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Authors (year) | Sample size | Age | MS duration (years) | EDSS | Study design | Intervention(s) (setting and schedule) | Functional main result(s) | Clinical correlation(s) | Structural correlation(s) |
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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] — | STROOP | Rivastigmine administration | Decrement of activation ratio | Correlation with STROOP and phonemic verbal fluency | Correlation with brain volume |
Mainero et al. (2004) [50] | 12 RR | — | — | — | Finger index to thumb opposition | Single oral dose of 3,4-diaminopyridine | Greater activation in the ipsilateral SMC and SII | Positive correlation between intracortical facilitation at TMS and activation of the ipsilateral SMC | — |
Morgen et al. (2004) [52] | 9 MS | 43.1 (10.4) | 9.6 (9.0) | 2.0 [1.0–6.0] | Thumb flexion and thumb extension | 30 minutes of thumb flexion training | MS patients did not show task-specific decreases in activation in the contralateral SMC, PMC, and IPL, as evidenced in HS | No significant results | No significant results |
Rasova et al. (2005) [102] | 17 MS active 11 MS control 13 HS | — — — | — — — | — — — | Finger index to thumb opposition | 2-month neurophysiological, sensorimotor learning and adaptation, rehabilitative therapy | Increased correlation between activities in the L and R hemispheres | No 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] — | PASAT | 5-week computer-based cognitive rehabilitation | Increased activity in several cerebellar areas | No 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] | PVSAT | Cognitive computer-assisted training | Greater activity in the R posterior cerebellar and L superior parietal lobules | Positive 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 memory | 6 weeks Mental visual imagery cognitive training | Higher activation in posterior cortical areas | Association 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 task | At least 15 days of the visuomotor task | Reduction in cortical activation in a greater number of cortical areas in MS than in HS | Negative 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 training | Different 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 training | 12 weeks INF beta therapy | Reduction 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 stimulation | Gait Imagery: increment of L motor and premotor cortex activity Working memory: increment of activation of the left DLPFC | — | — |
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