White matter hyperintensity-associated structural disconnection, resting state functional connectivity, and cognitive control in older adults

Abhishek Jaywant; Katharine Dunlop; Lindsay W. Victoria; Lauren Oberlin; Charles Lynch; Matteo Respino; Amy Kuceyeski; Matthew Scult; Matthew Hoptman; Conor Liston; Michael W. O’Dell; George S. Alexopoulos; Faith M. Gunning

doi:10.1101/2020.04.14.039065

Abstract

White matter hyperintensities (WMH) are linked to cognitive control; however, the structural and functional mechanisms are largely unknown. We investigated the relationship between WMH-associated disruptions of structural connectivity, resting state functional connectivity (RSFC), and cognitive control in older adults. Fifty-eight cognitively-healthy older adults completed cognitive control tasks, structural MRI, and resting state fMRI scans. We estimated inferred, WMH-related disruptions in structural connectivity between pairs of subcortical and cortical regions by overlaying each participant’s WMH mask on a normative tractogram dataset. For region-pairs in which structural disconnection was associated with cognitive control, we calculated RSFC between nodes in those same regions. WMH-related structural disconnection and RSFC in the cognitive control network and default mode network were both associated with poorer cognitive inhibition. These regionally-specific, WMH-related structural and functional changes were more strongly associated with cognitive inhibition compared to standard rating of WMH burden. Our findings highlight the role of circuit-level disruptions to the cognitive control network and default mode network that are related to WMH and impact cognitive control in aging.

Competing Interest Statement

G.S. Alexopoulos has served on the speakers’ bureaus of Allergan, Otsuka, and Takeda-Lundbeck and on advisory groups for Janssen and Eisai. Drs. Jaywant, Dunlop, Victoria, Oberlin, Lynch, Kuceyeski, Respino, Hoptman, Scult, Liston, O’Dell, and Gunning report no financial disclosures.

Abbreviations

ARWMC: Age-Related White Matter Change scale
ChaCo: Change in Connectivity
DMN: Default Mode Network
FDR: False Discovery Rate
HVLT-R: Hopkins Verbal Learning Test-Revised
PLSR: Partial Least Square Regression
RSFC: Resting State Functional Connectivity
TMT: Trail Making Test
TMT-B/A: Trail Making Test, ratio of B over A
VIP: Variable importance in the projection
WMH: White Matter Hyperintensities

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