Using electrophysiology to index non-invasive brain stimulation effects on reward system neurobiology in depression

利用电生理学来索引非侵入性脑刺激对抑郁症奖励系统神经生物学的影响

基本信息

批准号：
10434926
负责人：
SUSANNA FRYER
金额：
$ 19.16万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434926
关键词：
Address Affective Anterior Attention Attenuated Behavior Behavioral Biological Assay Brain Clinical Clinical Trials Contingent Negative Variation Control Groups Corpus striatum structure Data Development Disease Dissociation Distal Electroencephalography Electrophysiology (science)Evaluation Event-Related Potentials Functional disorder Future Goals Health Care Costs Individual Intervention Lead Literature Major Depressive Disorder Measures Mental Depression Meta-Analysis Methods Morbidity - disease rate Motivation Motor Neurobiology Nicotine Dependence Outcome Outcome Measure Performance Play Positive Valence Process Psychiatry Psychopathology Research Rewards Role Speed Stimulus System Techniques United States Food and Drug Administration Work base biomarker validation case control cingulate cortex depressive symptoms driving behavior financial incentive improved indexing innovation mortality neural circuit neuroregulation noninvasive brain stimulation novel pleasure primary outcome repetitive transcranial magnetic stimulation response reward anticipation reward circuitry reward processing secondary outcome skills societal costs therapy development treatment response

项目摘要

Rewards play a central role in driving behavior. Reward system dysfunctions are increasingly conceptualized as transdiagnostic phenomena 1,2, relevant to many psychopathologies. The opportunity to directly modulate reward processing through targeted intervention could have broad mechanistic and clinical value in psychiatry, both for disorders in which reward-responsive circuits are overactive or underactive. The overarching goal of this R21 proposal focuses on one such opportunity in individuals with depression: we will evaluate whether an electrophysiological measure of reward consummation, the Reward Positivity (RewP), which is consistently blunted in depression, can be moved by targeted neurostimulation of a prefrontal-striatal reward circuit. The premise of the proposed work is a well-developed empirical literature that substantiates the RewP as a measure of subjective reward valuation, with depression-associated blunting of the RewP likely reflecting attenuated reward consummation. Non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), modulate cortical activity and offer novel avenues to probe reward circuitry. Previous research establishes that excitation of a fronto-cingulate reward circuit with rTMS increases RewP magnitude in nicotine addiction, but the extent to which blunted RewP in depression can be rescued via rTMS is unknown. We therefore propose pilot research to begin to address this literature gap via a repeated-measures study that uses a multi-measure approach to probe reward system functioning under passive and performance-dependent reward conditions. We will examine sham-controlled effects of single session intermittent theta burst stimulation (iTBS) to a dorsomedial prefrontal/anterior cingulate cortex (dmPFC/dACC) target in individuals with major depressive disorder (MDD). We will examine iTBS effects on anticipatory and later consummatory reward measures in addition to our primary focus on the RewP, thus capitalizing on the temporal precision EEG affords by decomposing reward processing into subcomponent processes and examining their differential sensitivity to neurostimulation. Specific Aim 1 examines case-control RewP differences before stimulation, and changes in RewP magnitude as a function of iTBS in MDD. Specific Aim 2 examines case-control and within-group MDD iTBS effects on a later-stage consummatory reward measure, the late positive potential (LPP). Specific Aim 3 examines case-control and within-group MDD iTBS effects on reward anticipation. Our approach is innovative because i) there is little precedent for using the well-validated RewP or similar measures as indices of rTMS modulation, despite putative hypofunction of reward circuitry in MDD and ii) we target a region strongly implicated in depressive pathophysiology3 but distinct from the Food and Drug Administration-approved dorsolateral prefrontal rTMS target for depression and ii). Here, we evaluate measures tapping reward anticipation and consummation to assay positive valence system functioning in response to iTBS, setting the stage for future biomarker validation and full-course rTMS clinical trials.

奖励在驾驶行为中起着核心作用。奖励系统功能障碍越来越概念化作为经诊断现象1,2，与许多心理病理学有关。直接调制的机会通过有针对性的干预进行奖励处理可能具有精神病学的广泛机械和临床价值，这两者都是奖励响应电路过度活跃或不足的疾病。总体目标该R21提案重点是抑郁症患者中的一个这样的机会：我们将评估是否奖励完成的电生理学度量，奖励积极性（REWP），这是一贯的在抑郁症中钝了，可以通过前额叶 - 纹状体奖励电路的靶向神经刺激移动。这拟议作品的前提是一部发达的经验文献，证实了REWP作为衡量标准主观奖励估值，与抑郁症相关的REWP可能反映了衰减奖励完成。非侵入性大脑刺激技术，例如重复的经颅磁刺激（RTMS），调节皮质活性并提供新的途径来探测奖励电路。以前的研究确定，用RTMS激发额额定奖励电路会增加REWP幅度在尼古丁成瘾中，但是尚不清楚通过RTMS挽救抑郁症中钝化的REWP的程度。因此，我们建议通过重复测量研究来解决这一文献差距，以解决这一文献差距使用多种措施方法来探测在被动和性能依赖性下运行的奖励系统奖励条件。我们将检查单个会话间歇性theta爆发的假对照效应刺激（ITB）到个体中背额前额/前扣带回皮层（DMPFC/DACC）靶标的刺激（ITB）患有重度抑郁症（MDD）。我们将研究ITB对预期和后来的影响的影响除了我们对REWP的主要关注之外，还采取了奖励措施，从而利用了时间精度脑电图通过将奖励处理分解为子组成过程并检查其差异来提供对神经刺激的敏感性。特定目标1检查刺激前病例对照REWP差异， REWP幅度随MDD中ITB的函数的变化。特定目标2检查病例对照和组内MDD ITB对后期的完整奖励措施的影响，晚期积极潜力（LPP）。特定目标3检查了病例对照和组内MDD ITB对奖励预期的影响。我们的方法具有创新性，因为i）使用验证良好的REWP或类似的先例尽管在MDD和II中推定的奖励电路功能性功能低下，但措施是RTMS调制的指标。靶向与抑郁病理生理学有关的区域3，但与食物和药物不同管理批准的背外侧前额叶RTMS抑郁症和II）。在这里，我们评估衡量奖励预期和完善以分析正价系统的功能对ITB的响应，为将来的生物标志物验证和完整的RTMS临床试验奠定了基础。