Manipulating the Reward Circuit with TMS

项目总结 在许多精神疾病中都发现了奖赏回路的异常 包括严重抑郁障碍、药物滥用、强迫症以及 精神分裂症。奖赏回路功能障碍与快感缺乏相关--这是一种主观上的损失 对愉悦刺激的反应。因此，奖励电路的正常化在 快感缺失及相关疾病的治疗。为此，需要采取可靠的跟踪措施 快感缺乏症和调节快感缺乏症的干预措施。我们已经做了大量的工作来确定 一种可靠的事件相关电位(ERP)标记，被称为奖励敏感性 正性(RewP)。REWP涉及奖励敏感度的行为和自我报告测量， 奖赏回路、抑郁风险和康复的结构和功能磁共振测量 从抑郁中解脱。在初步数据中，我们发现单次间歇的theta- 针对奖赏回路的突发性经颅磁刺激(ITBS)可增加REWP 在健康的年轻人中，相对于ITBS被送到对照地点。如果奖励电路以ITBS为目标 可以改善REWP，这是一种可能调节快感缺乏的干预措施。 然而，这一目的需要更好地理解ITBS改变 奖励回路，REWP和快感缺乏症。 本提案旨在迎接这一挑战。60名快感缺乏症患者将 被招募接受针对ITBS的奖励电路，为期5天，为期1周，以及ITBS到 对照场地为期5天超过1周，每隔1周再进行1周的冲刷平衡， 交叉设计。奖励敏感度将通过在每个结束时测量的REWP进行跟踪 一周后出现自我报告的快感缺乏症。奖励回路将在基线时检查，并在 每个ITBS周结束时使用血氧水平依赖(BOLD)连接和 与奖励相关的激活。我们假设以ITBS为目标的奖励回路将既有局部的 (皮质靶点)和下游(皮质下)对BOLD激活的影响，以及对 奖励回路内的连通性。我们假设这些对奖赏回路的影响将 REWP和自我报告的快感缺乏的变化也证明了这一点。总的来说，这些数据 将测试针对ITBS的奖励回路影响奖励回路、奖励的假设 敏感性和快感缺乏，为干预快感缺乏铺平了道路。

PROJECT SUMMARY Abnormalities of the reward circuit have been identified in numerous psychiatric disorders including major depressive disorder, substance abuse, obsessive-compulsive disorder, and schizophrenia. Reward circuit dysfunction is associated with anhedonia – a subjective loss in reactivity to pleasurable stimuli. Normalization of the reward circuit thus holds promise in the treatment of anhedonia and associated disorders. This end requires measures that reliably track anhedonia, and interventions that modulate anhedonia. We have done extensive work identifying a reliable event-related potential (ERP) marker of reward sensitivity referred to as the reward positivity (RewP). The RewP relates to behavioral and self-report measures of reward sensitivity, structural and functional MRI measures of the reward circuit, risk for depression, and recovery from depression. In preliminary data, we have found that a single session of intermittent theta- burst transcranial magnetic stimulation (iTBS) targeted at the reward circuit increases the RewP in healthy, young adults relative to iTBS delivered to a control site. If reward circuit targeted iTBS can improve the RewP, this holds promise as an intervention that could modulate anhedonia. However, this end requires better understanding of the mechanisms by which iTBS alters the reward circuit, the RewP, and anhedonia. The present proposal aims to meet this challenge. Sixty individuals with elevated anhedonia will be recruited to receive reward circuit targeted iTBS for 5 days over 1 week, as well as iTBS to a control site for 5 days over 1 week, each followed by a week of washout in a counter-balanced, cross-over design. Reward sensitivity will be tracked by the RewP measured at the end of each week along with self-reported anhedonia. The reward circuit will be examined at baseline, and at the end of each iTBS week using blood-oxygenation level dependent (BOLD) connectivity and reward-related activations. We hypothesize that reward circuit targeted iTBS will have both local (cortical target) and downstream (sub-cortical) effects on BOLD activation, as well as effects on connectivity within the reward circuit. We hypothesize that these effects on the reward circuit will also be borne out in changes in the RewP and self-reported anhedonia. Collectively, these data will test the hypothesis that reward circuit targeted iTBS impacts the reward circuit, reward sensitivity, and anhedonia, paving the way towards interventions for the treatment of anhedonia.