The goal of this clinical trial is to validate the efficacy of a Brain-Computer Interface (BCI)-based intervention for hand motor recovery in subacute cervical spinal cord injured (SCI) patients during rehabilitation. The study will provide evidence for the clinical/neurophysiological efficacy of the BCI intervention as a means to promote cortical sensorimotor plasticity (remote plasticity) and thus maximize recovery of arm functions in subacute cervical SCI. Participants will undergo an extensive clinical, neurophysiological, neuropsychological and neuroimaging assessment before and after a BCI training based on motor Imagery (MI) of hands. The intervention will be delivered with a system that was originally validated for stroke patients and adapted to the aims of this study. Researchers will compare the BCI intervention with an active MI training without BCI support (active comparator).

Despite its relatively low incidence SCI represents a devastating chronic condition for which there is still no cure or consistent approach for intervention. Cervical SCI tremendously affects the quality of life since the use of the upper extremities is critical for completing basic activities of daily living. Extensive research conducted on SCI animal models and humans has revealed that cortical and subcortical reorganization (ie., remote plasticity) takes place after SCI and it is associated with recovery of sensorimotor function (in humans the relevance of these aspect has been mainly emphasised in incomplete SCI). Current rehabilitation after traumatic SCI mainly consists of intensive training of lost/impaired function that is assumed to augment activity-dependent plasticity of spared circuits and thus, leading to functional improvements. Recently, neuromodulatory interventions targeting the sensorimotor systems at various levels has been applied in humans with SCI in combination with training to enhance functional recovery. Neurological rehabilitation of SCI can also benefit of cognitive training based on MI, that enables active stimulation of brain motor areas promoting brain plasticity associated with positive effects on motor performance. In the effort of encouraging the top-down contribution of supraspinal sensorimotor signaling in SCI rehabilitation, the BCI technology may provide for fundamental tools not only for restoring but even recovering sensorimotor function. The long history of BCI research in SCIs has been substantially devoted to develop systems to control external devices to restore function. However, recent findings indicate that non invasive BCI training in combination with intensive rehabilitation can be beneficial to chronic SCI patients for gait, as well as arm function recovery. The current study relies on the hypothesis that monitoring and modulating brain plasticity occurring as a consequence of a SCI is a key factor in shaping clinically valuable top-down rehabilitation strategies that target the recovery of sensorimotor function in patients with SCI. To ground such vision, the researchers will use a goal-oriented action imagery training which is controlled and objectified by a BCI as a means to engage sensorimotor system and thus to facilitate neuroplasticity and optimize functional recovery in SCI during the subacute phase in which brain and spinal plasticity is at its climax.

In this study researchers will test the superiority of a BCI-assisted MI training (up to 12 weeks duration) with respect to MI practiced without BCI feedback (similar training setting and duration) to promote recovery of sensorimotor functions in traumatic cervical SCI subjects. The main hypothesis is that establishing a real-time contingency between the content of MI and an ecological feedback specifically designed to train MI in SCI patients will boost the effect of MI training in engaging the sensorimotor system. Primary and secondary outcome measures (reported in the dedicated section) include the most commonly used clinical and functional scales to assess SCI patients recovery. Neurophysiological and Neuroimaging outcomes are reported as other outcome measures in the dedicated session. Neuropsychological evaluation will include Test of Attentional Performance (TAP), Stroop Test, Trail Making Test (TMT), assessment of depression and anxiety; body ownership and representation. Furthermore, motivation, satisfaction, workload and usability will be evaluated along training.

Inclusion Criteria:

• subacute cervical SCI (30-90 days from event)
• classification according to ISNCSCI AIS A-D, lesion level C1-T1
• Upper Extremity Motor Score (UEMS) < 40

Exclusion Criteria:

• other conditions (present or previous) potentially affecting sensorimotor upper limb function
• inability to give informed consent and understand the requirements for the training

Clinical, Neurophysiological, Neuropsychological and Neuroimaging Data will eventually be shared upon reasonable request (anonymized)

Outcome assessors performing clinical evaluation and data analysts will be blinded to patient allocation.