Hippocampal-ANT connectivity and ANT DBS: Circadian trends and response to stimulation

Although hippocampal (HC)-anterior nucleus of the thalamus (ANT) interactions are implicated in limbic epilepsy, their dynamics over the circadian cycle and following ANT deep brain stimulation (DBS) remain unclear. We used ultra-long, ambulatory, HC and ANT intracranial electroencephalographic recordings to describe HC-ANT connectivity in a patient with bilateral temporal lobe epilepsy. The patient was implanted with the investigational Medtronic Summit RC+S ™ sensing and stimulating DBS device. Electrodes were implanted into the long axis of the hippocampus and ANT bilaterally. Therapeutic stimulation was delivered to the ANT. HC-ANT coherence was calculated in the Berger bands (4-125 Hz) in 10 second segments from one month of baseline recordings and from a three week period of night-off stimulation that followed a month of continuous low frequency ANT stimulation (2Hz). Only coherence measurements wherein both contacts had spectral peaks in the relevant band, without seizures, spikes, or stimulation, were analyzed. Coherence values over the circadian cycle were compared across hemispheres and between baseline and post-stimulation periods. At baseline, concurrent spectral peaks in HC and ANT occurred across the circadian cycle, primarily in the high beta and low gamma frequency bands bilaterally, with the less epileptogenic, right hemisphere showing significantly greater high beta coherence (Wilcoxon Rank-Sum, n1 = 2638, n2 = 2515, p < 0.0001). Post-stimulation, nighttime left HC-ANT high beta coherence did not change, but the central frequency of coherent high beta peaks did increase significantly (Wilcoxon Rank-Sum, n1 = 368, n2 = 492, p < 0.0001). Our finding that HC-ANT high beta coherence was decreased in the more epileptogenic hemisphere is consistent with reports of functional isolation of epileptogenic zone. The stimulation-associated change in central frequency at which beta peaks occurred, but not in overall magnitude of HC-ANT coherence, suggests that low frequency ANT-DBS influences the spectral composition of HC-ANT connectivity.