For this project the investigators ask, how the activation and organization of muscle synergies may be disrupted by brain lesions, and whether it is possible to modify synergy activations by means of specific therapies. Will be investigated whether there is a relationship between post-stroke cortical plasticity and changes in synergy activations due to a therapy.

It has been widely recognized that neurorehabilitation can facilitate recovery of motor function after stroke. There has been increasing evidence suggesting that the execution of voluntary movement relies critically on the functional integration of the motor areas and the spinal circuitries. More precisely, it was suggested that the central nervous system may generate neural motor commands through a linear combination of spinal modules, each of which activates a group of muscles as a single unit (muscle synergy). The investigators hypothesize that descending motor cortical signals generate movements by combining and activating muscle synergies. With this background, the goal is to further improve the efficacy of rehabilitation utilizing knowledge on modular motor control. The investigators also seek to provide a better understanding of the links between brain activations and movements.

The project MO-SE has three aims, one primary and two secondary. The main primary aim is to test whether the use of virtual reality rehabilitation based therapies are superior in terms of clinical efficacy to conventional therapies (randomized clinica trial, RCT). The other two secondary aims of the project will be accomplished with further instrumental analysis in sub-samples of the group of patients enrolled for the RCT.

Inclusion Criteria:

• diagnosis of first stroke;
• a score between 1 and 3 (included) at the upper limb sub-item on the Italian version of the National Institute of Health stroke scale (IT - NIHSS) (Pezzella et al., 2009)
• a score higher than 6 out of 66 on the Fugl - Meyer upper extremity (F-M UE) scale (Fugl-Meyer et al., 1975).

Exclusion Criteria:

• the presence of a moderate cognitive decline defined as a Mini Mental State Examination (Folstein et al., 1975) score < 20/30 points;
• the finding of severe verbal comprehension deficit defined as a number of errors > 13 (Tau Points < 58/78) on the Token Test (Huber et al., 1984);
• evidence of apraxia and visuospatial neglect interfering with upper arm movements and manipulation of simple objects in all the directions within the visual field, as assessed through neurological examination;
• report in the patient's clinical history or evidence from the neurological examination of behavioural disturbances (i.e. delusions, aggressiveness and severe apathy/depression) that could affect compliance with the rehabilitation programs;
• non stabilised fractures;
• diagnosis of depression/delusion;
• associated traumatic brain injury;
• drug resistant epilepsy;
• evidence of ideomotor apraxia;
• evidence of visuospatial neglect;
• severe impairment of verbal comprehension defined as a score higher than 13 errors on Token test (i.e. score<58 out of 78 Tau points).

A simple random number sequence will be generated by a computer and the allocation concealment will be guaranteed using sequentially numbered, opaque sealed envelopes. The therapists responsible for randomization and allocation procedures will be independent of the blind therapists and medical doctors involved in patients' screening and treatment.