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The factors that control the occurrence of interictal epileptiform discharges (IEDs) are not well understood. We suspected that this phenomenon reflects an attention-dependent suppression of interictal epileptiform activity. We hypothesized that IEDs would occur less frequently when a subject viewed a task-relevant stimulus compared to viewing a blank screen. Furthermore, IEDs have been shown to impair memory when they occur in certain regions during the encoding or recall phases of a memory task. Although these discharges have a short duration, their impact on memory suggests that they have longer lasting electrophysiological effects. We found that IEDs were associated with an increase in low frequency power and a change in the balance between low and high frequency oscillations for several seconds. We found that the occurrence of IEDs is modified by whether a subject is attending to a word displayed on screen or is observing a blank screen. Additionally, we found that discharges in brain regions in every lobe impair memory. These findings elucidate the relationship between IEDs and memory impairment and reveal the task dependence of the occurrence of IEDs.

Objective This study was undertaken to evaluate the influence that subject‐specific factors have on intracranial interictal epileptiform discharge (IED) rates in persons with refractory epilepsy. Methods One hundred fifty subjects with intracranial electrodes performed multiple sessions of a free recall memory task; this standardized task controlled for subject attention levels. We utilized a dominance analysis to rank the importance of subject‐specific factors based on their relative influence on IED rates. Linear mixed‐effects models were employed to comprehensively examine factors with highly ranked importance. Results Antiseizure medication (ASM) status, time of testing, and seizure onset zone (SOZ) location were the highest‐ranking factors in terms of their impact on IED rates. The average IED rate of electrodes in SOZs was 34% higher than the average IED rate of electrodes outside of SOZs (non‐SOZ; p < .001). However, non‐SOZ electrodes had similar IED rates regardless of the subject's SOZ location (p = .99). Subjects on older generation (p < .001) and combined generation (p < .001) ASM regimens had significantly lower IED rates relative to the group taking no ASMs; newer generation ASM regimens demonstrated a nonsignificant association with IED rates (p = .13). Of the ASMs included in this study, the following ASMs were associated with significant reductions in IED rates: levetiracetam (p < .001), carbamazepine (p < .001), lacosamide (p = .03), zonisamide (p = .01), lamotrigine (p = .03), phenytoin (p = .03), and topiramate (p = .01). We observed a nonsignificant association between time of testing and IED rates (morning–afternoon p = .15, morning–evening p = .85, afternoon–evening p = .26). Significance The current study ranks the relative influence that subject‐specific factors have on IED rates and highlights the importance of considering certain factors, such as SOZ location and ASM status, when analyzing IEDs for clinical or research purposes.

Objectives To study the effects of auditory stimuli on interictal epileptiform discharge (IED) rates evident with intracranial monitoring. Materials and methods Eight subjects undergoing intracranial EEG monitoring for refractory epilepsy participated in this study. Auditory stimuli consisted of a 40‐Hz tone, a 440‐Hz tone modulated by a 40‐Hz sinusoid, Mozart's Sonata for Two Pianos in D Major (K448), and K448 modulated by a 40‐Hz sinusoid (modK448). Subjects were stratified into high‐ and low‐IED rate groups defined by baseline IED rates. Subject‐level analyses identified individual responses to auditory stimuli, discerned specific brain regions with significant reductions in IED rates, and examined the influence auditory stimuli had on whole‐brain sigma power (12–16 Hz). Results All subjects in the high baseline IED group had a significant 35.25% average reduction in IEDs during the 40‐Hz tone; subject‐level reductions localized to mesial and lateral temporal regions. Exposure to Mozart K448 showed significant yet less homogeneous responses. A post hoc analysis demonstrated two of the four subjects with positive IED responses had increased whole‐brain power at the sigma frequency band during 40‐Hz stimulation. Conclusions Our study is the first to evaluate the relationship between 40‐Hz auditory stimulation and IED rates in refractory epilepsy. We reveal that 40‐Hz auditory stimuli may be a noninvasive adjunctive intervention to reduce IED burden. Our pilot study supports the future examination of 40‐Hz auditory stimuli in a larger population of subjects with high baseline IED rates.

There is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. Nonetheless, little is known about the mechanism underlying this beneficial “Mozart K448 effect” for persons with epilepsy. Here, we measured the influence that K448 had on intracranial interictal epileptiform discharges (IEDs) in sixteen subjects undergoing intracranial monitoring for refractory focal epilepsy. We found reduced IEDs during the original version of K448 after at least 30-s of exposure. Nonsignificant IED rate reductions were witnessed in all brain regions apart from the bilateral frontal cortices, where we observed increased frontal theta power during transitions from prolonged musical segments. All other presented musical stimuli were associated with nonsignificant IED alterations. These results suggest that the “Mozart K448 effect” is dependent on the duration of exposure and may preferentially modulate activity in frontal emotional networks, providing insight into the mechanism underlying this response. Our findings encourage the continued evaluation of Mozart’s K448 as a noninvasive, non-pharmacological intervention for refractory epilepsy.