Posterior Cortical Atrophy: Altered Language Processing System Connectivity and Its Implications on Language Comprehension and Production
<b>Background</b>: Posterior cortical atrophy (PCA) patients typically show progressive visual decline, although language impairment can be a prominent feature. Previous studies have explored language connectivity impairment in PCA; not much is known about the exact nature of language processing disruptions in PCA. <b>Methods</b>: Thirty-seven PCA patients were compared with 39 cognitively unimpaired (CU) individuals. Functional connectivity was evaluated for the language processing system, which consisted of language, perceptual, motor, and cognitive networks. Linear regression was performed to compare within- and between-network connectivity across networks and within the language network in PCA compared to CU individuals. Relationships between language network connectivity, clinical performance, and gray matter volumes were also evaluated. <b>Results</b>: PCA showed reduced connectivity within the language and perceptual networks, along with reduced between-network connectivity compared to CU individuals. Regional connectivity breakdown within the language network was also noted. Language processing system connectivity was not associated with clinical performance on language processing tests. However, a breakdown in Broca-Wernicke, Wernicke-middle frontal gyrus, and Wernicke-frontal orbital gyrus connectivity was related to worse performance on sentence repetition. Lastly, gray matter volume was not associated with language network connectivity. <b>Discussion</b>: Together, these results reiterate the breakdown of language network connectivity in PCA and highlight the disruption in connectivity at the regional level within the language network. Reduced connectivity within the perceptual network and associations between reduced language network connectivity and worse performance on sentence repetition imply a breakdown within the language processing systems in PCA.
Authors
- Val J. Lowe (ORCID: https://orcid.org/0000-0002-5612-1667)
- Keith A. Josephs (ORCID: https://orcid.org/0000-0003-2930-8634)
- Jennifer Whitwell
- Mary M. Machulda (ORCID: https://orcid.org/0000-0003-4834-5967)
- Neha Atulkumar Singh (ORCID: https://orcid.org/0000-0002-3614-9179)
- Watanabe Hiroyuki (ORCID: https://orcid.org/0009-0009-1623-6599)
- Ryota Satoh (ORCID: https://orcid.org/0000-0002-3418-2987)
- Jonathan Graff-Radford
Institutions
- Mayo Clinic (US)
- WinnMed (US)
- Mayo Clinic in Florida (US)
Publication Details
- Journal
- Brain Sciences
- Published
- 2025-11-29
- DOI
- https://doi.org/10.3390/brainsci15121287
- Primary Topic
- Epilepsy research and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Eli Lilly and Company
- Eisai
- National Institutes of Health
- Avid Radiopharmaceuticals
- National Institute on Aging
- National Cancer Institute