Anterior temporal lobe degeneration produces widespread network-driven dysfunction

Christine C. Guo, Maria Luisa Gorno-Tempini, Benno Gesierich, Maya Henry, Andrew Trujillo, Tal Shany-Ur, Jorge Jovicich, Simon D. Robinson, Joel H. Kramer, Katherine P. Rankin, Bruce L. Miller, William W. Seeley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

176 Scopus citations


The neural organization of semantic memory remains much debated. A 'distributed-only' view contends that semantic knowledge is represented within spatially distant, modality-selective primary and association cortices. Observations in semantic variant primary progressive aphasia have inspired an alternative model featuring the anterior temporal lobe as an amodal hub that supports semantic knowledge by linking distributed modality-selective regions. Direct evidence has been lacking, however, to support intrinsic functional interactions between an anterior temporal lobe hub and upstream sensory regions in humans. Here, we examined the neural networks supporting semantic knowledge by performing a multimodal brain imaging study in healthy subjects and patients with semantic variant primary progressive aphasia. In healthy subjects, the anterior temporal lobe showed intrinsic connectivity to an array of modality-selective primary and association cortices. Patients showed focal anterior temporal lobe degeneration but also reduced physiological integrity throughout distributed modality-selective regions connected with the anterior temporal lobe in healthy controls. Physiological deficits outside the anterior temporal lobe correlated with scores on semantic tasks and with anterior temporal subregion atrophy, following domain-specific and connectivity-based predictions. The findings provide a neurophysiological basis for the theory that semantic processing is orchestrated through interactions between a critical anterior temporal lobe hub and modality-selective processing nodes.

Original languageAmerican English
Pages (from-to)2979-2991
Number of pages13
Issue number10
StatePublished - Oct 2013
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institute of Aging (NIA grants AG19724 and AG1657303 to B.L.M. and W.W.S.), the National Institute of Neurological Diseases and Stroke (NS050915 grant to M.L.G.T) the Larry L. Hillblom Foundation (J.H.K.), Marie Curie International Grant (MIRG-CT-2007-046512 to M.L.G.T.), Provincia Autonoma di Trento, Fondazione Cassa di Risparmio di Trento e Rovereto, Italy.


  • anterior temporal lobe
  • cognition
  • functional neuroimaging
  • semantic dementia
  • semantics


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