Charting vulnerability of brainstem functional pathways in aging and prodromal synucleinopathy

Long-range brainstem–cortical connectivity weakened with aging and further in iRBD, with aging and iRBD disrupting distinct brainstem–cortex functional systems.

• Why it matters: It is unknown whether aging and prodromal synucleinopathy disrupt shared or distinct brainstem functional pathways to the cortex.
• What they did: Using high-resolution 7-Tesla fMRI, connectivity between 58 brainstem nuclei and cortical regions was mapped in young adults, older adults, and individuals with isolated REM sleep behavior disorder (iRBD), with independent 3-Tesla replication.
• The result: Aging implicated arousal- and cognition-related nuclei and association cortex, while iRBD implicated sleep- and autonomic-related nuclei extending to sensory-motor cortex, with distinct neurophysiological, metabolic, neurotransmitter, and spatial transcriptomic signatures.