Corticocortical paired associative stimulation for treating motor dysfunction after stroke: study protocol for a randomised sham-controlled double-blind clinical trial

IntroductionStroke survivors can have a high disability rate with low quality of daily life, resulting in a heavy burden on family and society. Transcranial magnetic stimulation has been widely applied to brain injury repair, neurological disease treatment, cognition and emotion regulation and so on. However, there is still much to be desired in the theories of using these neuromodulation techniques to treat stroke-caused hemiplegia. It is generally recognised that synaptic plasticity is an important basis for functional repair after brain injury. This study protocol aims to examine the corticocortical paired associative stimulation (ccPAS) for inducing synaptic plasticity to rescue the paralysed after stroke.Methods and analysisThe current study is designed as a 14-week double-blind randomised sham-controlled clinical trial, composed of 2-week intervention and 12-week follow-up. For the study, 42 patients who had a stroke aged 40–70 will be recruited, who are randomly assigned either to the ccPAS intervention group, or to the control group at a 1:1 ratio, hence an equal number each. In the intervention group, ccPAS is practised in conjunction with the conventional rehabilitation treatment, and in the control group, the conventional rehabilitation treatment is administered with sham stimulation. A total of 10 interventions will be made, 5 times a week for 2 weeks. The same assessors are supposed to evaluate the participants’ motor function at four time points of the baseline (before 10 interventions), treatment ending (after 10 interventions), and two intervals of follow-up (1 and 3 months later, respectively). The Fugl-Meyer Assessment Upper Extremity is used for the primary outcomes. The secondary outcomes include changes in the assessment of Action Research Arm Test (ARAT), Modified Barthel Index (MBI), electroencephalogram (EEG) and functional MRI data. The adverse events are to be recorded throughout the study.Ethics and disseminationThis study was approved by the Medical Ethics Committee of Yueyang Hospital. All ethical work was performed in accordance with the Helsinki declaration. Written informed consent was obtained from all individual participants included in the study. Study findings will be disseminated in the printed media.Trial registration numberChinese Clinical Trial Registry: ChiCTR2000036685.

Effects of Non-invasive Brain Stimulation on Multiple System Atrophy: A Systematic Review

Background/Objective: Multiple system atrophy (MSA) refers to a progressive neurodegenerative disease characterized by autonomic dysfunction, parkinsonism, cerebellar ataxia, as well as cognitive deficits. Non-invasive brain stimulation (NIBS) has recently served as a therapeutic technique for MSA by personalized stimulation. The primary aim of this systematic review is to assess the effects of NIBS on two subtypes of MSA: parkinsonian-type MSA (MSA-P) and cerebellar-type MSA (MSA-C).Methods: A literature search for English articles was conducted from PubMed, Embase, Web of Science, Cochrane Library, CENTRAL, CINAHL, and PsycINFO up to August 2021. Original articles investigating the therapeutics application of NIBS in MSA were screened and analyzed by two independent reviewers. Moreover, a customized form was adopted to extract data, and the quality of articles was assessed based on the PEDro scale for clinical articles.Results: On the whole, nine articles were included, i.e., five for repetitive transcranial magnetic stimulation (rTMS), two for transcranial direct current stimulation (tDCS), one for paired associative stimulation, with 123 patients recruited. The mentioned articles comprised three randomized controlled trials, two controlled trials, two non-controlled trials, and two case reports which assessed NIBS effects on motor function, cognitive function, and brain modulatory effects. The majority of articles demonstrated significant motor symptoms improvement and increased cerebellar activation in the short term after active rTMS. Furthermore, short-term and long-term effects on improvement of motor performance were significant for tDCS. As opposed to the mentioned, no significant change of motor cortical excitability was reported after paired associative stimulation.Conclusion: NIBS can serve as a useful neurorehabilitation strategy to improve motor and cognitive function in MSA-P and MSA-C patients. However, further high-quality articles are required to examine the underlying mechanisms and standardized protocol of rTMS as well as its long-term effect. Furthermore, the effects of other NIBS subtypes on MSA still need further investigation.

Transcranial Magnetic Stimulation Following A Paired Associative Stimulation Protocol Based On A Videogame Potentiates Cortical Plasticity And Motor Behavior

BackgroundTranscranial Magnetic Stimulation (TMS) can induce synaptic plasticity potentiation following a paired associative stimulation (PAS) protocol, synchronizing a TMS single pulse with a movement task, named movement-related cortical stimulation (MRCS). However, MRCS plasticity induction and performance potentiation has been related exclusively to single movement tasks.MethodIn order to unveil the changes in motor learning produced by the MRCS protocol in complex movements, associated to Activities of Daily Living (ADL), we induced PAS changes in synchronization with a movement-related dynamic task by performing a customized videogame. We measured the task performance as well as nervous system excitability neuromodulation in 22 healthy subjects, analyzing Reaction Time (RT) and the peak-to-peak amplitude of the Motor Evoked Potentials (MEPs) respectively. The MEPs were recorded in the main task executor muscle, Abductor Pollicis Brevis (APB), and a secondary muscle, Abductor Digiti Minimi (ADM), before, right after, and 30 minutes after the intervention, in a real against sham group experimental parallel design. ResultsPAS application in synchronization with a complex task resulted in a motor performance potentiation effect, inducing shorter RTs when compared to the sham group. Moreover, it triggered long-term corticospinal plasticity mechanisms reflected in a MEP amplitude depression for the APB muscle at the higher intensity of recruitment curve and an enhancement of the corticospinal excitability of ADM muscle at around threshold intensity. RTs and ADM MEP amplitudes correlated positively in around threshold and high intensity assessments.ConclusionsWe conclude that the proposed PAS protocol facilitated the learning of time-accuracy movement in complex movement tasks, even if fatigue could be affecting the executor muscle excitability, and enhanced potentiation towards a passive muscle. This phenomenon can be very useful to develop neurorehabilitation strategies with complex movements (more similar to ADLs) and to avoid maladaptive plasticity related likely to fatigue.