REDUCING THALAMO-CORTICAL SYSTEM SUSCEPTIBILITY TO LARGE-SCALE PAROXYSMAL OSCILLATIONS THROUGH CUSTOMIZED CENTRAL THALAMIC ELECTRICAL STIMULATION IN A RODENT MODEL OF GENERALIZED SEIZURES
Abstract number :
3.157
Submission category :
1. Translational Research
Year :
2009
Submission ID :
10251
Source :
www.aesnet.org
Presentation date :
12/4/2009 12:00:00 AM
Published date :
Aug 26, 2009, 08:12 AM
Authors :
Sean Nagel, A. Alexopoulos, R. O'dwyer, T. Chen and I. Najm
Rationale: Generalized seizures co-opt the thalamo-cortical system(TCS) to recruit the cortex into a large-scale, semi-stable network configuration. The TCS can be manipulated transiently through pulsed, central thalamic (CT) low frequency electrical stimulation (LFS)(Dempsey, 1942) Recent investigations confirm large scale integration is inversely related to the frequency of the interaction (Buzsaki and Draguhn, 2004). If ES is subject to this same relationship, then to optimize effect, stimulation frequency likely needs to be customized to the size of the network. Modulation of a large network such as the TCS would favor LFS to maximize the spatial response at the cortex in order to attenuate seizure-specific paroxysmal activity. To test if chronic LFS desensitized the TCS to paroxysmal events, rats were stimulated (24hr) with LFS, HFS (high frequency stimulation) or sham stimulation and then administered the chemoconvulsant pentylenetetrazole (PTZ). Methods: Adult rats (n=44 ) were implanted with four recording screws and 2 microelectrodes stereotactically placed in the central laminar nucleus. Current intensity was increased in 10 μA increments until a definitive time-locked cortical response was detected on the EEG consistent with an augmenting response. HFS was set at 130 Hz and LFS was set at 17 Hz. Rats were randomized to start with chronic (24hr) stimulation or sham testing (Test 1). Rats were crossed-over for the second test (Test 2). Stimulation remained on during PTZ (60mg/kg) administration. Seizure severity was determined using a 5 point (GTC=5) scoring system (Pohl and Mares,1987). Results: Low intensity, LFS significantly reduced behavioral seizure severity compared to sham stimulation in test 1 (SHAM 2.60+/- 0.34;STIM 1.42+/-0.31) and test 2 (SHAM 3.22+/-0.36; STIM 1.41+/-0.33) (fig 1). Rats treated with chronic LFS showed a statistically significant time delay in the onset of motor clonic seizures. There was no statistically significant difference between animals treated with low intensity HFS stimulation and sham stimulation in test 1(SHAM 2.0+/-0.74 ;STIM 2.4+/-0.66) or test 2 (SHAM 2.6+/-0.56; STIM 2.87+/-0.74)(fig 2). Conclusions: We have shown for the first time that the frequency and intensity of electrical stimulation can be customized to the size of the network of interest in order to modulate properties that may enhance resistance to paroxysmal activity.These findings merit the continued support of research efforts aimed at reestablishing stable, local and long-range synchronized oscillations in a number of neurologic diseases including epilepsy using ES.
Translational Research