Neurostimulation for Cognitive Rehabilitation in Autistic Spectrum Disorders
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Sự miêu tả
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that has multiple causes and very heterogeneous degrees. The main symptoms involve deficits in social interactions, difficulties in verbal and nonverbal communication, repetitive and stereotyped movements, and restricted patterns of interest. In the context of ASD rehabilitation, there is no specific treatment for autism so far, being the behavioral therapy the most used therapeutic strategy, but with still unsatisfactory results. Transcranial Direct Current Stimulation (tDCS) has been shown to be a promising technique for the treatment of different disorders, including ASD. The tDCS consists of electrical signals emitted through two electrodes in different areas of the scalp, according to the purpose of the study. The anodic current reduces the firing threshold of the neurons that are located in the cortex (that is, they increase the spontaneous firing of these neurons), whereas the cathodic current increases the firing threshold of the neurons (that is, it inhibits the activity of these neurons). Considering neuroplasticity mechanisms as fundamental in cognitive processing, tDCS becomes a promising tool in neuropsychological rehabilitation in the treatment of autistic symptoms. Previous research using protomagnetic resonance spectroscopy (H-MRS) showed lower levels of N-acetyl aspartate (NAA, a marker of mitochondrial function and neuronal density) in the left DLFPC (F3) of autistic patients, compared to healthy individuals. The findings suggest that left DLFPC dysfunction may be a component of the pathogenesis of autism. Such aspects could explain why anodic neurostimulation in F3 can improve the efficacy of autism treatment through the beneficial effects on the cognitive processes associated with DLFPC activity, such as attention and memory, executive functions, and social cognition. Social cognition can be understood as a neurobiological process that facilitates the interpretation of social signs, leading individuals to behave adaptively. In this perspective, investigations have been made that use noninvasive neuromodulatory techniques as promising tools for the promotion of social neuroplasticity, that is, the modulation of the functional and structural substrates of the nervous system associated with social cognition aiming at more adaptive social interactions.In this sense, this study is a sham-controlled, double-blind, randomized clinical trial aiming to evaluate the efficacy of anodic tDCS in aspects of social cognition of children with mild ASD. Considering that tDCS can modulate neuronal activity in patients with ASD, presented as a promising tool in the promotion of social neuroplasticity, it was hypothesized that participants treated with active current will present better performance in the social cognition tests than those submitted to sessions with simulated current. Participants treated with active current will present less number and duration of fixations in the ocular tracing during the execution of the test of recognition of emotional expressions than those submitted to the sessions with simulated current. Furthermore, cognitive processes such as executive functions are essential for social cognition because they enable the individual to engage in socially relevant activities, make decisions and behaviors to achieve goals. Deficits in social cognition as well as executive functioning have been considered central elements in the understanding and functionality of people with ASD. Thus, it was hypothesized that participants who are treated with active current will present better performance in the tests of executive functions than those submitted to the sessions with simulated current. Participants treated with active current will present less number and duration of fixations during ocular screening in the executive function test than those submitted to the simulated current sessions. Considering that there were no prior data on the effects of tDCS on patients with ASD using the primary outcome measure of the present study, a formal sample size calculation was not possible; thus, it was estimated that enrolling 20 patients would be a reasonable approach for an exploratory trial. Patients are being recruited from the appointment of rehabilitators of multidisciplinary rehabilitation centers for temporary or permanent disability and global developmental disorders in Paraíba, Brazil. Children diagnosed with ASD according DSM-V, will be randomized to two groups, one with active stimulation (1.5 mA) and the other with a sham current, in which the anode will be positioned over the left dorsolateral prefrontal cortex (F3), while the cathode (reference electrode) will be placed in the right supraorbital area. The intervention will be applied for 5 consecutive days for 20 minutes. Furthermore, everyone will receive Social Cognition Training concomitantly with neurostimulation to enhance social skills in children with ASD. To control adverse effects, reports of patients with feelings/sensations of itching, tingling, burning, headache or other discomfort (1 none, 2 mild, 3 moderate, or 4 strong) will be recorded, along with whether this effect could be related to stimulation on a Likert scale; 1 (no relation) to 5 (strongly related).
The Descriptive and inferential statistical analyzes will be performed through SPSS (Statistical package for the social sciences), version 20. The design of the statistical analyzes is based on previous literature studies of randomized and placebo-controlled clinical trials using tDCS. The intention-to-treat analysis will be used with the last observation carried forward method for patients who initiate treatment and receive at least 1 session. In this way, all participants, including in case of withdrawal of the treatment before its completion, will be included in the analysis. It will be used as significance level p <0.05.
The descriptive statistics will be used to describe the clinical and sociodemographic characteristics, as well as the primary and secondary outcomes of each group in T0. The groups will be compared using Student's t test for continuous variables, or chi-square, for categorical variables.
