Neuroanatomical Changes After Ventral Capsulotomy for Intractable OCD: A Translat

顽固性强迫症腹膜切开术后的神经解剖学变化：翻译

• 批准号: 8978342
• 负责人: NICOLE CR MCLAUGHLIN
• 金额: $ 18.52万
• 依托单位: BUTLER HOSPITAL (PROVIDENCE, RI)
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-09 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8978342
• 关键词: Ablation; Affect; Aftercare; Animals; Anisotropy; Anterior; Area; Behavior; Behavioral; Behavioral Mechanisms; Biological Neural Networks; Brain; Brain Diseases; Corpus striatum structure; Critiques; Data; Deep Brain Stimulation; Development; Devices; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Electric Stimulation; Excision; Fiber; Goals; Health; Health Benefit; Hospitals; Human; Image; Internal Capsule; Intervention; K-Series Research Career Programs; Knowledge; Lateral; Lead; Lesion; Macaca; Magnetic Resonance Imaging; Magnetism; Maps; Measures; Medial; Mediating; Mental disorders; Mentors; Modeling; Mood Disorders; Neuroanatomy; Neurosciences; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Operative Surgical Procedures; Participant; Pathway interactions; Patients; Perception; Population; Prefrontal Cortex; Public Health; Reaction Time; Recruitment Activity; Reporting; Research; Research Personnel; Research Training; Rest; Severities; Signal Transduction; Site; Stroke; Symptoms; Task Performances; Testing; Thalamic structure; Therapeutic; Training; Travel; Treatment outcome; Ventral Striatum; ablative procedure; anxiety-related disorders; base; control trial; conventional therapy; experience; frontal lobe; healthy volunteer; improved; individualized medicine; interest; neural model; neuroimaging; neuromechanism; neuropsychiatric disorder; neuropsychological; neurosurgery; next generation; novel; outreach; patient oriented; programs; response; responsible research conduct; skills; social stigma; statistics; symptomatic improvement

DESCRIPTION (provided by applicant): This study will be the first demonstration of changes in connectivity following a direct ablative intervention in neurocircuitry. Interest in neurosurger for psychiatric illness is increasing dramatically. Controlled trials of stereotactic ablation and deep brain stimulation (DBS) are underway. However, knowledge of behavioral and brain mechanisms underlying these therapies remains limited. This Mentored Patient-Oriented Career Development Award (K23) focuses on mechanisms of therapeutic change after thermocapsulotomy for intractable obsessive-compulsive disorder (OCD). The research focuses on a surgical procedure that has continued in use for decades for OCD, but whose mechanisms of action remain virtually unstudied: ventral capsulotomy. Twenty-four patients undergoing ventral capsulotomy for intractable OCD will be recruited from the longstanding psychiatric neurosurgery program at Butler Hospital. Twenty-four healthy control participants will also be recruited. Aim 1 uses probabilistic tractography-derived human neural models, informed by known macaque neuroanatomy from histological data, to delineate neuroanatomical nodes and pathways affected by ventral capsulotomy for severe OCD. This will generate regions of interest for Aim 2, and will allow for analysis of changes in structural (diffusion tensor imaging) connectivity pre- and post- ventral capsulotomy for OCD. Aim 2 will examine resting state and task-based (response inhibition) effective connectivity changes pre- and post-ventral capsulotomy for severe OCD. This study represents an unparalleled opportunity to test hypotheses of the relationship between connectivity and therapeutic improvement after a planned ablation. The applicant will obtain a virtually unique combination of skills, building on prior knowledge of neuropsychological tasks and morphometric MRI analysis. To achieve the goal of conducting independent research in this area, the K23 training plan will emphasize 1) an in-depth understanding of neuroanatomy and how it can be used to inform neuroimaging analysis; 2) analysis and application of DTI and MRI connectivity data; and 3) advancing the applicant's knowledge of mechanisms of therapeutic change after treatments for neuropsychiatric disorders. This career development award provides a rich set of collaborators, with leading researchers in this field, for both training and research. The Applicant proposes comprehensive training in neuroimaging, neuroanatomy, multivariate statistics, and responsible research conduct. She is seeking to be trained to fill a niche in an area (interventional neuroscience) that is greatly expanding. She will acquire advanced skills needed to lead independent research on behavioral and brain mechanisms of therapeutic change after neurosurgery and other neurocircuitry-based interventions for OCD and related disorders.

描述（由申请人提供）：这项研究将首次证明神经回路直接消融干预后连接性的变化。人们对神经外科医生治疗精神疾病的兴趣正在急剧增加。立体定向消融和深部脑刺激（DBS）的对照试验正在进行中。然而，对这些疗法背后的行为和大脑机制的了解仍然有限。这项以患者为导向的职业发展奖（K23）重点关注顽固性强迫症（OCD）热囊切开术后治疗变化的机制。这项研究的重点是一种几十年来一直用于治疗强迫症的外科手术，但其作用机制实际上尚未被研究：腹侧囊切开术。巴特勒医院长期的精神科神经外科项目将从中招募 24 名因顽固性强迫症而接受腹侧囊切开术的患者。还将招募二十四名健康对照参与者。目标 1 使用概率纤维束成像衍生的人类神经模型，根据组织学数据中已知的猕猴神经解剖学信息，描绘受严重强迫症腹侧囊切开术影响的神经解剖学节点和通路。这将为目标 2 生成感兴趣区域，并允许分析强迫症腹侧囊切开术前后结构（扩散张量成像）连接的变化。目标 2 将检查严重强迫症腹侧囊切开术前后静息状态和基于任务（反应抑制）的有效连接变化。这项研究提供了一个无与伦比的机会来测试计划消融后连通性与治疗改善之间关系的假设。申请人将获得几乎独特的技能组合，以神经心理学任务和形态测量 MRI 分析的先验知识为基础。为了实现在该领域进行独立研究的目标，K23培训计划将强调：1）深入了解神经解剖学以及如何利用它来指导神经影像分析； 2）DTI和MRI连通性数据的分析与应用； 3) 增进申请人对神经精神疾病治疗后治疗变化机制的了解。该职业发展奖为培训和研究提供了丰富的合作者，包括该领域的领先研究人员。申请人提出在神经影像学、神经解剖学、多元统计和负责任的研究行为方面进行全面的培训。她正在寻求接受培训，以填补一个正在大幅扩张的领域（介入神经科学）的空白。她将获得在针对强迫症和相关疾病进行神经外科手术和其他基于神经回路的干预措施后领导行为和大脑治疗改变机制的独立研究所需的高级技能。