Translational Research

Absence Epilepsy, Attention and fMRI

PI: Hal Blumenfeld, MD, PhD

Summary: 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.

Bioimaging and Intervention in Neocortical Epilepsy

PI: 

James Duncan, Ph.D. 
Todd Constable, Ph.D. 
Dennis D. Spencer, M.D.

Summary: 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.

Multimodal Clinical Image Co-Registration in Epilepsy

PI: 

Hal Blumenfeld, MD, PhD 

Xenophon Papademetris, PhD

Summary: 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

Computational Neurophysiology Laboratory

PI: Hitten Zaveri, PhD

Summary: 

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:
  • accurately locate the seizure onset area in patients with partial epilepsy
  • detect and predict the onset of seizures and intervene to terminate or abort seizures once they have been detected or predicted

Our work is both highly translational and interdisciplinary. Projects in these various areas are being conducted through collaborations with investigators, in academia and industry, who are trained in, or are being trained in, multiple disciplines including neurology, neurosurgery, neurobiology, neuroscience, lab-medicine, pathology, physiology, biomedical engineering, electrical engineering, material science and mathematics. 
For further information, contact Hitten Zaveri, Ph.D. 
Laboratory Website: https://medicine.yale.edu/labs/cnl

Molecular and Neuropathological Studies of Human Seizure Foci

Functional MRI for Neurosurgical Planning in Epilepsy

PI: Todd Constable, PhD

Summary: Functional MR imaging (fMRI) has the potential to replace, or significantly enhance, the current methods used in Neurosurgical planning. It is noninvasive and has been shown to be able to localize cortical activity.

Energy and Metabolism in Temporal Lobe Epilepsy

PI: 

Xenophon Papademetris, PhD  

Dennis D. Spencer, M.D.

Summary: Energy and Metabolism in Temporal Lobe Epilepsy 

A variety of metabolic imaging studies, including FDG PET and MRS, have suggested metabolic and energy deficiencies in epileptogenic regions of certain symptomatic epilepsies.

Brain Microdialysis and Stimulation in Epilepsy

PI:

Tore Eid, MD, PhD 

Dennis Spencer, M.D. 

Ognen Petroff, M.D. 

Summary: 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.

MR Imaging of Epilepsy

PI: Richard Bronen, M.D.

Summary: This project involves the investigation of MR imaging of epilepsy i.e., MR imaging features of epileptogenic anomalies, with emphasis on cortical dysplasia. Using a systematic approach developed for interpretation of MR scans of seizure patients, we are performing prospective studies that will correlate MR imaging features with clinical and surgical characteristics.

Nuclear Medicine Imaging in Epilepsy

PI: Hal Blumenfeld, MD, PhD

Summary: 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.

PET Imaging of SV2 channels

NeuroPace Responsive Neurostimulator (RNS™) System

PI: Lawrence Hirsch, MD

Summary: 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: CenterWatchNational Library of Medicine.

Seizure Awareness

PI: Hal Blumenfeld, MD, PhD

Summary: 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.

Epileptogenic Tissue Localization using EEG-fMRI

PI:

Todd Constable, Ph.D. 

Hal Blumenfeld, M.D., Ph.D. 

Summary: 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.

Virtual Reality to Test Driving Safety in Epilepsy

PI: Hal Blumenfeld, MD, PhD


Summary: 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.