Abstracts

Low Frequency ([lt][lt]100Hz) applied electric fields have been shown to modulate neuronal activity both In Vitro and in acute whole animal studies. This mode of interacting with neuronal activity has two advantages over pulse stimulation for neural prosthetics design. First, it has a modulatory effect on neuron activity proportional to the field amplitude and polarity. Second, when instrumented correctly, neural recordings can be done simultaneously with stimulation with minimal artifact. Therefore, this mode of interaction is ideal for use in continuous feedback controllers., All procedures were carried out under IACUC approval. Tetanus toxin (5 ng/ul) was injected into the right ventral hippocampus of adult male rats. A pair of stimulation depth electrodes (0.25mm in diameter by 2.5mm long, electrochemically deposited with iridium oxide film) were inserted, one aligned in the arc of the ventral CA3, and one 3.5 mm anterior, along with bipolar hippocampal depth and cortical screw electrodes for EEG. EEG was continuously recorded for 3-16 days while various open loop stimulation protocols were applied, including 1 hr. on / 1 hr. off sinusoidal stimulation (frequencies from 0.5-16 Hz)., We observed transient entrainment of spike-and-wave activity both near seizure onset and seizure offset in response to sinusoidal stimulation for frequencies between 9-15 Hz in 4/4 animals stimulated. In the figure we show both hippocampal depth recordings and frequency spectra from two seizures. In (a), no stimulation was applied and many spectral peaks are observed. In (b), the animal was stimulated with sinusoidal fields of order [sim]15 mV/mm (peak amplitude at soma), and a prominent narrow peak is observed in the spectra. As shown in (c), spike times are phase synchronized with the stimulation. Therefore, the sharp spectral peak indicates a neural response to the stimulation., Prevously, we had demonstrated neural modulation in acutely instrumented animals. (Richardson, et. al, Epilepsia 2003). We have now developed electronics for simultaneously recording neural activity while stimulating with low frequency fields in chronically implanted animals. This work is the first observation of interaction of neuronal activity with electric fields in chronically implanted animals.[figure1], (Supported by NIH grants R01EB001507, R01MH50006, and K02MH01493.)