Influence of Gonadal Hormones on Fear Extinction

性腺激素对恐惧消退的影响

• 批准号: 7454494
• 负责人: Mohammed R Milad
• 金额: $ 18.37万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7454494
• 关键词: Anxiety Disorders; Attenuated; Brain; Brain region; Clinical Research; Data; Depth; Estrogens; Exhibits; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; General Hospitals; Goals; Gonadal Hormones; Hormonal Change; Human; Human Volunteers; Learning; Luteal Phase; Massachusetts; Measures; Medial; Memory; Menstrual cycle; Mentored Research Scientist Development Award; Neurobiology; Neuroendocrinology; Phase; Placebos; Prefrontal Cortex; Prevalence; Process; Progesterone; Protocols documentation; Psychiatric Hospitals; Psychophysiology; Relative (related person); Research; Research Ethics; Research Personnel; Resources; Rodent; Role; Safety; Sexual Development; Signal Transduction; Skin; Testing; Training; Treatment Protocols; Woman; Women' s Group; base; bioimaging; career; cognitive neuroscience; conditioned fear; day; emotional stimulus; indexing; learning extinction; memory recall; men; neural circuit; neuroimaging; programs; proliferative phase Menstrual cycle; research study; response; sex; skills

DESCRIPTION (provided by applicant): This is an application for a K01 Mentored Research Scientist Development Award entitled "Influence of Gonadal Hormones on Fear Extinction." Rodent and human neuroimaging studies indicate that the ventral medial prefrontal cortex (vmPFC) is critical for extinction memory recall. The candidate will use functional MRI and psychophysiological measures to examine the influence of sex and variance of gonadal hormones on the functional activity of brain regions involved in extinction recall. Two hypotheses will be tested: 1) elevated estrogen levels during menstrual cycle will attenuate functional activity of the extinction circuit, specifically vmPFC, and thus extinction capacity will be reduced, and 2) administration of progesterone will facilitate functional activity of this extinction circuitry during extinction recall that will result in enhanced extinction capacity. To test these hypotheses, healthy human volunteers will undergo a two-day fear conditioning and extinction protocol while measuring brain responses using fMRI. Skin conductance responses will be measured and used as an index of fear. The resources for the proposed research are provided by Massachusetts General Hospital (MGH) Psychiatric Neuroimaging Research Program, the MGH/MIT/HMS Athinolas A. Martinos Center for Biomedical Imaging, and the MGH/MIT General Clinical Research Center. The immediate objective of the candidate is to obtain in-depth training in functional MRI, cognitive neuroscience, and neuroendocrinology and to enhance skills in research and ethics. The long-term career goal is for the candidate to become an established investigator with expertise to study the influence of gonadal hormones on brain function during processing of emotional stimuli. Relevance: The prevalence of anxiety disorders, characterized by increased fear, is twice as high in women relative to men. This proposal will begin to examine the neurobiological basis for these differences by first studying how healthy men and women may differ in learning not to fear. The experiments herein will investigate the influence of hormonal changes (i.e. estrogen and progesterone) during different phases of the menstrual cycle on the activity of brain regions involved in signaling memory for safety. This proposal will also examine the influence of progesterone administration on boosting the brain's signal for safety. Findings from this proposal may help the development of sex-specific treatments for anxiety disorders.

描述（由申请人提供）：这是一份题为“性腺激素对恐惧消退的影响”的 K01 指导研究科学家发展奖的申请。 啮齿动物和人类神经影像学研究表明，腹侧内侧前额叶皮层 (vmPFC) 对于消退记忆回忆至关重要。 考生将使用功能性 MRI 和心理生理学测量来检查性别和性腺激素变化对参与消退回忆的大脑区域功能活动的影响。 将测试两个假设：1）月经周期期间雌激素水平升高将减弱消退回路（特别是 vmPFC）的功能活动，从而降低消退能力，2）黄体酮的施用将促进消退期间该消退回路的功能活动请记住，这将导致增强的灭绝能力。 为了测试这些假设，健康的人类志愿者将接受为期两天的恐惧调节和消除方案，同时使用功能磁共振成像测量大脑反应。 皮肤电导反应将被测量并用作恐惧指数。 拟议研究的资源由麻省总医院 (MGH) 精神病学神经影像研究计划、MGH/MIT/HMS Athinolas A. Martinos 生物医学影像中心和 MGH/MIT 普通临床研究中心提供。 候选人的直接目标是获得功能性核磁共振、认知神经科学和神经内分泌学方面的深入培训，并提高研究和伦理方面的技能。 候选人的长期职业目标是成为一名成熟的研究人员，具有研究情绪刺激处理过程中性腺激素对大脑功能影响的专业知识。 相关性：以恐惧增加为特征的焦虑症的患病率在女性中是男性的两倍。 该提案将首先研究健康男性和女性在学习不恐惧方面的差异，从而探讨这些差异的神经生物学基础。 本文的实验将研究月经周期不同阶段荷尔蒙变化（即雌激素和黄体酮）对涉及安全信号记忆的大脑区域活动的影响。 该提案还将研究黄体酮给药对增强大脑安全信号的影响。 该提案的结果可能有助于开发针对焦虑症的针对性别的治疗方法。