Functional and Structural Brain Plasticity Enhanced by Motor and Cognitive Rehabilitation in Multiple Sclerosis

Table 2

Summary of studies investigating the effect of cognitive rehabilitation or training on brain plasticity, assessed by task-related fMRI.

Authors (year)	Sample size	Main clinical characteristics	Study design	Intervention(s) and setting intervention schedule	Clinical outcome(s)	MRI outcome(s)
Penner and Kappos (2006) [32]	11	N/R	Nonrandomized pre-/postcomparison study	Computer-assisted attention training with the AIXTENT package 3-4 weeks	Not reported	Increased activation of regions in the cingulate gyrus, precuneus, and frontal cortex was found after the training
Sastre-Garriga et al. (2011) [33]	15	Mean age: ~51 years; Mean MS duration ~14 years; Median EDSS: 6.0; Course: SP 10, RR 3, and PP 2	Nonrandomized pre-/postcomparison study	Mixed intervention: computer-assisted cognitive rehabilitation and game-like group activities 1-hour sessions, 3 times per week, for 5 weeks	Improvement in digit span after the intervention	Increased activation of right posterior cerebellar lobe and left anterior and posterior cerebellar lobe after the intervention
Chiaravalloti et al. (2012) [34]	16	Mean age: ~48 years; Mean MS duration ~15 years; Median EDSS: N/R; Course: 13 RR, 2 PP, and 1 SP	Double-blind randomized controlled group	Active group: modified story memory technique 45–60-minute sessions, 2 times per week, for 5 weeks; Control group: story reading and answering questions 45–60-minute sessions, 2 times per week, for 5 weeks	CVLT short-delay free recall improved in active group	Increased activation of some areas of frontal, parietal, temporal, and occipital lobes and cerebellum in active group
Ernst et al. (2012) [35]	8	Mean age: ~38 years; Mean MS duration ~14 years; Median EDSS: 2.0; Course: 8 RR	Nonrandomized controlled trial	Active group: Motor visual imagery training 2-hour sessions, 1 time per week, for 6 weeks; Control group: no intervention	Autobiographic memory improved in active group	Increased activation of some areas located in posterior regions (right cuneus, left precuneus, left inferior and superior occipital gyri, and left lateral temporal cortex)
Filippi et al. (2012) [36]	20	Mean age: ~46 years; Mean MS duration ~14 years; Median EDSS: 2.0; Course: 20 RR	Randomized controlled trial	Active group: outpatient cognitive training using the RehaCom package 1-hour sessions, 3 times per week, for 12 weeks; Control group: no intervention	The PASAT, WCST, and oral word association test improved in active group	(i) Increased activation of posterior cingulated cortex and/or prefrontal cortex (bilaterally) in active group; (ii) increased activation at rest of anterior cingulated cortex (salience processing), left dorsolateral prefrontal cortex (executive function), right inferior parietal lobule and posterior cingulated cortex, and/or precuneus (default-mode networks I and II); (iii) no significant WM and GM changes
Cerasa et al. (2013) [37]	23	Mean age: ~32 years; Mean MS duration ~9 years; Median EDSS: 2.5; Course: 23 RR	Double-blind randomized controlled trial	Active group: outpatient cognitive training using the RehaCom package 1-hour sessions, 2 times per week, for 6 weeks; Control group: home-based training with a simple visuomotor coordination task (in-house software) 1-hour sessions, 2 times per week, for 6 weeks	The Stroop test improved in active group	Increased activation of the right posterior cerebellar lobule and left superior parietal lobule in active group

CVLT: California Verbal Learning Test; GM: grey matter; N/R: not reported; PASAT: Paced Auditory Serial Addition Test; PP: primary progressive; RR: relapsing-remitting; SP: secondary progressive; WCST: Wisconsin Card Sort Test; WM: white matter.
The number within parentheses refers to the sample size of healthy subjects.