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.

项目概要/摘要 数十年的动物模型告诉我们，成瘾确实是一种神经回路失调的疾病。 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) 的治疗方式 治疗。目前，多次 10 Hz 重复 TMS (rTMS) 被动地应用于左侧背外侧 前额皮质 (DLPFC) 20 至 30 分钟（2000-3000 次脉冲）最近已被用于治疗 尼古丁使用障碍 (NUD)，特别是减少烟瘾和香烟消费。有人建议 观察到的 10 Hz 前额叶 rTMS 对中皮质边缘奖励电路的调节可能会介导 TMS 对 NUD 和其他物质相关疾病的治疗效果。但在临床实践中，半 每周 5 天每小时 TMS 治疗可能需要数周时间才能完全生效，而且其治疗效果仍然存在 有限且因人而异。因此，该提案的主要目标是开发一个更快、更 更集中的 TMS 方案可缩短治疗时间并提高临床效率 通过更精确地识别并积极瞄准奖励回路和近端功能。建立在最近的基础上 TMS 与 EEG 相结合的进展，使得 TMS 协议可以直接由 EEG 信号控制 （闭环调制），我们的目标是测试一种新颖的闭环 TMS 干预，能够实时跟踪和 尼古丁依赖性奖励相关中扣带皮层（MCC）活动的不同发作的调节 个人。这种方法有可能提供空间、时间和认知上的双向治疗 精确的。我们的实验室和其他人已经在额叶部位（额叶）的 theta 波段中识别出振荡脑电图信号 中线 theta，FMT）伴随着多巴胺能奖励预测错误，并且在 NUD 和 其他物质使用障碍。由于脑电图振荡的相位可以反映局部处理，因此时间 TMS 脉冲在这些节律期间的精确周期应该具有直接的神经、行为和计算能力 效果，从而改善临床结果。因此，我们开发了一种新颖的闭环系统，能够 实时跟踪这些 θ 振荡并使用该信息来控制 TMS 的传输。这个提议 旨在测试这些协议调节 MCC 奖励的神经、计算和行为功效 功能（目标1），然后测试是否精确触发TMS与FMT的波峰或波谷同步 振荡会暂时减少因接触尼古丁中的吸烟线索而引发的主观渴望 受抚养的成年吸烟者（目标 2）。该项目具有创新性，因为它可以立即 探测 MCC 神经反应模式并在奖励导向期间进行 TMS 操作 行为。拟议的研究意义重大，因为科学知识将为 选择刺激参数，以促进所涉及的特定神经认知过程的治疗 NUD 和其他物质相关疾病。