Developing Methods for Brain Stimulation Enhanced Fear Reversal in PTSD

开发脑刺激方法可增强 PTSD 患者的恐惧逆转

• 批准号: 8683995
• 负责人: Desmond Oathes
• 金额: $ 7.05万
• 依托单位: PALO ALTO VETERANS INSTIT FOR RESEARCH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8683995
• 关键词: Achievement; Amygdaloid structure; Animal Model; Animals; Anterior; Area; Behavior; Behavioral; Blinking; Brain; Brain region; Cues; Data; Diagnosis; Distress; Dorsal; Effectiveness; Etiology; Event; Extinction (Psychology); FDA approved; Failure; Fright; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hippocampus (Brain); Human; Image; Individual; Learning; Location; Magnetic Resonance Imaging; Maintenance; Major Depressive Disorder; Maps; Measures; Medial; Memory; Methods; Modeling; Monitor; Mood Disorders; Neurobiology; Outcome; Participant; Patients; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Psychopathology; Psychophysiology; Reaction; Recovery; Recruitment Activity; Regulation; Research; Reversal Learning; Role; Site; Specificity; Structure; Testing; Time; Training; Transcranial magnetic stimulation; Translating; Trauma; Work; affective neuroscience; base; behavior influence; behavior test; biological adaptation to stress; chemical genetics; cognitive neuroscience; conditioned fear; design; emotion regulation; experience; genetic manipulation; improved; interest; learning extinction; memory retention; neural circuit; neuroimaging; neuroregulation; novel; public health relevance; relating to nervous system; repetitive transcranial magnetic stimulation; research study; response; tool

DESCRIPTION (provided by applicant): Electrical, chemical, and genetic manipulation of brain circuitry in non-human animals has led to important advances in our understanding of how learned fear is acquired, how it is extinguished (lessened by experience with contradictory evidence), and how in some cases fear memories persist in eliciting stress reactions despite evidence that the feared aversive event will not recur. In the case of posttraumatic stress disorder (PTSD) in humans, evidence suggests that fear memories persist and the location of brain abnormalities underlying this persistence are consistent with the evidence for the neurobiological substrates of fear memory extinction retention gathered from non-human animal studies. By manipulating this same circuitry in humans in the context of fear extinction, it may be possible to augment the lessening of stress reactions to learned fear cues. The proposed study seeks to determine the parameters best suited for this augmentation in healthy participants using repetitive transcranial magnetic stimulation (rTMS). By testing behavioral and psychophysiological responses to learned fear cues before and after extinction in conjunction with applying rTMS to multiple brain targets, the effectiveness of each target in augmenting fear memory extinction will be evaluated. Applying rTMS interleaved with neuroimaging (functional magnetic resonance imaging) to these targeted brain areas will yield additional evidence of how induced plasticity in key brain circuits implicated in the task and in PTSD pathophysiology may relate to fear learning and extinction. Multiple targets will be evaluated this way in healthy participants before one or more can be selected for testing in patients diagnosed with PTSD. The effectiveness of rTMS to influence behavioral and psychophysiological responding to learned fear cues will thus be explored in healthy populations as a function of induced plasticity mechanisms measured in this context for the first time combining TMS/fMRI methods. The evidence gathered from these measures will provide a novel framework for evaluating neurobiological improvements in PTSD and may also support particular brain regions for targeting in a subsequent rTMS treatment.

描述(申请人提供)：对非人类动物的大脑电路进行电、化学和遗传操作，使我们在理解获得性恐惧是如何获得的、如何消除恐惧(通过相互矛盾的证据的经验而减少)方面取得了重要进展，以及在某些情况下恐惧记忆如何持续引发应激反应，尽管有证据表明害怕的厌恶事件不会再次发生。在人类创伤后应激障碍(PTSD)的案例中，证据表明恐惧记忆持续存在，这种持续存在的大脑异常的位置与从非人类动物研究中收集的恐惧记忆消退保持的神经生物学底物的证据一致。通过在恐惧消退的背景下操纵人类的这一相同电路，它可能是 有可能增强对后天恐惧暗示的压力反应的减轻。这项拟议的研究试图确定最适合使用重复经颅磁刺激(RTMS)的健康参与者进行这种增强的参数。通过测试消退前后对习得恐惧线索的行为和心理生理反应，结合对多个大脑目标进行rTMS，将评估每个目标在增强恐惧记忆消退方面的有效性。将rTMS与神经成像(功能磁共振成像)交叉应用于这些目标大脑区域，将产生额外的证据，证明在任务和创伤后应激障碍病理生理学中涉及的关键大脑回路的诱导可塑性可能与恐惧学习和消退有关。在选择一个或多个指标对被诊断为创伤后应激障碍的患者进行测试之前，将以这种方式在健康参与者中评估多个指标。因此，将首次结合TMS/fMRI方法在健康人群中作为诱导可塑性机制的函数来探索rTMS影响对获得性恐惧线索的行为和心理生理反应的有效性。从这些措施中收集的证据将为评估创伤后应激障碍的神经生物学改善提供一个新的框架，并可能支持在随后的rTMS治疗中靶向特定的大脑区域。