Relationship between resting-state functional connectivity and change in motor function after motor imagery intervention in patients with stroke: a scoping review.

BACKGROUND: In clinical practice, motor imagery has been proposed as a treatment modality for stroke owing to its feasibility in patients with severe motor impairment. Motor imagery-based interventions can be categorized as open- or closed-loop. Closed-loop intervention is based on voluntary motor imagery and induced peripheral sensory afferent (e.g., Brain Computer Interface (BCI)-based interventions). Meanwhile, open-loop interventions include methods without voluntary motor imagery or sensory afferent. Resting-state functional connectivity (rs-FC) is defined as a significant temporal correlated signal among functionally related brain regions without any stimulus. rs-FC is a powerful tool for exploring the baseline characteristics of brain connectivity. Previous studies reported changes in rs-FC after motor imagery interventions. Systematic reviews also reported the effects of motor imagery-based interventions at the behavioral level. This study aimed to review and describe the relationship between the improvement in motor function and changes in rs-FC after motor imagery in patients with stroke. REVIEW PROCESS: The literature review was based on Arksey and O'Malley's framework. PubMed, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science were searched up to September 30, 2023. The included studies covered the following topics: illusion without voluntary action, motor imagery, action imitation, and BCI-based interventions. The correlation between rs-FC and motor function before and after the intervention was analyzed. After screening by two independent researchers, 13 studies on BCI-based intervention, motor imagery intervention, and kinesthetic illusion induced by visual stimulation therapy were included. CONCLUSION: All studies relating to motor imagery in this review reported improvement in motor function post-intervention. Furthermore, all those studies demonstrated a significant relationship between the change in motor function and rs-FC (e.g., sensorimotor network and parietal cortex).

Neural bases characterizing chronic and severe upper-limb motor deficits after brain lesion.

Chronic and severe upper-limb motor deficits can result from damage to the corticospinal tract. However, it remains unclear what their characteristics are and whether only corticospinal tract damage determines their characteristics. This study aimed to investigate the clinical characteristics and neural bases of chronic and severe upper-limb motor deficits. Motor deficits, including spasticity, of 45 patients with brain lesions were assessed using clinical scales. Regarding their scores, we conducted a principal component analysis that statistically extracted the clinical characteristics as two principal components. Using these principal components, we investigated the neural bases underlying their characteristics through lesion analyses of lesion volume, lesion sites, corticospinal tract, or other regional white-matter integrity. Principal component analysis showed that the clinical characteristics of chronic and severe upper-limb motor deficits could be described as a comprehensive severity and a trade-off relationship between proximal motor functions and wrist/finger spasticity. Lesion analyses revealed that the comprehensive severity was correlated with corticospinal tract integrity, and the trade-off relationship was associated with the integrity of other regional white matter located anterior to the posterior internal capsule, such as the anterior internal capsule. This study indicates that the severity of chronic and severe upper-limb motor deficits can be determined according to the corticospinal tract integrity, and such motor deficits may be further characterized by the integrity of other white matter, where the corticoreticular pathway can pass through, by forming a trade-off relationship where patients have higher proximal motor functions but more severe wrist/finger spasticity, and vice versa.

Effects of kinesthetic illusion induced by visual stimulation (KINVIS) therapy on patients with stroke in the subacute phase: a visual analysis based on paralysis severity.

We explored the effect of kinesthetic illusion induced by visual stimulation (KINVIS) therapy on motor function in patients with stroke during the subacute phase based on paralysis severity. The study was performed using an ABAB design (A1, B1, A2, B2; for 10 days each). KINVIS therapy was additionally administered in periods B1 and B2. Ten patients with stroke were classified according to severity. The improvement in upper limb motor function was higher after B1 and B2 than after A1 and A2 in the moderate group. The effect of KINVIS therapy increases the degree of improvement in motor function, especially in the moderate group.

Visually Induced Kinaesthetic Illusion Combined with Therapeutic Exercise for Patients with Chronic Stroke: A Pilot Study.

OBJECTIVE: Kinaesthetic perceptional illusion by visual stimulation (KINVIS) combined with neuromuscular electrical stimulation (NMES) and conventional therapeutic exercise (TherEX) has been shown previously to enhance motor function in stroke patients with chronic hemiparesis. The aim of this preliminary study is to assess the effects of a repetitive KINVIS intervention combined with TherEX, but without NMES, on upper limb motor function of patients with stroke-induced hemiparesis. DESIGN: A quasi-experimental study, with pretest-posttest for 1 group Patients: Ten patients with stroke-induced, chronic, severe upper limb hemiparesis. METHODS: Patients were evaluated before and after a 10-day intervention, during which KINVIS and TherEX were applied for 20 and 60 min, respectively, for 5 days per week (Monday to Friday). Upper limb motor function was assessed using Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT), and resistance to passive movement in flexor muscles was assessed using the Modified Ashworth Scale (MAS). In addition, the amount of use and quality of movement of the affected upper limb in daily life were assessed using Motor Activity Log (MAL). RESULTS: Clinical assessments with FMA, ARAT, MAS, and MAL significantly improved after the intervention period. CONCLUSION: A repetitive KINVIS intervention combined with TherEX may improve upper limb motor function in patients with chronic stroke and severe hemiparesis.

