Sub-second neurochemistry of error signals and affective processing in depression

抑郁症中错误信号和情感处理的亚秒神经化学

基本信息

批准号：
10453962
负责人：
PEARL H CHIU
金额：
$ 75.09万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-15 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10453962
关键词：
Affective Anhedonia Anterior Biological Brain region Chemicals Clinic Clinical Cognition Computer software Conflict (Psychology)Decision Making Disease Dopamine Electrochemistry Electrodes Emotional Epilepsy Foundations Functional disorder Future Goals Hospitals Human Impairment Implanted Electrodes Individual Investigation Learning Major Depressive Disorder Measures Medical Mental Depression Methods Monitor Moods Neuromodulator Neurotransmitters Participant Pharmaceutical Preparations Phase Positron-Emission Tomography Process Public Health Resistance Resolution Role Serotonin Signal Transduction Specificity Symptoms System Testing Virginia affective neuroscience arm awake base cingulate cortex clinical research site clinically significant depressive symptoms functional magnetic resonance imaging/electroencephalography in vivo machine learning algorithm negative mood neurochemistry neuroimaging neurosurgery new technology novel therapeutics relating to nervous system response symptomatic improvement temporal measurement

项目摘要

PROJECT SUMMARY Serotonin and dopamine dysfunction have been long implicated in the pathophysiology of major depression. However, to date, delineating the role of these neuromodulators in depression has largely and necessarily relied on inference, with neuroimaging (including PET, fMRI, EEG) studies revealing responses in brain regions associated with dopamine and serotonin release and medications targeting the dopaminergic and serotoninergic systems improving symptoms for some individuals. In order to make significant advances in understanding the neural underpinnings of depression and developing novel therapeutics for the disorder, tracking neuromodulator responses quickly, accurately, and in vivo is required. Recent advances allow exactly the unprecedented ability to track neuromodulator responses with high temporal resolution and chemical specificity. Specifically, we are able to directly and simultaneously measure dopamine and serotonin responses in awake humans with the temporal resolution (~ 10 ms) required to examine the relationship of neuromodulator release with decision-making processes. The product of these advances is recordings of in vivo neuromodulator fluctuations at sub-second resolution. This application merges the clinical and affective neuroscience expertise of MPI Chiu with these advances of MPI Montague to directly examine the relationship of dopamine and serotonin responses to depression. To achieve this goal, we will record neuromodulator responses in participants with medication-resistant epilepsy who already have intracranial depth electrodes in place for phase-II monitoring. The depth electrodes are implanted by our neurosurgery colleagues at Virginia Tech’s medical affiliate Carilion Clinic (Project Co-I Witcher; Carilion Clinic clinical site PI). During recording, participants will be in a standard (i.e., non-surgical) hospital monitoring suite and perform i) an affective processing task (emotional Stroop) and ii) a value-based learning task (two-arm bandit) that have been shown by our group and others both to engage processes thought to be related to serotonin and dopamine function, and also to be related to negative mood and anhedonia symptoms, respectively, of depression.

项目概要血清素和多巴胺功能障碍长期以来一直与重度抑郁症的病理生理学有关。然而，迄今为止，描述这些神经调节剂在抑郁症中的作用在很大程度上也是必然的。依赖于推理，神经影像（包括 PET、功能磁共振成像、脑电图）研究揭示了大脑的反应与多巴胺和血清素释放相关的区域以及针对多巴胺能和血清素的药物血清素能系统改善某些人的症状，以取得重大进展。了解抑郁症的神经基础并开发针对该疾病的新疗法，需要在体内快速、准确地跟踪神经调节剂的反应。最近的进展使得追踪神经调节剂反应的能力达到前所未有的高度具体来说，我们能够直接并同时测量。清醒人类的多巴胺和血清素反应具有所需的时间分辨率（约 10 毫秒）检查神经调节剂释放与决策过程的关系。该应用的进展是以亚秒分辨率记录体内神经调节剂波动。将 MPI Chiu 的临床和情感神经科学专业知识与 MPI Montague 的这些进步相结合，直接检查多巴胺和血清素反应与抑郁症的关系。为了实现这一目标，我们将记录耐药参与者的神经调节剂反应已安装颅内深度电极进行第二阶段监测的癫痫患者。由弗吉尼亚理工大学医疗附属机构 Carilion Clinic（Project Co-I）的神经外科同事植入 Witcher；Carilion Clinic 临床现场 PI) 在录制期间，参与者将处于标准状态（即非手术）。医院病房监控并执行 i) 情感处理任务（情感 Stroop）和 ii) 基于价值的任务我们的小组和其他人都证明了学习任务（双臂强盗）都参与了流程据认为与血清素和多巴胺功能有关，也与消极情绪和快感缺失症状分别为抑郁症。