Neuroanatomical Changes After Ventral Capsulotomy for Intractable OCD: A Translat

项目摘要/摘要：这项研究将是在以下情况下连接变化的首次演示 神经回路的直接消融干预。对神经外科治疗精神疾病的兴趣与日俱增 戏剧性的。立体定向消融和脑深部刺激(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 以患者为导向的指导职业发展奖(K23)关注治疗变化的机制 热囊切开术治疗顽固性强迫症(OCD)后。这项研究的重点是一个 几十年来一直用于强迫症的外科手术，但其作用机制仍然存在 几乎没有研究：腹侧囊膜切开术。腹侧囊膜切开术治疗顽固性白内障24例 强迫症将从巴特勒医院长期的精神神经外科项目中招募。二十四岁 健康对照参与者也将被招募。目标1使用概率纤维束造影术衍生的人类神经 根据已知的猕猴神经解剖学从组织学数据中获得信息的模型，以描绘神经解剖 严重强迫症腹侧囊膜切开术对结节和通路的影响这将生成感兴趣的区域 目标2，并将能够分析结构(扩散张量成像)连通性在治疗前后的变化 腹侧囊膜切开术治疗强迫症目标2将检查静息状态和基于任务(反应抑制)的有效性 严重强迫症腹侧截囊前后连接性改变。这项研究代表了一个 无与伦比的机会来检验关于连接和治疗之间关系的假设 经过有计划的消融后情况有所改善。申请者将获得几乎独特的技能组合，构建 关于神经心理任务和形态核磁共振分析的先验知识。实现…的目标 在这一领域进行独立研究，K23培训计划将强调1)深入 了解神经解剖学，以及如何将其用于神经成像分析；2)分析和 DTI和MRI连通性数据的应用；以及3)提高申请者对 神经精神障碍治疗后的治疗变化。这个职业发展奖提供了一个 丰富的合作者，以及该领域的领先研究人员，用于培训和研究。申请人 建议在神经成像、神经解剖学、多元统计学和责任感方面进行全面培训 研究行为。她正在寻求接受培训，以填补一个领域(介入神经科学)的空缺 极大地扩张。她将获得所需的高级技能来领导关于行为和 神经外科手术和其他基于神经回路的干预措施后治疗变化的脑机制 强迫症及相关疾病。

Project Summary/Abstract: This study will be the first demonstration of changes in connectivity following a direct ablative intervention in neurocircuitry. Interest in neurosurgery 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.