Abstracts

Rationale: Inter-ictal epileptiform discharges (IEDs) are a prominent feature in the neural activity of patients with epilepsy. IEDs are commonly used as indicators of a spreading epileptogenesis, but their relationship to seizures is complex. They are implicated in the development of cognitive impairment, and can induce cortical oscillations in anatomically remote brain regions. How IEDs interact with brain rhythms across distributed neural networks remains poorly elucidated. This study investigates the effects of IEDs on large-scale cortical networks, and their ability to couple with oscillatory activity such as sleep spindles.  Methods: Sleep electrocorticography recordings were obtained from six subjects implanted with subdural grid, strip, and depth electrodes as part of the work-up for epilepsy surgery. Statistical analysis was performed using MATLAB.  Results: We found that IEDs are temporally coupled to spindles in epilepsy patients during NREM sleep (n=6). IED-spindle coupling does not have anatomical preference, occurring in frontal, temporal, parietal, and occipital lobes. IEDs can generate sleep spindles in both nearby and remote cortical areas, and these spindles have similar electrophysiological characteristics (duration, frequency, amplitude; p>0.05) compared to physiological spindles. Importantly, the spatial distribution of IED-spindle coupling did not fully overlap with the IED network (n=6).   Conclusions: This study reveals that IED-spindle coupling is prominent in epileptic networks, but has variable anatomical distribution across subjects. Moreover, pathological coupling can occur in brain regions that do not exhibit IEDs. This finding suggests that IED-spindle coupling is a possible mechanism by which IEDs can disrupt physiologic networks through synaptic connections, implying that IED-spindle coupling can serve as a biomarker for brain tissue at risk for recruitment into the epileptic network.   Funding: This study was supported by Columbia University Medical Center, Marie Curie Actions, and Human Frontier Science Program.