Charting vulnerability of brainstem functional pathways in aging and prodromal synucleinopathy
Abstract
The brainstem is vulnerable to aging and prodromal synucleinopathy, yet whether these processes disrupt shared or distinct functional pathways linking the brainstem to the cortex remains unknown. Using high-resolution 7-Tesla fMRI, we mapped connectivity between 58 brainstem nuclei and cortical regions in young adults, older adults and individuals with isolated REM sleep behavior disorder (iRBD), a prodromal synucleinopathy. Long-range brainstem-cortical connectivity weakened with aging and further in iRBD. However, the two conditions affected distinct systems: aging involved arousal- and cognition-related nuclei and association cortex, whereas iRBD involved sleep- and autonomic-related nuclei and extended to sensory-motor cortex. These alterations were associated with distinct neurophysiological, metabolic and neurotransmitter architectures and spatial transcriptomic signatures. Brainstem-cortical connectivity also followed the cortical unimodal-transmodal hierarchy, with reduced differentiation in aging. Independent 3-Tesla data reproduced the broader connectivity patterns. Together, our findings reveal shared and distinct multiscale patterns of brainstem pathway vulnerability in aging and prodromal synucleinopathy.
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BibTeX
@misc{hua2026charting,
title = {{Charting vulnerability of brainstem functional pathways in aging and prodromal synucleinopathy}},
author = {Lin Hua and Kavita Singh and Maria Guadalupe Garcia-Gomar and Firdaus Fabrice Hannanu and Simone Cauzzo and Subhranil Koley and Ambra Stefani and Stephan Grimaldi and Aleksandar Videnovic and Marta Bianciardi},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.760186},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.760186v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Charting vulnerability of brainstem functional pathways in aging and prodromal synucleinopathy
AU - Lin Hua
AU - Kavita Singh
AU - Maria Guadalupe Garcia-Gomar
AU - Firdaus Fabrice Hannanu
AU - Simone Cauzzo
AU - Subhranil Koley
AU - Ambra Stefani
AU - Stephan Grimaldi
AU - Aleksandar Videnovic
AU - Marta Bianciardi
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.760186
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.760186v1
AB - The brainstem is vulnerable to aging and prodromal synucleinopathy, yet whether these processes disrupt shared or distinct functional pathways linking the brainstem to the cortex remains unknown. Using high-resolution 7-Tesla fMRI, we mapped connectivity between 58 brainstem nuclei and cortical regions in young adults, older adults and individuals with isolated REM sleep behavior disorder (iRBD), a prodromal synucleinopathy. Long-range brainstem-cortical connectivity weakened with aging and further in iRBD. However, the two conditions affected distinct systems: aging involved arousal- and cognition-related nuclei and association cortex, whereas iRBD involved sleep- and autonomic-related nuclei and extended to sensory-motor cortex. These alterations were associated with distinct neurophysiological, metabolic and neurotransmitter architectures and spatial transcriptomic signatures. Brainstem-cortical connectivity also followed the cortical unimodal-transmodal hierarchy, with reduced differentiation in aging. Independent 3-Tesla data reproduced the broader connectivity patterns. Together, our findings reveal shared and distinct multiscale patterns of brainstem pathway vulnerability in aging and prodromal synucleinopathy.
SN - 2692-8205
ER -