Regional Strength of Large-Scale Functional Brain Networks is Associated with Regional Volumes in Older Adults and in Alzheimer's Disease

Abstract

Background: The association between regional volumes and resting-state functional networks was tested within the default-mode network (DMN), influenced by Alzheimer pathology, salience network (SalN), not under similar pathological influence, and sensorimotor network (SMN), usually spared by pathology. Methods: A total of 148 participants, with Alzheimer's disease (AD) dementia, mild cognitive impairment (MCI), and healthy controls underwent multimodal brain magnetic resonance imaging (MRI). Functional network identification was achieved with group-level independent-component analysis of functional MRI (fMRI) scans. T1 weighted images were also analyzed. Ten regions of interest (ROI) were defined in core hubs of the three networks. Gray-matter volume/functional network strength association was tested within-ROI and cross-ROI in each group by using partial-correlation models and ROI-to-ROI, ROI-to-voxel, and voxel-to-voxel correlations. Results: In controls, a negative association was found between right inferior-parietal volumes and SMN expression in the left precentral gyrus, as revealed by ROI-to-ROI models. In AD, DMN expression was positively associated with the volume of the left insula and the right inferior parietal lobule, and SalN expression was positively associated with volume of the left inferior parietal lobule. ROI-to-voxel models revealed significant associations between the volume of the posterior cingulate cortex and SMN expression in sensorimotor and premotor regions. No significant findings emerged in the MCI nor from voxel-to-voxel analyses. Discussion: Regional volumes of main network hubs are significantly associated with hemodynamic network expression, although patterns are intricate and dependent on diagnostic status. Since distinct networks are differentially influenced by Alzheimer pathology, it appears that pathology plays a significant role in influencing the association between regional volumes and regional functional network strength.

Altered Interplay Among Large-Scale Brain Functional Networks Modulates Multi-Domain Anosognosia in Early Alzheimer’s Disease

“…This pattern of alteration among these networks' dynamic interactions was observed in association with all aspects of anosognosia in this study. Changes in inter-network activity expressed as increased connectivity between the DMN and the salience network, also found in this study in association with anosognosia, have been previously reported in mild probable AD dementia (Sarli et al, 2021). It might be suggested, therefore, that changes in activity in anticorrelated networks would alter the level of mutual inhibition exerted among their regions leading to a progressive loss of network integration and, in turn, to detectable cognitive and functional impairments, including alterations of awareness.…”

Functional MRI-Specific Alterations in Salience Network in Mild Cognitive Impairment: An ALE Meta-Analysis

“…The brain areas of the SN were summarized as follows: (1) Use ICA: bilateral anterior insula (Yi et al, 2015 ), bilateral frontoinsular cortex, bilateral anterior cingulate cortex (ACC) (Han et al, 2011 ), bilateral dorsal ACC (dACC), bilateral insula lobule (Chand et al, 2017 ), right supplementary motor area (SMA), left superior temporal gyrus (STG), bilateral supramarginal gyrus (SG), left precuneus (Conwell et al, 2018 ; Cai et al, 2020b ), preSMA (Yi et al, 2015 ), dorsal anterior cingulate cortex/medial prefrontal cortex (dACC/MPFC), dorsolateral prefrontal cortex (DLPFC) (He et al, 2014 ), bilateral caudate (Agosta et al, 2012 ), the thalamus (Wang et al, 2020 ), bilateral ventrolateral prefrontal cortex, bilateral STG/insula, midcingulate cortex/preSMA, medial orbitofrontal cortex, and bilateral orbital/frontoinsular (Agosta et al, 2012 ) and (2) Use seed ROI: bilateral frontoinsular cortex (Joo et al, 2017 ), bilateral anterior insula, bilateral dACC, dACC/MPFC, bilateral anterior insula (Zhu et al, 2016 ), bilateral insula (Sarli et al, 2021 ), and bilateral SG (Liang et al, 2012 ).…”

White-Matter Hyperintensity Load and Differences in Resting-State Network Connectivity Based on Mild Cognitive Impairment Subtype

“…It has also been proposed that the pattern of regional atrophy typically seen in ageing may act as a promoter of functional plasticity, because task activation in older adults tends to increase in areas that are subjected to age-associated volumetric decrease (Greenwood, 2007). A recent study confirmed this negative association between regional structure and network expression in healthy adults, and also found inverse (positive) associations in patients with AD, indicating that those with reduced atrophy were also those with a stronger network expression (Sarli et al, 2021). Within this context, WMHs are a further contributor to the reorganisation of the neurofunctional architecture, as reported by a number of investigations (Reijmer et al, 2015;Zhou et al, 2015;Cheng et al, 2017;De Marco et al, 2017b;Liu et al, 2019).…”