Intraoperative microseizure detection using a high-density micro-electrocorticography electrode array.

One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue. We have previously developed novel thin-film, subdural electrode arrays with hundreds of microelectrodes over a 100-1000 mm2 area to enable high-resolution mapping of neural activity. Here, we used these high-density arrays to study microscale properties of human epileptiform activity. We performed intraoperative micro-electrocorticographic recordings in nine patients with epilepsy. In addition, we recorded from four patients with movement disorders undergoing deep brain stimulator implantation as non-epileptic controls. A board-certified epileptologist identified microseizures, which resembled electrographic seizures normally observed with clinical macroelectrodes. Recordings in epileptic patients had a significantly higher microseizure rate (2.01 events/min) than recordings in non-epileptic subjects (0.01 events/min; permutation test, P = 0.0068). Using spatial averaging to simulate recordings from larger electrode contacts, we found that the number of detected microseizures decreased rapidly with increasing contact diameter and decreasing contact density. In cases in which microseizures were spatially distributed across multiple channels, the approximate onset region was identified. Our results suggest that micro-electrocorticographic electrode arrays with a high density of contacts and large coverage are essential for capturing microseizures in epilepsy patients and may be beneficial for localizing epileptogenic tissue to plan surgery or target brain stimulation.

Millimeter-scale epileptiform spike propagation patterns and their relationship to seizures.

OBJECTIVE: Current mapping of epileptic networks in patients prior to epilepsy surgery utilizes electrode arrays with sparse spatial sampling (∼1.0 cm inter-electrode spacing). Recent research demonstrates that sub-millimeter, cortical-column-scale domains have a role in seizure generation that may be clinically significant. We use high-resolution, active, flexible surface electrode arrays with 500 µm inter-electrode spacing to explore epileptiform local field potential (LFP) spike propagation patterns in two dimensions recorded from subdural micro-electrocorticographic signals in vivo in cat. In this study, we aimed to develop methods to quantitatively characterize the spatiotemporal dynamics of epileptiform activity at high-resolution. APPROACH: We topically administered a GABA-antagonist, picrotoxin, to induce acute neocortical epileptiform activity leading up to discrete electrographic seizures. We extracted features from LFP spikes to characterize spatiotemporal patterns in these events. We then tested the hypothesis that two-dimensional spike patterns during seizures were different from those between seizures. MAIN RESULTS: We showed that spatially correlated events can be used to distinguish ictal versus interictal spikes. SIGNIFICANCE: We conclude that sub-millimeter-scale spatiotemporal spike patterns reveal network dynamics that are invisible to standard clinical recordings and contain information related to seizure-state.

Breast cancer detection using high-density flexible electrode arrays and electrical impedance tomography.

While mammography remains the gold standard for breast cancer screening, additional adjunctive tools for early detection of breast cancer are needed especially for young women, women with dense breast tissue and those at increased risk due to genetic factors. These patient populations, along with those populations for whom mammography is not readily available, require alternative technologies capable of effectively detecting breast cancer. One such adjunctive modality for breast cancer detection is Electrical Impedance Tomography (EIT). It is a non-invasive technique that measures tissue conductivity by injecting a small current through a surface electrode while measuring electrode voltage(s). The surface measurements are then used to reconstruct a conductivity mapping of the tissue. The difference in conductivities between healthy tissue and that of carcinoma enable EIT to detect cancer. Electrical Impedance Tomography does not subject the patient to ionizing radiation, and offers significant potential for detecting very small tumors in early stages of development at a low cost. While prior systems have demonstrated success using EIT for breast cancer detection, the resolution of the reconstructed image was limited by the spatial resolution of the sensing electrode array. Here, we report the use of higher density (3mm spacing) flexible micro-electrode arrays to obtain tissue impedance maps. Accurate EIT reconstruction is highly dependent on the spatial resolution and fidelity of the surface measurements. High-density, flexible arrays that conform to the breast surface can offer great potential in reconstructing higher resolution conductivity maps than have been previously achieved.

Development of high resolution, multiplexed electrode arrays: Opportunities and challenges.

More than one third of the world's 60 million people with epilepsy have seizures that cannot be controlled by medication. Some of these individuals may be candidates for surgical removal of brain regions that generate seizures, but the chance of being seizure free after epilepsy surgery is as low as 35% in many patients. Even when surgery is successful, patients risk neurological deficits like memory loss and speech difficulties. The need for new treatments is clear. A central barrier to better treatments for epilepsy is technological: we do not have devices capable of interfacing with the brain with small enough electrodes over large enough regions to map epileptic networks in sufficient detail to enable treatment. Our collaborative group has developed new implantable brain devices to address this challenge. Our devices, made from flexible silicon nanoribbons, can record from these very small brain regions, with electrodes ½ millimeter apart or less, and can be scaled up to clinically useful sizes, on the order of 64 cm(2). They consist of thousands of individually controllable microelectrodes.