A Transdiagnostic Assessment of Electroconvulsive Therapy Modulation of Anhedonia and Reward circuitry: Targets, Biomarkers and Predictors of Response

电惊厥治疗快感缺失和奖励回路调节的跨诊断评估：目标、生物标志物和反应预测因子

• 批准号: 10171912
• 负责人: Joan A Camprodon
• 金额: $ 70.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-05 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171912
• 关键词: Amygdaloid structure; Anatomy; Anhedonia; Anisotropy; Anterior; Ants; Area; Behavior; Behavioral; Bilateral; Biological Markers; Biology; Bipolar Depression; Brain; Brain imaging; Clinical; Clinical Trials; Data; Diagnosis; Diffuse; Dimensions; Disease; Dorsal; Electroconvulsive Therapy; Generalized seizures; Goals; Hippocampus (Brain); Human; Image; Imaging technology; Inferior; Inferior frontal gyrus; Insula of Reil; Lead; Learning; Lobule; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Medicine; Methodology; Mood Disorders; Motivation; National Institute of Mental Health; Neurosciences; Nucleus Accumbens; Parietal; Pathologic; Pathway interactions; Patients; Positive Valence; Property; Protocols documentation; Psychiatry; Psychological reinforcement; Radial; Research Domain Criteria; Rewards; Severities; Structure; Structure of superior frontal gyrus; Subcategory; Symptoms; Syndrome; System; Therapeutic; Therapeutic Human Experimentation; Time; Unipolar Depression; Ventral Tegmental Area; base; behavior measurement; biomarker performance; cingulate cortex; cohort; connectome; dentate gyrus; effective therapy; experience; improved; innovation; morphometry; multimodality; neuroimaging; neuropsychiatric disorder; neuroregulation; novel; pleasure; predicting response; putamen; response; reward circuitry; reward processing; stem; targeted biomarker; therapeutic target; tool; tractography; translational approach

Electroconvulsive Therapy (ECT) is the most effective treatment in psychiatry, and among the most effective in medicine. Despite its apparent non-focal effects leading to a generalized seizure, its therapeutic benefits are specific to a few clinical syndromes, including major depressive disorder (MDD) and bipolar depression (BD). These two syndromes share core deficits in reward processing (i.e. anhedonia). ECT improves anhedonia across mood disorders and syndromes, implying selective effects on the functional dynamics and structural properties of reward networks. Reward-related functions represent key behavioral dimensions of pathological relevance across neuropsychiatric disorders, and have a central place as positive valence constructs in the RDoC matrix. There has been a growing recognition that “anhedonia” does not represent a unitary dimension; among its subcategories, three constructs emerge with clear relevance to behavior and disease: consummation (liking), motivation (wanting) and reinforcement (learning). Quantitative behavioral measures exist for each of these three, with clinical validity as biomarkers and predictors of response. The anatomy of the reward network is well known, with a core in the ventral tegmental area (VTA) and the Nucleus Accumbens (NAc), and projections to cortical and subcortical nodes via the mesocorticolimbic pathway and its ramifications. The Human Connectome Project (HCP) has significantly advanced the technologies for imaging brain connections in humans, accelerating innovation in the emerging field of Connectomics. Preliminary data from our group describes the feasibility of obtaining multimodal MRI measures of reward circuit biology (morphometry, tractography, functional connectivity) in patients undergoing ECT, and extracting clinically meaningful information to identify treatment targets and develop biomarkers and predictors. At a time when therapeutic research is stalled due to the absence of clear targets and useful biomarkers, understanding the mechanisms of our most effective treatments is a priority for our field. In this study, we propose a novel translational strategy that takes advantage of the high efficacy and fast response of ECT, and uses it to probe target engagement at the circuit level. With a systems neuroscience framework, in line with NIMH strategic priorities and the RDoC Initiative, we will focus on reward circuitry and its clinical dimensions across two clinical syndromes that are commonly treated with ECT: MDD and BD. We will use HCP multimodal MRI protocols combined with validated behavioral measures of reward constructs to assess patients before, during and after ECT, in addition to a cohort of matched healthy controls that will be imaged twice. This study is innovative in its proposal to combine ECT with multimodal MRI as a framework to study anhedonia transdiagnostically, with the translational aims to (1) discover treatment targets, (2) develop biomarkers and (3) identify predictors of response.

电休克疗法（ECT）是最有效的精神病学治疗方法之一

项目成果

Rapid whole-brain electric field mapping in transcranial magnetic stimulation using deep learning.

• DOI: 10.1371/journal.pone.0254588
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Xu G;Rathi Y;Camprodon JA;Cao H;Ning L
• 通讯作者: Ning L

Individual response to electroconvulsive therapy is not correlated between multiple treatment courses.

• DOI: 10.1016/j.jad.2021.11.002
• 发表时间: 2022-02-01
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Hart KL;Henry ME;McCoy TH;Seiner SJ;Luccarelli J
• 通讯作者: Luccarelli J

Transcranial direct current stimulation of default mode network parietal nodes decreases negative mind-wandering about the past.

• DOI: 10.1007/s10608-019-10044-9
• 发表时间: 2020-02
• 期刊: Cognitive therapy and research
• 影响因子: 2.8
• 作者: Chou T;Hooley JM;Camprodon JA
• 通讯作者: Camprodon JA

Changes in seizure duration during acute course electroconvulsive therapy.

• DOI: 10.1016/j.brs.2021.05.016
• 发表时间: 2021-07
• 期刊: Brain stimulation
• 影响因子: 7.7
• 作者: Luccarelli J;McCoy TH Jr;Seiner SJ;Henry ME
• 通讯作者: Henry ME

Transcranial Direct Current Stimulation to the Left Dorsolateral Prefrontal Cortex Improves Cognitive Control in Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Behavioral and Neurophysiological Study.

• DOI: 10.1016/j.bpsc.2020.11.006
• 发表时间: 2021-04
• 期刊: Biological psychiatry. Cognitive neuroscience and neuroimaging
• 作者: Dubreuil-Vall L;Gomez-Bernal F;Villegas AC;Cirillo P;Surman C;Ruffini G;Widge AS;Camprodon JA
• 通讯作者: Camprodon JA