Neuroanatomical Changes After Ventral Capsulotomy for Intractable OCD: A Translat

描述(由申请人提供)：这项研究将是第一次证明在神经回路直接消融干预后连接性的变化。人们对治疗精神疾病的神经外科的兴趣正在急剧增加。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。这项以患者为导向的指导职业发展奖(K23)专注于热囊切开术治疗顽固性强迫症(OCD)后治疗变化的机制。这项研究的重点是一种持续使用了几十年的强迫症手术程序，但其作用机制实际上仍未被研究：腹侧囊膜切开术。24名因顽固性强迫症接受腹侧囊膜切开术的患者将从巴特勒医院长期的精神神经外科项目中招募。24名健康对照参与者也将被招募。目的1利用概率纤维束造影术建立的人类神经模型，结合已知的猕猴神经解剖学资料，描述严重强迫症腹侧囊膜切开术对神经解剖结节和神经通路的影响。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膜切开术前后结构(扩散张量成像)连接性的变化。目的2将检查静息状态和基于任务(反应抑制)的有效连接性在严重强迫症腹侧截囊手术前后的变化。这项研究代表着一个无与伦比的机会，可以检验计划消融后连接性和治疗改善之间的关系的假设。申请者将获得几乎独特的技能组合，建立在先前的神经心理学任务和形态核磁共振分析知识的基础上。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，以及如何将其用于为神经成像分析提供信息；2)分析和应用DTI和MRI连接数据；以及3)提高申请者对神经精神疾病治疗后治疗变化机制的知识。这一职业发展奖为培训和研究提供了一组丰富的合作者，包括该领域的领先研究人员。申请者建议在神经成像、神经解剖学、多元统计学和负责任的研究指导方面进行全面培训。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。她将获得所需的高级技能，领导对神经外科手术和其他基于神经回路的强迫症及相关疾病干预后治疗变化的行为和大脑机制的独立研究。

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.