Estimated regional white matter hyperintensity burden, resting state functional connectivity, and cognitive functions in older adults

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.

Disconnectome associated with progressive white matter hyperintensities in aging: a virtual lesion study

“…For example, our finding that disconnection between the striatum and middle frontal gyrus appears early and increases progressively across older decades is consistent with the known role of these connections in age-associated decrements in memory and executive function ( Buckner, 2004 ). Similarly, the observed disconnection between the thalamus and middle frontal gyrus also becomes more severe in older decades and is consistent with previous studies linking disrupted frontal-striatal-thalamocortical pathways with the decline of cognitive control ( Jaywant et al, 2020 ). Disconnection of the precuneus to the cingulate gyrus (e.g., ventral posterior cingulate gyrus) is seen in the oldest decade.…”

“…One key mechanism by which WMH are thought to affect cognition is through the disconnection of associated gray matter regions ( Jaywant et al, 2020 ). Structural connectivity in the human brain can be inferred using diffusion tractography, and several studies have used diffusion tensor imaging (DTI) data to show that alterations in overall brain network connectivity are associated with cognitive deficits in cohorts of older subjects ( Tuladhar et al, 2016 ; Wiseman et al, 2018 ).…”

The Structural and Functional Neuroanatomy of Post-Stroke Depression and Executive Dysfunction: A Review of Neuroimaging Findings and Implications for Treatment

“…88 Both structural and functional disconnection contribute unique variance to predicting cognitive functioning 89 and in cerebrovascular disease are associated with executive functioning. 90 The possibility that functional connectivity may shift or compensate for structural disconnection over time is also a relevant question to ensure that appropriate treatments are delivered depending on the time period post-stroke, especially as chronic stroke survivors can experience secondary degeneration in the thalamus, amygdala, hippocampus, and cingulum bundle. 91 A limitation of our review and of the literature is that is that it is often clinically and conceptually difficult to differentiate PSD from standalone apathy.…”

Integrating multimodal connectivity improves prediction of individual cognitive abilities

“…As shown in Figures 3 and 5, cortico-subcortical connections involving the caudate, putamen, thalamus, and amygdala with regions of the frontal, parietal, and temporal lobes emerge as predictive of fluid cognition. The cortical regions implicated in fluid cognition comprise nodes of the frontoparietal network, dorsal attention network, cingulo-opercular task control network, and default mode network, all of which have been implicated in executive function (Reineberg et al, 2015, Spreng et al, 2010, Leech et al, 2011, Jaywant et al, 2020 and memory (Iidaka et al, 2006, Wallis et al, 2015, Dixon et al, 2017. The frontoparietal, dorsal attention, and cingulo-opercular networks are frequently implicated in maintaining and updating information in mind, shifting attention, inhibiting distractions, and facilitating goal-directed behaviour (Spreng et al, 2010, Iidaka et al, 2006, Wallis et al, 2015, Dixon et al, 2017.…”

“…In our results, we observe that many distributed cortical and subcortical regions are equally important when using SC to predict cognition, but only a few regions are important when using FC to predict cognition. Previous work (Jaywant et al, 2020) using a partial least squares regression approach to identify the relationship between inferred structural disconnection and cognitive inhibition observed that it was mostly structural connections that were important to predict cognition, with only two functional connections contributing additional unique variance. Our results here align with those findings; While functional and structural connections uniquely predict cognitive abilities, at a regional level there are more regions that are important for the prediction when using structural connectivity than when using functional connectivity.…”