Combined non-invasive neuromodulation using transcranial direct current stimulation, motor imagery and action observation for motor, cognitive and functional recovery in cortico-basal degeneration: a single case study.

This case report presents a comprehensive assessment and therapeutic intervention using non-invasive motor cortex neuromodulation for a 70-year-old female patient diagnosed with corticobasal degeneration (CBD). The study followed the CARE guidelines. The patient meets the criteria for probable CBD, with neuroimaging evidence of exclusively cortical impairment. The patient underwent a non-invasive neuromodulation protocol involving transcranial direct current stimulation (tDCS) and action observation plus motor imagery (AO+MI). The neuromodulation protocol comprised 20 sessions involving tDCS over the primary motor cortex and combined AO+MI. Anodal tDCS was delivered a 2 mA excitatory current for 20 minutes. AO+MI focused on lower limb movements, progressing over four weeks with video observation and gradual execution, both weekly and monthly. The neuromodulation techniques were delivered online (i.e. applied simultaneously in each session). Outcome measures were obtained at baseline, post-intervention and follow-up (1 month later), and included motor (lower limb), cognitive/neuropsychological and functional assessments. Walking speed improvements were not observed, but balance (Berg Balance Scale) and functional strength (Five Times Sit-to-Stand Test) improved post-treatment. Long-term enhancements in attentional set-shifting, inhibitory control, verbal attentional span, and working memory were found. There was neurophysiological evidence of diminished intracortical inhibition. Functional changes included worsening in Cortico Basal Ganglia Functional Scale score. Emotional well-being and general health (SF-36) increased immediately after treatment but were not sustained, while Falls Efficacy Scale International showed only long-term improvement. The findings suggest potential benefits of the presented neuromodulation protocol for CBD patients, highlighting multifaceted outcomes in motor, cognitive, and functional domains.

Effects of motor imagery-based neurofeedback training after bilateral repetitive transcranial magnetic stimulation on post-stroke upper limb motor function: an exploratory crossover clinical trial.

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.

Robotic exoskeleton embodiment in post-stroke hemiparetic patients: an experimental study about the integration of the assistance provided by the REFLEX knee exoskeleton.

Hemiparetic gait is the most common motor-disorder after stroke and, in spite of rehabilitation efforts, it is persistent in 50% of community dwelling stroke-survivors. Robotic exoskeletons have been proposed as assistive devices to support impaired joints. An example of these devices is the REFLEX knee exoskeleton, which assists the gait of hemiparetic subjects and whose action seems to be properly embodied by stroke survivors, who were able to adapt the motion of their non-assisted limbs and, therefore, reduce their compensation mechanisms. This paper presents an experimental validation carried out to deepen into the effects of REFLEX's assistance in hemiparetic subjects. Special attention was paid to the effect produced in the muscular activity as a metric to evaluate the embodiment of this technology. Significant differences were obtained at the subject level due to the assistance; however, the high dispersion of the measured outcomes avoided extracting global effects at the group level. These results highlight the need of individually tailoring the action of the robot to the individual needs of each patient to maximize the beneficial outcomes. Extra research effort should be done to elucidate the neural mechanisms involved in the embodiment of external devices by stroke survivors.

Repetitive transcranial magnetic stimulation of primary motor cortex for stroke upper limb motor sequelae rehabilitation: A systematic review.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) over the primary motor cortex (M1) has been used to treat stroke motor sequelae regulating cortical excitability. Early interventions are widely recommended, but there is also evidence showing interventions in subacute or chronic phases are still useful. OBJECTIVE: To synthetize the evidence of rTMS protocols to improve upper limb motor function in people with subacute and/or chronic stroke. METHODS: Four databases were searched in July 2022. Clinical trials investigating the effectiveness of different rTMS protocols on upper limb motor function in subacute or chronic phases post-stroke were included. PRISMA guidelines and PEDro scale were used. RESULTS: Thirty-two studies representing 1137 participants were included. Positive effects of all types of rTMS protocols on upper limb motor function were found. These effects were heterogeneous and not always clinically relevant or related to neurophysiological changes but produced evident changes if evaluated with functional tests. CONCLUSION: rTMS interventions over M1 are effective for improving upper limb motor function in people with subacute and chronic stroke. When rTMS protocols were priming physical rehabilitation better effects were achieved. Studies considering minimal clinical differences and different dosing will help to generalize the use of these protocols in clinical practice.

