Spectral dynamic causal modelling of resting-state fMRI: an exploratory study relating effective brain connectivity in the default mode network to genetics

Abstract

We conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer’s disease and mild cognitive impairment. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set which is obtained out-of-sample from 663 ADNI subjects having only genome-wide data. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). In both cases we implement a parametric bootstrap for testing SNP coefficients and make comparisons with p-values obtained from asymptotic null distributions. In both networks at an initial q-value threshold of 0.1 no effects are found. We report on exploratory patterns of associations with relatively high ranks that exhibit stability to the differing assumptions made by both FSR and LME.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jun 01, 2020
Source ID
10.1515/sagmb-2019-0058

Entities

People

  • Eugene Opoku
  • Farouk S. Nathoo
  • Jie Wang
  • Jiguo Cao
  • Jodie Gawryluk
  • Laila Yasmin
  • Liangliang Wang
  • Sidi Wu
  • Vanessa Scarapicchia
  • Yin Song
  • Yunlong Nie

Organizations

  • National Institutes of Health
  • Natural Sciences and Engineering Research Council
  • Simon Fraser University
  • United States Department of Defense
  • University of Victoria

Tags

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Statistical inference.
  • Traumatic Brain Injury (TBI) and Cognitive Aging in the Guam and Border Populations Affected by Alzheimer's Disease and Tau-Associated Dementias.

Technology Areas

  • Biotechnology