Neuronal Pathways for Social Rejection: fMRI Studies

描述（由申请人提供）：该指导研究科学家发展奖将支持候选人过渡到专注于情绪障碍的转化研究的独立研究者。具有动物研究背景，候选人建议进行人类功能磁共振成像（fMRI）培训，以研究与社会排斥和接受相关的大脑活动。社会排斥（一个人不被喜欢的明确声明）对情绪和行为有强大的影响，包括自尊心降低、严重抑郁、冒险行为、药物滥用和暴力。一些功能磁共振成像研究发现，使用不同的社会排斥范式时，前扣带皮层的活动增加。该项目的第一个目标是测试社会排斥的实验操作，探索其参数，并适应在功能磁共振成像实验中使用的刺激呈现。第二个目标是使用功能磁共振成像检查与社会排斥有关的神经通路。根据在大鼠和猴子身上发现的解剖通路，假设除了前扣带皮层外，在导水管周围灰质、丘脑、杏仁核、伏隔核和亚属皮层也会被激活。众所周知，这些结构与压力反应、严重抑郁以及对奖励的反应有关。一个探索性的目的是评估在没有功能磁共振成像的情况下重度抑郁症（MDD）患者对社会排斥的行为反应。一旦行为反应被研究，我的长期目标是用神经影像学检查重度抑郁症患者对社会排斥的异常神经元反应。例如，非典型抑郁症的独特特征是强烈的社会排斥敏感性。确定抑郁症亚型的独特生物学特征可能会改善其定义、诊断和治疗。

DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award will support the candidate in transitioning into an independent investigator in translational research with a focus on mood disorders. With a background in animal research, the candidate proposes training in human functional magnetic resonance imaging (fMRI) to investigate brain activity associated with social rejection and acceptance. Social rejection (an explicit declaration that an individual is not liked) has powerful effects on emotion and behavior including lowered self- esteem, major depression, risk-taking behavior, substance abuse, and violence. A few fMRI studies have found increased activity in the anterior cingulate cortex using different paradigms for social rejection. The first aim of the project is to test experimental manipulations for social rejection, explore its parameters, and adapt a stimulus presentation for use in fMRI experiments. The second aim is to use fMRI to examine neuronal pathways involved in social rejection. Based on anatomical pathways found in rats and monkeys, it is hypothesized that in addition to the anterior cingulate cortex, activation will be found in the periaqueductal gray, thalamus, amygdala, nucleus accumbens, and subgenual cortex. These structures are known to be involved in stress responses and major depression, as well as responding to rewards. An exploratory aim will assess behavioral responses to social rejection in patients with Major Depressive Disorder (MDD) without fMRI. Once the behavioral responses are studied, my long-term goal is to examine abnormal neuronal responses to social rejection in MDD with neuroimaging. Atypical depression, for example, is uniquely characterized by intense social rejection sensitivity. Identifying a unique biological profile for a depressive subtype may improve its definition, diagnosis, and treatment.