Review Article

The Role of fMRI in the Assessment of Neuroplasticity in MS: A Systematic Review

Table 3

Interventional t-fMRI papers.

Authors (year)Sample sizeAgeMS duration (years)EDSSStudy designIntervention(s) (setting and schedule)Functional main result(s)Clinical correlation(s)Structural correlation(s)

Parry et al. (2003) [49]10 MS
11 HS
41.0 [31.0–54.0]
42.0 [26.0–61.0]
10.0 [5.0–21.0]
2.0 [0.0–6.0]
STROOPRivastigmine administrationDecrement of activation ratioCorrelation with STROOP and phonemic verbal fluencyCorrelation with brain volume
Mainero et al. (2004) [50]12 RRFinger index to thumb oppositionSingle oral dose of 3,4-diaminopyridineGreater activation in the ipsilateral SMC and SIIPositive correlation between intracortical facilitation at TMS and activation of the ipsilateral SMC
Morgen et al. (2004) [52]9 MS43.1 (10.4)9.6 (9.0)2.0 [1.0–6.0]Thumb flexion and thumb extension30 minutes of thumb flexion trainingMS patients did not show task-specific decreases in activation in the contralateral SMC, PMC, and IPL, as evidenced in HSNo significant resultsNo significant results
Rasova et al. (2005) [102]17 MS active
11 MS control
13 HS






Finger index to thumb opposition2-month neurophysiological, sensorimotor learning and adaptation, rehabilitative therapyIncreased correlation between activities in the L and R hemispheresNo significant results
Sastre-Garriga et al. (2010) [54]15 MS
5 HS
50.7 (10.9)
14.4 (8.9)
6.0 [3.5–7.0]
PASAT5-week computer-based cognitive rehabilitationIncreased activity in several cerebellar areasNo significant results
Cerasa et al. (2013) [53]12 RR
active
11 RR
control
31.7 (9.2)
33.7 (10.3)
4.3 (3.0)
5.1 (5.2)
3.0 [1.0–4.0]
2.0 [2.0–4.0]
PVSATCognitive computer-assisted trainingGreater activity in the R posterior cerebellar and L superior parietal lobulesPositive correlation with changes in STROOP score
Ernst et al. (2012) [55]4 RR
active
4 RR
control
37.3 (5.5)
39.8 (5.1)
15.0 (9.3)
13.5 (7.2)
1.5 [0.0–4.0]
2.5 [0.0–4.0]
Autobiography and episodic memory6 weeks
Mental visual imagery cognitive training
Higher activation in posterior cortical areasAssociation between increased activation of posterior regions and autobiographical memory
Tomassini et al. (2012) [2]19 RR, 4 SP
12 HS
45.0 (8.5)
43.0 (2.7)
12.0 (1.5)4.0 [0.0–7.0]Visuomotor taskAt least 15 days of the visuomotor taskReduction in cortical activation in a greater number of cortical areas in MS than in HSNegative correlation between performance improvement and occipital activation in HS but not in MS
Hubacher et al. (2015) [56]6 RR active
4 RR control
47.5 (6.4)
44.8 (5.6)
2.5 (1.4)
4 (2.7)
2.0 [1.0–3.5]
1.0 [1.0–2.5]
N-Back ()Computer-based cognitive trainingDifferent and opposed changes in activation after rehabilitation
Tomassini al. (2016) [51]26 MS
22 HS
36.1 (1.4)
33.5 (1.7)
1.8 (0.5)
1.5 [0.0–3.0]
Two runs of thumb flexion separated by 25 minutes of training12 weeks INF beta therapyReduction of between-run signal changes in secondary visual areas and motor, temporal, and parietal cortical areas
Leonard et al. (2017) [103]7 MS
active
7 MS
control
47.7 (28.0–61.0)
49.7 (38.0–62.0)
11.2 (3.0–26.0)
22.3 (9.0–37.0)
4.2 [3.0–6.0]
4.8 [3.0–6.0]
Gait Imagery
Working memory
14-week cognitive rehabilitation combined with tongue stimulationGait Imagery: increment of L motor and premotor cortex activity
Working memory: increment of activation of the left DLPFC

SMC: sensorimotor cortex; SII: secondary sensory/sensorimotor cortex; PMC: premotor cortex; IPL: inferior parietal lobule; DLPFC: dorsolateral prefrontal cortex. L: left; R: right; italic font: mean; round parenthesis: standard deviation; squared parenthesis: range.