A vast network of structural connections in the brain supports functional communication within the brain. Structural-functional-connectivity coupling, or SFC, determines how anatomical connections in the brain support neural activity or brain communications.
Given the interconnectedness of aging, age-related impairments in cognition, and increased incidence of small vessel disease (SVD) in aging humans, a recent study published in GeroScience examined how variations in cognitive abilities, cognitive reserve, and SVD-related neuropathologies impacted SFC in aging adults.
Study: The structural–functional-connectivity coupling of the aging brain. Image Credit: Komsan Loonprom/Shutterstock.com
Background
The structural network, which consists of complex anatomical connections within the brain, supports the effective functioning of the organ, including communication between various parts of the brain.
Recent studies exploring the relationship between brain structure and cognition and behavior have explored biomarkers that can jointly analyze the structural and functional networks in the brain.
SFC is one such biomarker that can be used to examine the extent to which the anatomical connections in the brain support neural activity.
Aging is strongly associated with increased cognitive impairments, especially those related to executive function and memory.
This gradual decline in cognitive reserve and function could also be linked to the increased incidence of SVD, which often causes vascular dementia and stroke. SVD commonly manifests as lacunes, white matter hyperintensities, cerebral microbleeds, and other such neuropathologies.
Given the association between structural changes in the brain due to aging, and the subsequent decline in cognitive function and reserve, it would be interesting to examine how SFC varies in association with aging, neuropathologies linked to SVD, and changing cognitive reserve and abilities.
About the Study
In the present study, the researchers examined a cohort of healthy, aging adults enrolled in the Harvard Aging Brain Study to study SFC-related changes related to aging, cognitive reserve, cognitive abilities, and neuropathologies linked to SVD.
Patients with Alzheimer's disease, bipolar disorder, epilepsy, Parkinson's disease, and multiple sclerosis were observed to have lower SFC in comparison to healthy individuals, while individuals with cognitive impairments without dementia were found to have higher SFC at the whole brain level.
However, for specific brain regions, a decrease in SFC was observed in association with diseases, indicating that SFC changes are dependent not only on the neurocognitive disease being studied but also determined by the scale at which the coupling between structural and functional communications is measured.
For the present study, the researchers enrolled individuals who were 62 years of age or older, scored 25 or more on the Mini-Mental State Examination, and scored zero on the dementia rating scale and less than 11 on the scale measuring geriatric depression.
The incidence of SVD was scored by a panel consisting of a neuroscientist and a neuroradiologist using manifestations of SVD-related neuropathologies.
The scoring of neuropathologies such as lacunes, enlarged perivascular spaces, and white matter hyperintensities was conducted based on T1- and T2-weighted magnetic resonance imaging (MRI) scans. Additionally, susceptibility-weighted imaging was used to define cerebral microbleeds.
A range of cognitive assessments was used for the annual evaluation of cognitive outcomes, after which MRI examinations were used to construct the structural connections in the brain and functional MRI was employed to obtain a functional connectome or a comprehensive map of functional connections.
The researchers then assigned individual parts or parcels of the brain to 12 functional brain clusters, which were used for determining SFC and the modularity within and between structural and functional networks in the brain.
Major findings
The study found that after adjusting for sex, age, and education levels, the global SFC, which was based on the correlation between the entire structural connectome and the entire functional connectome, as well as the SFC between the structural and functional networks for the dorsal attention and dorsolateral somatomotor brain clusters, decreased with age.
Additionally, the SFC between the frontoparietal and dorsolateral somatomotor networks also decreased with age.
Furthermore, SFC at the whole brain level decreased with increases in cognitive score, suggesting that cognition in healthy aging adults might be determined by cognitive processes that are not strongly bound to structural connections.
In contrast, older adults with worsening cognitive abilities show more rigid structure-function connections.
The inter-network SFCs also showed significant interactions between education levels and SVD-related neuropathologies such as cerebral microbleeds and white matter hyperintensities. However, inter-network SFC showed no linear associations with education levels.
Furthermore, a higher inter-network SFC was observed between retrosplenial temporal and cingulo-parietal networks in healthy older adults with enlarged perivascular spaces in the basal ganglia compared to those without.
Given that studies have reported a decline in information processing, language, episodic memory, and executive function associated with enlarged perivascular spaces in the basal ganglia, the researchers believe that the higher SFC between these two networks might be necessary to protect against the effect of the SVD-related neuropathology.
Conclusions
Overall, the results suggested that global-scale brain coupling was associated with cognitive ability in aging adults.
In contrast, brain coupling between networks at a functional level was associated with a cognitive reserve and modulated by SVD-related neuropathologies such as cerebral microbleeds and white matter hyperintensities.
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