Developmental Pilot Study of External Trigeminal Nerve Stimulation for ADHD

描述（由申请人提供）：据估计，注意力缺陷/多动障碍（ADHD）影响高达9.5%的学龄儿童和4.4%的成年人。注意缺陷多动障碍与功能障碍增加、共病精神病理和总体医疗费用有关。尽管采用了各种社会心理干预措施，但药物治疗仍然是ADHD治疗的主要手段。据估计，美国有超过280万儿童服用精神兴奋剂，主要是治疗多动症。虽然这些在急性治疗中通常是安全有效的，但对副作用和缺乏证明的长期益处仍然存在相当大的担忧。父母对使用ADHD药物非常矛盾。虽然对非药物治疗ADHD的需求很大，但大多数流行的替代方法与大脑过程的任何机制理解都没有联系，同样缺乏重要的科学证据来支持它们的使用。外部三叉神经刺激（eTNS）是一种非侵入性脑调节方法，在治疗成人耐药癫痫和抑郁症方面取得了成功。在eTNS中，三叉神经通过一个电极接受低电流的电刺激，电极放在前额，在睡眠时佩戴。初步的成人研究显示，在情绪、睡眠和注意力方面有显著改善。PET成像显示，在涉及注意力和执行功能的大脑区域，与etns相关的急性激活。一项基于这项工作的初步儿科研究评估了eTNS治疗ADHD的可行性。结果表明，eTNS具有良好的耐受性和可接受性，并且与ADHD症状的显著改善以及反应抑制和工作记忆的实验室测量结果相关。本R34提出了一项为期三年的临床试验开发项目，以进一步标准化eTNS，为明确的ADHD疗效试验做准备，并阐明潜在的大脑机制，这些机制将潜在地支持在ADHD以及其他行为、情绪和认知障碍中使用eTNS。该项目是一项为期四周的双盲随机试验，在治疗停止后进行为期四周的随访。参与者将通过脑电图（EEG）对行为评分、认知过程和皮层激活进行重复评估。本研究将评估eTNS治疗ADHD的首个随机对照试验中不同条件的结果轨迹差异，作为盲法对照的假eTNS的有效性和逼真度，有关反应的起效和抵消的时间过程效应，以及与治疗结果相关的大脑变化的潜在机制。该建议与NIMH的几个优先事项是一致的，包括发展创新的干预措施和干预研究的设计，发展对大脑障碍过程的综合理解，为理解精神障碍提供基础，以及评估有效干预措施在大脑中的作用机制。

DESCRIPTION (provided by applicant): Attention-Deficit/Hyperactivity Disorder (ADHD) is estimated to affect up to 9.5% of school-aged children and 4.4% of adults. ADHD is associated with increased functional impairments, comorbid psychopathology, and overall health care costs. Although various psychosocial interventions are employed, medication remains the mainstay of ADHD treatment. It is estimated that over 2.8 million children in the United States are prescribed psychostimulants, mostly for ADHD. Although these are generally safe and effective in acute treatment, considerable concerns remain about side effects and the absence of demonstrated long-term benefit. Parents are highly ambivalent about using ADHD medications. While there is great demand for non- medication approaches to ADHD, most popular alternatives are not linked to any mechanistic understanding of brain processes and similarly lack significant scientific evidence to support their use. External trigeminal nerve stimulation (eTNS) is a non-invasive method of brain modulation with demonstrated success in treating adults with medication-resistant epilepsy and depression. In eTNS, the trigeminal nerve receives low current electrical stimulation via an electrode applied to the forehead and worn during sleep. Preliminary adult studies revealed significant improvements in mood, sleep, and attention. PET imaging demonstrated acute eTNS-related activation in brain areas involved in attention and executive functioning. A preliminary pediatric study based on this work assessed the feasibility of eTNS for ADHD. Results demonstrated that eTNS was well tolerated and accepted, and was associated with significant improvements in ADHD symptoms and laboratory measures of response inhibition and working memory. This R34 proposes a three-year clinical trial development project to further standardize eTNS in preparation for definitive ADHD efficacy trials and to elucidate underlying brain mechanisms that will potentially support use of eTNS in ADHD as well as other behavioral, emotional, and cognitive disorders. The project is a four-week double-blind randomized trial of active vs. sham eTNS followed by four weeks follow-up after treatment discontinuation. Participants will have repeated assessments on behavioral ratings, cognitive processes, and cortical activation via electroencephalography (EEG). This study will assess differences in outcome trajectories by condition in the first randomized controlled trial of eTNS for ADHD, validity and fidelity of sham eTNS as a blinded control, time course effects regarding onset and offset of response, and underlying mechanisms of brain change that are associated with treatment outcomes. The proposal is consistent with several NIMH priorities, including the development of innovative interventions and designs for intervention studies, development of an integrated understanding of brain disorder processes that provide the foundation for understanding mental disorders, and assessment of the mechanisms of action of efficacious interventions in the brain.