Background: Regional gray matter pathology is associated with hand motor impairment in people with multiple sclerosis (PwMS). Objectives: To assess neural correlates of digital measures of hand motor function obtained from smartphone sensor-based tests of upper extremity function in PwMS. Methods: As part of a prospective, 24-week study (NCT02952911), adult PwMS (EDSS: 05.5) performed daily remote, smartphone sensor-based assessments including two tests of upper extremity function: the Pinching Test and the Draw a Shape Test. Performance on the Pinching Test was measured by the number of pinches, double touch asynchrony (time between first and second finger touching the screen) and the gap duration between pinches. On the Draw a Shape Test, performance on six different shapes was measured by trace accuracy, trace celerity (trace accuracy divided by the drawing time) and variability of drawing velocity. Measures from both tests were correlated with the volume of 23 atlas-based cortical and subcortical brain regions segmented and parcellated in structural MRI scans, using cross-sectional Spearman rank correlation after adjusting for age, gender and height. Results: Seventy-six PwMS were recruited. On the Pinching Test, both the number of pinches and the gap duration between pinches correlated with visual cortical areas (lateral occipital lobe: r=0.34 and r=?0.38, respectively; medial occipital lobe: r=0.34 and r=?0.36, respectively; all P<0.01) and superior frontal lobe, a region putatively linked to attention and decision-making (r=0.31 and r=?0.29, respectively; all P<0.05). By comparison, double touch asynchronya measure of finger coordinationcorrelated significantly with the anterior cingulate cortex (r=0.37; P<0.01), a region implicated in tasks requiring motor control. On the Draw a Shape Test, trace accuracy correlated most strongly with visual cortical areas such as the lateral and medial occipital lobe (r=0.35, P<0.01 and r=0.29, P<0.05, respectively). In contrast, temporal measures such as trace celerity, variability of figure 8 drawing velocity and variability of spiral radial drawing velocity showed stronger associations with deep gray matter (r=0.39, r=?0.44 and r=?0.28, respectively; all P<0.05), which includes the basal ganglia, a group of nuclei key to temporal information processing. Conclusions: This analysis provides evidence that novel digital measures obtained with the Pinching and the Draw a Shape Test show distinctive correlations with regional brain volumes in PwMS.