西班牙 Neuroelectrics 经颅电刺激脑电系统 Starstim

摘要 · 中文整理：引言：原理验证性人体研究提示，作用于背外侧前额叶皮层（DLPFC）的经颅直流电刺激（tDCS）可能改善抑郁严重程度。本项开放标签多中心研究在 35 例重性抑郁障碍（MDD）患者中检验了居家实施的远程监督多通道 tDCS。首要目的是评估该方案的可行性与安全性；作为探索性目的，评价治疗效果，主要疗效指标为观察者评定的蒙哥马利-艾斯伯格抑郁评定量表（MADRS）从基线到治疗后 4 周随访期结束时的中位数百分比变化。方法：受试者在 8 周内接受 37 次居家刺激（每次 30 分钟），采用专门设计的靶向左侧 DLPFC 的多通道 tDCS（4 周每日治疗加 4 周逐减），末次刺激后随访 4 周。刺激方案（电极位置与电流）通过对同类人群结构影像数据建立的多通道 tDCS 电场计算模型进行群体优化确定。研究全程远程实施，在基线、治疗第 4 周与第 8 周以及 4 周随访访视时使用 MADRS 评估。结果：34 例患者（85.3% 为女性，平均年龄 59 岁，符合 DSM-5 的 MDD 诊断且入组时 MADRS≥20）完成了全部访视。基线时自 MDD 诊断以来的平均病程为 24.0（标准差 19.1）个月。依从性方面，85%（n=29）在家完成了全部 37 次刺激，97% 完成至少 36 次。未观察到有害效应，包括自杀意念与行为。治疗后 4 周 MADRS 评分中位数下降 64.5%（48.6，72.4）（Hedge's g = -3.1）。从基线到治疗后 4 周末次访视的应答率（MADRS 改善≥50%）为 72.7%（n=24）。次要指标呈现类似改善。结论：这些结果提示远程监督与支持下的居家多通道 tDCS 安全可行，其抗抑郁效果值得开展进一步的适当对照临床研究。

原文摘要：Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies.

关键词：经颅直流电刺激、重性抑郁障碍、经颅电刺激、远程医疗、居家经颅直流电刺激、多通道经颅直流电刺激、Starstim 系统

研究目标：解决传统 tDCS 抗抑郁治疗靶向不精确、需患者反复到院从而限制治疗依从性与可及性的问题，验证经计算模型优化的多通道 tDCS 能否在完全远程监督的居家场景中安全、可行地实施并产生抗抑郁效果。

主要结论：远程监督与技术支持下的居家多通道 tDCS 方案依从性高（85% 完成全部 37 次刺激）、安全性良好（未出现严重不良事件或自杀相关事件），治疗后 4 周 MADRS 评分中位下降 64.5%、应答率 72.7%，表明该模式可行且具有值得进一步验证的抗抑郁潜力。

创新点：其一，将基于群体结构影像的电场计算优化用于确定四电极多通道蒙太奇，使左侧 DLPFC 靶区法向电场达到预设的 0.75 V/m；其二，构建了包含无线刺激主机、彩色编码电极帽、平板引导应用与远程监控门户的完整居家闭环，使排程、阻抗监控与依从性追踪可实时远程完成；其三，首次在完全远程的多中心条件下完成 37 次长程多通道 tDCS 抑郁治疗的可行性验证。

后续建议：开展随机、假刺激对照的双盲试验以排除开放标签设计带来的期望效应；采用个体化头模型替代群体优化蒙太奇，比较个体优化是否进一步提升疗效；延长随访时间并设计维持刺激方案，评估疗效的持久性与复发率；纳入年龄与性别分布更均衡的样本，改善当前受试者以中老年女性为主的代表性不足；结合静息态脑电或功能影像标志物，探索可预测应答的生物学指标

APA 引文：Ruffini, G., Salvador, R., Castaldo, F., Baleeiro, T., Camprodon, J. A., Chopra, M., Cappon, D., & Pascual-Leone, A. (2024). Multichannel tDCS with advanced targeting for major depressive disorder: a tele-supervised at-home pilot study. Frontiers in Psychiatry, 15, 1427365. https://doi.org/10.3389/fpsyt.2024.1427365

仪器引用：This study used the Starstim Home Kit (Neuroelectrics). Neuroelectrics developed this system for home-based tDCS. Stimulation was applied using the Starstim device, with current delivered via four NG Pi electrodes (circular Ag/AgCl electrodes using gel with a contact area of 3.14 cm2) embedded in a neoprene cap.

