IN VIVO MODULATION OF EPILEPTIFORM ACTIVITY WITH RADIAL HIPPOCAMPAL ELECTRIC FIELDS
Abstract number :
3.301
Submission category :
Year :
2002
Submission ID :
893
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Kristen A. Richardson, Bruce J. Gluckman, Steven L. Weinstein, Caryn E. Glosch, Jessica B. Moon, Ryder P. Gwinn, Karen Gale, Steven J. Schiff. Krasnow Institute, George Mason University, Fairfax, VA; Department of Physics and Astronomy, George Mason Unive
RATIONALE: Adaptive electrical fields have been demonstrated to suppress In Vitro seizures (J. Neurosci. 21: 590-600, 2001). We investigated translating these results to In Vivo modulation of epileptiform activity using radial electrical fields generated from depth electrodes within the central axis of the hippocampus.
METHODS: Male Sprague-Dawley rats were anesthetized and a bilateral craniotomy performed. Bilateral epileptiform activity was induced by unilateral injection of Kainic acid into the right hippocampus. A left neocortical window was created to enter the lateral ventricle and expose the dorsal surface of the left hippocampus. A field generating Ag-AgCl depth electrode was inserted along the central axis of the left hippocampus to a depth of 2-3mm. A current return plate electrode was placed within an artificial cerebrospinal fluid layer in the neocortical window. Neural activity was monitored through differential amplification of paired tungsten microelectrodes (0.24mm spacing). Two electrode pairs were placed in the CA1 region of the exposed hippocampus, and a third electrode pair was placed homologously within the right hippocampus. The left hippocampus was stimulated with both sinusoidal and biphasic square waveforms of varying amplitude and frequency while neuronal activity was simultaneously recorded bilaterally. Brains were fixed in formalin and histologically sectioned and stained.
RESULTS: Analysis of the recorded hippocampal activity indicated clear modulation of neural activity in phase with the sinusoidal field in 5/6 experiments, and in 6/6 experiments with the biphasic stimuli. In 1/6 experiments we simultaneously observed similar modulation in the right hippocampus (contralateral to stimulation). Histological analysis of the trajectories suggests that variability of the electrode placement correlated with different stimulation results. At the highest current densities (above 1.5 milli Coulombs per square mm per phase), AgCl deposition and cavitation were observed along the electrode track.
CONCLUSIONS: We have demonstrated In Vivo electric field modulation of hippocampal epileptiform activity. This finding suggests that such electric field control of seizure is technically feasible. An important next step will include establishing an accurate lesion threshold using human compatible electrode materials.
[Supported by: Whitaker Foundation, NIH 2R01MH50006 and 7K02MH01493.]