The first objective of the study was to determine whether functional magnetic resonance imaging (fMRI) signal was correlated with motor performance at different stages of poststroke recovery. The second objective was to assess the existence of prognostic factors for recovery in early functional MR images. Eight right-handed patients with pure motor deficit secondary to a first lacunar infarct localized on the pyramidal tract were included. This study concerned moderately impaired patients and recovery of handgrip strength and finger-tapping speed. The fMRI task was a calibrated flexion-extension movement. Ten healthy subjects served as a control group. The intensity of the activation in the "classical" motor network (ipsilesional S1M1, ipsilesional ventral premotor cortex [BA 6], contralesional cerebellum) 20 days after stroke was indicative of the performance (positive correlation). The cluster in M1 was posterior and circumscribed to BA 4p. No area was associated with bad performance (negative correlation). No correlation was found 4 and 12 months after stroke. Prognosis factors were evidenced. The higher early the activation in the ipsilesional M1 (BA 4p), S1, and insula, the better the recovery 1 year after stroke. Although the lesions partly deefferented the primary motor cortex, patients who activated the posterior primary motor cortex early had a better recovery of hand function. This suggests that there is benefit in increasing ipsilesional M1 activity shortly after stroke as a rehabilitative approach in mildly impaired patients.

We have demonstrated that purely passive proprioceptive training applied for 4 weeks is able to modify brain sensorimotor activity after a stroke. This training revealed fMRI change in the ventral premotor and parietal cortices of the contralesional hemisphere, which are secondary sensorimotor areas. Recent studies have demonstrated the crucial role of these areas in severely impaired patients. We propose that increased contralesional activity in secondary sensorimotor areas likely facilitates control of recovered motor function by simple proprioceptive integration in those patients with poor recovery.

It has been shown on hand muscles in normal subjects that paired associative stimulation (PAS) combining peripheral nerve stimulation and transcranial magnetic stimulation (TMS) induces lasting changes in cortical motor excitability (Stefan et al., Brain 123 (Pt3):572-584, 2000). Because the motor recovery of distal upper limb and particularly wrist extension in post-stroke patients is one of the major rehabilitation challenge, we investigate here the effect of one session of paired associative stimulation on the excitability of the corticospinal projection to extensor carpi radialis (ECR) muscle (motor evoked potential size) before and after PAS in 17 healthy subjects and in two patients 5 months after stroke. The time course, the topographical specificity, changes in rest motor threshold (RMT), short intracortical inhibition and intracortical facilitation (SICI and ICF), the respective role of cutaneous and muscular afferents and the effect of a prolonged peripheral stimulation alone were also studied in normal subjects. Using a protocol derived from that of Ridding et al. J Physiol 537:623-631 (2001), PAS was able to induce lasting changes in the excitability of corticospinal projection to wrist muscles in healthy subjects and in the two post-stroke patients studied. Electrophysiological features of these plastic changes were similar to those previously observed in hand muscles: rapid evolution, 30-60 min duration, reversibility, relative topographical specificity and associative dependence suggesting an LTP-like mechanism. A contribution of cutaneous afferents in inducing PAS effects was also demonstrated. The decrease in ECR RMT after PAS observed in patients and in healthy subjects was an unexpected result because it has not been previously reported in the hand muscles of healthy subjects. However, it has been observed in dystonic patients (Quartarone et al., Brain 126:2586-2596, 2003). This suggests that other mechanisms like changes in membrane excitability could be involved in ECR facilitation after PAS. Further studies performed on patients using daily repeated PAS protocols and showing a functional improvement in hand motor function will be necessary to confirm that this technique could be relevant in motor rehabilitation, at least for some selected patients.