Functional activation changes at ultra-high field related to upper and lower limb impairments in multiple sclerosis

Upper and lower limb impairments are common in people with multiple sclerosis (pwMS), yet difficult to clinically identify in early stages of disease progression. Tasks involving complex motor control can potentially reveal more subtle deficits in early stages, and can be performed during functional MRI acquisition, to investigate underlying neural mechanisms, providing markers for early motor progression. We investigated brain activation during visually-guided force-matching of hand or foot in 28 minimally disabled pwMS and 17 healthy controls (HC) using ultra-high field 7-Tesla fMRI, allowing us to visualise sensorimotor network activity in high detail. Task activations and performance (tracking lag and error) were compared between groups, and correlations were performed. PwMS showed delayed (+124 s, p=0.002) and more erroneous (+0.15 N, p=0.001) lower limb tracking, together with higher primary motor and premotor cortex activation, and lower cerebellar activation compared to HC. No differences were seen in upper limb performance or activation. Functional activation levels of cerebellar, visual and motor areas correlated with task performance. These results demonstrate that ultra-high field fMRI during complex hand and foot tracking can identify subtle impairments in movement and brain activity, and differentiates upper and lower limb impairments in minimally disabled pwMS.