Functional Architecture of Developmental Brain Disorder

发育性脑障碍的功能结构

• 批准号: 7225508
• 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/7225508
• 关键词: Affect; Anatomy; Architecture; Area; Biochemical; Biological Assay; Brain; Brain Diseases; Brain region; Cerebral cortex; Cerebrum; Choline; Clinical; Complement; Cortical Malformation; Creatine; Data Set; Development; Disease; Disruption; Epilepsy; Failure; Fellowship; Functional Magnetic Resonance Imaging; Genes; Goals; Human; Individual; Institution; Intelligence; Israel; Laboratories; Lead; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Medical center; Mentors; Methods; Molecular Genetics; Motor; Mutation; N-acetylaspartate; Nervous System Physiology; Neurologist; Neuronal Migration Disorder; Neurons; Neurosciences Research; Nodule; Patients; Pattern; Performance; Physiological; Refractory; Research; Research Personnel; Resolution; Role playing therapy; Seizures; Short-Term Memory; Standards of Weights and Measures; Structure; Supervision; Surface; Techniques; Testing; Thick; Training; Ventricular; Visual Perception; base; career; developmental disease; experience; filamin; gray matter; in vivo; interest; migration; neuroimaging; periventricular heterotopia; programs; skills

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）越来越多地被认为是难治性癫痫的常见原因。虽然现在对许多MCDs的遗传和分子基础了解很多，但它们的解剖和功能结构尚未得到充分研究。脑室周围异位是一种多发性硬化症，表现为脑室内的灰质结节错位。这些结节包含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覆盖结节的六层大脑皮层。尽管在解剖结构上发生了这种巨大的变化，但大多数PH患者的智力正常，仅患有癫痫发作。我们假设这些异位灰质结节可以参与生理性脑功能，并且上覆的大脑皮层虽然缺乏完整的神经元，但保留了其通常的区域特异性功能。本研究将采用无创性磁共振成像（MRI）为基础的技术来评估灰质结构和功能的PH受试者。首先，高分辨率MRI的皮质厚度分析将被用来调查解剖灰质的变化，在PH。其次，灰质将在体内使用MR波谱进行生化分析。最后，我们将使用功能性磁共振成像来绘制这种疾病中异位结节和上覆大脑皮层中灰质的激活模式。申请人是一名委员会认证的神经科医生，他还完成了癫痫/EEG研究金。他将在Beth Israel Deaconess Medical Center的两位导师的监督下进行这项研究：该机构神经影像实验室主任Gottfried Schlaug博士和大脑皮质发育领域的专家Christopher沃尔什博士，他在MCDs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。