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 led to implantable devices that target specific neurological disease; and epilepsy is one of the most active areas with two first-generation stimulation devices recently proven in clinical trials. Results from brain stimulation trials using first-generation devices have demonstrated excellent safety, but improvements in efficacy are needed.
The Bioelectronics Neurophysiology and Engineering Lab is exploring many facets of epilepsy spanning:
- Development of epilepsy in animal models (epileptogenesis)
- Spatial localization of epileptic brain using electrophysiology and multimodal imaging
- The transition from normal brain activity to seizures (ictogenesis) in human and animal models of epilepsy
- Seizure forecasting
- Diagnostic and therapeutic brain stimulation
The Bioelectronics Neurophysiology and Engineering Lab has pioneered in the area of wide-bandwidth, high spatial resolution human brain electrophysiology. This research has focused on novel electrophysiological biomarkers (microseizures and pathological high-frequency oscillations) of epileptic networks present at submillimeter 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).
In a recent series of articles in Biomarkers in Medicine, the topic of epilepsy biomarkers was reviewed (1). The National Institutes of Health (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 indicates that pathological high-frequency oscillations (2), (3), (4), (5) and microdomain seizures (6), (7) are potential biomarkers of epileptogenic brain.
The Bioelectronics Neurophysiology and Engineering Lab 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 neuroimaging is used for functional characterization and precise anatomic localization. Identification of seizure-generating brain tissue using ictal SPECT, PET, and structural and functional MRI and CT imaging is performed using advanced image-processing methods including statistical parametric mapping and FreeSurfer. Localization of intracranial electrodes in stereotactic and conventional intracranial EEG implantation is performed using high-resolution MRI and CT imaging.
Brain Stimulation Diagnostics and Therapeutics
This project is a collaboration with the International Clinical Research Center to advance the science and clinical translation of brain stimulation theranostics for neurological disease. We are investigating stimulation-response using transcranial stimulation and direct electrical stimulation combined with scalp and intracranial EEG.
AI-Powered Bioelectronic Medicine
Currently, most therapeutic strategies for disease are either pharmaceutical or surgical. Bioelectronic medicine provides a complementary approach for directly manipulating the cells, circuits and systems that underlie many diseases. Bioelectronic therapy treats disease symptoms and has potential for restoration.
Our vision is artificial intelligence (AI)-powered bioelectronic medicine that leverages advances in biology, engineering and AI to understand and manipulate the communication between cells, organs and systems to correct the abnormal signaling that underlies many diseases. The implementation involves integrating implantable and wearable sensing and electrical stimulation devices with off-the-body AI coprocessors running on consumer devices (iPhone, Android). Our vision is a system that directly senses, electrically stimulates and adaptively controls cellular biology and organ function.
The cornerstone of our effort is an AI-powered bioelectronics platform. We have implemented this strategy in a proof of concept in canines and humans with epilepsy using a Medtronic research device, as an initial-use case. Expanding to other diseases is largely an engineering challenge. The technology elements (electrode interface, devices, computing, biological understanding) are poised for integration and rapid advance to serve our patients.
The Mayo Bioelectronic Platform will include an open-source system of biological interfaces, implantable and wearable devices, and AI-powered integration tools to enable disease tracking, digital phenotyping, prediction and adaptive therapeutic stimulation. Within a platform approach, we will provide the scientific, engineering and regulatory infrastructure for physicians to mount investigational device exemption (IDE) trials. The program will be tightly coupled to active extramural grants, entrepreneurship and industry collaboration.