Our prior investigation of adults with chronic localization-related (temporal lobe) epilepsy and healthy controls has shown childhood onset epilepsy to be associated with a generalized adverse neurodevelopmental impact on brain structure and cognitive function (NS-37738). The purpose of this proposal is to directly characterize the timing, cause and consequences of this adverse neurodevelopmental impact. Using a combined cross-sectional and longitudinal design, 75 children (age 8-18) with new onset localization-related epilepsy will be compared to 75 age and gender matched controls. Cross-sectional and two-year longitudinal assessment of neuropsychological status and neuroimaging (quantitative MRI, diffusion tensor imaging, and magnetization transfer imaging) will be integrated with information regarding neurodevelopmental history, clinical epilepsy characteristics and psychiatric morbidity in order to clarify the timing, etiology and consequences of evident abnormalities in brain structure and cognition. We hypothesize the following: (1) children with new onset localization-related epilepsy will exhibit generalized cognitive impairment, generalized reduction in total brain tissue volumes (especially cerebral white matter volumes), and microstructural abnormalities in cerebral white matter compared to controls, (2) frequency of preexisting neurodevelopmental abnormalities will be significantly increased in children with new onset epilepsy compared to controls and will be associated with neuroimaging and cognitive abnormalities at epilepsy onset, (3) ongoing childhood onset epilepsy will be associated with lags in normal cognitive and brain development (especially cerebral white matter) and increased psychiatric morbidity compared to controls, and (4) earlier age of epilepsy onset will be the strongest predictor of lags in brain growth and cognitive development while seizure severity will be most strongly associated with increased psychiatric morbidity.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1-BDCN-5 (01))
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Fureman, Brandy E
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University of Wisconsin Madison
Schools of Medicine
United States
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Garcia-Ramos, Camille; Dabbs, Kevin; Lin, Jack J et al. (2018) Progressive dissociation of cortical and subcortical network development in children with new-onset juvenile myoclonic epilepsy. Epilepsia 59:2086-2095
Garcia-Ramos, Camille; Dabbs, Kevin; Meyerand, Elizabeth et al. (2018) Psychomotor slowing is associated with anomalies in baseline and prospective large scale neural networks in youth with epilepsy. Neuroimage Clin 19:222-231
Srnka, Kyle; Seidenberg, Michael; Hermann, Bruce et al. (2018) Intraindividual variability in attentional vigilance in children with epilepsy. Epilepsy Behav 79:42-45
Karrasch, Mira; Tiitta, Petri; Hermann, Bruce et al. (2017) Cognitive Outcome in Childhood-Onset Epilepsy: A Five-Decade Prospective Cohort Study. J Int Neuropsychol Soc 23:332-340
Hermann, Bruce; Loring, David W; Wilson, Sarah (2017) Paradigm Shifts in the Neuropsychology of Epilepsy. J Int Neuropsychol Soc 23:791-805
Garcia-Ramos, Camille; Bobholz, Sam; Dabbs, Kevin et al. (2017) Brain structure and organization five decades after childhood onset epilepsy. Hum Brain Mapp 38:3289-3299
Hanson, Melissa; Morrison, Blaise; Jones, Jana E et al. (2017) Control groups in paediatric epilepsy research: do first-degree cousins show familial effects? Epileptic Disord 19:49-58
Garcia-Ramos, C; Song, J; Hermann, B P et al. (2016) Low functional robustness in mesial temporal lobe epilepsy. Epilepsy Res 123:20-8
Garcia-Ramos, Camille; Lin, Jack J; Bonilha, Leonardo et al. (2016) Disruptions in cortico-subcortical covariance networks associated with anxiety in new-onset childhood epilepsy. Neuroimage Clin 12:815-824
Jones, Jana E; Siddarth, Prabha; Almane, Dace et al. (2016) Identification of risk for severe psychiatric comorbidity in pediatric epilepsy. Epilepsia 57:1817-1825

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