Anterior temporal lobe, word comprehension, and physiology of atrophy in semantic primary progressive aphasia

Sep 29, 2026

Peak focal atrophy in the anterior temporal lobe (ATL) is central to word comprehension in semantic variant primary progressive aphasia (svPPA), yet whether peak atrophy sites reliably mark dysfunctional brain regions for clinicopathologic links remains untested. Using structural MRI and FDG-PET in 32 PPA individuals (11 svPPA) and 10 controls, the study quantified atrophy and hypometabolism maps and related them to Peabody Picture Vocabulary Test performance via statistical tests and regressions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Introduction

Methods

Imaging and analysis

Results

Discussion

Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript | | HHS Public Access
Author manuscript
Neurocase. Author manuscript; available in PMC 2026 January 05. | | --- | --- | Published in final edited form as: Neurocase. 2025 December ; 31(6): 260–267. doi:10.1080/13554794.2025.2587123 . Anterior temporal lobe, word comprehension, and physiology of atrophy in semantic primary progressive aphasia Jordan Q. Behna, Elena Barbieria,b, M. Marsel Mesulama,c, Borna Bonakdarpoura,caMesulam Institute for Cognitive Neurology and Alzheimer’s Disease, Northwestern University, Chicago, IL, USA b Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, USAc Department of Neurology, Northwestern University, Chicago, IL, USA Abstract Peak focal atrophy in the anterior temporal lobe (ATL) highlights the critical role of this area for word comprehension in semantic variant primary progressive aphasia (svPPA) . However, the assumption that peak atrophy sites are specific markers of dysfunctional brain sites, and therefore reliable variables for clinicopathologic correlations, has not been rigorously tested. Using structural MRI and FDG-PET, we assessed atrophy and hypometabolism in 32 individuals with PPA (11 svPPA) and 10 healthy controls. Word comprehension was measured using the Peabody Picture Vocabulary Test. Voxel-based morphometry and standardized uptake value ratios were used to generate atrophy and hypometabolism maps. Two-sample t-tests compared svPPA and controls, and regression analyses evaluated the relationship between imaging metrics and word comprehension. Findings revealed significant bilateral ATL atrophy and hypometabolism (left > right) . Structural and metabolic measures were independently associated with impaired comprehension. There was substantial overlap between atrophy and hypometabolism within the ATLs, with dysfunction extending into posterior temporal regions. However, there was no evidence of peak hypometabolism in traditional Wernicke’s area. Degeneration – both anatomical and metabolic – of the ATL serves as a robust predictor of comprehension impairment, highlighting its role a critical locus for word comprehension. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ([http://creativecommons.org/](http://creativecommons.org/)[ ](http://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. CONTACT Jordan Q. Behn, [jordan-behn@northwestern.edu](jordan-behn@northwestern.edu), Mesulam Institute for Cognitive Neurology and Alzheimer’s Disease, Feinberg School of Medicine, Northwestern University, 300 E. Superior, Tarry 8, Chicago, IL 60611, USA. Author contributions Jordan Behn: Drafting/revision of the manuscript for content, including medical writing for content; Study concept or design; Analysis or interpretation of data; Elena Barbieri: Drafting/revision of the manuscript for content, including medical writing for content; Study concept or design; Analysis or interpretation of data; Marsel Mesulam: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Study concept or design; Analysis or interpretation of data; Borna Bonakdarpour FAAN: Drafting/revision of the manuscript for content, including medical writing for content; Study concept or design; Analysis or interpretation of data. Disclosure statement No potential conflict of interest was reported by the author(s) . Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript Behn et al. Page 2 Keywords TDP-C; MRI; PET; language; atrophy; neuroimaging; PPA

FAQs

What question does the study address about peak atrophy in svPPA?

It tests whether peak atrophy sites truly act as specific markers of dysfunctional brain areas and reliable variables for clinicopathologic correlations.

How were atrophy and brain metabolism measured?

Structural MRI provided atrophy maps, and FDG-PET assessed hypometabolism using standardized uptake value ratios.

What relationship did the study find between ATL degeneration and word comprehension?

Both anatomical (atrophy) and metabolic (hypometabolism) degeneration of the ATL independently predicted impaired word comprehension, with dysfunction extending beyond the ATLs into posterior temporal regions.

Sep 29, 2026

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