Manipulating the Reward Circuit with TMS

项目摘要 奖赏回路的缺失在许多精神疾病中被发现 包括重度抑郁症、药物滥用、强迫症， 精神分裂症奖赏回路功能障碍与快感缺乏有关--一种主观的丧失， 对愉悦刺激的反应。因此，奖励电路的正常化在 治疗快感缺乏和相关病症。为此，需要采取措施， 快感缺乏和调节快感缺乏的干预措施。我们做了大量的工作 一个可靠的事件相关电位（ERP）标记的奖励敏感性被称为奖励 正性（RewP）。RewP涉及奖励敏感性的行为和自我报告措施， 奖励回路的结构和功能MRI测量，抑郁症的风险和恢复 从抑郁症。在初步数据中，我们发现一次间歇性的θ- 靶向奖赏回路的脉冲串经颅磁刺激（iTBS）增加了RewP 在健康的年轻成人中相对于递送到对照部位的iTBS。如果奖励电路针对iTBS 可以改善RewP，这有望作为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改变细胞增殖的机制。 奖赏回路，RewP，和快感缺乏 本提案旨在应对这一挑战。60名快感缺失症患者将 被招募接受奖励电路为目标的iTBS为5天超过1周，以及iTBS到一个 对照部位持续5天，持续1周，每次之后在平衡， 交叉设计奖励敏感度将通过在每个周期结束时测量的RewP进行跟踪。 沿着而来的是自我报告的快感缺失。奖励回路将在基线时进行检查， 每个iTBS周结束时使用血氧水平依赖（BOLD）连接， 与奖励有关的活动。我们假设，奖励电路靶向iTBS将有两个本地 （皮质靶点）和下游（皮质下）对BOLD激活的影响，以及对 奖励回路中的连通性。我们假设这些对奖赏回路的影响 RewP的变化和自我报告的快感缺失也证实了这一点。这些数据共同 将测试奖励回路目标iTBS影响奖励回路的假设，奖励 敏感性和快感缺乏，为治疗快感缺乏的干预措施铺平了道路。

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.