The evaluation and efficacy of tDCS in all variables of the primary and secondary outcomes will be examined with mixed two-way ANOVA, repeated measures, one dependent variable and two independent variables, one intra-group (time, with 3 levels, T0, T2 and T3), and between-groups (two levels: Active, Sham). Covariance analyzes (ANCOVA) will be used to identify significant differences between groups using the T0 scores as covariables. In addition, adverse effects will be analyzed using the chi-square test.
Linear logistic regression will be used to identify predictors of response. The independent variables are: tDCS active and sham, the predictive variables, analyzed one at a time, will be: age and severity of symptoms. Patients will undergo three social cognitive assessments: at baseline, week 2 (after stimulation), and 1 month later. Adverse effects will be computed at each session. Thus, this clinical trial aims to investigate the combined effects of transcranial direct current stimulation and social cognition training in improving the social skills of children with ASD.
ngày
Xác minh lần cuối: | 04/30/2019 |
Đệ trình đầu tiên: | 04/29/2019 |
Đăng ký ước tính đã được gửi: | 05/07/2019 |
Đăng lần đầu: | 05/12/2019 |
Cập nhật lần cuối được gửi: | 05/12/2019 |
Cập nhật lần cuối đã đăng: | 05/14/2019 |
Ngày bắt đầu nghiên cứu thực tế: | 04/29/2018 |
Ngày hoàn thành chính ước tính: | 09/29/2018 |
Ngày hoàn thành nghiên cứu ước tính: | 05/29/2019 |
Tình trạng hoặc bệnh tật
Can thiệp / điều trị
Device: Active TDCS Group
Device: Sham tDCS Group
Behavioral: Cognitive Training
Giai đoạn
Nhóm cánh tay
Cánh tay | Can thiệp / điều trị |
---|---|
Active Comparator: Active TDCS Group Participants will receive active Transcranial Direct Current Stimulation (TDCS) (1.5 mA). Furthermore, everyone will receive Social Cognition Training concomitantly with neurostimulation to enhance social skills. | Device: Active TDCS Group A constant current stimulator (TCT Research Limited) will be used using electrodes of 5 × 5 cm2 embedded in saline (0.9 % NaCl) and application of 1.5 mA current for 20 minutes for 5 consecutive days. The cathode will be positioned in the right supra-orbital region, and while the anode will have the following provision in the left dorsolateral prefrontal cortex (F3). |
Sham Comparator: Sham tDCS Group Participants will receive sham TDCS. The protocol is identical for placebo stimulation, but the current will stop after 30 seconds from the start of stimulation. Furthermore, everyone will receive Social Cognition Training concomitantly with neurostimulation to enhance social skills. | Device: Sham tDCS Group The protocol for participants receiving simulated current is identical, but the device ceases to emit current after 30 seconds of initiation of pacing. |
Đủ tiêu chuẩn
Tuổi đủ điều kiện để học | 8 Years Đến 8 Years |
Giới tính đủ điều kiện để nghiên cứu | Male |
Chấp nhận tình nguyện viên lành mạnh | Đúng |
Tiêu chí | Inclusion Criteria: - Clinical diagnosis of ASD - Degree of mild autistic symptomatology - Normal or corrected acuity. Exclusion Criteria: - Intellectual deficits - Cardiac pacemaker or implanted metallic or electronic device - Severe neurological disorders - Poor skull formation - Epilepsy |
Kết quả
Các biện pháp kết quả chính
1. Facial emotion recognition [The test will be measured immediately before the intervention.]
2. Facial emotion recognition [The test will be measured immediately after the intervention.]
3. Facial emotion recognition [The test will be measured 4 weeks after the intervention.]
4. Theory of mind- Verbal task [The test will be measured immediately before the intervention.]
5. Theory of mind- Contextual task [The test will be measured immediately before the intervention.]
6. Theory of mind- Verbal task [The test will be measured immediately after the intervention.]
7. Theory of mind- Contextual task [The test will be measured immediately after the intervention.]
8. Theory of mind- Verbal task [The test will be measured 4 weeks after the intervention.]
9. Theory of mind- Contextual task [The test will be measured 4 weeks after the intervention.]
Các biện pháp kết quả thứ cấp
1. Memory for Digit Span [The test will be measured immediately before the intervention.]
2. Memory for Digit Span [The test will be measured immediately after the intervention.]
3. Memory for Digit Span [The test will be measured 4 weeks after the intervention.]
4. Trail Making Test A e B [The test will be measured immediately before the intervention.]
5. Trail Making Test A e B [The test will be measured immediately after the intervention.]
6. Trail Making Test A e B [The test will be measured 4 weeks after the intervention.]
7. Seven Errors Test [The test will be measured immediately before the intervention.]
8. Seven Errors Test [The test will be measured immediately after the intervention.]
9. Seven Errors Test [The test will be measured 4 weeks after the intervention.]