Modulation of Instantaneous Synchrony During Seizures by Deep Brain Stimulation Ananda S. Fine Department of Bioengineering University of Illinois, Chicago David P. Nicholls Department of Mathematics, Statistics and Computer Science University of Illinois, Chicago David J. Mogul Department of Biomedical Engineering Illinois Institute of Technology Abstract—Epileptic seizures were experimentally induced in the CA3 region of rat hippocampus in vivo. Recordings of seizure activity were made in both hippocampi as well as anteromedial region of the thalamus in order to analyze the instantaneous activity for synchronous oscillators. A new method is introduced for detecting this synchrony which combines empirical mode decomposition, the Hilbert analytic signal method and eigenvalue decomposition. Effects of targeted deep brain stimulation on multi-site synchrony were assessed as a means to extinguish hypersynchrony during epileptic seizures. Keywords - empirical mode decomposition; synchrony; epilepsy I. INTRODUCTION Synchronous oscillatory activity has been found to be a critical component in both normal brain states such as binding of visual information [1] as well as pathological states such as Parkinson’s disease [2] [3], schizophrenia [4], Alzheimer’s disease [5] and epilepsy [6] [7]. However, detecting synchronization behavior in the brain represents an extraordinarily difficult problem in neurological science. Although various statistics have been proposed for the detection of phase synchrony from multiple electrodes placed at varying degrees of neuronal resolution (i.e. depth, subdural and/or surface), many of these methods rely on several assumptions that render them inappropriate for detecting synchrony in the brain. All electrophysiological signals besides single cell recordings are a summation of activity from areas surrounding the electrode. In particular, local field potentials (LFPs) represent a sum of dendritic activity that may be inhibitory or excitatory (inhibitory or excitatory post- synaptic potentials, respectively). Thus, these signals represent multiple components leading to a necessity for filtering. Most often, filtering of these signals involves either clinically determined ranges (e.g. alpha, beta, etc.) or Fourier spectrum derived bandwidths. Although these bandwidths determined a priori may, in many cases, yield useful narrow band signals, it would be more advantageous for a filtering algorithm to make no assumptions as to the underlying components of the signal under study. An ideal analysis method would be capable of extracting proper waveforms adaptively from the time series without any a priori assumptions and without the need to build complicated mathematical models derived from first principles (a daunting task for modeling dynamics beyond anything but a small population of neurons). A relatively recent technique combining well-known results in linear algebra and mean-field theory has been proposed to obtain significant synchrony clusters within bivariate phase data measures. This method, termed the “eigenvalue decomposition method”, utilizes directional statistical features of the phase dynamics between any two oscillatory signals to define significantly synchronized clusters of oscillators [8] [9]. This type of analysis relies on an assumption that there are several mean fields of globally coupled phase oscillators within the signal set. This approach figures prominently in our new analysis. We present here an analytic process applied to intracranial EEG information recorded in multiple deep brain nuclei bilaterally in the rat brain that merges the techniques of empirical mode decomposition, the Hilbert analytic signal method, mean phase coherence measures and finally eigenvalue decomposition to ultimately identify complex instantaneous synchronous behavior. Such a procedure may provide important new insights as a seizure or any other complex neurological process in the brain evolves in time and space. II. METHODS A. Surgical Procedure/Data Acquisition Male Sprague-Dawley rats, 48-57 days old and weighing approximately 225-280 gm were used in this study. Experiments were conducted in accordance with the National Institutes of Health for the care and use of laboratory animals. Rats were anesthetized by a mixture of Ketamine (70 mg/kg) and Xylazine (2 mg/kg) delivered intraperitoneally. All procedures were performed in a Kopf stereotactic frame (KOPF Model 900, CA, USA). Stereotactic targets were calculated using a stereotactic rat brain atlas [10]. The skull was perforated using a high speed stereotactic drill (Micromotor TM Drill, Stoelting Co, IL USA) with 1.2-2 mm diameter drill tips. Bipolar electrodes surrounding a single stainless steel injection cannula in one integrated electrode assembly (C315G-MS 303: PlasticsOne, Roanoke, VA, USA) were stereotactically implanted into the CA3 region of the left hippocampus (-3.5 mm Bregma, 2.8 mm lateral, 3.7 mm deep). Bipolar recording electrodes (without cannula) were implanted into the contralateral hippocampus and anteromedial thalamus (-1.8 mm Bregma, 0.3 mm lateral, 6.1 mm deep). After injection of epileptogenic chemicals into the CA3 region of the left hippocampus, the internal cannula 3310 31st Annual International Conference of the IEEE EMBS Minneapolis, Minnesota, USA, September 2-6, 2009 978-1-4244-3296-7/09/$25.00 ©2009 IEEE