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The neurophysiological architecture of semantic dementia: spectral dynamic causal modelling of a neurodegenerative proteinopathy.

Abstract：

:The selective destruction of large-scale brain networks by pathogenic protein spread is a ubiquitous theme in neurodegenerative disease. Characterising the circuit architecture of these diseases could illuminate both their pathophysiology and the computational architecture of the cognitive processes they target. However, this is challenging using standard neuroimaging techniques. Here we addressed this issue using a novel technique-spectral dynamic causal modelling-that estimates the effective connectivity between brain regions from resting-state fMRI data. We studied patients with semantic dementia-the paradigmatic disorder of the brain system mediating world knowledge-relative to healthy older individuals. We assessed how the effective connectivity of the semantic appraisal network targeted by this disease was modulated by pathogenic protein deposition and by two key phenotypic factors, semantic impairment and behavioural disinhibition. The presence of pathogenic protein in SD weakened the normal inhibitory self-coupling of network hubs in both antero-mesial temporal lobes, with development of an abnormal excitatory fronto-temporal projection in the left cerebral hemisphere. Semantic impairment and social disinhibition were linked to a similar but more extensive profile of abnormally attenuated inhibitory self-coupling within temporal lobe regions and excitatory projections between temporal and inferior frontal regions. Our findings demonstrate that population-level dynamic causal modelling can disclose a core pathophysiological feature of proteinopathic network architecture-attenuation of inhibitory connectivity-and the key elements of distributed neuronal processing that underwrite semantic memory.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Benhamou E,Marshall CR,Russell LL,Hardy CJD,Bond RL,Sivasathiaseelan H,Greaves CV,Friston KJ,Rohrer JD,Warren JD,Razi A

doi

10.1038/s41598-020-72847-1

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

16321

issue

issn

2045-2322

pii

10.1038/s41598-020-72847-1

journal_volume

pub_type

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The neurophysiological architecture of semantic dementia: spectral dynamic causal modelling of a neurodegenerative proteinopathy.