Abstract Details

Title Phonological Alexia/Agraphia Reflects Damage to the Dorsal Language Pathway: Evidence from Multimodal Imaging

Topic Behavioral Neurology

Presentation(s) S18 - (-)

Poster/Presentation
Number 005

Objective

Background Contemporary neuroanatomical models of language postulate a dorsal pathway specialized for mapping phonological representations to articulatory networks during speech production and tasks involving phonological working memory. Because maintenance and manipulation of sublexical phonological information plays a critical role in reading/spelling unfamiliar nonwords, we hypothesized that damage to the dorsal pathway should be associated with the clinical profile of phonological alexia/agraphia.

Design/Methods We conducted voxel-based lesion-symptom mapping (VLSM) in a large group of post-stroke aphasic patients with MRI/CT evidence of left-hemisphere damage (n=70) who were administered a comprehensive reading/spelling battery. In a subgroup with phonological alexia/agraphia, DTI (n=7) and fMRI data during real word and nonword reading (n=5) were also collected.

Results VLSM indicated that impaired nonword reading/spelling and an enlarged lexicality effect (words > nonwords) were associated with damage to the dorsal language pathway, including posterior superior temporal gyrus, supramarginal gyrus, inferior frontal gyrus/operculum, precentral gyrus, and insula. DTI showed that patients with phonological alexia/agraphia sustained damage to white matter tracts connecting these perisylvian cortical regions, including the superior longitudinal/arcuate fasciculus. fMRI revealed reduced activation in dorsal pathway regions compared to controls (n=8) and increased recruitment of extrasylvian cortical areas that are components of the ventral language pathway implicated in lexical-semantic processing.

Conclusions Our findings confirm that phonological alexia/agraphia results from damage to the dorsal pathway that includes core perisylvian language areas and their connecting white matter tracts. In functional terms, the written language disorder reflects defective engagement of perisylvian cortical networks critical for processing sublexical phonological information during nonword reading/spelling and compensatory over-reliance on a lexical-semantic strategy mediated by preserved ventral pathway regions responsible for mapping phonological and orthographic representations of familiar words to their meanings.

Authors/Disclosures
Steven Z. Rapcsak, MD PRESENTER	No disclosure on file
Katharine A. Nicholson, MD	Dr. Nicholson has received personal compensation for serving as an employee of Sanofi. Dr. Nicholson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Nicholson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx Pharmaceuticals. Dr. Nicholson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Life Sciences. Dr. Nicholson has stock in Sanofi. The institution of Dr. Nicholson has received research support from Alector LLC. The institution of Dr. Nicholson has received research support from AI Therapeutics. The institution of Dr. Nicholson has received research support from Brainstorm Cell Therapeutics. The institution of Dr. Nicholson has received research support from Biogen. The institution of Dr. Nicholson has received research support from NIH. The institution of Dr. Nicholson has received research support from Muscular Dystrophy Association. The institution of Dr. Nicholson has received research support from ALS Association. The institution of Dr. Nicholson has received research support from ALS Finding a Cure. The institution of Dr. Nicholson has received research support from Target ALS.
Andrew T. DeMarco, PhD, CCC-SLP (Georgetown University)	No disclosure on file
Stephen M. Wilson, PhD	No disclosure on file
	No disclosure on file

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