William Nobis, M.D., Ph.D.

Assistant Professor of Neurology

VKC Faculty

Overview of Interests

Dr. Nobis' research program focuses on the most common cause of mortality in refractory epilepsy patients -- sudden unexplained death in epilepsy (SUDEP) and the most common reason for poor quality of life -- the psychiatric comorbidities associated with epilepsy. Epilepsy is a complex neurological disorder that encompasses more than simply repeated seizures and requires a multidisciplinary approach to make scientific advances.

Epilepsy is very often associated with neurodevelopmental disorders. Cognitive decline, psychiatric comorbidities, altered stress responses, and alterations in the autonomic nervous system are all found in patients with epilepsy, neurodevelopmental disorders and in animal models of these pathologies. This suggests circuit alterations and neural adaptations that include not only higher order structures such as hippocampus and cortex that are traditionally thought of as seizure initiation zones, but also brain regions that are interconnected with stress pathways and implicated in the development of mood disorders and autonomic nervous system control. Epilepsy is a common comorbidity in a number of intellectual and developmental syndromes, many of which are associated with neuropsychiatric disease and autonomic nervous system abnormalities.

Dr. Nobis' recent work studying a Dravet Syndrome rodent model, a developmental disorder characterized by multiple neuropsychiatric comorbidities and intractable epilepsy, found altered excitability in neurons of the extended amygdala, including those that project to the brainstem. These alterations could potentially be driving comorbid aspects of DS outside of seizures, including mood disorders, feeding, cardiac and respiratory dysfunction, and risk for sudden death. The extended amygdala is uniquely situated to critically influence both cardiac and respiratory function during seizures, and arousal after a seizure. This brain region is also implicated in stress response and the development of mood disorders, suggesting that alterations here could be responsible for development of other comorbidities seen in epilepsy and other neurodevelopmental disorders. There is currently very limited research in the context of epilepsy in these brain regions and little research in the role of epilepsy, seizures, and seizure-driven changes in brain circuits in the development of such comorbidities in neurodevelopmental disorders.

Dr. Nobis' research program will investigate alterations in these regions and the larger circuits and provide insights into mechanisms of autonomic nervous system dysfunction in seizures, mood disorders, involvement of stress in epilepsy and developmental disorders and epilepsy and cognitive decline in neurodevelopmental disorders.