Serrano Paul Vicuña, Zortea Maxciel, Alves Rael Lopes, Beltrán Gerardo, Bavaresco Cibely, Ramalho Leticia, Alves Camila Fernanda da Silveira, Medeiros Liciane, Sanches Paulo R S, Silva Danton P, Lucena da Silva Torres Iraci, Fregni Felipe, Caumo Wolnei
Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Laboratory of Pain and Neuromodulation at Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
Front Hum Neurosci. 2022 Nov 24;16:992742. doi: 10.3389/fnhum.2022.992742. eCollection 2022.
Transcranial Direct Current Stimulation (tDCS) is a promising approach to improving fibromyalgia (FM) symptoms, including cognitive impairment. So, we evaluated the efficacy and safety of home-based tDCS in treating cognitive impairment. Besides, we explored if the severity of dysfunction of the Descendant Pain Modulation System (DPMS) predicts the tDCS effect and if its effect is linked to changes in neuroplasticity as measured by the brain-derived neurotrophic factor (BDNF).
This randomized, double-blind, parallel, sham-controlled clinical trial, single-center, included 36 women with FM, aged from 30 to 65 years old, assigned 2:1 to receive a-tDCS ( = 24) and s-tDCS ( = 12). The primary outcome was the Trail Making Test's assessment of executive attention, divided attention, working memory (WM), and cognitive flexibility (TMT-B-A). The secondary outcomes were the Controlled Oral Word Association Test (COWAT), the WM by Digits subtest from the Wechsler Adult Intelligence Scale (WAIS-III), and quality of life. Twenty-minute daily sessions of home-based tDCS for 4 weeks (total of 20 sessions), 2 mA anodal-left (F3) and cathodal-right (F4) prefrontal stimulation with 35 cm carbon electrodes.
GLM showed a main effect for treatment in the TMT-B-A [Wald χ2 = 6.176; Df = 1; = 0.03]. The a-tDCS improved cognitive performance. The effect size estimated by Cohen's d at treatment end in the TMT-B-A scores was large [-1.48, confidence interval (CI) 95% = -2.07 to-0.90]. Likewise, the a-tDCS effects compared to s-tDCS improved performance in the WM, verbal and phonemic fluency, and quality-of-life scale. The impact of a-tDCS on the cognitive tests was positively correlated with the reduction in serum BDNF from baseline to treatment end. Besides, the decrease in the serum BDNF was positively associated with improving the quality of life due to FM symptoms.
These findings revealed that daily treatment with a home-based tDCS device over l-DLPFC compared to sham stimulation over 4 weeks improved the cognitive impairment in FM. The a-tDCS at home was well-tolerated, underlining its potential as an alternative treatment for cognitive dysfunction. Besides, the a-tDCS effect is related to the severity of DPMS dysfunction and changes in neuroplasticity state.
[www.ClinicalTrials.gov], identifier [NCT03843203].
经颅直流电刺激（tDCS）是一种有望改善纤维肌痛（FM）症状（包括认知障碍）的方法。因此，我们评估了家庭式tDCS治疗认知障碍的疗效和安全性。此外，我们探讨了下行疼痛调制系统（DPMS）功能障碍的严重程度是否能预测tDCS的效果，以及其效果是否与脑源性神经营养因子（BDNF）所测量的神经可塑性变化有关。
这项单中心、随机、双盲、平行、假对照临床试验纳入了36名年龄在30至65岁之间的FM女性患者，按2:1分配接受主动tDCS（n = 24）和假tDCS（n = 12）。主要结局是连线测验对执行注意力、分散注意力、工作记忆（WM）和认知灵活性（TMT-B-A）的评估。次要结局包括受控口语联想测验（COWAT）、韦氏成人智力量表（WAIS-III）数字分测验中的WM以及生活质量。每天在家进行20分钟的tDCS治疗，持续4周（共20次），使用35厘米碳电极进行2毫安阳极-左侧（F3）和阴极-右侧（F4）前额叶刺激。
广义线性模型显示在TMT-B-A中治疗有主效应[Wald χ2 = 6.176；自由度 = 1；P = 0.03]。主动tDCS改善了认知表现。治疗结束时TMT-B-A分数的Cohen's d估计效应量很大[-1.48，95%置信区间（CI）= -2.07至-0.90]。同样，与假tDCS相比，主动tDCS在WM、言语和语音流畅性以及生活质量量表方面的效果改善了表现。主动tDCS对认知测试的影响与从基线到治疗结束时血清BDNF 的降低呈正相关。此外，血清BDNF的降低与因FM症状导致的生活质量改善呈正相关。
这些发现表明，与假刺激相比，在4周内使用家庭式tDCS设备对左侧背外侧前额叶皮质（l-DLPFC）进行每日治疗可改善FM患者的认知障碍。家庭式主动tDCS耐受性良好，突出了其作为认知功能障碍替代治疗方法的潜力。此外，主动tDCS的效果与DPMS功能障碍的严重程度和神经可塑性状态的变化有关。
