Selective impairments of motor sequence learning in multiple sclerosis patients with minimal disability

Patients with Multiple Sclerosis (PwMS) with severe sensorimotor and cognitive deficits show reduced ability in motor sequence learning. Conversely, in PwMS with minimal disability (EDSS≤2), showing only subtle neurological impairments and no particular deficits in everyday life activities, motor sequence learning has been poorly addressed. Here, we investigated whether PwMS with minimal disability already show a specific impairment in motor sequence learning and which component of this process can be first affected in MS. We implemented a serial reaction time task based on thumb-to-finger opposition movements in response to visual stimuli. Each session included 14 blocks of 120 stimuli presented randomly or in ten repetitions of a 12-item sequence. Random (R) and sequence (S) blocks were temporally alternated (R1, R2, S1/S5, R3, S6/S10, R4). Random blocks were designed to evaluate the motor component; sequence blocks, beside the motor component, allowed to discriminate the procedural performance. Twenty-two PwMS and 22 control healthy subjects were asked to perform the task under implicit or explicit instructions (11 subjects for each experimental condition). PwMS with minimal disability improved motor performance in random blocks reducing response time with practice with a trend similar to control subjects, suggesting that short-term learning of simple motor tasks is nearly preserved at this disease stage. Conversely, they found difficulties in sequence-specific learning in implicit and explicit condition, with more pronounced impairment in the implicit condition. These findings could suggest an involvement of different circuits in implicit and explicit sequence learning that could deteriorate at different disease stages.