A clinical and neuroimaging approach to the evaluation of virtual reality efficacy for upper limb recovery after stroke.

The treatment of upper limb motor function impairments and associated participation restrictions still represent a challenging therapy target in stroke neurorehabilitation. Recent evidence showed that virtual reality (VR) is better than conventional physiotherapy for the treatment of upper limb, after stroke. Both genetics and neurophysiological factors drive functional recovery and carrying the Val66Met single nucleotide polymorphism (SNP) of the brain derived neurotrophic factor (BDNF) was argued to be a potential determinant of poor motor recovery. Motor control theories postulate that the motor system pools groups of muscles in functional units called muscle synergies, to control voluntary movements. A determined number of muscle synergies, which is stable across subjects, but affected by stroke, allows the description of natural motor behaviour. Evidence from animals proposed a subcortical and spinal substrate for muscle synergies. In this thesis, a virtual reality environment commonly applied in real clinical settings for the treatment of upper limb after stroke, was used as a reference framework to test hypotheses on both the genetics and neurophysiological factors described above. The first part of the thesis explores whether carrying the Val66Met SNP BDNF determines a bad recovery of upper limb motor function and whether different brain morphologies are associated with each genotype, in stroke survivors. The second part of the thesis explores whether muscle synergies are represented in the human brain and whether their representation is affected by stroke. The third part of the thesis explores whether muscle synergies might represent a robust neurophysiological outcome to test differences in efficacy between VR-based treatments and conventional therapy. With regard to genetics, the key findings were that polymorphisms of the BDNF do not determine clinically detectable differences, but brain morphological differences exist, because of the genotypes, with bigger brain areas in carriers of the Val66Met SNP BDNF. Neurophysiological findings showed that muscle synergies are represented in the brain structures of the pyramidal motor system, but their representation extends to brain areas devoted to higher order cognitive functions, after stroke. Finally, it was found that VR-based therapy determines a better functional brain reorganisation around muscle synergies brain seeds, than conventional physiotherapy. More research is needed to determine whether these findings represent reliable modules which can be incorporated within a computational model of neurorehabilitation