The epilepsies are a family of disorders of brain dynamics. These disorders may arise from a variety of underlying deficits whose cellular physiology is still not well understood but which share an overlapping symptomatology. Those who suffer from epilepsy are susceptible to seizures, which are changes in sensation, awareness, or behavior caused by brief electrical disturbances in the brain. Often, the electrical disturbances originate from a "focus" or "epileptogenic zone" in part of the brain, from which the disturbances are propagated to other parts of the brain. Epilepsy affects approximately 2.5 million persons in the United States, and over 37 million persons worldwide. 150,000 to 200,000 new cases occur annually in the U.S. The estimated annual financial cost (both direct and indirect) is $12.5 billion. Although most epilepsy patients can control their seizures with the use of antiepileptic drugs, these can have toxic side effects, and 20% to 40% of patients cannot bring their seizures under control using drug therapy. Over 75% of epilepsy costs in the U.S. have been attributed to these medically refractory (unresponsive) cases. Many patients with pharmacologically intractable seizures can eliminate their disability completely or substantially by neurosurgical intervention, which typically involves resection (removal) of tissue in the epileptogenic zone or transection (cutting of neural connections) to prevent the spread of electrical disturbances. The typical cost of epilepsy surgery in the United States is about $40,000 to $50,000, or higher, whereas the alternative cost of foregoing surgery is approximately 10 times higher over the lifetime of a patient (due to inability to work, lost income, nursing home placement, etc.). Consequently, epilepsy surgery, though expensive, may be highly cost-effective. Candidates for epilepsy surgery are generally evaluated first with scalp EEG telemetric monitoring to determine seizure type and attempt to locate the seizure onset site. While telemetry monitoring combined with MR imaging is usually successful in identifying the location of seizure onset, in approximately 20% of cases, intracranial telemetry (iEEG) with surface (ECoG) and/or depth electrodes is required to determine the site(s) of seizure onset. In the Phase I final report, we show several examples of ECoG electrode grids after placement on the brain surface. The patient may stay in the hospital for several weeks while the ECoG recordings are monitored for the presences of interictal spikes and seizure activity, using video digital EEG equipment. Thus, invasive ECoG and depth recordings are used in those cases where it has proven difficult to determine the seizure onset site from non-invasive measurements. These are then the most difficult patients to evaluate, since correct identification of seizure onset location strongly predicts surgical outcome. We predict, therefore, that improved software tools for ECoG multimodal integration, visualization, and analysis, will assist the neurologist and neurosurgeon in the evaluation of these particularly difficult patients, increasing the accuracy in identifying seizure onset location, thus increasing the likelihood of successful surgical outcome.

Noninvasive alternatives to ECoG include PET, SPECT, fMRI, and source analysis from interictal MEG and/or interictal or ictal EEG. At the present time, however, the sensitivity, specificity, and localization accuracy of these methods has not been sufficient to eliminate the need for invasive recordings in a significant minority of surgical candidates. In addition, these methods do not offer "real-time" assessment of the epileptogenic focus during the actual seizure but instead are methods that either are employed between seizures (interictal) or after the seizures have begun (SPECT). In this proposal, we plan to develop both a noninvasive clinical tool and an enabling technology that will allow for the "real-time" visualization of the epileletogenic focus during a seizure. This tool will aid, for example, in seizure onset zone identification and in the understanding of interictal spike propagation, thus aiding the interpretation of difficult cases, where the actual onset location may be in doubt. The development of these methods will provide us with a competitive advantage over existing technologies, none of which, to our knowledge, include the feature set that we are proposing. These features include innovative and novel imaging methods for the identification of the seizure onset zone and epileptogenic networks.