Transcranial Direct Current Stimulation Combined with Computerized Cognitive Training Synergistically Enhances Efficacy in Autism Spectrum Disorder: A Randomized Controlled Trial Based on Behavioral and Neurophysiological Evidence
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摘要:
目的 探讨经颅直流电刺激(transcranial direct current stimulation,tDCS)联合计算机认知训练(computerized cognitive training,CCT)治疗孤独症谱系障碍(autism spectrum disorder,ASD)的疗效。 方法 选取2021年1月至2024年8月深圳市龙岗区妇幼保健院收治的208例ASD患儿,按照随机数表法分为CCT组(n = 52)、tDCS组(n = 52)、研究组(n = 52)、假刺激组(n = 52)。4组均给予常规康复治疗措施,在此基础上,CCT组给予CCT,tDCS组给予tDCS,研究组给予tDCS联合CCT,假刺激组给予假tDCS联合CCT。比较4组治疗效果、治疗前后儿童孤独症评定量表(childhood autism rating scale,CARS)、异常行为量表(aberrant behavior checklist,ABC)、相关发育障碍儿童心理教育量表-3(chinese version of the psychoeducational profile,third edition,C-PEP-3)、儿童神经心理行为检查量表评分、脑电图指标[fz、cz导联失匹配负波(mismatch negativity,MMN)潜伏期和波幅、额叶θ相对功率、睡眠期放电指数]以及不良反应发生率。 结果 4组治疗有效率整体比较,差异无统计学意义(χ2 = 6.811,P = 0.078);治疗3个月后,研究组ABC量表中躯体运动、语言、感觉、交往、生活自理维度评分与CARS总评分低于CCT组、tDCS组、假刺激组,C-PEP-3总评分与儿心量表中语言、社交行为、发育商、智龄、适应能力、大运动、精细动作评分维度评分高于CCT组、tDCS组、假刺激组(F = 7.575、14.741、7.616、6.817、6.896、21.804、12.175、13.034、17.661、11.925、12.690、9.691、8.777、13.485,P < 0.05),CCT组、tDCS组与假刺激组ABC量表各维度评分、CARS评分、C-PEP-3评分、儿心量表各维度评分比较,差异无统计学意义(P > 0.05);治疗3个月后,研究组Fz导联、Cz导联MMN潜伏期、额叶θ相对功率、睡眠期放电指数低于CCT组、tDCS组、假刺激组,Fz导联、Cz导联MMN波幅高于CCT组、tDCS组、假刺激组(F = 15.593、12.714、12.072、48.912、6.901、5.723,P < 0.05),CCT组、tDCS组与假刺激组Fz导联、Cz导联MMN潜伏期和波幅、额叶θ相对功率、睡眠期放电指数比较,差异无统计学意义(P > 0.05);4组不良反应总发生率比较,差异无统计学意义(P = 0.123)。 结论 tDCS联合CCT治疗ASD疗效显著,可能改善患儿认知、社交功能及异常行为,改善其脑电活动。 Abstract:Objective To investigate the efficacy of transcranial direct current stimulation (tDCS) combined with computerized cognitive training (CCT) in treating autism spectrum disorder (ASD). Methods A total of 208 children with ASD admitted to Longgang District Maternal and Child Health Hospital, Shenzhen from January 2021 to August 2024 were selected, and randomly divided into four groups using a random number table: CCT group (n = 52), tDCS group (n = 52), combination group (n = 52), and sham stimulation group (n = 52). All four groups received standard rehabilitation treatment. Additionally, the CCT group received CCT, the tDCS group received tDCS, the combination group received tDCS combined with CCT, and the sham stimulation group received sham tDCS combined with CCT. Therapeutic efficacy, Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Chinese Version of Psychoeducational Profile-3 (C-PEP-3), and Children’ s Neuropsychological Behavioral Scale (abbreviated as China Children Development Scale) scores, electroencephalographic