Neuroanatomical Changes After Ventral Capsulotomy for Intractable OCD: A Translat

描述（由申请方提供）：本研究将首次证明神经回路直接消融干预后连接性的变化。对精神疾病的神经外科手术的兴趣正在急剧增加。立体定向消融和脑深部电刺激（DBS）的对照试验正在进行中。然而，这些疗法背后的行为和大脑机制的知识仍然有限。这个指导以病人为导向的职业发展奖（K23）的重点是热囊切开术治疗顽固性强迫症（OCD）后的治疗变化的机制。这项研究的重点是一种持续使用了几十年的强迫症手术，但其作用机制仍然几乎没有研究：腹侧囊切开术。从巴特勒医院长期的精神神经外科项目中招募24名因顽固性强迫症接受腹侧囊切开术的患者。还将招募24名健康对照参与者。目的1使用概率纤维束成像衍生的人类神经模型，从组织学数据已知的猕猴神经解剖学，描绘神经解剖学节点和路径腹侧囊切开术严重强迫症的影响。这将生成目标2的感兴趣区域，并将允许分析OCD腹侧囊切开术前后的结构（扩散张量成像）连通性变化。目的2将检查静息状态和基于任务（反应抑制）的有效连接变化前和后腹侧囊切开术的严重强迫症。本研究提供了一个无与伦比的机会来检验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，建立在神经心理学任务和形态测量MRI分析的先验知识基础上。为了实现在这一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将其用于神经影像学分析; 2）分析和应用DTI和MRI连接数据; 3）提高申请人对神经精神疾病治疗后治疗变化机制的认识。这个职业发展奖提供了丰富的合作者，在这个领域的领先研究人员，培训和研究。申请人建议在神经影像学、神经解剖学、多元统计学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，以填补一个领域（介入神经科学），这是大大扩大利基。她将获得领导对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行为和大脑机制的独立研究所需的高级技能。

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.