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The Wernicke conundrum revisited: evidence from connectome-based lesion-symptom mapping

Poster D34 in Poster Session D with Social Hour, Friday, October 7, 5:30 - 7:15 pm EDT, Millennium Hall

William Matchin1, Dirk den Ouden1, Gregory Hickok2, Argye Hillis3, Leonardo Bonilha4, Julius Fridriksson1; 1University of South Carolina, 2University of California, Irvine, 3Johns Hopkins University, 4Emory University

***---INTRODUCTION---*** Wernicke’s area has been assumed since the 1800s to be the primary region supporting word and sentence comprehension. However, Mesulam et al. (2015) raised the ‘Wernicke conundrum’, noting widespread variability in anatomical definitions and presenting conflicting data from primary progressive aphasia. To resolve the conundrum, they posited a ‘double disconnection’ hypothesis: word and sentence comprehension deficits in stroke-based aphasia result from disconnection of anterior temporal and inferior frontal regions from other parts of the brain due to white matter damage, rather than dysfunction of Wernicke’s area itself. Here we test this hypothesis using combined lesion-symptom mapping (LSM) and connectome-based lesion-symptom mapping (CLSM) in four large, partially overlapping groups of English-speaking chronic left hemisphere stroke survivors. ***---METHODS---*** All subjects were assessed on the Western Aphasia Battery-Revisited. Our primary measures were Word Comprehension (WAB-R auditory word recognition, with Pyramids and Palm Trees, PPT, as a covariate), Noncanonical Sentence Comprehension (performance on a sentence-picture matching task for complex, noncanonical structures), WAB-R Repetition, and perceptual assessments of Expressive Agrammatism. Lesion maps were manually drawn from anatomical MRI scans, and connectomes assessed using diffusion tensor imaging. Using NiiStat ( we performed both voxel-based and ROI-based LSM analyses relating each of the four selected behavioral variables to lesion location, using total lesion volume as a covariate. Analyses were only performed within voxels/regions that had at least 10% of subjects with damage located there and were corrected for multiple comparisons using permutation tests (10,000 permutations) with a corrected alpha threshold of p < 0.05. For CLSM, we analyzed the diffusion-weighted images that were acquired for each subject and estimated the pairwise connection strength between all regions within the JHU atlas, including both the left and right hemispheres. We combined the LSM and CLSM data by assessing whether lesion-deficit correlations would still be statistically robust when incorporating relevant connection strength as a covariate. See Matchin et al. ( for full methodological details. ***---RESULTS---*** After removing variance due to object recognition and associative semantic processing, the same middle and posterior temporal lobe regions were implicated in both word comprehension deficits and complex noncanonical sentence comprehension deficits. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and noncanonical sentence comprehension, including the temporal pole. We found an additional significant temporal-parietal disconnection for noncanonical sentence comprehension deficits, which may indicate a role for phonological working memory in processing complex syntax, but no significant frontal disconnections. Moreover, damage to these middle-posterior temporal lobe regions was associated with both word and noncanonical sentence comprehension deficits even when accounting for variance due to the strongest anterior temporal and inferior frontal white matter disconnections, respectively. ***---CONCLUSIONS---*** Our results largely agree with the classical notion that Wernicke’s area, defined here as middle superior temporal gyrus and middle-posterior superior temporal sulcus, supports both word and sentence comprehension, suggest a supporting role for temporal pole in both word and sentence comprehension, and speak against the hypothesis that comprehension deficits in Wernicke’s aphasia result from double disconnection.

Topic Areas: Disorders: Acquired, Meaning: Lexical Semantics

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