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• W3090022549 abstract "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." @default.
• W3090022549 created "2020-10-08" @default.
• W3090022549 creator A5008052905 @default.
• W3090022549 creator A5045981641 @default.
• W3090022549 creator A5054692399 @default.
• W3090022549 creator A5066792343 @default.
• W3090022549 creator A5068675261 @default.
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• W3090022549 creator A5086581430 @default.
• W3090022549 creator A5086852785 @default.
• W3090022549 date "2020-10-01" @default.
• W3090022549 modified "2023-10-17" @default.
• W3090022549 title "The neurophysiological architecture of semantic dementia: spectral dynamic causal modelling of a neurodegenerative proteinopathy" @default.
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