Delta oscillation underlies the interictal spike changes after repeated transcranial direct current stimulation in a rat model of chronic seizures

Background: Transcranial direct current stimulation (tDCS) provides a noninvasive polarity-specific constant current to treat epilepsy, through a mechanism possibly involving excitability modulation and neural oscillation. Objective: To determine whether EEG oscillations underlie the interictal spike changes after tDCS in rats with chronic spontaneous seizures. Methods: Rats with kainic acid-induced spontaneous seizures were subjected to cathodal tDCS or sham stimulation for 5 consecutive days. Video-EEG recordings were collected immediately pre- and post-stimulation and for the subsequent 2 weeks following stimulation. The acute pre-post stimulation and subacute follow-up changes of interictal spikes and EEG oscillations in tDCS-treated rats were compared with sham. Ictal EEG with seizure behaviors, hippocampal brain-derived neurotrophic factor (BDNF) protein expression, and mossy fiber sprouting were compared between tDCS and sham rats. Results: Interictal spike counts were reduced immediately following tDCS with augmented delta and diminished beta and gamma oscillations compared with sham. Cathodal tDCS also enhanced delta oscillations in normal rats. However, increased numbers of interictal spikes with a decrease of delta and theta oscillations were observed in tDCS-treated rats compared with sham during the following 2 weeks after stimulation. Resuming tDCS suppressed the increase of interictal spike activity. In tDCS rats, hippocampal BDNF protein expression was decreased while mossy fiber sprouting did not change compared with sham. Conclusions: The inverse relationship between the changes of delta oscillation and interictal spikes during tDCS on and off stimulation periods indicates that an enhanced endogenous delta oscillation underlies the tDCS inhibitory effect on epileptic excitability.