Neuroanatomical Changes After Ventral Capsulotomy for Intractable OCD: A Translat

描述（由申请人提供）：本研究将首次展示神经回路直接消融干预后连通性的变化。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。本指导患者导向的职业发展奖（K23）关注难治性强迫症（OCD）热包膜切开术后治疗改变的机制。这项研究的重点是一种治疗强迫症的外科手术，这种手术已经使用了几十年，但其作用机制几乎没有被研究过：腹侧囊切开术。从巴特勒医院长期开展的精神神经外科项目中招募24名接受腹膜切除术治疗顽固性强迫症的患者。还将招募24名健康对照参与者。Aim 1使用概率神经束造影衍生的人类神经模型，根据已知的猕猴神经解剖学的组织学数据，来描绘腹侧包膜切开术对严重强迫症的神经解剖学节点和通路的影响。这将为Aim 2产生感兴趣的区域，并将允许分析强迫症腹侧囊切除术前后结构（弥散张量成像）连通性的变化。目的2将检查静息状态和基于任务（反应抑制）的有效连通性在腹侧囊切除术前和后对严重强迫症的影响。这项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和治疗改善之间关系的假设。申请人将获得一个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。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)对神经解剖学的深入理解以及如何将其用于神经影像学分析；2) DTI与MRI连通性数据分析与应用；3)提高申请人对神经精神疾病治疗后治疗改变机制的认识。这个职业发展奖项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。申请人建议在神经影像学、神经解剖学、多元统计和负责任的研究行为方面进行综合培训。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）的空缺。她将获得所需的高级技能，在神经外科手术和其他基于神经回路的干预治疗强迫症及相关疾病后的治疗变化的行为和大脑机制方面进行独立研究。

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.