Table 1: Summary of studies investigating the effect of motor rehabilitation or training on brain plasticity, assessed by nonconventional functional or structural MRI techniques.

Authors (year)Sample sizeMain clinical characteristicsStudy designIntervention(s) and setting setting and scheduleClinical outcome(s) MRI study outcome(s)

Rasova et al. (2005) [26]28 (13)N/RNon-randomized parallel group trialActive group: outpatient eclectic sensori-motor learning and adaptation 1-hour sessions, 2 times per week, for 2 months
Control group: no special exercise (MS)
The 9-HPT, 25-FWT, PASAT, postural reactions, MS QoL-54, and BDI improved in active groupNo changes detectable by task-related fMRI

Ibrahim et al. (2011) [28]11 (11)Mean age: ~43 years
Mean MS duration: ~6 years
Median EDSS: 3.5
Course: 11 RR
Non-randomized pre-post comparison study Operator-assisted facilitation physiotherapy 2-hour sessions, once a week, for 2 monthsPASAT improved after the interventionSignificant increase of FA and decrease in MD and RD were observed after the intervention

Tomassini et al. (2012) [27] 23 (12)Mean age: ~45 years
Mean MS duration: ~12 years
Median EDSS: 4.0
Course: N/R
Non-randomized pre-post comparison studyHome-based visuo-motor task training 12-minute sessions, once a day, for 15 daysOverall tracking error during the visu-motor task execution decreased afte the trainingAfter the training, a significant reduction in fMRI activation was observed in the occipital and parietal cortices

Bonzano et al. (2014) [29] 30Mean age: ~43 years
Mean MS duration: ~18 years
Median EDSS: 4.0
Course: 22 RR, 18 SP
Randomized controlled trialActive group: outpatient active motor rehabilitation of upper limbs 1-hour sessions, 3 times per week, for about 2 months
Control group: outpatient passive motor rehabilitation of upper limbs 1-hour sessions, 3 times per week, for about 2 months
Both groups improved on unimanual motor performance, but bimanual coordination worsened in control groupReduced FA and increased RD of corticospinal tracts and corpus callosum were found in control group, as detected by DT-MRI measures

Prosperini et al. (2014) [30] 27Mean age: ~36 years
Mean MS duration: ~10 years
Median EDSS: 3.0
Course: 26 RR, 1 SP
Randomized two-period cross-over trialActive group: home-based video game balance board 30-minute sessions, 5 times per week for 12 weeks
Control group: no intervention
Static balance detected at static posturography improved in active groupIncreased FA and reduced RD of superior cerebellar peduncles were found in active group, as detected by DT-MRI; DTI changes were significantly related to improved static balance

Rasova et al. (2015) [31] 12Mean age: ~40 years
Mean MS duration: ~7 years
Median EDSS: 3.5
Course: 11 RR, 1 PP
Non-randomized uncontrolled comparison trialMotor programme activating therapy 1-hour sessions, 2 times per week, for about 2 monthsThe MAS, 25-FWT, 9-HPT, and cerebellar functions improved immediately after and one month apart from the end of rehabilitationIncreased FA and reduced MD of corpus callosum immediately after and one month apart from the end of rehabilitation; no changes were detected with task-related fMRI

9-HPT: 9-hole peg test; 25-FWT: 25-foot walking test; BDI: Beck Depression Inventory; DTI: diffusion tensor imaging; EDSS: Expanded Disability Status Scale; fMRI: functional magnetic resonance imaging; FA: fractional anisotropy; MAS: Modified Ashworth Scale; MD: mean diffusivity; MS QoL-54: 54-item Multiple Sclerosis Quality of Life; N/R: not reported; PASAT: Paced Auditory Serial Addition Test; PP: primary progressive; RR: relapsing-remitting; SP: secondary progressive.
The number within parentheses refers to the sample size of healthy subjects.