Brain Correlates of Self-Focused Processing as a Biomarker of Treatment Response

大脑与自我聚焦处理的相关性作为治疗反应的生物标志物

• 批准号: 9178258
• 负责人: Angela Fang
• 金额: $ 17.23万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9178258
• 关键词: Address; Advisory Committees; Algorithms; Anterior; Anxiety; Area; Attention; Behavioral; Belief; Biological Markers; Body Dysmorphic Disorder; Brain; Classification; Clinical; Cognitive; Cognitive Therapy; Data; Data Analyses; Development; Diagnosis; Dimensions; Disease; Eating; Ensure; Event; Feeling; Formulation; Functional Magnetic Resonance Imaging; Future; Goals; Health Care Costs; Image; Impaired cognition; Individual; Individual Differences; Intervention; Link; Maps; Measures; Mental Depression; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; National Institute of Mental Health; Neurosciences; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Outcomes Research; Pathology; Patients; Plague; Predictive Value; Prefrontal Cortex; Process; Psychotherapy; Recruitment Activity; Response Latencies; Rest; Sampling; Scanning; Scientist; Social Environment; Statistical Methods; Surrogate Markers; Symptoms; Task Performances; Techniques; Testing; Thinking; Training; Treatment outcome; Work; anxiety symptoms; base; behavior measurement; career development; cingulate cortex; connectome; design; indexing; neural circuit; neural correlate; neuroimaging; personalized medicine; physical state; predict clinical outcome; predictive of treatment response; relating to nervous system; response; response biomarker; social anxiety; success; trait; treatment planning; treatment response

First-line interventions for psychiatric disorders do not work for everyone and factors impacting treatment response are poorly understood. There is a clear need to identify reliable predictors of treatment response in order to optimize treatment outcomes, provide more targeted referrals, and reduce healthcare costs. Neuroimaging-based predictors of treatment response offer better predictive utility than clinical variables alone, yet these predictors are largely lacking. This 5-year mentored patient-oriented research career development award will address this need. Specifically, this project will test the hypothesis that individual differences in maladaptive self-focused processing predict treatment response and that neuroimaging-based markers are better predictors than behavioral ones. Each aim of the study corresponds to specific training goals, which will map onto competency in four main areas: (1) fMRI neuroimaging techniques in terms of event-related design, image acquisition, and data analysis, (2) neuroscience-informed treatment outcome research, (3) statistical methods involving multidimensional classification, and (4) career development. Such training will transform the applicant into an independent translational clinical scientist who examines the neural basis of cognitive dysfunction in anxiety and obsessive-compulsive spectrum disorders to inform personalized formulations of pathology and aid in individual treatment decisions. Training goals will be implemented with the expert guidance of Dr. Sabine Wilhelm (primary mentor), Dr. Dara Manoach (co-mentor), and the advisory team consisting of Drs. Luan Phan, Jamie Feusner, and Mark Vangel. First, we propose to identify the neural correlates of self-focused processing. We will assess baseline resting state connectivity within the default network, as well as regional brain activation using a well-validated event-related fMRI task that manipulates self-focused processing in patients with body dysmorphic and socially anxious symptoms, compared to healthy controls. We selected this clinical sample because such patients display heightened self-focused attention, and sampling individuals across these symptom dimensions will ensure greater variability on this dimension of maladaptive self-focused processing. Second, we will examine the neural correlates of self-focused processing as a predictor of treatment response. Neuroimaging data will be acquired from patients with body dysmorphic and socially anxious symptoms during two scan sessions, before and after 12 weeks of individual cognitive- behavioral therapy, and compared with healthy controls scanned twice at a 12-week interval. Finally, we will compare the prediction of treatment response between neural measures and behavioral measures of self- focused processing. We will assess the behavioral correlates of self-focused processing using a self-reference effect paradigm, and assess their relation to treatment response. If our hypotheses are borne out, we will have new targets for treatment, a method to identify promising candidates for treatment, and sensitive surrogate markers of treatment response.

精神疾病的一线干预措施对每个人都无效，影响治疗的因素 回应知之甚少。显然需要确定可靠的治疗反应预测指标 为了优化治疗结果，提供更多针对性的转诊并降低医疗费用。 基于神经成像的治疗反应预测指标可提供比仅临床变量更好的预测效用， 然而，这些预测因素在很大程度上缺乏。这项为期5年的指导以患者为导向的研究职业发展 奖项将满足这种需求。具体而言，该项目将检验以下假设 适应不良的自我关注的处理预测治疗反应，基于神经影像学的标记是 比行为的预测因子更好。研究的每个目标都对应于特定的培训目标，这将 在四个主要领域的能力上映射：（1）fMRI神经影像学技术在与事件相关的设计方面， 图像采集和数据分析，（2）神经科学知识的治疗结果研究，（3）统计 涉及多维分类和（4）职业发展的方法。这样的培训将改变 申请人进入独立的翻译临床科学家，他检查了认知的神经基础 焦虑和强迫症的功能障碍，以告知个性化的表述 病理学和帮助个人治疗决策。培训目标将与专家实施 Sabine Wilhelm博士（小学导师），Dara Manoach博士（Co-Incertor）和咨询团队的指导 由Drs组成。 Luan Phan，Jamie Feusner和Mark Vangel。首先，我们建议识别神经 相关的自我关注处理。我们将评估默认的基线静止状态连接 网络，以及使用验证良好的事件相关的fMRI任务来操纵的区域大脑激活 与健康相比 控件。我们之所以选择此临床样本，是因为此类患者表现出更高的自我关注，并且 对这些症状维度进行抽样个人将确保在此维度上更大的可变性 适应不良的自我关注的处理。其次，我们将检查自我关注处理的神经相关性 作为治疗反应的预测指标。神经影像学数据将从身体畸形患者中获取 在两次扫描课程中，在个人认知12周之前和之后出现社会焦虑的症状 - 行为疗法，并与健康对照组以12周的间隔进行了两次扫描。最后，我们会的 比较神经测量和自我行为度量之间治疗反应的预测 集中处理。我们将使用自我参考评估自我关注处理的行为相关性 影响范式，并评估其与治疗反应的关系。如果我们的假设得到了证实，我们将有 治疗的新目标，一种确定有希望的治疗候选者的方法和敏感的替代品 治疗反应的标记。