Model-Based Analyses for the Causal Relationship Between Post-stroke Impairments and Functional Brain Connectivity Regarding the Effects of Kinesthetic Illusion Therapy Combined With Conventional Exercise.

Aims: Therapy with kinesthetic illusion of segmental body part induced by visual stimulation (KINVIS) may allow the treatment of severe upper limb motor deficits in post-stroke patients. Herein, we investigated: (1) whether the effects of KINVIS therapy with therapeutic exercise (TherEx) on motor functions were induced through improved spasticity, (2) the relationship between resting-state functional connectivity (rs-FC) and motor functions before therapy, and (3) the baseline characteristics of rs-FC in patients with the possibility of improving their motor functions. Methods: Using data from a previous clinical trial, three path analyses in structural equation modeling were performed: (1) a mediation model in which the indirect effects of the KINVIS therapy with TherEx on motor functions through spasticity were drawn, (2) a multiple regression model with pre-test data in which spurious correlations between rs-FC and motor functions were controlled, and (3) a multiple regression model with motor function score improvements between pre- and post-test in which the pre-test rs-FC associated with motor function improvements was explored. Results: The mediation model illustrated that although KINVIS therapy with TherEx did not directly improve motor function, it improved spasticity, which led to ameliorated motor functions. The multiple regression model with pre-test data suggested that rs-FC of bilateral parietal regions is associated with finger motor functions, and that rs-FC of unaffected parietal and premotor areas is involved in shoulder/elbow motor functions. Moreover, the multiple regression model with motor function score improvements suggested that the weaker the rs-FC of bilateral parietal regions or that of the supramarginal gyrus in an affected hemisphere and the cerebellar vermis, the greater the improvement in finger motor function. Conclusion: The effects of KINVIS therapy with TherEx on upper limb motor function may be mediated by spasticity. The rs-FC, especially that of bilateral parietal regions, might reflect potentials to improve post-stroke impairments in using KINVIS therapy with TherEx.

Effect of primary motor cortex excitability changes after quadripulse transcranial magnetic stimulation on kinesthetic sensitivity: A preliminary study.

Muscle spindles provide the greatest contribution to kinesthetic perception. Primary motor cortex (M1) excitability changes in parallel with the intensity of kinesthetic perception inputs from muscle spindles; M1 is therefore involved in kinesthetic perception. However, the causal relationship between changes in kinesthetic sensitivity and M1 excitability is unclear. The purpose of this study was to test whether artificially and sustainably modulated M1 excitability causes changes in kinesthetic sensitivity in healthy individuals. We evaluated motor evoked potentials (MEP) in Experiment 1 and joint motion detection thresholds (JMDT) in Experiment 2 before and after quadripulse transcranial magnetic stimulation (QPS). Nine healthy right-handed male volunteers were recruited. In each experiment, participants received QPS or sham stimulation (Sham) on separate days. MEP amplitude and JMDT were recorded before and at 0, 15, 30, 45, and 60 min after QPS and Sham. Our results showed that M1 excitability and kinesthetic sensitivity increased after QPS, whereas neither changed after Sham. In the five subjects who participated in both experiments, there was a significant moderate correlation between M1 excitability and kinesthetic sensitivity. Thus, the long-lasting change in kinesthetic sensitivity may be due to changes in M1 excitability. In addition, M1 may play a gain adjustment role in the neural pathways of muscle spindle input.

Kinesthetic illusion induced by visual stimulation influences sensorimotor event-related desynchronization in stroke patients with severe upper-limb paralysis: A pilot study.

