Epilepsy and EEG

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This project is a prospective multimodal outcome study funded by NIH and based at Yale which includes 6 other sites, and follows the seizure, quality of life, cognitive and psychiatric outcomes of respective epilepsy surgery with standard interventions and instruments to measure those aspects of patient response. Ongoing analyses will focus on the interplay between these outcomes, predictors of outcomes, differences in procedures involving various cerebral locations, and other questions that can be addressed using this remarkable database. Individual diagnostic methods, for example MRI with standardized interpretation, or SPECT with ictal injection and co-registration and subtraction processing are part of the diagnostic evaluation, and their interpretation, inter-rater reliability, correlation with other localizing studies, and predictive value for pathology and outcome can be examined in this large contemporary surgical population.

We are engaged in a longitudinal study of children with newly diagnosed epilepsy, started in 1993. The first phase of the study concerned the prediction of remission, relapse, and intractability early in the course of the disorder. We have addressed several issues concerning the mid-term (5-10 years) seizure outcomes, mortality, status epilepticus, developmental and educational outcomes. We hope to provide information regarding: occurrence of later-appearing intractable epilepsy and the association with hippocampal volumetric measurements. We recently published a paper on the social, educational, behavioral, psychiatric and quality of life outcomes in young adults with childhood onset epilepsy related to seizure outcome. This information will be central to informing evaluation, treatment, management, and counseling approaches for children with epilepsy and their families.

The research efforts of the Computational Neurophysiology Laboratory (CNL) at Yale University broadly involve functional neurosurgery, cognitive neuroscience, and monitoring in OR and NICU settings. The primary focus of our research is to improve our understanding of epilepsy and the control of seizures. In our work on epilepsy we seek to:

• Understand how seizure are generated
• Improve our methodology for sensing, analyzing and controlling aberrant brain activity
• Employ our knowledge of seizure generation, sophisticated continuous brain sensing methods, and advanced computational methods to:

NeuroPace Responsive Neurostimulator (RNS™) System
The Yale Epilepsy Program is participating in a clinical trial of responsive electrical stimulation of the brain as a treatment for intractable partial epilepsy using an implanted medical device. NeuroPace, Inc. is sponsoring this investigational device study of their Responsive Neurostimulator (RNS™) system. The NeuroPace RNS™ is designed to detect abnormal electrical activity in the brain and to deliver small amounts of electrical stimulation to suppress seizures before there are any seizure symptoms. The study is open to patients 18 years of age or older with partial onset seizures that are resistant or hard to treat using two or more antiepileptic medications. Candidates will continue to receive their epilepsy medications while participating in the trial.
Additional links: CenterWatch, National Library of Medicine.

This proposal is aimed at further developing and understanding combined electroencephalography and functional magnetic resonance imaging (EEG-fMRI). The experiments are designed to improve our understanding of the relationship between MR measures of neuronal activity in the presence of epileptiform activity, and neuronal signatures of activity based on surface or depth recorded EEG.

Magnetic resonance functional and spectroscopic imaging (fMRI, MRS) of the brain provides tremendous opportunities in the study and treatment of epilepsy. We will develop high resolution MRS and fMRI at 4T and advanced analysis and integration methods to better define the epileptogenic tissue and surrounding regions, and enhance our understanding of the biochemical mechanisms underlying the dysfunction in neocortical epilepsy.

Xenophon Papademetris, PhD
Dennis D. Spencer, M.D.

BioImage Suite is an integrated image analysis software suite developed at Yale. It uses a combination of C++ and Tcl in the same fashion as that pioneered by the Visualization Toolkit (VTK) and it leverages both VTK and the Insight Toolkit. It has extensive capabilities for both neuro/cardiac and abdominal image analysis and state of the art visualization.
Additional Links:Yale Bioimage Suite

Major goal in our laboratory is to elucidate the neurochemical mechanisms underlying epilepsy using brain microdialysis, intracranial electrode recording and stimulation in conscious neurosurgical epilepsy patients. We are also interested in the neurochemical and electrophysiological changes during cognitive processing, sleep, and in the effects of sex steroids on brain neurochemistry. HPLC is used to analyze the microdialysate samples obtained from the human brain for several neurotransmitters and neurometabolites. Another line of research is to study the effects of direct brain stimulation on neurotransmitter dynamics and brain excitability in order to develop better treatments for brain disorders such as refractory epilepsy and depression. The work involves close collaboration between the departments of neurosurgery, neurology and psychiatry.

