Effect of tDCS timing on safety memory in PTSD

tDCS 计时对 PTSD 安全记忆的影响

• 批准号: 10548178
• 负责人: Mascha van 't Wout-Frank
• 金额: $ 33.83万
• 依托单位: BUTLER HOSPITAL (PROVIDENCE, RI)
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10548178
• 关键词: Affect; Amygdaloid structure; Animal Model; Animals; Anodes; Arousal; Brain; Centers of Research Excellence; Clinic; Clinical; Clinical Research; Clinical Trials; Data Collection; Development; Diagnosis; Effectiveness; Exposure to; Extinction; Fright; Functional Magnetic Resonance Imaging; Galvanic Skin Response; Genetic Complementation Test; Goals; Hippocampus; Hour; Human; Image; Impairment; Individual; Intervention; Knowledge; Laboratories; Laboratory Research; Learning; Magnetic Resonance Imaging; Memory; Mental disorders; Neurons; Participant; Patients; Physiological; Pilot Projects; Play; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Procedures; Process; Protocols documentation; Psychophysiology; Psychotherapy; Randomized; Regulation; Relapse; Research; Rest; Rodent; Role; Safety; Standardization; Stimulus; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Uses; Time; Trauma; Work; analog; clinical development; conditioned fear; fear memory; forgetting; improved; learning extinction; member; memory retention; neural; neuroimaging; neuroregulation; novel; reduce symptoms; response; standard care; success; transcranial direct current stimulation

PROJECT SUMMARY/ABSTRACT Posttraumatic stress disorder (PTSD) is the 5th most prevalent mental disorder in the USA. The gold-standard treatment for PTSD includes exposure-based therapy, which relies on adequate extinction processes to be successful in reducing symptoms. Although the efficacy of exposure therapy is scientifically established, many patients do not satisfactorily benefit and symptomatic relapse following treatment is common. Therefore, there is a pressing need to identify effective novel options to improve the effectiveness of exposure therapy for PTSD treatment. A laboratory analogue for exposure-based therapy is the extinction of conditioned fear, often designated as “extinction learning”. The goal of extinction, in the clinic and research laboratory, is to form new safety memories that can be recalled in order to inhibit fear responses associated with the original trauma. The ability to remember new safety memories after extinction is termed “extinction retention”. Adequate extinction learning and retention is supported by the ventromedial prefrontal cortex (VMPFC), signifying “top-down” prefrontal regulation of fear expression. Abnormalities in VMPFC functioning and extinction retention are extensively associated with PTSD. Accordingly, our group piloted the use of noninvasive transcranial direct current stimulation (tDCS) to facilitate VMPFC function during extinction in a Pavlovian fear conditioning paradigm. Preliminary results suggests that tDCS could enhance extinction retention, but this effect appears to depend on the timing of stimulation in relation to extinction learning. Specifically, our preliminary evidence suggests tDCS after extinction learning might have stronger effects on extinction retention versus stimulation during extinction learning. An essential next step is to determine the effect of timing of VMPFC-targeted tDCS, and thus whether tDCS during or immediately following extinction learning more effectively enhances extinction retention in individuals with PTSD. This will provide critical knowledge on the optimal, i.e. most effective, tDCS timing protocol to enhance extinction memory fundamental to successful exposure-based treatment. Results of the proposed research will directly inform further development of clinical trials aimed to test the application of tDCS to enhance exposure-based therapeutic interventions for PTSD. The current COBRE proposal will use a well-established fear-conditioning paradigm to systematically test how tDCS timing in relation to extinction learning affects physiological arousal (skin conductance responses) and associated neural responses using neuroimaging at time of extinction retention.

项目总结/摘要 创伤后应激障碍（PTSD）是美国第五大流行的精神障碍。金本位 创伤后应激障碍的治疗包括基于焦虑的治疗，这种治疗依赖于足够的消退过程， 成功减轻症状。虽然暴露疗法的疗效是科学确定的，但许多人认为， 患者不能令人满意地获益，并且治疗后症状复发是常见的。因此 迫切需要找到有效的新方法来提高创伤后应激障碍暴露疗法的有效性 治疗一个实验室的类似物，以消除恐惧为基础的治疗是条件性恐惧，往往 称为“灭绝学习”。灭绝的目标，在临床和研究实验室，是形成新的 安全记忆可以被唤起，以抑制与原始创伤相关的恐惧反应。的 在消退后记住新的安全记忆的能力被称为“消退保持”。充分消光 学习和记忆是由腹内侧前额叶皮层（VMPFC）支持的，意味着“自上而下” 恐惧表达的前额叶调节VMPFC功能和消光保留的异常是 与创伤后应激障碍有关因此，我们的小组试点使用无创经颅直接 在巴甫洛夫恐惧条件反射的消退过程中，电流刺激（tDCS）促进VMPFC功能 范例初步结果表明，tDCS可以增强消光保留，但这种作用似乎 取决于与消退学习相关的刺激时机。具体来说，我们的初步证据 提示，与刺激相比，消退学习后的tDCS可能对消退保持有更强的影响 在灭绝学习中。重要的下一步是确定靶向VMPFC的tDCS的时间效应， 因此，在消退学习期间或紧接消退学习之后的tDCS是否更有效地增强消退 PTSD患者的记忆力这将提供关于最佳（即最有效）tDCS的关键知识 定时协议，以增强消退记忆的基础，成功的基于记忆的治疗。结果 拟议的研究将直接为旨在测试 tDCS旨在加强基于暴露的创伤后应激障碍治疗干预措施。目前的COBRE提案将使用 一个成熟的恐惧条件反射范式，系统地测试tDCS时间与灭绝的关系 学习影响生理唤醒（皮肤电导反应）和相关的神经反应， 神经影像学检查。