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In vivo assay of cortical microcircuitry in frontotemporal dementia: a platform for experimental medicine studies

Shaw, Alexander, Hughes, Laura E, Moran, Roslayn, Coyle-Gilchrist, Ian, Rittman, Tim and Rowe, James B 2019. In vivo assay of cortical microcircuitry in frontotemporal dementia: a platform for experimental medicine studies. Cerebral Cortex 10.1093/cercor/bhz024

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Abstract

The analysis of neural circuits can provide crucial insights into the mechanisms of neurodegeneration and dementias, and offer potential quantitative biological tools to assess novel therapeutics. Here we use behavioral variant frontotemporal dementia (bvFTD) as a model disease. We demonstrate that inversion of canonical microcircuit models to noninvasive human magnetoencephalography, using dynamic causal modeling, can identify the regional- and laminar-specificity of bvFTD pathophysiology, and their parameters can accurately differentiate patients from matched healthy controls. Using such models, we show that changes in local coupling in frontotemporal dementia underlie the failure to adequately establish sensory predictions, leading to altered prediction error responses in a cortical information-processing hierarchy. Using machine learning, this model-based approach provided greater case–control classification accuracy than conventional evoked cortical responses. We suggest that this approach provides an in vivo platform for testing mechanistic hypotheses about disease progression and pharmacotherapeutics.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Psychology
Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Oxford University Press
ISSN: 1047-3211
Date of First Compliant Deposit: 7 June 2019
Date of Acceptance: 26 January 2019
Last Modified: 24 Jun 2019 12:28
URI: http://orca.cf.ac.uk/id/eprint/123301

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