Effect of tDCS combined with virtual reality for post-stroke cognitive impairment: a randomized controlled trial study protocol.

Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects' speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

Cheng XP ，Wang ZD ，Zhou YZ ，Zhan LQ ，Wu D ，Xie LL ，Luo KL ，He JP ，Lin W ，Ni J ，Lv L ，Chen XY ... -  《BMC Complementary Medicine and Therapies》

Non-pharmacological interventions for improving language and communication in people with primary progressive aphasia.

Primary progressive aphasia (PPA) accounts for approximately 43% of frontotemporal dementias and is mainly characterised by a progressive impairment of speech and communication abilities. Three clinical variants have been identified: (a) non-fluent/agrammatic, (b) semantic, and (c) logopenic/phonological PPA variants. There is currently no curative treatment for PPA, and the disease progresses inexorably over time, with devastating effects on speech and communication ability, functional status, and quality of life. Several non-pharmacological interventions that may improve symptoms (e.g. different forms of language training and non-invasive brain stimulation) have been investigated in people with PPA. To assess the effects of non-pharmacological interventions for people with PPA on word retrieval (our primary outcome), global language functions, cognition, quality of life, and adverse events. We searched the Cochrane Dementia and Cognitive Improvement Group's trial register, MEDLINE (Ovid SP), Embase (Ovid SP), four other databases and two other trial registers. The latest searches were run on 26 January 2024. We included randomised controlled trials (RCTs) evaluating the effects of non-pharmacological interventions in people with PPA. We used standard methodological procedures expected by Cochrane. There were insufficient data available to conduct the network meta-analyses that we had originally planned (due to trial data being insufficiently reported or not reported at all, as well as the heterogeneous content of the included interventions). Therefore, we provide a descriptive summary of the included studies and results. We included 10 studies, with a total of 132 participants, evaluating non-pharmacological interventions. These were: transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) as stand-alone treatments (used by two and one studies, respectively); tDCS combined with semantic and phonological word-retrieval training (five studies); tDCS combined with semantic word-retrieval training (one study); and tDCS combined with phonological word-retrieval training (one study). Results for our primary outcome of word retrieval were mixed. For the two studies that investigated the effects of tDCS as stand-alone treatment compared to placebo ("sham") tDCS, we rated the results as having very low-certainty evidence. One study found a significant beneficial effect on word retrieval after active tDCS; one study did not report any significant effects in favour of the active tDCS group. Five studies investigated tDCS administered to the dorsolateral prefrontal cortex, inferior frontal cortex, left frontotemporal region, or the temporoparietal cortex, combined with semantic and phonological word-retrieval training. The most consistent finding was enhancement of word-retrieval ability for trained items immediately after the intervention, when behavioural training was combined with active tDCS compared to behavioural training plus sham tDCS. We found mixed effects for untrained items and maintenance of treatment effects during follow-up assessments. We rated the certainty of the evidence as very low in all studies. One study investigated tDCS combined with semantic word-retrieval training. Training was provided across 15 sessions with a frequency of three to five sessions per week, depending on the personal preferences of the participants. tDCS targeted the left frontotemporal region. The study included three participants: two received 1 mA stimulation and one received 2 mA stimulation. The study showed mixed results. We rated it as very low-certainty evidence. One study investigated tDCS combined with phonological word-retrieval training. Training was again provided across 15 sessions over a period of three weeks. tDCS targeted the left inferior frontal gyrus. This study showed a significantly more pronounced improvement for trained and untrained words in favour of the group that had received active tDCS, but we rated the certainty of the evidence as very low. One study compared active rTMS applied to an individually determined target site to active rTMS applied to a control site (vertex) for effects on participants' word retrieval. This study demonstrated better word retrieval for active rTMS administered to individually determined target brain regions than in the control intervention, but we rated the results as having a very low certainty of evidence. Four studies assessed overall language ability, three studies assessed cognition, five studies assessed potential adverse effects of brain stimulation, and one study investigated quality of life. There is currently no high-certainty evidence to inform clinical decision-making regarding non-pharmacological treatment selection for people with PPA. Preliminary evidence suggests that the combination of active tDCS with specific language therapy may improve impaired word retrieval for specifically trained items beyond the effects of behavioural treatment alone. However, more research is needed, including high-quality RCTs with detailed descriptions of participants and methods, and consideration of outcomes such as quality of life, depressive symptoms, and overall cognitive functioning. Moreover, studies assessing optimal treatments (i.e. behavioural interventions, brain stimulation interventions, and their combinations) for individual patients and PPA subtypes are needed. We were not able to conduct the planned (network) meta-analyses due to missing data that could not be obtained from most of the authors, a general lack of RCTs in the field, and heterogeneous interventions in eligible trials. Journals should implement a mandatory data-sharing requirement to assure transparency and accessibility of data from clinical trials.

