Authors :
Presenting Author: Thomas Richner, PhD – Mayo Clinic
Nicholas Gregg, MD – Mayo Clinic
Keith Starnes, MD – Mayo Clinic
Dora Hermes, PhD – Mayo Clinic
Jamie Van Gompel, MD – Mayo Clinic
Gregory Worrell, MD, PhD – Mayo Clinic
Brian Lundstrom, MD, PhD – Mayo Clinic
Rationale:
Propagation of focal seizures across the epilepsy network depends on neural gain, i.e., the degree to which signals are amplified or dampened. Brain regions that suppress outputs by decreasing gain over time can prevent seizure propagation. However, time-dependent gain modulation is rarely quantified.
Previously, we showed that single excitatory neurons in rats reduce their time-dependent gain in response to a wide range of stimulus frequencies, consistent with fractional dynamics [1,2]. Modeling suggests these dynamics may be relevant for EEG waveforms [3]. We hypothesized that cortico-cortical evoked potentials (CCEPs) in patients with epilepsy can measure time-dependent gain at the macroscale. Specifically, we hypothesized that the amplitude of CCEPs will show a phase advance relative to sine-modulated stimulus pulse trains, i.e., the response will anticipate the stimulus.
Methods:
Five epilepsy patients undergoing invasive stereotactic EEG evaluation gave informed consent to receive sinusoidally modulated pulse trains. Biphasic pulses were delivered at 5 Hz with a width of 0.16 ms and amplitudes up to 3.0 mA. The amplitudes were sinusoidally modulated by 30% with modulation frequency envelopes of 0.1, 0.2 & 0.5 Hz.
Results:
CCEP amplitudes preceded the stimulus (positive phase advance) at all three modulation frequencies (see figure). For each modulation frequency, we fit a mixed-effects linear model using maximum likelihood estimation. The phase advance was typically 5-30 degrees and greater than zero in all instances (0.1, 0.2, & 0.5 Hz; Bonferroni corrected p< 0.01). Standardized effect sizes were 1.3 (0.1 Hz), 2.1 (0.2 Hz), and 1.5 (0.5 Hz). The phase-advanced fixed effect explained a large proportion of the variance and is non-zero.