Abstracts

Rationale: Deep brain stimulation (DBS) is being clinically applied to the human brain for the treatment of drug-resistant epilepsy. Open loop stimulation protocols have been extensively used in human patients with chronic seizures but their efficacy in modulating or disrupting seizure evolution has been largely unpredictable. Sometimes the treatment can demonstrate significant disruption whereas for other patients, little therapeutic benefit is observed. One of the underlying causes of this disparity is likely to be differences in the dynamics of seizure evolution between different patients, even those with the same epilepsy diagnosis. In this research, we sought to better understand how the dynamics of both synchrony and connectivity may evolve between patients with different types of focal epilepsy. Methods: Empirical mode decomposition (EMD) is an adaptive, data-driven method of decomposing signals into a set of finite and nearly orthogonal oscillators, called intrinsic mode functions (IMFs) that can be used to measure phase coherence across different recording streams without making any assumptions of signal linearity and stationarity. In this study, a version of EMD that avoids problems of mode aliasing and misalignment, called Noise Assisted-Multivariate EMD (NA-MEMD), was performed on iEEG data segments recorded in human epilepsy patients as part of pre-surgical evaluation to obtain its corresponding IMFs. The instantaneous phases of IMFs were measured using the Hilbert transform. The strength of the phase relationship at different IMF frequencies were measured across all recording sites and between different pairs of recording sites to assess how global synchrony and network connectivity were evolving during seizure onset and natural termination. Results: A reduction in phase-synchrony was observed in all patients around seizure onset. However, phase-synchrony started to gradually increase from mid-ictal and achieved its maximum level at seizure termination. This result suggests that hyper-synchronization of the epileptic network may be a crucial mechanism by which the brain naturally terminates seizure. Stimulation frequency and locations that matched the network phase-synchrony at seizure termination were extracted using phase-connectivity analysis. One patient with temporal lobe epilepsy (TLE) had a synchrony frequency ~15 Hz with the stimulation locations confined to the hippocampus. Two other patients with extra-temporal lobe epilepsy (ETE) had a synchrony frequency ~90 Hz with at least one stimulation location outside of hippocampus. Conclusions: These results suggest that DBS parameters and locations should vary based on the patient's underlying pathology. The proposed methodology provides an algorithm for tuning DBS parameters for individual patients in an effort to increase the clinical efficacy of the therapy. Funding: NIH R01 NS092760