Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis

The neural mechanisms underlying motor impairment in multiple sclerosis (MS) remain unknown. Motor cortex dysfunction is implicated in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies, but the role of neural-vascular coupling underlying BOLD changes remains unknown. We sought to independently measure the physiologic factors (i.e., cerebral blood flow (Delta CBF), cerebral metabolic rate of oxygen (Delta CMRO2), and flow-metabolism coupling (Delta CBF/Delta CMRO2), utilizing dual-echo calibrated fMRI (cfMRI) during a bilateral finger-tapping task. We utilized cfMRI to measure physiologic responses in 17 healthy volunteers and 32 MS patients (MSP) with and without motor impairment during a thumb-button-press task in thumb-related (task-central) and surrounding primary motor cortex (task-surround) regions of interest (ROIs). We observed significant Delta CBF and Delta CMRO2 increases in all MSP compared to healthy volunteers in the task-central ROI and increased flow-metabolism coupling (Delta CBF/Delta CMRO2) in the MSP without motor impairment. In the task-surround ROI, we observed decreases in Delta CBF and Delta CMRO2 in MSP with motor impairment. Additionally, Delta CBF and Delta CMRO2 responses in the task-surround ROI were associated with motor function and white matter damage in MSP. These results suggest an important role for task-surround recruitment in the primary motor cortex to maintain motor dexterity and its dependence on intact white matter microstructure and neural-vascular coupling.

Automated summary

In multiple sclerosis patients, increased cerebral blood flow and oxygen metabolic rate were observed in the central motor regions, while decreased responses were found in the surrounding areas. Additionally, the physiological responses in the central and surrounding areas were correlated with motor function and white matter damage.