Musical components important for the Mozart K448 effect in epilepsy.

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.

40-Hz auditory stimulation for intracranial interictal activity: A pilot study.

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.