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

Alexander D. Shaw, Laura E. Hughes, Rosalyn Moran, Ian Coyle-Gilchrist, Tim Rittman, James B. Rowe

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1837–1847
Number of pages11
JournalCerebral Cortex
Volume31
Issue number3
Early online date19 Jun 2019
DOIs
Publication statusPublished - Mar 2021

Keywords

  • Dcm
  • Dementia
  • Machine learning
  • Meg
  • Microcircuitry

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