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 size	Main clinical characteristics	Study design	Intervention(s) and setting [setting and schedule]	Clinical outcome(s)	MRI study outcome(s)
Rasova et al. (2005) [26]	28 (13)∗	N/R	Non-randomized parallel group trial	Active 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 group	No 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 months]	PASAT improved after the intervention	Significant 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 study	Home-based visuo-motor task training [12-minute sessions, once a day, for 15 days]	Overall tracking error during the visu-motor task execution decreased afte the training	After the training, a significant reduction in fMRI activation was observed in the occipital and parietal cortices
Bonzano et al. (2014) [29]	30	Mean age: ~43 years Mean MS duration: ~18 years Median EDSS: 4.0 Course: 22 RR, 18 SP	Randomized controlled trial	Active 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 group	Reduced 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]	27	Mean age: ~36 years Mean MS duration: ~10 years Median EDSS: 3.0 Course: 26 RR, 1 SP	Randomized two-period cross-over trial	Active 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 group	Increased 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]	12	Mean age: ~40 years Mean MS duration: ~7 years Median EDSS: 3.5 Course: 11 RR, 1 PP	Non-randomized uncontrolled comparison trial	Motor programme activating therapy [1-hour sessions, 2 times per week, for about 2 months]	The MAS, 25-FWT, 9-HPT, and cerebellar functions improved immediately after and one month apart from the end of rehabilitation	Increased 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.