Epilepsy is a disorder characterized by recurrent unprovoked seizures and affects over 50 million people worldwide. For many patients the seizures are not controlled by currently available medical therapies. Treatment options for these patients include epilepsy surgery, vagus nerve stimulation, and brain stimulation. Advances in neuroengineering have lead to implantable devices that target specific neurological disease; and epilepsy is one of the most active areas with two 1st generation stimulation devices recently proven in clinical trials. Results from brain stimulation trials using 1st generation devices have demonstrated excellent safety, but improvements in efficacy are needed.
MSEL is exploring many facets of epilepsy spanning:

  1. Development of epilepsy in animal models (Epileptogenesis).
  2. Spatial localization of epileptic brain using electrophysiology and multi-modal imaging.
  3. The transition from normal brain activity to seizures (Ictogenesis) in human and animal models of epilepsy.
  4. Seizure forecasting.
  5. Diagnostic and therapeutic brain stimulation.

Recorded microseizure density
Gamma HFOs following picture presentation

Multi-scale Electrophysiology

MSEL has pioneered in the area of wide-bandwidth, high spatial resolution human brain electrophysiology. This research has focused on novel electrophysiological biomarkers (microseizures & pathological high frequency oscillations) of epileptic networks present at sub-millimeter spatial scales that are not detected with narrow bandwidth clinical recording technologies. In particular, we are using quantitative tools to analyze the spatial-temporal dynamics of putative pathological signatures of epileptic brain (microseizures, high frequency oscillations, ultraslow/DC potentials, and epileptiform spikes).

Electrophysiological Biomarkers

In a recent series of articles in Biomarkers Medicine the topic of epilepsy biomarkers was reviewed [1]. The NIH defines a biomarker as an objectively measured characteristic of a normal or pathological biological process, such as blood sugar in diabetes and prostate-specific antigen in prostate cancer. A surrogate biomarker is defined as an indirect measure of disease presence or progression. Emerging evidence from multiple laboratories indicated that pathological high frequency oscillations ( [2], [3], [4], [5] ) and microdoman seizures ( [6], [7] ) are potential biomarkers of epileptogenic brain.

MSEL is currently investigating a range of electrophysiological biomarkers of normal and epileptic brain to understand and track the process by which normal brain evolves into epilepsy (epileptogenesis) and normal brain activity spontaneously transitions to seizure activity (ictogenesis).

Multimodality Imaging

Multi-modality neuroimaging is used for functional characterization and precise anatomic localization. Identification of seizure-generating brain tissue using ictal SPECT, PET, structural and functional MRI and CT imaging is performed using advanced image processing methods including Statistical Parametric Mapping and Freesurfer. Functional imaging is used to Localization of intracranial electrodes in stereotactic and conventional intracranial EEG implantation is performed using high-resolution MRI and CT imaging.

Electrophysiology and Stimulation for Human Memory

From the DARPA RAM website:

"Through the Restoring Active Memory (RAM) program, DARPA seeks to accelerate the development of technology able to address this public health challenge and help service members and others overcome memory deficits by developing new neuroprosthetics to bridge gaps in the injured brain. The end goal of RAM is to develop and test a wireless, fully implantable neural-interface medical device for human clinical use, but a number of significant advances will be targeted on the way to achieving that goal."

RAM is part of a broader portfolio of programs within DARPA that support President Obama's BRAIN initiative. MSEL is one of 10 participating sites (Columbia, Dartmouth, Emory, Medtronic, NINDS, Thomas Jefferson, UT-Southwestern, University of Washington) all of which are coordinated by Dr. Michael Kahana and his team at University of Pennsylvania.

Gamma HFOs following picture presentation

Brain Stimulation Diagnostics and Therapeutics

This project is a collaboration with ICRC to advance the science and clinical translation of Brain Stimulation Theranostics for Neurological Disease. We are investigating Stimulation-Response using trans-cranial stimulation and direct electrical stimulation combined with scalp and intracranial EEG.