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. ? ?
| Vernet, Marine; Walker, Linsey; Yoo, Woo-Kyoung et al. (2012) EEG onset of a seizure during TMS from a focus independent of the stimulation site. Clin Neurophysiol 123:2106-8 |
| Stamoulis, Catherine; Gruber, Lawrence J; Schomer, Donald L et al. (2012) High-frequency neuronal network modulations encoded in scalp EEG precede the onset of focal seizures. Epilepsy Behav 23:471-80 |
| Christodoulou, Joanna A; Walker, Linsey M; Del Tufo, Stephanie N et al. (2012) Abnormal structural and functional brain connectivity in gray matter heterotopia. Epilepsia 53:1024-32 |
| Felker, Marcia V; Walker, Linsey M; Sokol, Deborah K et al. (2011) Early cognitive and behavioral problems in children with nodular heterotopia. Epilepsy Behav 22:523-6 |
| Walker, Linsey M; Poduri, Annapurna; Chang, Bernard S (2011) Cerebral volumetric analysis over time in children with malformations of cortical development: a quantitative investigation. J Child Neurol 26:171-8 |
| Selvitelli, Megan F; Walker, Linsey M; Schomer, Donald L et al. (2010) The relationship of interictal epileptiform discharges to clinical epilepsy severity: a study of routine electroencephalograms and review of the literature. J Clin Neurophysiol 27:87-92 |
| Poduri, Annapurna; Chitsazzadeh, Vida; D'Arrigo, Stefano et al. (2010) The syndrome of perisylvian polymicrogyria with congenital arthrogryposis. Brain Dev 32:550-5 |
| Stamoulis, Catherine; Gruber, Lawrence J; Chang, Bernard S (2010) Network dynamics of the epileptic brain at rest. Conf Proc IEEE Eng Med Biol Soc 2010:150-3 |
| Mellado, Cecilia; Poduri, Annapurna; Gleason, Danielle et al. (2010) Candidate gene sequencing of LHX2, HESX1, and SOX2 in a large schizencephaly cohort. Am J Med Genet A 152A:2736-42 |
| Walker, Linsey M; Katzir, Tami; Liu, Tianming et al. (2009) Gray matter volumes and cognitive ability in the epileptogenic brain malformation of periventricular nodular heterotopia. Epilepsy Behav 15:456-60 |
Showing the most recent 10 out of 16 publications
