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bioRxiv · 10.64898/2026.10.26.760492

Cerebello-basal ganglia networks and behavior across adulthood and aging

Delaney, C.·Herrejon, I.·Magalhaes, T. N. C.·Jackson, T. B.·Hicks, T. H.·Bernard, J. A.
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Abstract

The cerebellum contributes to aging, cognition, and reward related processing, but has been relatively understudied in these domains. The cerebello-basal ganglia (CB-BG) circuit may be key to better understanding how the brain ages. Prior work has implicated this circuit in aging in a small sample, though it is also of interest in age-related neurodegenerative disease, particularly Parkinson's Disease. Here, we investigated the CB-BG network, which has been implicated in modulation of cognitive, motor, and reward-related functions. In a sample of 138 participants between the ages of 35 and 86 we looked at network connectivity in cognitive and motor sub-circuits. Participants completed motor and cognitive testing batteries followed by 26 minutes of resting state functional connectivity magnetic resonance imaging (fcMRI). This data was analyzed using the CONN toolbox with an ROI-ROI approach targeting the CB-BG circuit. We replicated the previously mapped cognitive subcircuit and motor subcircuits. When examining connectivity by age group (early and late middle age and older adult hood), we found higher functional connectivity in early middle age compared to older adulthood, with no results related to late middle age. Analysis of connectivity as it relates to performance on the Stroop task showed higher connectivity-behavior associations in early middle-aged adults compared to older adults. We also explored sex differences and found higher functional connectivity in females compared to males. Analysis of steroid hormone levels revealed higher connectivity associated with progesterone in females relative to males. Together, we have replicated motor and cognitive CB-BG subcircuits and further demonstrated that this network has altered connectivity associated with age, sex, progesterone, and cognitive performance. This expanded investigation of CB-BG networks represents an essential new step in increasing our knowledge of age-related cognitive and motor declines and may be particularly relevant for consideration in Parkinson's Disease.

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Delaney, C., Herrejon, I., Magalhaes, T. N. C., Jackson, T. B., Hicks, T. H., Bernard, J. A.. 2026-10-27. Cerebello-basal ganglia networks and behavior across adulthood and aging. https://doi.org/10.64898/2026.10.26.760492

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