BACKGROUND: Repetition of motor imagery improves the motor function of patients with stroke. However, patients who develop severe upper-limb paralysis after chronic stroke often have an impaired ability to induce motor imagery. We have developed a method to passively induce kinesthetic perception using visual stimulation (kinesthetic illusion induced by visual stimulation [KINVIS]). OBJECTIVE: This pilot study further investigated the effectiveness of KINVIS in improving the induction of kinesthetic motor imagery in patients with severe upper-limb paralysis after stroke. METHODS: Twenty participants (11 with right hemiplegia and 9 with left hemiplegia; mean time from onset [±standard deviation], 67.0±57.2 months) with severe upper-limb paralysis who could not extend their paretic fingers were included in this study. The ability to induce motor imagery was evaluated using the event-related desynchronization (ERD) recorded during motor imagery before and after the application of KINVIS for 20 min. The alpha- and beta-band ERDs around the premotor, primary sensorimotor, and posterior parietal cortices of the affected and unaffected hemispheres were evaluated during kinesthetic motor imagery of finger extension and before and after the intervention. RESULTS: Beta-band ERD recorded from the affected hemisphere around the sensorimotor area showed a significant increase after the intervention, while the other ERDs remained unchanged. CONCLUSIONS: In patients with chronic stroke who were unable to extend their paretic fingers for a prolonged period of time, the application of KINVIS, which evokes kinesthetic perception, improved their ability to induce motor imagery. Our findings suggest that although KINVIS is a passive intervention, its short-term application can induce changes related to the motor output system.

Region-dependent bidirectional plasticity in M1 following quadripulse transcranial magnetic stimulation in the inferior parietal cortex.

BACKGROUND: The ability to manipulate the excitability of the network between the inferior parietal lobule (IPL) and primary motor cortex (M1) may have clinical value. OBJECTIVE: To investigate the possibility of inducing long-lasting changes in M1 excitability by applying quadripulse transcranial magnetic stimulation (QPS) to the IPL, and to ascertain stimulus condition- and site-dependent differences in the effects. METHODS: QPS was applied to M1, the primary somatosensory cortex (S1), the supramarginal gyrus (SMG) and angular gyrus (AG) IPL areas, with the inter-stimulus interval (ISI) in the train of pulses set to either 5 ms (QPS-5) or 50 ms (QPS-50). QPS was repeated at 0.2 Hz for 30 min, or not presented (sham condition). Excitability changes in the target site were examined by means of single-pulse transcranial magnetic stimulation (TMS). RESULTS: QPS-5 and QPS-50 at M1 increased and decreased M1 excitability, respectively. QPS at S1 induced no obvious change in M1 excitability. However, QPS at the SMG induced mainly suppressive effects in M1 for at least 30 min, regardless of the ISI length. Both QPS ISIs at the AG yielded significantly different MEP compared to those at the SMG. Thus, the direction of the plastic effect of QPS differed depending on the site, even under the same stimulation conditions. CONCLUSIONS: QPS at the IPL produced long-lasting changes in M1 excitability, which differed depending on the precise stimulation site within the IPL. These results raise the possibility of noninvasive induction of functional plasticity in M1 via input from the IPL.

A Case Series Clinical Trial of a Novel Approach Using Augmented Reality That Inspires Self-body Cognition in Patients With Stroke: Effects on Motor Function and Resting-State Brain Functional Connectivity.

Barring a few studies, there are not enough established treatments to improve upper limb motor function in patients with severe impairments due to chronic stroke. This study aimed to clarify the effect of the kinesthetic perceptional illusion induced by visual stimulation (KINVIS) on upper limb motor function and the relationship between motor function and resting-state brain networks. Eleven patients with severe paralysis of upper limb motor function in the chronic phase (seven men and four women; age: 54.7 ± 10.8 years; 44.0 ± 29.0 months post-stroke) participated in the study. Patients underwent an intervention consisting of therapy using KINVIS and conventional therapeutic exercise (TherEX) for 10 days. Our originally developed KiNvis™ system was applied to induce KINVIS while watching the movement of the artificial hand. Clinical outcomes were examined to evaluate motor functions and resting-state brain functional connectivity (rsFC) by analyzing blood-oxygen-level-dependent (BOLD) signals measured using functional magnetic resonance imaging (fMRI). The outcomes of motor function (Fugle-Meyer Assessment, FMA) and spasticity (Modified Ashworth Scale, MAS) significantly improved after the intervention. The improvement in MAS scores for the fingers and the wrist flexors reached a minimum of clinically important differences. Before the intervention, strong and significant negative correlations between the motor functions and rsFC of the inferior parietal lobule (IPL) and premotor cortex (PMd) in the unaffected hemisphere was demonstrated. These strong correlations were disappeared after the intervention. A negative and strong correlation between the motor function and rsFC of the bilateral inferior parietal sulcus (IPS) significantly changed to strong and positive correlation after the intervention. These results may suggest that the combination approach of KINVIS therapy and TherEX improved motor functions and decreased spasticity in the paralyzed upper extremity after stroke in the chronic phase, possibly indicating the contribution of embodied-visual stimulation. The rsFC for the interhemispheric IPS and intrahemispheric IPL and PMd may be a possible regulatory factor for improving motor function and spasticity. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01274117.