Background and Objectives: The motor sequelae after a stroke are frequently persistent and cause a high degree of disability. Cortical ischemic or hemorrhagic strokes affecting the cortico-spinal pathways are known to cause a reduction of cortical excitability in the lesioned area not only for the local connectivity impairment but also due to a contralateral hemisphere inhibitory action. Non-invasive brain stimulation using high frequency repetitive magnetic transcranial stimulation (rTMS) over the lesioned hemisphere and contralateral cortical inhibition using low-frequency rTMS have been shown to increase the excitability of the lesioned hemisphere. Mental representation techniques, neurofeedback, and virtual reality have also been shown to increase cortical excitability and complement conventional rehabilitation. Materials and Methods: We aim to carry out a single-blind, randomized, controlled trial aiming to study the efficacy of immersive multimodal Brain–Computer Interfacing-Virtual Reality (BCI-VR) training after bilateral neuromodulation with rTMS on upper limb motor recovery after subacute stroke (>3 months) compared to neuromodulation combined with conventional motor imagery tasks. This study will include 42 subjects in a randomized controlled trial design. The main expected outcomes are changes in the Motricity Index of the Arm (MI), dynamometry of the upper limb, score according to Fugl-Meyer for upper limb (FMA-UE), and changes in the Stroke Impact Scale (SIS). The evaluation will be carried out before the intervention, after each intervention and 15 days after the last session. Conclusions: This trial will show the additive value of VR immersive motor imagery as an adjuvant therapy combined with a known effective neuromodulation approach opening new perspectives for clinical rehabilitation protocols.

To evaluate the effects of transcranial direct current stimulation (tDCS) on Parkinson's disease (PD)-related pain. This triple-blind randomized controlled trial included twenty-two patients (age range 38-85, 10 male) with PD-related pain. Eleven subjects received ten sessions of 20 minutes tDCS over the primary motor cortex contralateral to pain at 2 mA intensity. Eleven subjects received sham stimulation. Outcome measures included changes in the Kinǵs Parkinsońs Pain Scale (KPPS), Brief Pain Inventory (BPI), widespread mechanical hyperalgesia (WMH), temporal summation of pain (TS), and conditioned pain modulation (CPM). Significant differences were found in KPPS between groups favoring the active-tDCS group compared to the sham-tDCS group at 15-days follow-up (p = 0.014) but not at 2 days post-intervention (p = 0.059). The active-group showed significant improvements over the sham-group after 15 days (p = 0.017). Significant changes were found in CPM between groups in favor of active-tDCS group at 2 days post-intervention (p = 0.002) and at 15 days (p = 0.017). No meaningful differences were observed in BPI or TS. tDCS of the primary motor cortex alleviates perceived PD-related pain, reduces pain sensitization, and enhances descending pain inhibition. This is the first study to test and demonstrate the use of tDCS for improving PD-related pain.

Objective: To examine the clinical effects of combining motor imagery-based neurofeedback training with bilateral repetitive transcranial magnetic stimulation for upper limb motor function in subacute and chronic stroke. Design: Clinical trial following an AB/BA crossover design with counterbalanced assignment. Subjects: Twenty individuals with subacute (n = 4) or chronic stroke (n = 16). Methods: Ten consecutive sessions of bilateral repetitive transcranial magnetic stimulation alone (therapy A) were compared vs a combination of10 consecutive sessions of bilateral repetitive transcranial magnetic stimulation with 12 non-consecutive sessions of motor imagery-based neurofeedback training (therapy B). Patients received both therapies (1-month washout period), in sequence AB or BA. Participants were assessed before and after each therapy and at 15-days follow-up, using the Fugl-Meyer Assessment-upper limb, hand-grip strength, and the Nottingham Sensory Assessment as primary outcome measures. Results: Both therapies resulted in improved functionality and sensory function. Therapy B consistently exhibited superior effects compared with therapy A, according to Fugl-Meyer Assessment and tactile and kinaesthetic sensory function across multiple time-points, irrespective of treatment sequence. No statistically significant differences between therapies were found for hand-grip strength. Conclusion: Following subacute and chronic stroke, integrating bilateral repetitive transcranial magnetic stimulation and motor imagery-based neurofeedback training has the potential to enhance functional performance compared with using bilateral repetitive transcranial magnetic stimulation alone in upper limb recovery.

Objective. Stroke is a major cause of adult disability worldwide, resulting in motor impairments. To regain motor function, patients undergo rehabilitation, typically involving repetitive movement training. For those who lack volitional movement, novel technology-based approaches have emerged that directly involve the central nervous system, through neuromodulation techniques such as transcranial magnetic stimulation (TMS), and closed-loop neurofeedback like brain-computer interfaces (BCIs). This, can be augmented through proprioceptive feedback delivered many times by embodied virtual reality (VR). Nonetheless, despite a growing body of research demonstrating the individual efficacy of each technique, there is limited information on their combined effects. Approach. In this study, we analyzed the Electroencephalographic (EEG) signals acquired from 10 patients with more than 4 months since stroke during a longitudinal intervention with repetitive TMS followed by VR-BCI training. From the EEG, the event related desynchronization (ERD) and individual alpha frequency (IAF) were extracted, evaluated over time and correlated with clinical outcome. Main results. Every patient’s clinical outcome improved after treatment, and ERD magnitude increased during simultaneous rTMS and VR-BCI. Additionally, IAF values showed a significant correlation with clinical outcome, nonetheless, no relationship was found between differences in ERD pre- post- intervention with the clinical improvement. Significance. This study furnishes empirical evidence supporting the efficacy of the joint action of rTMS and VR-BCI in enhancing patient recovery. It also suggests a relationship between IAF and rehabilitation outcomes, that could potentially serve as a retrievable biomarker for stroke recovery.

Right hemisphere stroke frequently results in hemispatial neglect, a disabling condition that can significantly impede the recovery process. The chronic presence of neglect has been linked to poorer outcomes in both cognitive and motor domains. As an adjunct to conventional neuropsychological interventions, transcranial direct current stimulation (tDCS)-a noninvasive technique that modulates neural excitability through low-intensity electrical currents-has gained attention for its potential to enhance cortical plasticity and support functional improvement in affected individuals. In this study, we propose a combined intervention protocol aimed at reducing symptoms of post-stroke hemispatial neglect. It consists of a cathodal tDCS protocol combined with a computerized neuropsychological rehabilitation program specifically designed for the rehabilitation of hemispatial neglect. The neuromodulation strategy is to reduce the hyperactivation of the undamaged hemisphere based on the interhemispheric rivalry model. The intervention consists of 2 weeks, 10 sessions (from Monday to Friday), 45 min each, of tDCS and conventional cognitive stimulation concurrently applied. The tDCS is applied by an 8-channel high definitiontDCS (HD- tDCS) device for 20 min and at 2 mA of intensity. The cathode is positioned over the left posterior parietal cortex (P3 following 10/20 system for electroencephalogram [EEG] electrode placement), and return electrodes are placed at C3, CP5, CP1, Pz, PO3, PO7, and P7. A neuropsychological and functional assessment was carried out at baseline and after the end of the intervention. The primary aim of the present study is to describe the protocol for a parallel, randomized, triple-blind experimental design. To ensure the feasibility of the protocol and its potential efficacy, a comprehensive description of the procedures applied to a single pilot participant is provided. Incorporating tDCS neuromodulation strategies into cognitive rehabilitation processes may lead to shortened intervention times and improve the functional status and quality of life of patients.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.