Functional Architecture of Developmental Brain Disorder

发育性脑障碍的功能结构

• 批准号: 6915614
• 负责人: Bernard S. Chang
• 金额: $ 16.69万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915614
• 关键词: actin binding protein; aspartate; brain disorders; brain electrical activity; brain metabolism; cell migration; cerebral cortex; choline; clinical research; creatine; developmental disease /disorder; developmental neurobiology; functional magnetic resonance imaging; gene mutation; gray matter; human subject; magnetic resonance imaging; morphometry; neuroanatomy; neurons; neurophysiology; patient oriented research; psychomotor function; short term memory; visual perception

DESCRIPTION (provided by applicant): How do disruptions in human brain development affect the structural and functional organization of the cerebral cortex? Malformations of cortical development (MCDs) are increasingly being recognized as a common cause of refractory epilepsy. Although much is now known about the genetic and molecular basis of many MCDs, their anatomical and functional architecture have not been as well-studied. Periventricular heterotopia (PH) is an MCD in which nodules of misplaced gray matter line the ventricles. These nodules contain neurons which have failed to migrate properly to the brain surface, while other neurons that have successfully migrated form a six-layered cerebral cortex overlying the nodules. Despite this dramatic alteration in anatomy, most patients with PH have normal intelligence and suffer only from seizures. We hypothesize that these heterotopic gray matter nodules can participate in physiological brain function and that the overlying cerebral cortex, although devoid of a full complement of neurons, retains its usual region-specific functionality. This study will employ noninvasive magnetic resonance imaging (MRI)-based techniques to evaluate gray matter structure and function in PH subjects. First, cortical thickness analysis from high-resolution MRI will be used to investigate the anatomical gray matter changes in PH. Secondly, gray matter will be biochemically assayed in vivo using MR spectroscopy. Finally, we will use functional MRI to map the activation patterns of gray matter in both the heterotopic nodules and the overlying cerebral cortex in this disorder. The applicant is a board-certified neurologist who has additionally completed a fellowship in epilepsy/EEG. He will perform this research at Beth Israel Deaconess Medical Center under the supervision of two mentors: Dr. Gottfried Schlaug, director of the Neuroimaging Laboratory at this institution, and Dr. Christopher Walsh, an expert in the field of cerebral cortical development who has extensive experience in the clinical and scientific study of MCDs. By combining training in these two areas, the candidate will gain the experience and skills necessary to transition to an independent career in clinical neuroscience research.

描述（由申请人提供）：人类大脑发育的中断如何影响大脑皮层的结构和功能组织？皮质发育畸形（MCDs）越来越被认为是难治性癫痫的常见病因。虽然现在对许多mcd的遗传和分子基础了解很多，但它们的解剖和功能结构还没有得到很好的研究。脑室周围异位（PH）是一种脑室周围灰质结节错位的MCD。这些结节包含了未能正确迁移到大脑表面的神经元，而其他成功迁移的神经元形成了覆盖在结节上的六层大脑皮层。尽管解剖结构发生了巨大的变化，但大多数PH患者的智力正常，只是癫痫发作。我们假设这些异位灰质结节可以参与生理脑功能，并且其上的大脑皮层虽然缺乏完整的神经元，但仍保留其通常的区域特异性功能。本研究将采用非侵入性磁共振成像（MRI）技术来评估PH受试者的灰质结构和功能。首先，将使用高分辨率MRI的皮质厚度分析来研究ph下灰质的解剖变化。其次，将使用磁共振光谱对灰质进行体内生化分析。最后，我们将使用功能性MRI来绘制这种疾病中异位结节和上覆大脑皮层灰质的激活模式。申请人是一名委员会认证的神经科医生，另外还完成了癫痫/脑电图的研究。他将在Beth Israel Deaconess医疗中心进行这项研究，在两位导师的监督下：该机构神经成像实验室主任Gottfried Schlaug博士和大脑皮层发育领域的专家Christopher Walsh博士，他在mcd的临床和科学研究方面拥有丰富的经验。通过结合这两个领域的培训，候选人将获得过渡到临床神经科学研究独立职业所需的经验和技能。