Brain structure-function decoupling increases and deviates from functional hierarchy during aging
Poster No:
905
Submission Type:
Abstract Submission
Authors:
Xing Qian1, Kwun Kei Ng1, Janice Koi1, Yu Juan Lim1, Juan Helen Zhou1
Institutions:
1National University of Singapore, Singapore, Singapore
First Author:
Co-Author(s):
Introduction:
The human brain undergoes structural and functional changes during aging, accompanied by cognitive decline. Functionally, the brain is organized into hierarchical networks from unimodal sensory to transmodal association regions (1, 2). Recent work using the structural-decoupling index (SDI), a measure of functional signal smoothness on the structural connectome, showed stronger structure-function coupling in primary sensorimotor networks and greater decoupling in higher-order networks (3). However, age-related changes in structure-function decoupling remain unclear. This study examined regional cross-sectional and longitudinal structure-function decoupling trajectories during aging using two datasets, hypothesizing distinct trajectories across regions reflecting their positions along the functional hierarchy.
Methods:
We analyzed 290 participants from HCP-Aging (age: 36–100 years, 179 females) and 1792 from UK Biobank (age: 48–80 years, 891 females) with follow-up after 1.5–6.6 years.
Resting-state time series were extracted from fMRI and structural connectomes (SC) were constructed from diffusion MRI, using a 419-region-of-interest (ROI) brain parcellation (4, 5). The time series were decomposed into coupled and decoupled components using the Laplacian eigenspectrum of SC (3). The SDI was calculated as the ratio of the norms of decoupled and coupled signals for each ROI. SDI values were averaged across the entire brain (global) or within specific networks (e.g., visual, somatomotor, default, and control networks) for each individual.
Linear regression (HCP) and mixed-effects models (UK Biobank) were used to assess age and time effects, controlling for sex and motion. Spatial distributions of SDI, and age and time effects on SDI were compared to the transmodality gradient of functional connectivity (FC) from young adults (1).
Resting-state time series were extracted from fMRI and structural connectomes (SC) were constructed from diffusion MRI, using a 419-region-of-interest (ROI) brain parcellation (4, 5). The time series were decomposed into coupled and decoupled components using the Laplacian eigenspectrum of SC (3). The SDI was calculated as the ratio of the norms of decoupled and coupled signals for each ROI. SDI values were averaged across the entire brain (global) or within specific networks (e.g., visual, somatomotor, default, and control networks) for each individual.
Linear regression (HCP) and mixed-effects models (UK Biobank) were used to assess age and time effects, controlling for sex and motion. Spatial distributions of SDI, and age and time effects on SDI were compared to the transmodality gradient of functional connectivity (FC) from young adults (1).
Results:
SDI exhibited a spatial gradient aligned with the functional hierarchy, with higher decoupling in transmodal regions (control/default networks) and lower decoupling in unimodal regions (visual/somatomotor networks) (Fig. 1A&M).
Cross-sectionally, both datasets demonstrated age-related increase in global SDI and network-level SDIs across all networks except the subcortical network (Fig. 1 B-J&N-V). Longitudinal analyses on UK Biobank revealed time-related increases in global SDI and network-level SDIs within the visual, dorsal attention, salience/ventral attention, and control networks. Interestingly, the lower global SDI and lower SDI in control, default, dorsal attention, and salience/ventral attention networks were associated with better fluid intelligence at the baseline visit (Fig. 2).
Regionally, ROI-level age and time effects were negatively correlated with ROI transmodality (Fig. 1 K, W&Y). This indicates that SDI in unimodal regions showed larger age effect (t-stat), suggesting greater decoupling with aging in these areas. This suggests that the functional signals of sensorimotor networks become increasingly less constrained by the underlying structural network with aging, thereby limiting their ability to support immediate perception.
Both cross-sectionally and longitudinally, the alignment of SDI patterns with the principal FC gradient decreased with age (Fig. 1 L&X). This shift suggests the spatial distribution of structure-function decoupling deviates progressively from the functional hierarchy organization as aging advances. This indicates a disruption in the efficiency of network-level processing and coordination, impairing immediate sensory perception (characterized by relatively lower decoupling) and flexible higher-order cognition (characterized by relatively higher decoupling).
Cross-sectionally, both datasets demonstrated age-related increase in global SDI and network-level SDIs across all networks except the subcortical network (Fig. 1 B-J&N-V). Longitudinal analyses on UK Biobank revealed time-related increases in global SDI and network-level SDIs within the visual, dorsal attention, salience/ventral attention, and control networks. Interestingly, the lower global SDI and lower SDI in control, default, dorsal attention, and salience/ventral attention networks were associated with better fluid intelligence at the baseline visit (Fig. 2).
Regionally, ROI-level age and time effects were negatively correlated with ROI transmodality (Fig. 1 K, W&Y). This indicates that SDI in unimodal regions showed larger age effect (t-stat), suggesting greater decoupling with aging in these areas. This suggests that the functional signals of sensorimotor networks become increasingly less constrained by the underlying structural network with aging, thereby limiting their ability to support immediate perception.
Both cross-sectionally and longitudinally, the alignment of SDI patterns with the principal FC gradient decreased with age (Fig. 1 L&X). This shift suggests the spatial distribution of structure-function decoupling deviates progressively from the functional hierarchy organization as aging advances. This indicates a disruption in the efficiency of network-level processing and coordination, impairing immediate sensory perception (characterized by relatively lower decoupling) and flexible higher-order cognition (characterized by relatively higher decoupling).
·Figure 1. Global and network-level changes of structural-decoupling index (SDI) in aging and the relationships of SDI changes with functional hierarchy.
·Figure 2. Baseline global and network-level SDIs were associated with fluid intelligence using UK Biobank dataset.
Conclusions:
Our results highlight regionally specific changes in structure-function decoupling throughout aging, which may contribute to cognitive decline. The age-related and time-related increases in decoupling, particularly in unimodal regions, reflect a progressive deviation from the brain's hierarchical functional organization.
Higher Cognitive Functions:
Higher Cognitive Functions Other 2
Lifespan Development:
Aging 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Task-Independent and Resting-State Analysis
Keywords:
Aging
Cognition
FUNCTIONAL MRI
White Matter
Other - structure-function decoupling
1|2Indicates the priority used for review
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