Modulating impulsivity in suicidal adolescents with tDCS: A proof concept study

摘要 自杀是青少年死亡的主要原因之一。提高我们预测和预防 自杀行为，这一领域的研究迫切需要超越识别风险因素 更加关注这种行为的风险机制。特别是，阐明神经 自杀行为风险的潜在途径是重要的，因为这些工作可能产生特定的， 可修改的临床干预目标。采用新的实验范式提供实验 控制潜在的可改变的风险因素已被推荐为有意义地推进 场在这方面。虽然尚未应用于自杀倾向的研究，但经颅直流电 刺激（tDCS），结合脑电图（EEG）和事件相关的措施 事件相关电位（ERPs），可能有希望作为一个实验范式，在研究潜在的可改变的风险 因素和潜在的神经机制。其中一个风险因素与以下方面特别相关： 青春期自杀是冲动的状态敏感方面。冲动一直与 自杀倾向，这种联系在青春期比成年期更强。作为迈向 研究冲动和相关神经通路的调节是否可以产生临床意义 青少年自杀行为风险的变化，拟议的R21是一项概念验证研究， tDCS靶向与行为冲动相关的脑区（右额下回）的潜力 [rIFG]）和认知冲动（左眶额皮质[IOFC]）来调节这些方面的冲动， 青少年自杀未遂者的样本。参与者将被随机分配接受阳极tDCS， 在三组设计中，rIFG、IOFC上的阳极tDCS或假刺激条件。任务型 在tDCS或假手术之前和之后将进行行为和认知冲动的测量 刺激.此外，将在冲动任务和静息状态期间收集EEG和ERP数据 将在tDCS给药前后收集EEG数据，以确认靶向大脑的参与 区域和描绘神经通路的影响tDCS的冲动。本研究 相关的研究目标，澄清与自杀风险有关的神经回路概况，概述了由 美国国立卫生研究院和国家自杀预防行动联盟在其最近的自杀研究议程 预防这也符合NIMH的战略计划，该计划强调需要研究 精神病理学的生物标志物和行为指标，以及利用神经行为学的研究 方法论。

Abstract Suicide is one of the leading causes of death in adolescence. To improve our ability to predict and prevent suicidal behavior, there is a pressing need for research in this area to advance beyond identifying risk factors toward a greater focus on the mechanisms of risk for this behavior. In particular, elucidating the neural pathways underlying risk for suicidal behavior is important insofar as such work may yield specific and modifiable targets for clinical intervention. The adoption of new experimental paradigms providing experimental control over potentially modifiable risk factors has been recommended as a means of meaningfully advancing the field in this regard. Although yet to be applied to the study of suicidality, transcranial direct current stimulation (tDCS), in conjunction with measures of electroencephalography (EEG) and event-related potentials (ERPs), may hold promise as an experimental paradigm in the study of potentially modifiable risk factors, and underlying neural mechanisms, for suicidality. One such risk factor of particular relevance to suicide in adolescence is state-sensitive aspects of impulsivity. Impulsivity has been consistently linked with suicidality, with this association appearing to be stronger in adolescence than adulthood. As a first step toward investigating whether modulation of impulsivity and associated neural pathways may yield clinically meaningful changes in risk for adolescent suicidal behavior, the proposed R21 is a proof-of-concept study evaluating the potential for tDCS targeting brain regions associated with behavioral impulsivity (right inferior frontal gyrus [rIFG]) and cognitive impulsivity (left orbitofrontal cortex [lOFC]) to modulate these facets of impulsivity in a sample of adolescent suicide attempters. Participants will be randomly assigned to receive anodal tDCS over the rIFG, anodal tDCS over the lOFC, or a sham stimulation condition, in a three-group design. Task-based measures of behavioral and cognitive impulsivity will be administered before and after tDCS or sham stimulation. Additionally, EEG and ERP data will be collected during the impulsivity tasks, and resting-state EEG data will be collected pre- and post-tDCS administration to confirm engagement of the targeted brain regions and to delineating the neural pathways underlying the effects of tDCS on impulsivity. This study is relevant to the research objective, of clarifying the neural circuitry profiles related to suicide risk, outlined by the NIH and the National Action Alliance for Suicide Prevention in their recent research agenda for suicide prevention. It is also consistent with NIMH’s Strategic Plan, which emphasizes the need for research on biomarkers and behavioral indicators of psychopathology, and for research utilizing neurobehavioral methodologies.