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: 10348847
• 负责人: RUSSELL L MARGOLIS
• 金额: $ 22.02万
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10348847
• 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; Life; 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; Time; 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

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.

项目摘要 精神分裂症是一种疾病，全世界的患病率为〜0.5％，造成毁灭性后果 对于受影响的个人，他们的家人和社会。对皮质干扰的理解有所改善 被认为是精神分裂症基础的巡回赛可能有很长的路要走 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，诊断和治疗。我们的指导假设是精神分裂症是 皮质皮质和皮质皮质功能障碍性，尤其是在 丘脑和皮质。了解这种障碍性可能会对该领域产生深远的影响。 在此提案中，我们将开发一种新的且潜在的功能方法来分析功能连接性 在丘脑子区域和皮质的深层和浅层层之间，使用复杂的 数学方法（差异法）准确地确定指定的皮质的厚度 大脑区域。在AIM 1中，我们将针对休息和激活的丘脑皮质优化此方法 连通性，使用超高场强度（7特斯拉）fMRI。在AIM 2中，我们将测试开发的协议 与20个健康对照相比，20个精神分裂症患者中有1个。我们将确定是否细分 使用差异计量学方法的皮质将更清楚地描述患者的障碍性， 潜在的好处是，调查可以使用较小的样本量，并且更细微的临床因素 与异常连通性相关联。另外，这种改进的皮质分辨率 可能会促进对异常信号的特定丘脑起源的更细微的理解和 不同皮层层之间的逆连接性差异。总体而言，目标是建立方法 可以用来进一步发展功能连通性，作为一种在牙质学和预后中有用的生物标志物，以及 在预测和监测治疗反应中。