension deficits resulting from disconnection of the anterior temporal lobe and sentence comprehension deficits resulting from disconnection of the frontal lobe. We performed lesion-deficit correlations, including connectome-based lesion-symptom mapping, in four large, partially overlapping groups of English-speaking chronic left hemisphere stroke survivors. After removing variance due to object recognition and associative semantic processing, the same middle and posterior temporal lobe regions were implicated both in word comprehension deficits (N = 180) and complex noncanonical sentence comprehension deficits (N = 131). Repetition deficits (N = 218) were associated with damage to the posterior temporal lobe and superior longitudinal fasciculus, and agrammatic production (N = 92) was associated with damage to the posterior middle frontal gyrus. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and noncanonical sentence comprehension, including the temporal pole. We found additional significant temporal-parietal disconnections for noncanonical sentence comprehension deficits, which may indicate a role for phonological working memory in processing complex syntax, but no significant frontal-temporal or frontal-parietal disconnections. By contrast, repetition deficits were associated with a very large set of significant disconnections, including frontal-temporal disconnections, and agrammatic production was associated primarily with significant disconnections within the frontal lobe. Our results largely agree with the classical notion that damage to Wernicke9s area causes both word and sentence comprehension deficits in stroke-based aphasia, suggest a supporting role for temporal pole in both word and sentence comprehension, and speak against the hypothesis that sentence comprehension deficits in Wernicke9s aphasia result from frontal-temporal or frontal-parietal disconnections.