Roheger M ，Riemann S ，Brauer A ，McGowan E ，Grittner U ，Flöel A ，Meinzer M ... -  《Cochrane Database of Systematic Reviews》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Effect of transcranial direct current stimulation combined with transcutaneous auricular vagus nerve stimulation on poststroke cognitive impairment: a study protocol for a randomised controlled trial.

Poststroke cognitive impairment is a common complication in stroke survivors, seriously affecting their quality of life. Therefore, it is crucial to improve cognitive function of patients who had a stroke. Transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS) are non-invasive, safe treatments with great potential to improve cognitive function in poststroke patients. However, further improvements are needed in the effectiveness of a single non-invasive brain stimulation technique for cognitive rehabilitation. This study protocol aims to investigate the effect and neural mechanism of the combination of tDCS and taVNS on cognitive function in patients who had a stroke. In this single-centre, prospective, parallel, randomised controlled trial, a total of 66 patients with poststroke cognitive impairment will be recruited and randomly assigned (1:1:1) to the tDCS group, the taVNS group and the combination of tDCS and taVNS group. Each group will receive 30 min of treatment daily, five times weekly for 3 weeks. Primary clinical outcome is the Montreal Cognitive Assessment. Secondary clinical outcomes include the Mini-Mental State Examination, Stroop Colour Word Test, Trail Marking Test, Symbol Digit Modalities Test and Modified Barthel Index. All clinical outcomes, functional MRI and diffusion tensor imaging will be measured at preintervention and postintervention. The trial has been approved by the Ethics Committee of the First Affiliated Hospital of Yangtze University (approval no: KY202390). The results will be submitted for publication in peer-reviewed journals or at scientific conferences. ChiCTR2300076632.

Liu W ，Cheng X ，Zhang Y ，Liao W ... -  《BMJ Open》

The Effectiveness of Therapeutic Exercise Interventions With Virtual Reality on Balance and Walking Among Persons With Chronic Stroke: Systematic Review, Meta-Analysis, and Meta-Regression of Randomized Controlled Trials.

Well-targeted balance, walking, and weight-shift training can improve balance capabilities in the chronic phase of stroke. There is an urgent need for a long-term approach to rehabilitation that extends beyond the acute and subacute phases, supporting participation without increasing the demand for health care staff. This study aims to evaluate the effectiveness of therapeutic exercise interventions with virtual reality (VR) training on balance and walking at the activity and participation levels in individuals with chronic stroke, compared with control groups receiving no treatment, conventional physical therapy, specific training, similar treatment, or identical treatment without VR. Studies were searched across 6 databases. The inclusion criteria were as follows: Adults aged 18 years or older with a stroke diagnosis for at least 6 months (population). Therapeutic exercises within a VR environment, using VR glasses or interactive games (intervention). Control groups without the use of VR (including no treatment, conventional physical therapy, specific training, similar treatment without VR, or identical treatment without the additional use of VR; comparison). We evaluated the Berg Balance Scale score, Functional Reach Test performance, Activities-specific Balance Confidence Scale score, Six-minute Walk Test, Two-minute Walk Test, 10-meter Walk Test results, and cadence (outcome measures). We investigated randomized controlled trials (study design). A meta-analysis and a meta-regression analysis were conducted to evaluate whether the content of VR interventions or control groups, as well as the level of VR immersion used, was related to balance or walking outcomes. A total of 43 randomized controlled trials involving 1136 participants were included in this review. The use of VR training in therapeutic exercise interventions had a large effect on balance (standardized mean difference 0.51, 95% CI 0.29-0.72; P<.001) and a moderate effect on walking (standardized mean difference 0.31, 95% CI 0.09-0.53; P=.006) in individuals with chronic stroke, compared with pooled control groups (no treatment, conventional physical therapy, specific training, similar treatment, or identical treatment without the use of VR). According to the meta-regression findings, the content of VR interventions (P=.52), the type of control groups (P=.79), and the level of VR immersion (P=.82) were not significantly related to the pooled balance or walking outcomes. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) was moderate for balance and low for walking. Therapeutic exercise training with VR had a positive, albeit moderate, effect on balance and a low impact on walking at the level of activity (capacity), even in the chronic phase of stroke, without serious side effects. The results are applicable to working-aged stroke rehabilitees who are able to walk without assistance. Further research is needed with defined VR methods and outcomes that assess performance at the level of real-life participation.

Krohn M ，Rintala A ，Immonen J ，Sjögren T ... -  《JOURNAL OF MEDICAL INTERNET RESEARCH》