Fingolimod is an immunomodulatory oral drug, that has been found to be reduce the rate of relapses in patients with relapsing remitting multiple sclerosis (RRMS)¹. However, disease progression may occur despite effective control of inflammation. Functional imbalance in and between brain networks in patients have been reported in patients with MS². Reduced right- and left-hemisphere primary motor cortex (M1) resting state functional connectivity (fcMRI) has been reported in MS³. In this study we investigated the correlation of change in fcMRI between left and right M1 with the change in timed 9 hole peg test (9-HPT) scores for both dominant and non-dominant hands, a test that is relevant to motor network.Twenty subjects with relapsing remitting MS (RRMS) were scanned using a 3T whole body Siemens Tim Trio scanner (Erlangen, Germany) with an IRB approved protocol prior to, 6 months and 12 months after initiating Fingolimod treatment. fcMRI scan parameters were as follows: TR/TE=2800/29 ms, 31 slices, slice thickness 4 mm, no gap, 128×128 matrix, 256 mm × 256 mm FOV, bandwidth 1954 Hz/pixel, 6/8 partial Fourier, 137 repetitions. A 12 channel head coil was used, bite bar was used to minimize subject motion, and the subjects were instructed to lie still in the scanner with eyes closed during the fcMRI scan. Cardiac and respiratory fluctuations were monitored using a pulse oximeter and respiratory bellow respectively. The fcMRI data analysis consisted of the following steps: (i) rejection of 1st 4 data points, (ii) physiologic noise correction, (iii) retrospective motion correction using 3dvolreg routine of AFNI⁴, (iv) 2d spatial filtering in Fourier domain, followed by temporal filtering to remove all fluctuations above 0.08 Hz⁵, (v) picking right and left M1 based upon maximum correlation using InstaCorr routine of AFNI and creating 9 voxel right and left M1 ROIs, (vi) creating whole brain correlation map with the left M1 voxel as seed, and (vii) computing the mean correlation within the right M1 ROI from the map. 9HPT data were collected by measuring the time taken by the patients to place 9 pegs into 9 empty holes of a block. Data were taken twice for both the dominant and non-dominant hands (DH and NDH respectively).Data from 3 subjects at baseline, 2 subjects at month 6, and 4 subjects at month 12 were discarded because of subject motion. Repeated ANOVA did not show any difference in fcMRI or 9HPT scores over a period of 12 months. While the fcMRI metrics did not correlate with DH or NDH 9HPT times at individual timepoints, a significant inverse correlation (p<0.03) was observed between the 6 to 12 months’ changes in fcMRI scores and DH 9HPT times (Fig. 1). Interestingly, no correlation were observed between baseline to 6 month’s changes of the same metrics, or for the changes in fcMRI over 6 months (baseline to 6 months or 6 to 12 months) and corresponding changes in NDH 9HPT times. The different p-values for correlation between left-right M1 fcMRI and DH/NDH 9HPT times are listed in Table 1. The results suggest (i) a difference in behavior of DH and NDH, and / or (ii) more (inverse) correlated changes in fcMRI and 9HPT after the 1st 6 months of treatment. Higher 9HPT time is linked with worse motor performance, and thus the results indicate that worsening of motor performance with dominant hand after 6 months of treatment is associated with decrease in fcMRI between left and right M1.fcMRI changes in patients with RRMS under Fingolimod are inversely correlated with the corresponding changes in DH 9HPT time betwesen 6 and 12 month period after start of treatment.