parameters [latency and amplitude of mismatch negativity (MMN) at Fz and Cz leads, frontal lobe relative θ power, sleep discharge index] before and after treatment, and the incidence of adverse reactions were compared among the four groups. Results The overall therapeutic efficacy rate showed no significant difference among the four groups (χ2 = 6.811, P = 0.078). After 3 months of treatment, the combination group showed significantly lower scores on ABC scale dimensions (somatic motor, language, sensory, social interaction, self-care) and CARS total scores compared with the CCT, tDCS, and sham stimulation groups, and significantly higher C-PEP-3 total scores and Child Neuropsychological Behavior Examination Scale scores in language, social behavior, developmental quotient, mental age, adaptive ability, gross motor, and fine motor dimensions compared with the other three groups (F = 7.575, 14.741, 7.616, 6.817, 6.896, 21.804, 12.175, 13.034, 17.661, 11.925, 12.690, 9.691, 8.777, 13.485, P < 0.05). No significant differences were found among the CCT, tDCS, and sham stimulation groups in ABC dimensions, CARS scores, C-PEP-3 scores, or Child Neuropsychological Behavior Examination Scale dimensions (P > 0.05). After 3 months of treatment, the combination group showed significantly lower MMN latency in Fz and Cz leads, relative frontal theta power, and sleep discharge index, and significantly higher MMN amplitude in Fz and Cz leads compared with the other three groups (F = 15.593, 12.714, 12.072, 48.912, 6.901, 5.723, P < 0.05). No significant differences were found among the CCT, tDCS, and sham stimulation groups in these EEG parameters (P > 0.05). The overall incidence of adverse reactions showed no significant difference among the four groups (P = 0.123). Conclusion tDCS combined with CCT demonstrates significant therapeutic efficacy in treating ASD, potentially improving cognitive and social functioning, reducing aberrant behaviors, and improving cerebral electrical activity in affected children. -
表 1 4组一般资料比较[($ \bar x \pm s $)/n(%)]
Table 1. Comparison of general data among four groups [($ \bar x \pm s $)/n(%)]
组别 n 性别 年龄(岁) 体质量(kg) 病程(年) 严重程度 男 女 轻~中度 重度 研究组 52 41(78.85) 11(21.15) 4.42 ± 0.72 16.40 ± 2.26 2.68 ± 0.48 32(61.54) 20(38.46) CCT组 52 42(80.77) 10(19.23) 4.26 ± 0.76 16.78 ± 2.09 2.84 ± 0.54 35(67.31) 17(32.69) tDCS组 52 39(75.00) 13(25.00) 4.09 ± 0.90 16.53 ± 2.34 2.73 ± 0.51 30(57.69) 22(42.31) 假刺激组 52 40(76.92) 12(23.08) 4.21 ± 0.83 16.65 ± 2.18 2.76 ± 0.50 33(63.46) 19(36.54) χ2/F 0.558 1.499 0.279 0.905 1.067 P 0.906 0.216 0.840 0.439 0.785 表 2 4组治疗效果比较n(%)
