Authors :
Presenting Author: Stefan Sumsky, PhD – Yale University School of Medicine
Rory Ashmeade, BS – Yale University School of Medicine
Jiayang Liu, PhD – Yale University
Yang Zheng, MD, PhD – Yale
Ben Gruenbaum, MD, PhD – Mayo Clinic
Cian McCafferty, PhD – University College Cork
Hal Blumenfeld, MD, PhD – Yale University
Rationale:
Absence epilepsy is characterized by brief episodes of impaired consciousness accompanied by generalized spike-wave discharges (SWDs) on EEG. The underlying neural mechanisms, particularly the involvement of specific brain regions in sensory processing deficits during SWDs, are not fully understood. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model, which closely replicates human absence seizures, is well-suited for exploring these mechanisms. Prior research indicates that sensory behavioral responses are impaired during SWDs, yet evoked neuronal activity and event-related potentials (ERPs) in the primary somatosensory cortex remain intact, suggesting that the disruption arises elsewhere. In this study, we examine the disruption of auditory sensory-motor processing in absence seizures, hypothesizing a key role for the anterior insular cortex (AIC), a region critical for sensory-motor integration.
Methods:
We performed in vivo electrophysiological recordings in awake, freely moving GAERS during an auditory response task. Bipolar electrodes captured auditory ERPs from the primary auditory cortex (A1) and AIC in 10 GAERS and 10 non-epileptic Wistar controls. We analyzed 1143 auditory stimuli at baseline, 1112 during SWDs, and 1058 from controls.Results:
Operant-conditioned lick responses to auditory stimuli were consistent at baseline and in controls but disrupted in over 99% of SWDs. Grand-averaged recordings revealed normal short-latency ERPs in A1, unaffected during SWDs. Conversely, AIC recordings displayed polyphasic oscillations with altered amplitude and frequency. In Wistar controls, stable, high-amplitude oscillations occurred at 8-9 Hz. In GAERS at baseline, amplitude was reduced, and frequency shifted to 10-12 Hz. During SWDs, oscillations were further altered, slowing to 4-6 Hz.
Conclusions:
Synchrony and oscillatory activity are believed to facilitate communication between brain regions, integrating multimodal sensory inputs. Our findings indicate that the AIC’s auditory evoked oscillatory signal, essential for sensory integration, is impaired in GAERS at baseline and further disrupted during SWDs, despite preserved A1 ERPs across all conditions. These results identify a novel auditory evoked potential in the AIC with unique oscillatory properties, suggesting a potential mechanism for sensory processing deficits in absence epilepsy.
Funding:
NIH/NINDS R37NS100901