Stanford Comprehensive Epilepsy Program Research
While each member of our team is involved in various clinical or basic science research projects, there are four active laboratories in the Stanford Comprehensive Epilepsy Program where investigators conduct systematic research. These laboratories are led by four of the faculty members in our program and funded by the National Institute of Health.
Temporal lobe epilepsy is common, frequently refractory to treatment, and devastating to those affected. Our long-term goal is to better understand the pathophysiological mechanisms of this disease so that rational and effective therapies can be developed. We use electrophysiological, molecular, and anatomical techniques to evaluate neuronal circuitry in normal and in epileptic brains.
We are interested in the neuronal mechanisms that underlie synchronous oscillatory activity in the thalamus, cortex and the massively interconnected thalamocortical system. Such oscillations are related to cognitive processes, normal sleep activities and certain forms of epilepsy.
Our approach is an analysis of the discrete components that make up thalamic and cortical circuits, and reconstitution of components into both in vitro biological and in silico computational networks. Accordingly, we have been able to identify genes whose products, mainly ion channels, play key roles in the regulation of thalamocortical network responses.
The general theme of our research is the study of the human brain from clinical and system neuroscience perspective using the tools of intracranial electrocorticography (ECoG), electrical brain stimulation (EBS), and functional imaging (fMRI). The main impetus for our research is to understand the anatomical and physiological signatures of behavioral expression and cognitive experience in humans and how these might be broken in patients with epilepsy. Using our sophisticated research tools, our goal is to help patients with uncontrolled epilepsy to gain seizure freedom without cognitive deficits.
Work in the Prince lab has focused on normal and abnormal regulation of excitability in neurons of mammalian cerebral cortex and thalamus and mechanisms underlying development and prophylaxis of epilepsy in animal models. Long-term goals are to understand how cortical injury and other pathological processes induce changes in structure and function of neurons and neuronal networks that lead to hyperexcitability and epileptogenesis. With this information, it will be possible to devise experimental strategies to prevent the occurrence of epilepsy after cortical injury and eventually apply them to individuals with significant brain trauma. We have already provided a proof in principal that prophylaxis of posttraumatic epilepsy is possible, using a rat model.
Dr. Soltesz's laboratory employs a combination of closely integrated experimental and theoretical techniques, including closed-loop in vivo optogenetics, paired patch clamp recordings, in vivo electrophysiological recordings from identified interneurons in awake mice, 2-photon imaging, machine learning-aided 3D video analysis of behavior, video-EEG recordings, behavioral approaches, and large-scale computational modeling methods using supercomputers. He is the author of a book on GABAergic microcircuits (Diversity in the Neuronal Machine, Oxford University Press), and editor of a book on Computational Neuroscience in Epilepsy (Academic Press/Elsevier). He co-founded the first Gordon Research Conference on the Mechanisms of neuronal synchronization and epilepsy, and taught for five years in the Ion Channels Course at Cold Springs Harbor. He has over 30 years of research experience, with over 20 years as a faculty involved in the training of graduate students (total of 16, 6 of them MD/PhDs) and postdoctoral fellows (20), many of whom received fellowship awards, K99 grants, joined prestigious residency programs and became independent faculty.