Influence of Gonadal Hormones on Fear Extinction

描述(由申请者提供)：这是一份K01指导研究科学家发展奖的申请书，题为“性腺激素对恐惧消退的影响”。啮齿动物和人类的神经成像研究表明，腹侧前额叶皮质(VmPFC)对消失性记忆回忆至关重要。候选人将使用功能磁共振成像和心理生理学方法来检查性别和性腺激素变化对参与灭绝记忆的大脑区域的功能活动的影响。将检验两个假设：1)月经周期中雌激素水平的升高将减弱消退回路，特别是vmPFC的功能活性，从而降低消退能力；2)黄体酮的应用将促进灭绝回忆过程中该消退回路的功能活动，从而导致消退能力的增强。为了验证这些假设，健康的人类志愿者将接受为期两天的恐惧条件作用和消除方案，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的指标。建议的研究资源由马萨诸塞州总医院(MGH)精神科神经成像研究计划、MGH/MIT/HMS阿蒂诺拉斯·A·马蒂诺斯生物医学成像中心和MGH/MIT综合临床研究中心提供。应聘者的近期目标是获得功能磁共振成像、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。应聘者的长期职业目标是成为一名有专业知识的研究人员，研究性腺激素在情绪刺激处理过程中对大脑功能的影响。相关性：以恐惧增加为特征的焦虑症在女性中的患病率是男性的两倍。这项建议将首先研究健康的男性和女性在学会不害怕方面可能存在的差异，从而开始研究这些差异的神经生物学基础。本实验将研究月经周期不同阶段的激素变化(即雌激素和孕激素)对参与安全记忆信号传递的脑区活动的影响。这项提案还将研究黄体酮对增强大脑信号安全的影响。这项提案的发现可能有助于开发针对焦虑症的性别特异性治疗方法。

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.