Discussion
cognitive decline
DISEASE PROGRESSION, DISEASE, PATHOLOGY
Digital measures captured by the Floodlight PoC app demonstrated robust correlations with volumetric measurements of specific brain regions. While many neural correlates were shared between clinical and digital measures, the latter showed associations with brain regions that clinical measures were unable to demonstrate. These results indicate that remotely administered digital tests may yield higher functional specificity and provide potential novel information on functional ability compared with standard clinical measures. Of note, these correlations were observed in an early, relapsing cohort of PwMS, suggesting that digital measures hold potential to capture silent pathology [As expected, both the e-SDMT and oral SDMT correlated with regions implicated in cognitive decline (ventricular expansion and smaller volume of the insula and cerebral white matter), information processing speed (deep gray matter), and working memory (superior temporal gyrus) [Several correlations were only observed for the digital measures, but not for the standard clinical measures. This was most evident in the upper extremity function domain. Temporal and spatiotemporal measures derived from the Draw a Shape Test such as the mean trace celerity and variability of drawing velocity while drawing round shapes specifically correlated with thalamic volume, which has been previously shown to be involved in information processing [The notion that digital measures may offer higher functional specificity is also supported by the explained variance analysis. A low There are some limitations to this study. First, MRI data were only collected for PwMS. Consequently, we were unable to disentangle physiologic from pathologic effects. Second, the relatively short study duration of 24 weeks did not allow us to perform longitudinal analyses or assess the relationship between the digital measures and disease progression. Third, PwMS enrolled in this study mostly had mild disease with limited functional impairment, which may have weakened the correlations. Structural, or even functional, cortical reorganization, that helps to maintain functional ability in early stages of the disease despite structural damage to the brain [In the future, using data from larger, ongoing, and forthcoming studies (CONSONANCE, NCT03523858; Floodlight™ MS—TONiC, ISRCTN11088592), we will explore both cortical and subcortical structural networks [