Table 2. Comparison of therapeuticffficacy among the four groups n(%)
组别 n 无效 有效 显效 总有效率 χ2 P 研究组 52 5(9.62) 31(59.62) 16(30.77) 47(90.38) 6.811 0.078 CCT组 52 15(28.85) 30(57.69) 7(13.46) 37(71.15) tDCS组 52 12(23.08) 32(61.54) 8(15.38) 40(76.92) 假刺激组 52 14(26.92) 28(53.85) 10(19.23) 38(73.08) 表 3 4组治疗前后ABC量表评分比较($ \bar x \pm s $,分)
Table 3. Comparison of ABC scale scores before and after treatment among the four groups($ \bar x \pm s $,scores)
时间 组别 n 躯体运动 语言 感觉 交往 生活自理 治疗前 研究组 52 24.31 ± 3.20 18.80 ± 2.77 18.46 ± 1.85 18.18 ± 2.63 17.90 ± 1.71 CCT组 52 24.65 ± 3.06 18.94 ± 2.52 18.52 ± 1.47 18.40 ± 2.29 18.02 ± 1.55 tDCS组 52 24.43 ± 3.14 19.01 ± 2.44 18.39 ± 1.61 18.22 ± 2.35 18.16 ± 1.59 假刺激组 52 24.48 ± 3.09 18.77 ± 2.60 18.50 ± 1.53 18.31 ± 2.42 18.11 ± 1.62 F 0.106 0.101 0.065 0.085 0.259 P 0.956 0.959 0.978 0.968 0.855 治疗3个月后 研究组 52 18.69 ± 4.10abcd 14.87 ± 1.40abcd 16.50 ± 1.24abcd 15.57 ± 1.17abcd 14.34 ± 1.34abcd CCT组 52 21.42 ± 3.17a 16.55 ± 1.48a 17.61 ± 1.31a 16.63 ± 1.33a 15.53 ± 1.62a tDCS组 52 21.35 ± 3.38a 16.29 ± 1.34a 17.40 ± 1.29a 16.31 ± 1.25a 15.23 ± 1.50a 假刺激组 52 21.20 ± 3.09a 16.18 ± 1.42a 17.33 ± 1.26a 16.40 ± 1.31a 15.41 ± 1.45a F 7.575 14.741 7.616 6.817 6.896 P <0.001* <0.001* <0.001* <0.001* <0.001* 与同组治疗前比较,aP < 0.05;与CCT组比较,bP < 0.0083 ;与tDCS组比较,cP <0.0083 ;与假刺激组比较,dP <0.0083 ;*P < 0.001。表 4 4组治疗前后CARS、C-PEP-3评分比较[($ \bar x \pm s $),分]
Table 4. Comparison of CARS and C-PEP-3 scores before and after treatment among the four groups [($ \bar x \pm s $),scores]
组别 n CARS C-PEP-3 治疗前 治疗3个月后 治疗前 治疗3个月后 研究组 52 44.31 ± 4.28 30.80 ± 3.03abcd 291.53 ± 21.16 347.29 ± 26.13abcd CCT组 52 43.85 ± 3.72 35.27 ± 3.39a 293.77 ± 24.57 322.50 ± 22.80a tDCS组 52 44.02 ± 4.05 34.91 ± 3.17a 293.15 ± 22.86 325.08 ± 23.79a 假刺激组 52 44.17 ± 3.86 34.59 ± 3.25a 292.68 ± 23.06 324.17 ± 24.17a F 0.128 21.804 0.089 12.175 P 0.943 <0.001* 0.966 <0.001* 与同组治疗前比较,aP < 0.05;与CCT组比较,bP < 0.0083 ;与tDCS组比较,cP <0.0083 ;与假刺激组比较,dP <0.0083 ;*P < 0.001。表 5 4组治疗前后儿心量表评分比较[($ \bar x \pm s $),分](1)
Table 5. Comparison of Children’s Mental Health Scale scores before and after treatment among the four groups [($ \bar x \pm s $),scores] (1)
时间 组别 n 语言 社交行为 发育商 智龄 适应能力 治疗前 研究组 52 13.16 ± 2.15 15.80 ± 2.74 52.28 ± 3.16 19.63 ± 3.07 19.80 ± 2.81 CCT组 52 13.35 ± 2.07 16.01 ± 2.48 52.71 ± 2.68 19.82 ± 3.13 20.02 ± 2.64 tDCS组 52 13.28 ± 2.02 15.96 ± 2.56 52.44 ± 3.07 19.57 ± 3.26 19.73 ± 2.59 假刺激组 52 13.25 ± 2.11 16.05 ± 2.60 53.04 ± 2.85 19.74 ± 2.98 20.04 ± 2.38 F 0.074 0.093 0.664 0.067 0.185 P 0.974 0.964 0.575 0.977 0.906 治疗3个月后 研究组 52 18.87 ± 3.11abcd 23.45 ± 4.10abcd 60.14 ± 4.33abcd 25.51 ± 3.62abcd 25.36 ± 3.37abcd CCT组 52 16.24 ± 2.43a 19.37 ± 3.27a 56.27 ± 3.52a 22.06 ± 3.18a 22.44 ± 3.09a tDCS组 52 16.45 ± 2.51a 19.62 ± 3.48a 56.63 ± 4.01a 22.35 ± 3.49a 22.68 ± 3.15a 假刺激组 52 16.17 ± 2.23a 19.18 ± 3.05a 56.49 ± 3.48a 22.21 ± 3.09a 22.79 ± 3.07a F 13.034 17.661 11.925 12.690 9.691 P <0.001* <0.001* <0.001* <0.001* <0.001* 表 5 4组治疗前后儿心量表评分比较[($ \bar x \pm s $),分](2)
Table 5. Comparison of Children’s Mental Health Scale scores before and after treatment among the four groups [($ \bar x \pm s $),scores](2)
时间 组别 n 大运动 精细动作 治疗前 研究组 52 27.26 ± 3.02 20.63 ± 2.50 CCT组 52 27.54 ± 2.63 21.05 ± 2.29 tDCS组 52 27.31 ± 2.88 20.87 ± 2.36 假刺激组 52 27.40 ± 2.91 20.93 ± 2.42 F 0.096 0.283 P 0.962 0.838 治疗3个月后 研究组 52 32.50 ± 3.14abcd 27.12 ± 2.96abcd CCT组 52 30.11 ± 2.57a 24.30 ± 2.41a tDCS组 52 30.30 ± 2.62a 24.58 ± 2.57a 假刺激组 52 30.27 ± 2.73a 24.61 ± 2.38a F 8.777 13.485 P <0.001* <0.001* 与同组治疗前比较,aP < 0.05;与CCT组比较,bP < 0.0083 ;与tDCS组比较,cP <0.0083 ;与假刺激组比较,dP <0.0083 ;*P < 0.001。表 6 4组治疗前后脑电图指标比较($ \bar x \pm s $)
Table 6. Comparison of EEG indicators before and after treatment among the four groups($ \bar x \pm s $)
时间 组别 n MMN潜伏期(ms) MMN波幅(μV) 额叶θ相对
功率(%)睡眠期放电
指数(次/min)Fz导联 Cz导联 Fz导联 Cz导联 治疗前 研究组 52 258.03 ± 16.49 260.03 ± 14.16 6.38 ± 2.05 7.03 ± 1.65 38.95 ± 5.22 0.38 ± 0.11 CCT组 52 256.41 ± 14.20 259.27 ± 13.34 6.44 ± 1.94 7.10 ± 1.83 39.03 ± 5.13 0.39 ± 0.12 tDCS组 52 256.94 ± 14.85 260.27 ± 13.80 6.40 ± 1.96 7.08 ± 1.71 39.10 ± 4.81 0.38 ± 0.10 假刺激组 52 257.43 ± 15.03 261.43 ± 14.08 6.35 ± 2.02 7.13 ± 1.76 38.74 ± 5.09 0.40 ± 0.12 F 0.108 0.217 0.019 0.030 0.049 0.375 P 0.955 0.884 0.997 0.993 0.986 0.771 治疗3个月后 研究组 52 231.62 ± 10.36abcd 233.23 ± 12.14abcd 10.10 ± 2.30abcd 9.76 ± 2.02abcd 29.16 ± 4.39abcd 0.12 ± 0.08abcd CCT组 52 244.37 ± 11.85a 246.08 ± 13.28a 8.41 ± 2.07a 8.58 ± 1.69a 33.57 ± 4.71a 0.28 ± 0.09a tDCS组 52 243.86 ± 12.03a 245.74 ± 12.76a 8.55 ± 2.18a 8.72 ± 1.54a 34.03 ± 5.06a 0.29 ± 0.09a 假刺激组 52 243.61 ± 10.75a 245.91 ± 13.09a 8.63 ± 2.12a 8.64 ± 1.44a 33.81 ± 5.14a 0.27 ± 0.07a F 15.593 12.714 6.901 5.723 12.072 48.912 P <0.001* <0.001* <0.001* 0.001* <0.001* <0.001* 与同组治疗前比较,aP < 0.05;与CCT组比较,bP < 0.0083 ;与tDCS组比较,cP <0.0083 ;与假刺激组比较,dP <0.0083 ;*P < 0.001。表 7 4组不良反应比较[n(%)]
Table 7. Comparison of adverse reactions among the four groups [n(%)]
组别 n 皮肤刺激反应 头痛 总发生率 χ2 P 研究组 52 4(7.69) 1(1.92) 5(9.62) - 0.123 CCT组 52 0(0.00) 0(0.00) 0(0.00) tDCS组 52 3(5.77) 2(3.85) 5(9.62) 假刺激组 52 1(1.92) 0(0.00) 1(1.92) 注:采用Fisher精确检验,无χ2值。 -
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