High-resolution structural connectivity mediates age-related differences in functional connectivity and fluid cognition.
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2025-01
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Abstract
Magnetic resonance imaging studies using diffusion-weighted imaging suggest that age-related cognitive decline and alterations in brain function, in healthy adults, are at least partly explained by the degradation of white matter pathways connecting distributed brain regions. Studies of younger adults and animal models suggest that more precise estimates of white matter connectivity may be achieved by higher resolution, relative to standard spatial resolution, diffusion-weighted imaging. Here, in a cross-sectional study of healthy adults across the lifespan (n = 140; ages 18-88 years; 72 females), we compared age-related differences in measures of white matter structural connectivity from standard (1.5 mm3 voxels; 3.375 µl volume) and high-resolution (1 mm3; 1 µl volume) diffusion-weighted imaging, and their ability to explain age-related differences in functional connectivity and cognition. We assessed cognition using tests of memory, executive function, and perceptual-motor speed, and assessed structural and functional (resting-state functional magnetic resonance imaging) connectivity using graph theory. Results revealed more pronounced age-related decreases in structural connectivity for sensorimotor, ventral attention, and sub-cortical networks for high-resolution than standard diffusion-weighted imaging. Age-related decreases in functional connectivity were evident across the brain and mediated by high-resolution structural connectivity in the default mode network. Age-related decline in fluid cognition was mediated by within-network connectivity from only high-resolution diffusion-weighted imaging, but by a combination of high-resolution and standard diffusion-weighted imaging for between-network connectivity. Thus, relative to standard diffusion-weighted imaging, high-resolution diffusion-weighted imaging may better capture age-related differences in white matter connectivity and their constraint on age-related alterations in brain function and cognitive performance.
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Merenstein, Jenna L, Allen W Song and David J Madden (2025). High-resolution structural connectivity mediates age-related differences in functional connectivity and fluid cognition. Brain communications, 7(5). p. fcaf376. 10.1093/braincomms/fcaf376 Retrieved from https://hdl.handle.net/10161/33726.
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Allen W Song
The research in our lab is concerned with advancing structural and functional MRI methodologies (e.g. fast and high-resolution imaging techniques) for human brain imaging. We also aim to improve our understanding of functional brain signals, including spatiotemporal characterizations of the blood oxygenation level dependent contrast and alternative contrast mechanisms that are more directly linked to the neuronal activities. Additional effort is invested in applying and validating the developed methods to study human functional neuroanatomy.
David Joseph Madden
My research focuses primarily on the cognitive neuroscience of aging: the investigation of age-related changes in perception, attention, and memory, using both behavioral measures and neuroimaging techniques, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI).
The behavioral measures have focused on reaction time, with the goal of distinguishing age-related changes in specific cognitive abilities from more general effects arising from a slowing in elementary perceptual processes. The cognitive abilities of interest include selective attention as measured in visual search tasks, semantic and episodic memory retrieval, and executive control processes.
The behavioral measures are necessary to define the cognitive abilities of interest, and the neuroimaging techniques help define the functional neuroanatomy of those abilities. The PET and fMRI measures provide information regarding neural activity during cognitive performance. DTI is a recently developed technique that images the structural integrity of white matter. The white matter tracts of the brain provide critical pathways linking the gray matter regions, and thus this work will complement the studies using PET and fMRI that focus on gray matter activation.
A current focus of the research program is the functional connectivity among regions, not only during cognitive task performance but also during rest. These latter measures, referred to as intrinsic functional connectivity, are beginning to show promise as an index of overall brain functional efficiency, which can be assessed without the implementation of a specific cognitive task. From DTI, information can be obtained regarding how anatomical connectivity constrains intrinsic functional connectivity. It will be important to determine the relative influence of white matter pathway integrity, intrinsic functional connectivity, and task-related functional connectivity, as mediators of age-related differences in behavioral measures of cognitive performance.
Ultimately, the research program can help link age-related changes in cognitive performance to changes in the structure and function of specific neural systems. The results also have implications for clinical translation, in terms of the identification of neural biomarkers for the diagnosis of neural pathology and targeting rehabilitation procedures.
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