摘要 · 中文整理：低强度经颅电刺激（tES），包括经颅直流电刺激（tDCS）、经颅交流电刺激（tACS）与振荡性经颅直流电刺激（otDCS）等技术，因其对运动、认知与行为过程的神经调控作用而被广泛研究。尽管其安全性已得到充分确认，这些技术仍可能引起不同程度的不适与副作用，从而影响其应用。本研究开展了一项被试内、假刺激对照实验，直接比较 tDCS、tACS 与 otDCS 的主观体验与副作用。被试在 20 分钟刺激会话期间的多个时间点报告不适程度，并在每次会话前后填写副作用问卷。结果表明，各条件下总体不适水平均较低，95% 以上的报告为无不适或仅有轻度的操作引起的不适。然而，与假刺激相比，tDCS 与 otDCS 的舒适度略低，尤其在刺激开始阶段；而 tACS 引起的不适水平总体上与假刺激相当。最常见的副作用/不良反应是轻度皮肤感觉，包括瘙痒与刺痛，在 tDCS 与 otDCS 中尤为明显；tACS 偶尔引起光幻视与视物模糊。这些发现系统比较了不同 tES 技术所致的不适与副作用，既凸显了 tES 的高安全性，也强调了在 tES 应用中考虑个体内与个体间变异以及时间进程效应的重要性。

原文摘要：Low-intensity transcranial electrical stimulation (tES), including techniques like transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and oscillatory transcranial direct current stimulation (otDCS), has been widely explored for its neuromodulatory effects on motor, cognitive, and behavioral processes. Despite well-established safety, these techniques can induce varying degrees of discomfort and side effects, potentially impacting their application. This study presents a within-subject sham-controlled experiment directly comparing the subjective experience and side effects of tDCS, tACS, and otDCS. Participants reported their discomfort levels at multiple time points during 20-min stimulation sessions and completed a side-effects questionnaire before and after each session. Results indicated that the overall discomfort levels were low across all conditions, with ≥95% reporting the absence of discomfort or mild procedure-induced discomfort. Nevertheless, tDCS and otDCS were slightly less comfortable compared to sham, especially at the beginning of stimulation, with tACS-induced discomfort levels being overall comparable to sham. The most common side / adverse effects were mild skin sensations, including itching and tingling, particularly with tDCS and otDCS, while tACS occasionally caused phosphenes and blurred vision. These findings provide a systematic comparison of tES-induced discomfort and side effects between different tES techniques, highlighting the high safety of tES, but also the importance of considering within- and between-person variability and time-course effects in tES applications.

关键词：经颅电刺激、经颅直流电刺激、经颅交流电刺激、振荡性经颅直流电刺激、耐受性、副作用、安全性、主观体验

研究目标：解决不同经颅电刺激模式（直流、交流、振荡直流）之间主观耐受性与副作用差异证据不足、以及假刺激程序在多种刺激模式下是否同样可信的问题。

主要结论：在相同电极配置与刺激时长下，tDCS、tACS 与 otDCS 均耐受良好，受试者报告的不适与副作用轻微且短暂，各主动刺激条件与假刺激之间的主观体验差异有限，表明现行假刺激程序在多种 tES 模式中均可维持有效盲法。

创新点：采用同一批受试者在同一电极配置下完成四种刺激条件的被试内对照，消除了以往跨研究比较中的个体与方案差异；并在刺激过程中设置多个时间点的不适感实时评定，将主观体验的时间动态与刺激前后的症状变化结合评估。

后续建议：将样本扩展至老年人与患者人群，验证耐受性结论在临床样本中的适用性；提高刺激强度或延长刺激时长，检验耐受性结论的参数边界；增加多通道高精度（HD）电极配置条件，比较不同电极面积与数量对皮肤感觉的影响；结合皮肤电导或红外热成像等客观生理指标，补充纯主观评分的局限；对首次接受刺激者与有经验者分别分析，考察经验对盲法有效性的影响

