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Neurotransmitter Influence on Frequency-Defined Neurophysiological Connectivity Supports Cognitive Reserve in Aging

Poster Session F - Tuesday, March 10, 2026, 8:00 – 10:00 am PDT, Fairview/Kitsilano Ballroom

Santiago I. Flores-Alonso^1,2 (), Jack Solomon^1,2, Simon Dobri^2,3, Anthony R. McIntosh^1,2, Alex I. Wiesman^1,2; ¹Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada, ²Institute for Neuroscience and Neurotechnology, Simon Fraser University, Burnaby, Canada, ³Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.

Neuronal oscillations exhibit temporal dependencies between cortical regions within distinct frequency bands, indicating frequency-resolved functional connectivity. However, the neurochemical influence on the connectivity patterns between distant brain regions remains largely unexplored. Drawing upon open MEG and cognitive testing data from the Cambridge Center for Aging and Neuroscience (Cam-CAN; N = 569) and cortical neurotransmitter receptor and transporter atlases from neuromaps, we examine whether neurochemical similarity profiles across cortical regions contributed to their frequency-resolved connectivity. We derived neurochemical similarity matrices from 19 distinct neurotransmitter systems across cortical regions using Pearson correlation, and computed band-limited functional connectivity using orthogonalized amplitude-envelope correlations. Linear mixed-effects models predicted neurochemical similarity from connectivity, controlling for age, sex, and inter-regional distance. Leave-one-out analyses isolated the contributions of specific regions and neurotransmitters. Findings provide evidence that inter-regional neurochemical similarity aligns with frequency-specific connectivity profiles, suggesting that neurochemical gradients shape long-distance electrophysiological communication in the brain. Slow neuromodulators such as norepinephrine (NET) and serotonin (5-HTT) appear to play an outsized role in this inter-regional coherence. Prefrontal cortical regions were identified to exert stronger contributions to the neurochemical-connectivity alignment, indicating a spatial hierarchy. These associations were moderated by age, highlighting how neurochemical constraints on connectivity shift across the lifespan. Older adults with increased neurochemical-connectivity alignment also exhibit better performance on fluid intelligence tests, potentially indicating cognitive resilience. Together, these results offer new insights into the mechanistic bases of commonly reported alterations in frequency-defined brain signaling across both healthy and pathological aging, with implications for emerging pharmacotherapies and early-stage disease monitoring.

Topic Area: METHODS: Neuroimaging