Effect of tDCS timing on safety memory in PTSD

tDCS 计时对 PTSD 安全记忆的影响

• 批准号: 10338142
• 负责人: Mascha van 't Wout-Frank
• 金额: $ 35.97万
• 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 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10338142
• 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 (Psychology); Fright; Functional Magnetic Resonance Imaging; Galvanic Skin Response; Goals; Gold; Hippocampus (Brain); 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; base; clinical development; conditioned fear; fear memory; forgetting; improved; learning ability; learning extinction; memory retention; neuroimaging; neuroregulation; novel; reduce symptoms; relating to nervous system; response; standard care; success

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.

项目摘要/摘要 创伤后应激障碍(PTSD)是美国第五大最常见的精神障碍。金本位 创伤后应激障碍的治疗包括基于暴露的治疗，这依赖于适当的消退过程 成功地减轻了症状。尽管暴露疗法的疗效是科学确定的，但许多 患者不能令人满意地受益，治疗后症状复发是常见的。因此，在那里 迫切需要找到有效的新选择来提高创伤后应激障碍暴露疗法的有效性 治疗。暴露疗法的实验室类比是消除条件性恐惧，通常 被指定为“灭绝学习”。在临床和研究实验室中，灭绝的目标是形成新的 可以回忆的安全记忆，以抑制与原始创伤相关的恐惧反应。这个 在物种灭绝后记忆新的安全记忆的能力被称为“物种灭绝保持”。足够大的灭绝 学习和保持受到腹内侧额前皮质(VMPFC)的支持，这意味着“自上而下”。 恐惧表情的前额调节。VMPFC功能和消退保持的异常 与创伤后应激障碍密切相关。因此，我们小组试行了非侵入性经颅直接入路 巴甫洛夫恐惧条件反射消退过程中促进VMPFC功能的电流刺激(TDC) 范例。初步结果表明，tdcs可以增强消光保持，但这种作用似乎 取决于刺激的时间与消退学习的关系。具体来说，我们的初步证据 提示灭绝学习后的tdcs可能比刺激对灭绝保持有更强的影响。 在学习灭绝的过程中。关键的下一步是确定以VMPFC为目标的TDC的定时的影响， 因此，无论是在灭绝学习期间还是紧接着灭绝学习之后，tdc都更有效地增强了灭绝。 创伤后应激障碍患者的滞留情况。这将提供关于最佳、即最有效的tDC的关键知识 增强消光记忆的计时协议，对成功的基于曝光的治疗至关重要。结果： 拟议的研究将直接为临床试验的进一步发展提供信息，旨在测试 加强创伤后应激障碍基于暴露的治疗干预。目前的Cobre提案将使用 建立了良好的恐惧条件作用范式，以系统地测试tdcs计时与灭绝的关系。 学习影响生理唤醒(皮肤电导反应)和相关的神经反应 绝迹保留时的神经成像。