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This study aims to examine the extent to which epilepsy patients are aware of their seizures as well as describe factors that account for differences in seizure recall and reporting observed across patients. Included among these factors are seizure type, hemisphere and lobe of origin, and impairment of consciousness. Determining the relationship between these factors and seizure reporting will help to determine the accuracy of patient self-reporting, which will in turn assist in treatment of epilepsy.

The mechanisms for impaired attention in absence epilepsy are not known. To determine how human brain networks are affected by absence seizures we perform simultaneous fMRI and EEG recordings in patients during absence seizures. We explore which regions are involved in maintaining human consciousness by examining the areas of the brain that are impaired during seizures. We also make recordings during normal human consciousness, which allows us to investigate how and where the brain moderates’ changes in attention, in both the short and long term. The aim of this work is to gain a better and more complete understanding of the mechanisms of normal and impaired attention in humans.

Our research study uses virtual reality driving simulation during video/EEG monitoring to learn more about driving safety in patients with epilepsy. One of the most devastating aspects of epilepsy is its effects on patients’ ability to drive. Some suffer motor vehicle accidents when they have seizures, and many others are prevented from driving for months or years at a time by state laws, doctors’ advice or fear of crashing. Given the risks, patients who show signs of epilepsy in EEG monitoring, but have had no seizures for a while, are not allowed to drive. The goal of our research is to determine how epileptic seizures affect driving performance, and to learn which brain regions lead to impaired driving safety during and following seizures. We are also examining whether we can predict the severity of patient’s seizures from their EEG recordings, allowing us to explore what types of seizures lead to impaired behavior. Our hope is that this research will provide useful information for clinicians when discussing driving risk with their patients. Knowledge of the brain networks affected when driving safety is impaired can also lead to treatments which prevent this problem. This will enhance safety, prevent injuries, and improve the quality of life for patients with epilepsy by providing clarity on risks associated with their condition.

Our nuclear imaging analysis team has developed novel methods for analyzing single photon emission computed tomography (SPECT) and positron emission tomography (PET) images in epilepsy patients. Improved methods of analyzing blood flow during seizures with SPECT has helped pinpoint seizure onset for surgical planning. The latest method developed by our group is Ictal-interictal SPECT Analyzed by SPM (ISAS). In addition, our group has developed novel methods for detecting the uncoupling of blood flow and metabolism in seizure generating regions of the brain using SPECT/PET ratio imaging.

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What changes in the brain’s activity cause a person to have a seizure? Our research using high field fMRI, electrophysiology, and behavioral data from animal models aim to shed light on this critical question. We look at activity in cortical and subcortical networks around and during multiple types of generalized seizure, and identify specific neuronal populations and patterns of activity that cause the behavioral symptoms of epilepsy. Highlighting these cells, and the intracellular components that dictate their activity, is crucial for understanding the mechanisms by which seizures are generated, and for the development of targeted therapies with better efficacy and fewer side effects.
For further information, contact Hal Blumenfeld, M.D., Ph.D.

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Focal seizures with impaired consciousness critically reduces quality of life in patients with temporal lobe epilepsy. Using an animal model, we aim to determine how focal seizures affect the brain networks and neuronal mechanisms causing impaired consciousness. Using various techniques such as electrophysiology recording, optogenetic, imaging or neuroanatomical tracing our research presents functional and anatomical evidence that focal seizures initiated from the hippocampus may lead to subcortical arousal inhibition that contributes to cortical depression. Understanding the neuronal networks for impaired consciousness in focal seizures may lead to more therapeutic options to treat this disorder. For further information, contact Hal Blumenfeld, M.D., Ph.D.

The sudden and unexpected impairments in conscious awareness during and following seizures has a major negative impact on quality of life for patients with epilepsy. Recent clinically-applicable techniques in neuromodulation, such as deep brain stimulation (DBS) and responsive neurostimulation, provide a unique opportunity to reverse or prevent impairments in consciousness associated with seizures. Disorders of consciousness other than epilepsy have long been known to arise from dysfunction of subcortical-cortical arousal circuits. Recent research has shown that transient impaired consciousness in temporal lobe epilepsy also depends on subcortical-cortical arousal, including intralaminar thalamic nuclei. Translational studies further demonstrate depressed intralaminar thalamic function in limbic seizures and thalamic stimulation has the potential to restore physiological and behavioral arousal in the ictal and postictal periods. We continue to research novel sites for intracranial stimulation to reverse or prevent loss of consciousness associated with the ictal and post-ictal periods with combined techniques in electrophysiology, functional neuro-imaging, and behavioral testing. These translational research projects support on-going efforts to investigate the effects of neurostimulation to prevent loss of consciousness in humans through clinical trials.