Cortico-cortical Stimulation and Robot-assisted Therapy for Upper Limb Recovery After Stroke (CCS&RAT) (CCS&RAT)

Cortico-cortical Stimulation and Robot-assisted Therapy for Upper Limb Recovery After Stroke (CCS&RAT)

Cortico-cortical Stimulation and Robot-assisted Therapy a New Approach of Upper Limb Functional Recovery After Stroke

The purpose of this study is to tested the effect of combination of a paired associative stimulation of two functional interconnected areas of the cerebral cortex (posterior-parietal cortex and primary motor cortex) with robot-assisted therapy in the recovery of upper limb after stroke.

BACKGROUND Stroke survivors reported upper limb impairment that contribute to reducing the overall quality of life, social participation and professional activities. The impairment of the upper limb is due to motor and sensory alteration that could compromise the sensorimotor integration. The posterior parietal cortex (PPC) is a potential circuit where this integration could occur during active somatosensation. Indeed, PPC is a site of massive confluence of visual, tactile, proprioceptive, and vestibular signals. This area may be involved in transforming information about the location of targets in space, into signals related to motor intentions. This process likely occurs through parietal-motor connections, which are known to be involved in the transfer of relevant sensitive information for planning, reaching, and grasping. Paired associative stimulation (PAS) of PPC and primary motor area (M1), by means of bi-focal trans-cranial magnetic stimulation, can modulate M1 excitability. This information reinforces the hypothesis that modulation of PPC-M1 connectivity can be used as a new approach to modify motor excitability and sensorimotor interaction. Parallel, robot assisted training (RAT) can induce a plastic reorganization at the muscular afferents, spinal motor neurons, interneuron system and beyond and facilitates neural plasticity and motor relearning through goal-oriented training. The robotics device allows to train patients in an intensive, task-oriented, and top-down therapy way, increasing patients' compliance and motivation. The cognitive top-down stimulation is allowed by means of the introduction of visual feedback performed through exergaming. Recently, it has been proposed the development of new intervention strategies that combine neurostimulation of a target brain area with neurorehabilitation, such as physical therapy or virtual reality. Although both TMS and RAT have shown individually promising effects in upper limb recovery after a stroke, their combination has not been tested to date. AIMS To determine whether robot-assisted therapy combined with cortico-cortical non-invasive stimulation of M1 and PPC areas can improve functional recovery of upper extremity in patients with hemiparesis due to stroke. To evaluate the feasibility of robot-assisted training exergaming technology for reaching and grasping training for stroke rehabilitation. To investigate the neurophysiological changes in PPC-M1 connectivity (through TMS EEG) to clarify the effectiveness of PAS on neuromodulation of the PPC-M1 network.

The recruiters, outcomes assessors, physical therapists, participants and their caregivers will be blinded with respect to participants' allocation for the entire period of the study.

15 sessions of cortico-cortical stimulation between the PPC and the M1 of the lesioned hemisphere and robot-assisted therapy. Paired-pulse stimulation (PAS) technique, with 5ms inter-stimulus time between the two areas (PPC to M1), will be done through two high-power Magstim 200 machines (Magstim® Rapid²). To stimulate the M1 area, the coil will be placed tangentially to the scalp at a 45° angle to the midline, to stimulate the PPC area the center of the coil will be positioned over P4 (10-20 EEG system) tangentially to the skull with the handle pointing downward and slightly medial (10°). Robot-assisted therapy will be performed with an Armeo® Power II (Hocoma), an integrative system composed by a robotic exoskeleton device connected to a laptop for the audio-visual biofeedback for the upper limb therapy.

15 sessions of sham cortico-cortical stimulation between the PPC and the M1 of the lesioned hemisphere and robot-assisted therapy. Sham paired-pulse stimulation (PAS) will be done through two high-power Magstim 200 machines (Magstim® Rapid²). To simulate the real stimulation, the coils will placed in the same sites with different inclination respect to the scalp (90°). Robot-assisted therapy will be performed with an Armeo® Power II (Hocoma), an integrative system composed by a robotic exoskeleton device connected to a laptop for the audio-visual biofeedback for the upper limb therapy.

Comprehensive clinical measurement tool of upper limb functions after stroke. Range score form 0 to 66 points, a higher score represents an improvement.

Clinical Scale used to assessed spasticity. Range score from 0 to 5, a lower score represents an improvement.

Change in the kinematics variables will be recorded via inertial measurement units and motion-analysis during a three-reaching tasks and the Box-and-Block test.

Stimulating a specific area with a single pulse of TMS evoke a so called Transcranial Evoked Potential (TEP), which is a well-know index of cortical excitability of the stimulated cortical area .

From TMS-EEG recording it is possible to analyze oscillatory activity of the stimulated brain area. Monitoring the frequency band during time after TMS-pulse we calculate Time-frequency Wavelets and from there the TMS-related spectral perturbation (TRSP) as output of the frequency bands (Delta, Theta, Alpha, Beta, Gamma) expressed.

Monitoring how TMS-pulse spreads from the stimulated area to the other areas, it is possible to assess the effective connectivity that area has with a widespread of network connected. So we calculate the Coherence between different areas and other connectivity indexes in the cortical oscillatory domain, i.e. Phase-locking Value (PLV) and Phase-amplitude coupling (PAC)

Inclusion Criteria: first ever chronic ischemic stroke; hemiparesis due to left or right subcortical or cortical lesion in the territory of the middle cerebral artery; severe or moderate residual upper limb impairment (FMA < 52 in the motor domain A/D) Exclusion Criteria: history of seizures; severe general impairment or concomitant diseases; treatment with benzodiazepines, baclofen, and antidepressants; Intracranial metal implants; cardiac pacemaker; pregnancy status; orthopedic contraindications for upper limb; upper limb pain; cognitive impairment (MMSE < 23); presence of unilateral spatial neglect

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