A novel therapeutic application of closed-loop neuromodulation of the brain reward system in nicotine use disorder

大脑奖励系统闭环神经调节在尼古丁使用障碍中的新治疗应用

• 批准号: 10583658
• 负责人: Travis E. Baker
• 金额: $ 22.7万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583658
• 关键词: Adopted; Adult; Affective; Algorithms; Animal Model; Anterior; Behavior; Behavioral; Biological Markers; Brain; Cigarette; Clinical; Cognitive; Computer Models; Consumption; Data; Decision Making; Disease; Dopamine; Dorsal; Educational process of instructing; Electroencephalography; Electrophysiology (science); Exposure to; Feedback; Goals; Health; Healthcare Systems; Hour; Human; Individual; Intervention; Investigation; Knowledge; Lateral; Left; Length; Link; Measures; Mediating; Methods; Monitor; Neurocognitive; Neurocognitive Deficit; Nicotine Dependence; Nicotine Use Disorder; Outcome; Pathway interactions; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Physiologic pulse; Play; Prefrontal Cortex; Process; Protocols documentation; Research; Rest; Rewards; Robotics; Role; Signal Transduction; Site; Smoker; Substance Use Disorder; Substance-Related Disorders; System; Testing; Therapeutic Effect; Time; Training; Transcranial magnetic stimulation; Treatment Efficacy; Work; addiction; brain based; cigarette craving; clinical practice; cognitive ability; craving; drug seeking behavior; efficacy testing; improved; innovation; neural; neural circuit; neuroregulation; nicotine cue; nicotine treatment; noninvasive brain stimulation; novel; novel therapeutics; operation; repetitive transcranial magnetic stimulation; response; reward circuitry; signal processing; smoking cue; substance use treatment; success; treatment program; virtual

PROJECT SUMMARY/ABSTRACT Decades of animal models have taught us that addiction is, indeed, a disorder of dysregulated neural circuits. However, there are currently no circuit-based biomarkers or treatments for human patients. Transcranial magnetic stimulation (TMS) has the potential to radically transform how substance use disorders (SUDs) are treated. Presently, multiple sessions of 10-Hz repetitive TMS (rTMS) passively applied over the left dorsal lateral prefrontal cortex (DLPFC) for 20 to 30 min (2000–3000 pulses) has recently been adopted for the treatment of nicotine use disorder (NUD), particularly reducing craving and cigarette consumption. It has been suggested that the observed modulation of the mesocorticolimbic reward circuitry by 10-Hz prefrontal rTMS might mediate the therapeutic effects of TMS in NUD and other substance-related disorders. However, in clinical practices, a half- hour TMS therapy 5 days a week could take weeks to be fully effective, and its therapeutic efficacy remains limited and varies greatly across individuals. Thus, the primary goal of this proposal is to develop a faster and more concentrated TMS protocol that may reduce the treatment time length and increase its clinical efficiency by more precisely identifying and actively targeting the reward circuitry and proximal functions. Building on recent advances in combining TMS with EEG, which allow TMS protocols to be directly controlled by the EEG signal (closed-loop modulation), we aim to test a novel close-loop TMS intervention capable of real-time tracking and modulation of distinct episodes of reward-related midcingulate cortex (MCC) activity in nicotine-dependent individuals. This approach potentially offers bidirectional treatments that are spatially, temporally, and cognitively precise. Our lab and others have identified oscillatory EEG signals in the theta band over frontal sites (frontal midline theta, FMT) that accompany dopaminergic reward prediction errors, and that are altered in NUD and other substance use disorders. Since the phase of oscillations in the EEG can reflect local processing, the timing of TMS pulses to precise periods during these rhythms should have direct neural, behavioral, and computational effects, and thereby improved clinical outcomes. Thus, we have developed a novel closed-loop system capable of tracking these theta oscillations in real-time and using that information to control delivery of TMS. This proposal seeks to test the neural, computational, behavioral efficacy of these protocols for modulating MCC reward function (Aim 1), and then test whether precisely triggering TMS synchronized with the peak or trough of FMT oscillations would temporarily reduce the subjective craving triggered by exposure to smoking cues in nicotine- dependent adult smokers (Aim 2). This project is innovative because it enables the possibility to instantaneously probe the MCC neural response pattern and to deliver TMS manipulations as they occur during reward-directed behavior. The proposed research is significant, because the scientific knowledge will provide best practices to choose stimulation parameters that will advance the treatment for particular neurocognitive processes involved in both NUD and other substance-related disorders.

项目摘要/摘要 几十年的动物模型告诉我们，上瘾确实是一种失调的神经回路紊乱。 然而，目前还没有针对人类患者的基于回路的生物标志物或治疗方法。经颅 磁刺激(TMS)有可能从根本上改变物质使用障碍(SUD)的方式 治疗过了。目前，多次10-Hz重复TMS(RTMS)被动地应用于左侧背侧 前额叶皮质(DLPFC)20-30分钟(2000-3000次脉冲)最近已被用于治疗 尼古丁使用障碍(NUD)，特别是减少渴望和香烟消费。有人建议， 观察到的10-Hz额叶rTMS对中皮质边缘奖赏回路的调制可能介导了 TMS治疗NUD及其他物质相关性疾病的疗效。然而，在临床实践中，有一半- 每周5天一小时的TMS疗法可能需要数周时间才能完全有效，其治疗效果仍然存在。 有限，且在不同个体之间差异很大。因此，这项提案的主要目标是开发一种更快和 更集中的TMS方案，可缩短治疗时间，提高临床效率 通过更准确地识别和积极瞄准奖励回路和近端功能。在最近的基础上 TMS与EEG相结合的进展，这使得TMS方案可以直接由EEG信号控制 (闭环调制)，我们的目标是测试一种新型的闭环TMS干预，能够实时跟踪和 尼古丁依赖者奖赏相关中扣带回(MCC)活动的不同时段的调制 个人。这种方法潜在地提供了空间、时间和认知上的双向治疗 很精确。我们的实验室和其他实验室已经在额叶部位(额叶)的theta频段发现了振荡的脑电信号 中线Theta，FMT)，伴随着多巴胺能奖赏预测错误，并在NUD和 其他物质使用障碍。由于脑电中振荡的相位可以反映局部处理，因此定时 在这些节律中，TMS脉冲的精确周期应该具有直接的神经、行为和计算 效果，从而改善临床结果。因此，我们开发了一种新型的闭环系统，能够 实时跟踪这些theta振荡并使用这些信息来控制TMS的传递。这项建议 旨在测试这些调节MCC奖励的方案的神经、计算和行为效能 功能(目标1)，然后测试精确触发TMS是否与FMT的波峰或波谷同步 这种振荡会暂时减少尼古丁中的吸烟线索引发的主观渴望-- 依赖成年吸烟者(目标2)。这个项目是创新的，因为它使瞬间 探索MCC神经反应模式，并在奖励定向期间进行TMS操作 行为。这项拟议的研究意义重大，因为科学知识将为 选择刺激参数，以促进特定神经认知过程的治疗 在NUD和其他与物质相关的疾病中都存在。