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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS049159-03
Application #
7058331
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fureman, Brandy E
Project Start
2004-07-01
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$166,857
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
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