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  1. Abstract

    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.

     
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  2. Abstract

    Identification of active electrodes that record task-relevant neurophysiological activity is needed for clinical and industrial applications as well as for investigating brain functions. We developed an unsupervised, fully automated approach to classify active electrodes showing event-related intracranial EEG (iEEG) responses from 115 patients performing a free recall verbal memory task. Our approach employed new interpretable metrics that quantify spectral characteristics of the normalized iEEG signal based on power-in-band and synchrony measures. Unsupervised clustering of the metrics identified distinct sets of active electrodes across different subjects. In the total population of 11,869 electrodes, our method achieved 97% sensitivity and 92.9% specificity with the most efficient metric. We validated our results with anatomical localization revealing significantly greater distribution of active electrodes in brain regions that support verbal memory processing. We propose our machine-learning framework for objective and efficient classification and interpretation of electrophysiological signals of brain activities supporting memory and cognition.

     
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  3. Abstract Objective

    Interictal epileptiform discharges (IEDs) were shown to be associated with cognitive impairment in persons with epilepsy. Previous studies indicated that IED rate, location, timing, and spatial relation to the seizure onset zone could predict an IED's impact on memory encoding and retrieval if they occurred in lateral temporal, mesial temporal, or parietal regions. In this study, we explore the influence that other IED properties (e.g., amplitude, duration, white matter classification) have on memory performance. We were specifically interested in investigating the influence that lateral temporal IEDs have on memory encoding.

    Methods

    Two hundred sixty‐one subjects with medication‐refractory epilepsy undergoing intracranial electroencephalographic monitoring performed multiple sessions of a delayed free‐recall task (n = 671). Generalized linear mixed models were utilized to examine the relationship between IED properties and memory performance.

    Results

    We found that increased IED rate, IEDs propagating in white matter, and IEDs localized to the left middle temporal region were associated with poorer memory performance. For lateral temporal IEDs, we observed a significant interaction between IED white matter categorization and amplitude, where IEDs with an increased amplitude and white matter propagation were associated with reduced memory performance. Additionally, changes in alpha power after an IED showed a significant positive correlation with memory performance.

    Significance

    Our results suggest that IED properties may be useful for predicting the impact an IED has on memory encoding. We provide an essential step toward understanding pathological versus potentially beneficial interictal epileptiform activity.

     
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  4. Abstract 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–afternoonp = .15, morning–eveningp = .85, afternoon–eveningp = .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.

     
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