Paneri Bhaskar, Adair Devin, Thomas Chris, Khadka Niranjan, Patel Vaishali, Tyler William J, Parra Lucas, Bikson Marom
Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave., New York 10031, USA.
School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287 USA.
Brain Stimul. 2016 Sep-Oct;9(5):740-754. doi: 10.1016/j.brs.2016.05.008. Epub 2016 May 24.
The safety and tolerability of limited output transcranial electrical stimulation (tES) in clinical populations support a non-significant risk designation. The tolerability of long-term use in a healthy population had remained untested.
We tested the tolerability and compliance of two tES waveforms, transcranial direct current stimulation (tDCS) and modulated high frequency transcranial pulsed current stimulation (MHF-tPCS) compared to sham-tDCS, applied to healthy subjects for three to five days (17-20 minutes per day) per week for up to six weeks in a communal setting. MHF-tPCS consisted of asymmetric high-frequency pulses (7-11 kHz) having a peak amplitude of 10-20 mA peak, adjusted by subject, resulting in an average current of 5-7 mA.
A total of 100 treatment blind healthy subjects were randomly assigned to one of three treatment groups: tDCS (n = 33), MHF-tPCS (n = 30), or sham-tDCS (n = 37). In order to test the role of waveform, electrode type and montage were fixed across tES and sham-tDCS arms: high-capacity self-adhering electrodes on the right lateral forehead and back of the neck. We conducted 1905 sessions (636 sham-tDCS, 623 tDCS, and 646 MHF-tPCS sessions) on study volunteers over a period of six weeks.
Common adverse events were primarily restricted to influences upon the skin and included skin tingling, itching, and mild burning sensations. The incidence of these events in the active tES treatment arms (MHF-tPCS, tDCS) was equivalent or significantly lower than their incidence in the sham-tDCS treatment arm. Other adverse events had a rarity (<5% incidence) that could not be significantly distinguished across the treatment groups. Some subjects were withdrawn from the study due to atypical headache (sham-tDCS n = 2, tDCS n = 2, and MHF-tPCS n = 3), atypical discomfort (sham-tDCS n = 0, tDCS n = 1, and MHF-tPCS n = 1), or atypical skin irritation (sham-tDCS n = 2, tDCS n = 8, and MHF-tPCS n = 1). The rate of compliance, elected sessions completed, for the MHF-tPCS group was significantly greater than the sham-tDCS group's compliance (p = 0.007). There were no serious adverse events in any treatment condition.
We conclude that repeated application of limited output tES across extended periods, limited to the hardware, electrodes, and protocols tested here, is well tolerated in healthy subjects, as previously observed in clinical populations.
有限输出经颅电刺激（tES）在临床人群中的安全性和耐受性支持其低风险认定。长期应用于健康人群的耐受性尚未得到测试。
我们测试了两种tES波形，即经颅直流电刺激（tDCS）和调制高频经颅脉冲电流刺激（MHF-tPCS）与假tDCS相比的耐受性和依从性，将其应用于健康受试者，每周进行三至五天（每天17 - 20分钟），共持续六周，在公共环境中进行。MHF-tPCS由不对称高频脉冲（7 - 11kHz）组成，峰值幅度为10 - 20mA峰值，可根据受试者情况进行调整，平均电流为5 - 7mA。
总共100名治疗盲态的健康受试者被随机分配到三个治疗组之一：tDCS（n = 33）、MHF-tPCS（n = 30）或假tDCS（n = 37）。为了测试波形的作用，tES和假tDCS组的电极类型和导联固定：右侧前额和颈部后侧使用高容量自粘电极。我们在六周内对研究志愿者进行了1905次治疗（636次假tDCS、623次tDCS和646次MHF-tPCS治疗）。
常见不良事件主要局限于对皮肤的影响，包括皮肤刺痛、瘙痒和轻度灼烧感。这些事件在活性tES治疗组（MHF-tPCS、tDCS）中的发生率等于或显著低于假tDCS治疗组。其他不良事件发生率较低（<5%），在各治疗组之间无显著差异。一些受试者因非典型头痛（假tDCS组n = 2、tDCS组n = 2、MHF-tPCS组n = 3）、非典型不适（假tDCS组n = 0、tDCS组n = 1、MHF-tPCS组n = 1）或非典型皮肤刺激（假tDCS组n = 2、tDCS组n = 8、MHF-tPCS组n = 1）退出研究。MHF-tPCS组的依从率（完成的选定治疗次数）显著高于假tDCS组（p = 0.007）。任何治疗条件下均未发生严重不良事件。
我们得出结论，如先前在临床人群中观察到的那样，在此测试的硬件、电极和方案范围内，长时间重复应用有限输出tES在健康受试者中耐受性良好。
