Diffeomorphometry applied to functional connectivity in schizophrenia using ultrahigh resolution MRI

使用超高分辨率 MRI 将微分形态测量应用于精神分裂症的功能连接

• 批准号: 10551860
• 负责人: RUSSELL L MARGOLIS
• 金额: $ 24.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-17 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10551860
• 关键词: 3-Dimensional; Address; Affect; Area; Biological Markers; Biology; Brain region; Clinical; Diagnosis; Disease; Family; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Image; Individual; Investigation; Magnetic Resonance Imaging; Major Mental Illness; Measurement; Measures; Medicine; Methods; Monitor; Patients; Pilot Projects; Prevalence; Prognosis; Protocols documentation; Resolution; Rest; Sample Size; Schizophrenia; Signal Transduction; Societies; Specific qualifier value; Structure; Surface; Symptoms; System; Testing; Thalamic structure; Thick; Variant; design; disease classification; frontal lobe; high risk; improved; mathematical methods; method development; novel; patient population; responders and non-responders; standard measure; tool; treatment response; ultra high resolution

Project Summary Schizophrenia is a disorder with a life-time world-wide prevalence of ~0.5% and devastating consequences for affected individuals, their families, and society. Improved understanding of the disruptions in cortical circuitry thought to underlie schizophrenia could go a long way toward addressing challenges in understanding the pathophysiology of schizophrenia, as well as the challenges of improving schizophrenia nosology, diagnosis, and treatment. Our guiding hypothesis is that schizophrenia is a consequence of cortical-cortical and cortical-subcortical functional dysconnectivity, and particularly the circuitry between the thalamus and the cortex. Understanding this dysconnectivity could have profound implications for the field. In this proposal, we will develop a new and potentially power method for the analysis of functional connectivity between thalamic subregions and deep and superficial layers of the cortex, using a sophisticated mathematical approach (diffeomorphometry) to precisely determine the thickness of the cortex at specified regions of the brain. In Aim 1, we will optimize this method for both resting and activated thalamocortical connectivity, using ultra-high field strength (7 Tesla) fMRI. In Aim 2, we will test the protocols developed in Aim 1 in 20 individuals with schizophrenia compared to 20 healthy controls. We will determine if subdividing the cortex using the diffeomorphometric approach will more clearly delineate the dysconnectivity in patients, with the potential benefit that investigations can use smaller sample sizes, and that more subtle clinical factors associated with aberrant connectivity can be discerned. In addition, this improved resolution at the cortex may facilitate more nuanced understanding of the specific thalamic origins of aberrant signals and the differences in dysconnectivity across different cortical layers. Overall, the goal is to establish methods that can be used to further develop functional connectivity as a biomarker useful in nosology and prognosis, and in the prediction and monitoring of treatment response.

项目概要 精神分裂症是一种在全球范围内终生患病率约为 0.5% 且后果严重的疾病 对于受影响的个人、他们的家庭和社会。加深对皮质破坏的理解 被认为是精神分裂症基础的电路可能对解决精神分裂症的挑战大有帮助 了解精神分裂症的病理生理学，以及改善精神分裂症的挑战 疾病分类学、诊断和治疗。我们的指导性假设是精神分裂症是以下原因的结果 皮质-皮质和皮质-皮质下功能失调，特别是大脑皮层之间的电路 丘脑和皮质。理解这种脱节可能对该领域产生深远的影响。 在本提案中，我们将开发一种新的、具有潜在功效的方法来分析功能连接 在丘脑亚区域和皮质的深层和浅层之间，使用复杂的 数学方法（微分形态测量法）精确确定指定位置的皮层厚度 大脑区域。在目标 1 中，我们将针对静息和激活的丘脑皮质优化此方法 连接，使用超高场强（7 特斯拉）fMRI。在目标 2 中，我们将测试开发的协议 目标是每 20 名精神分裂症患者中就有 1 人与 20 名健康对照者进行比较。我们将确定是否细分 使用微分形态测量方法的皮质将更清楚地描绘患者的连接失调， 潜在的好处是研究可以使用较小的样本量，以及更微妙的临床因素 可以辨别与异常连接相关的情况。此外，皮层的分辨率也得到了提高 可能有助于更细致地了解异常信号的特定丘脑起源和 不同皮质层之间的连接失调存在差异。总体而言，目标是建立方法 可用于进一步开发功能连接作为用于疾病学和预后的生物标志物，以及 预测和监测治疗反应。