APA 引文：Bjekić, J., Živanović, M., Stanković, M., Paunović, D., Konstantinović, U., & Filipović, S. R. (2024). The subjective experience of transcranial electrical stimulation: a within-subject comparison of tolerability and side effects between tDCS, tACS, and otDCS. Frontiers in Human Neuroscience, 18, 1468538. https://doi.org/10.3389/fnhum.2024.1468538

仪器引用：The tES was administered using the Starstim32 device (Neuroelectrics Inc., Barcelona, Spain), remotely operated through the Neuroelectrics® Instrument Controller (NIC2) software

摘要 · 中文整理：下丘脑是能量稳态的关键调节中枢，并与对食欲抑制控制至关重要的纹状体和皮层区域存在功能连接。因此，无创调控下丘脑网络的能力有望为代谢性疾病的治疗开辟新途径。本研究检验了一种新型网络靶向经颅直流电刺激（net-tDCS）方法，用以影响参与食欲控制的脑区兴奋性。研究基于下丘脑的静息态功能连接图谱生成了 12 通道的 net-tDCS 方案（Neuroelectrics Starstim 系统），包含阳极、阴极与假刺激三种条件。10 名超重或肥胖受试者参加了这项假刺激对照的交叉研究。在刺激或假刺激过程中，受试者完成停止信号任务以测量抑制控制。总体而言刺激耐受良好。阳极 net-tDCS 相比假刺激（p = 0.039）与阴极 net-tDCS（p = 0.042）产生了更快的停止信号反应时（SSRT）。靶网络的基线功能连接与阳极相对假刺激后的 SSRT 相关（p = 0.016）。这些初步数据提示，通过 net-tDCS 调控下丘脑功能网络连接可能改善抑制控制。后续研究需进一步评估其对摄食行为与代谢的影响。

原文摘要：The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.

关键词：肥胖、认知控制、下丘脑

研究目标：解决传统双电极 tDCS 难以触及下丘脑等深部结构、无法按脑网络而非单一靶点施加刺激的问题，验证以静息态功能连接图谱为依据的多通道网络靶向刺激能否安全可行地调控食欲控制网络并改善抑制控制。

主要结论：12 通道网络靶向 net-tDCS 在超重与肥胖人群中耐受良好；阳极刺激显著缩短停止信号反应时，优于假刺激与阴极刺激，且靶网络基线功能连接强度可预测阳极刺激的行为获益，提示调控下丘脑功能网络连接有望改善抑制控制能力。

创新点：首次将个体静息态功能连接图谱直接转化为多通道刺激电流分配的优化目标，实现由"靶点"到"靶网络"的刺激范式转变；并在同一硬件平台上以极性反转方式构建阳极、阴极与假刺激三条件双盲交叉设计，使网络极性效应可被直接比较。

后续建议：扩大样本量并延长刺激疗程，验证行为效应的稳定性与可重复性；增加摄食行为与代谢指标（如进食量、胰岛素敏感性）作为临床相关终点；采用刺激中或刺激后同步功能磁共振，直接验证靶网络连接的即时改变；比较群体优化与个体化头模型优化方案在深部靶网络上的电场精度差异；纳入正常体重对照组，区分效应是肥胖特异性的还是普遍存在的

APA 引文：Ester-Nacke, T., Berti, K., Veit, R., Dannecker, C., Salvador, R., Ruffini, G., Heni, M., Birkenfeld, A. L., Plewnia, C., Preissl, H., & Kullmann, S. (2024). Network-targeted transcranial direct current stimulation of the hypothalamus appetite-control network: a feasibility study. Scientific Reports, 14(1), 11341. https://doi.org/10.1038/s41598-024-61852-3

仪器引用：Stimulation was delivered by a network-targeted multichannel tDCS device (Starstim® 32, Neuroelectrics Barcelona S.L.U., Barcelona, Spain) with the corresponding NIC 2.0 software. Twelve circular Ag/AgCl gelled electrodes were inserted into a neoprene cap with predefined positions (Headcap R, Neuroelectrics Barcelona S.L.U., Barcelona, Spain) according to the 10–20 EEG international system.