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Transcranial Direct Current Stimulation (tDCS) as a Treatment for Acute Fear

经颅直流电刺激 (tDCS) 治疗急性恐惧

基本信息

批准号：
8874641
负责人：
ANDREW D KRYSTAL
金额：
$ 46.51万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-15 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8874641
关键词：
Acute Adverse event Affect Anxiety Disorders Auditory Brain Brain Stem Breathing Caliber Carbon Dioxide Clinical Clinical Trials Cross-Over Studies Data Development Diagnostic and Statistical Manual of Mental Disorders Dose Double-Blind Method Electrodes Fright Future Genetic Crossing Over Goals Head Individual Intervention Literature Measures Mediating Mental disorders Methods Modeling Mydriasis Neurosciences Phase Pilot Projects Play Prevention Public Health Pupil Randomized Randomized Controlled Trials Research Domain Criteria Safety Scalp structure Series Severities Skin Staging Stimulus Symptoms Testing Translating active control active method anxiety treatment base brain circuitry cohort control trial density dosage electric field healthy volunteer improved locus ceruleus structure neural circuit novel pre-clinical prevent primary outcome public health relevance relating to nervous system response treatment effect

项目摘要

DESCRIPTION (provided by applicant): This application responds to RFA-MH-15-300 (Exploratory Clinical Trials of Novel Interventions for Mental Disorders [R21/R33]) by proposing to translate neuroscience findings into a novel non-pharmacologic treatment for Acute Fear, a Research Domain Criteria (RDoC) construct common to many DSM defined anxiety disorders. The neuroscience findings which serve as the basis for this effort are an extensive pre- clinical literature documenting that the region of the brainstem known as the locus coeruleus (LC) plays a key role in mediating symptoms of Acute Fear. We capitalize on evidence that LC activity can be non-invasively measured with pupillometry and our pilot data indicating that we can modulate LC activity with transcranial direct current stimulation (tDCS) applied via electrodes attached to the skin/scalp. Our approach is to develop tDCS as a means of inhibiting LC activity and then determine if this diminishes symptoms of Acute Fear. Our translational effort will consist of two stages, a 2 year R21 phase where we establish feasibility, tolerability, safety, and proof-of-concept (POC) in terms of capacity to engage the neural target, followed by a 3 year R33 parallel-group, double-blind, controlled trial. In the R21 phase we will employ an iterative approach where we use electric field modeling with a realistic head model to identify promising treatment electrode placements which we will test across a series of electrical doses in 3 cohorts of healthy controls to attempt to identify a tDCS treatment electrode configuration with which we can identify a dosage in each subject that is: (1) tolerable (5-point Likert ratings of no more than mild discomfort); and (2) engages the target neural circuitry by transiently inhibiting LC activity as reflected in prevention of the pupil dilation response to rare stimuli in the auditoy oddball task (AOT), which reliably activates LC. If successful we will proceed to a 3 year R33 parallel- group trial where 60 healthy volunteers are randomized to electrical dose-personalized active tDCS vs an active control therapy (tDCS that delivers the same skin current density as the active but does not affect LC) where clinical symptoms Acute Fear, the primary outcome, are elicited by inhalation of 7.5% CO2. Future development viability will be assumed if there is preliminary evidence that engaging the target (inhibiting LC) safely diminishes clinical Acute Fear symptoms. Our broad scientific goal is to evaluate if engagement of the target brain circuitry, inhibition of LC, is a viable target for treating Acute Fear. This is of high public heath importance as Acute Fear is extremely widespread and debilitating problem and current treatment options are quite limited.