Journal Article

Motor-cognitive aging: The role of motor cortex and its pathways

Xu, Xiaojun, Wen, Jiaqi, Guan, Xiaojun, Jiang, Li, Ge, Yulin, Liang, Zifei, Li, Jiayi, Zhang, Jiangyang, Li, Chenyang, Pang, Huize, Rusinek, Henry

2025

Overview

•M1 showed age-related atrophy, hemodynamic decline, and iron/myelin alterations.•CST showed localized age-related microstructural degeneration near the M1.•CStrT exhibited more widespread age-related microstructural degeneration.•Integrity of tracts was associated with M1 structural and hemodynamic changes.•CStrT mediated the impact of M1 atrophy on both motor and cognitive decline. Motor and cognitive decline are hallmark features of aging. In the primary motor cortex (M1), pyramidal neurons project to the corticospinal tract (CST), a well-established motor pathway, and send collaterals to the ipsilateral striatum, forming the corticostriatal tract (CStrT). While the CST has been extensively studied, the role of the CStrT in motor and cognitive aging remains poorly understood. We analyzed T1- and T2-weighted MRI, multi-delay arterial spin labeling, and multi-shell diffusion MRI data from 339 right-handed healthy adults (aged 36–90 years) in the Human Connectome Project–Aging dataset. Age-related trajectories of M1 structure and hemodynamics, as well as CST and CStrT microstructure, were assessed. Segment-wise along-tract analyses were conducted to identify localized tract degeneration. Mediation analyses were performed to examine whether tract integrity linked M1 atrophy to motor and cognitive performance. With age, M1 exhibited reduced volume and hemodynamics, altered T1/T2 ratio, and increased cortical curvature, reflecting structural and hemodynamic alterations. Along-tract analyses revealed localized microstructural degeneration in the CST adjacent to M1, whereas the CStrT showed more extensive degeneration along its trajectory. These tract changes were associated with structural and hemodynamic alterations in M1. Furthermore, integrity of the dominant (left) CST and CStrT mediated the relationship between ipsilateral M1 atrophy and motor decline. Notably, CStrT integrity also mediated the association between M1 atrophy and motor cognition decline. These findings establish age-related structural and functional degeneration of M1 and its pathways, highlighting the CStrT as a critical mediator between motor cortical atrophy and both motor and cognitive decline. These normative imaging markers of healthy aging may help inform the early detection of neurodegenerative diseases.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adult / Age / Aged / Aged, 80 and over / Aging / Aging - pathology / Aging - physiology / Atrophy / Brain research / Cognition & reasoning / Cognitive ability / Cognitive Aging - physiology / Connectome - methods / Cortex (motor) / Datasets / Dementia / Female / Handedness / Hemodynamics / Human connectome project / Humans / Magnetic Resonance Imaging / Male / Middle Aged / Motor Cognition / Motor Cortex - diagnostic imaging / Motor Cortex - pathology / Motor Cortex - physiology / Motor task performance / Neostriatum / Neurodegeneration / Neurodegenerative diseases / Neuroimaging / Older people / Primary motor cortex / Pyramidal cells / Pyramidal tracts / Pyramidal Tracts - diagnostic imaging / Pyramidal Tracts - pathology / Pyramidal Tracts - physiology / Radiology/Diagnostic Imaging / Spin labeling / Structure / Structure-function relationships / White matter tracts