A unilateral robotic knee exoskeleton to assess the role of natural gait assistance in hemiparetic patients.

BACKGROUND: Hemiparetic gait is characterized by strong asymmetries that can severely affect the quality of life of stroke survivors. This type of asymmetry is due to motor deficits in the paretic leg and the resulting compensations in the nonparetic limb. In this study, we aimed to evaluate the effect of actively promoting gait symmetry in hemiparetic patients by assessing the behavior of both paretic and nonparetic lower limbs. This paper introduces the design and validation of the REFLEX prototype, a unilateral active knee-ankle-foot orthosis designed and developed to naturally assist the paretic limbs of hemiparetic patients during gait. METHODS: REFLEX uses an adaptive frequency oscillator to estimate the continuous gait phase of the nonparetic limb. Based on this estimation, the device synchronically assists the paretic leg following two different control strategies: (1) replicating the movement of the nonparetic leg or (2) inducing a healthy gait pattern for the paretic leg. Technical validation of the system was implemented on three healthy subjects, while the effect of the generated assistance was assessed in three stroke patients. The effects of this assistance were evaluated in terms of interlimb symmetry with respect to spatiotemporal gait parameters such as step length or time, as well as the similarity between the joint's motion in both legs. RESULTS: Preliminary results proved the feasibility of the REFLEX prototype to assist gait by reinforcing symmetry. They also pointed out that the assistance of the paretic leg resulted in a decrease in the compensatory strategies developed by the nonparetic limb to achieve a functional gait. Notably, better results were attained when the assistance was provided according to a standard healthy pattern, which initially might suppose a lower symmetry but enabled a healthier evolution of the motion of the nonparetic limb. CONCLUSIONS: This work presents the preliminary validation of the REFLEX prototype, a unilateral knee exoskeleton for gait assistance in hemiparetic patients. The experimental results indicate that assisting the paretic leg of a hemiparetic patient based on the movement of their nonparetic leg is a valuable strategy for reducing the compensatory mechanisms developed by the nonparetic limb.

Clinical Effects of Immersive Multimodal BCI-VR Training after Bilateral Neuromodulation with rTMS on Upper Limb Motor Recovery after Stroke. A Study Protocol for a Randomized Controlled Trial.

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.

Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson's Disease: Study Protocol for a Randomized Controlled Trial.

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.

New Approaches Based on Non-Invasive Brain Stimulation and Mental Representation Techniques Targeting Pain in Parkinson's Disease Patients: Two Study Protocols for Two Randomized Controlled Trials.

Pain is an under-reported but prevalent symptom in Parkinson's Disease (PD), impacting patients' quality of life. Both pain and PD conditions cause cortical excitability reduction and non-invasive brain stimulation. Mental representation techniques are thought to be able to counteract it, also resulting effectively in chronic pain conditions. We aim to conduct two independent studies in order to evaluate the efficacy of transcranial direct current stimulation (tDCS) and mental representation protocol in the management of pain in PD patients during the ON state: (1) tDCS over the Primary Motor Cortex (M1); and (2) Action Observation (AO) and Motor Imagery (MI) training through a Brain-Computer Interface (BCI) using Virtual Reality (AO + MI-BCI). Both studies will include 32 subjects in a longitudinal prospective parallel randomized controlled trial design under different blinding conditions. The main outcomes will be score changes in King's Parkinson's Disease Pain Scale, Brief Pain Inventory, Temporal Summation, Conditioned Pain Modulation, and Pain Pressure Threshold. Assessment will be performed pre-intervention, post-intervention, and 15 days post-intervention, in both ON and OFF states.