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1. Features of intracranial interictal epileptiform discharges associated with memory encoding

   https://doi.org/10.1111/epi.17060  

   Quon, Robert J. ; Camp, Edward J. ; Meisenhelter, Stephen ; Song, Yinchen ; Steimel, Sarah A. ; Testorf, Markus E. ; Andrew, Angeline S. ; Gross, Robert E. ; Lega, Bradley C. ; Sperling, Michael R. ; et al ( September 2021 , Epilepsia)

   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.

   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.

   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.

   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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2. Interaction of interictal epileptiform activity with sleep spindles is associated with cognitive deficits and adverse surgical outcome in pediatric focal epilepsy

   https://doi.org/10.1111/epi.17810  

   Yu, Han ; Kim, Woojoong ; Park, David K. ; Phi, Ji Hoon ; Lim, Byung Chan ; Chae, Jong‐Hee ; Kim, Seung‐Ki ; Kim, Ki Joong ; Provenzano, Frank A. ; Khodagholy, Dion ; et al ( November 2023 , Epilepsia)

   Temporal coordination between oscillations enables intercortical communication and is implicated in cognition. Focal epileptic activity can affect distributed neural networks and interfere with these interactions. Refractory pediatric epilepsies are often accompanied by substantial cognitive comorbidity, but mechanisms and predictors remain mostly unknown. Here, we investigate oscillatory coupling across large‐scale networks in the developing brain.

   We analyzed large‐scale intracranial electroencephalographic recordings in children with medically refractory epilepsy undergoing presurgical workup (n = 25, aged 3–21 years). Interictal epileptiform discharges (IEDs), pathologic high‐frequency oscillations (HFOs), and sleep spindles were detected. Spatiotemporal metrics of oscillatory coupling were determined and correlated with age, cognitive function, and postsurgical outcome.

   Children with epilepsy demonstrated significant temporal coupling of both IEDs and HFOs to sleep spindles in discrete brain regions. HFOs were associated with stronger coupling patterns than IEDs. These interactions involved tissue beyond the clinically identified epileptogenic zone and were ubiquitous across cortical regions. Increased spatial extent of coupling was most prominent in older children. Poor neurocognitive function was significantly correlated with high IED–spindle coupling strength and spatial extent; children with strong pathologic interactions additionally had decreased likelihood of postoperative seizure freedom.

   Our findings identify pathologic large‐scale oscillatory coupling patterns in the immature brain. These results suggest that such intercortical interactions could predict risk for adverse neurocognitive and surgical outcomes, with the potential to serve as novel therapeutic targets to restore physiologic development.

    

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3. Factors correlated with intracranial interictal epileptiform discharges in refractory epilepsy

   https://doi.org/10.1111/epi.16792  

   Quon, Robert J. ; Meisenhelter, Stephen ; Adamovich‐Zeitlin, Richard H. ; Song, Yinchen ; Steimel, Sarah A. ; Camp, Edward J. ; Testorf, Markus E. ; MacKenzie, Todd A. ; Gross, Robert E. ; Lega, Bradley C. ; et al ( December 2020 , Epilepsia)

   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.

   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.

   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).

   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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4. Musical components important for the Mozart K448 effect in epilepsy

   https://doi.org/10.1038/s41598-021-95922-7  

   Quon, Robert J. ; Casey, Michael A. ; Camp, Edward J. ; Meisenhelter, Stephen ; Steimel, Sarah A. ; Song, Yinchen ; Testorf, Markus E. ; Leslie, Grace A. ; Bujarski, Krzysztof A. ; Ettinger, Alan B. ; et al ( September 2021 , Scientific Reports)

   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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5. The interictal mesial temporal lobe epilepsy network

   https://doi.org/10.1111/epi.13959  

   Karunakaran, Suganya ; Rollo, Matthew J. ; Kim, Kamin ; Johnson, Jessica A. ; Kalamangalam, Giridhar P. ; Aazhang, Behnaam ; Tandon, Nitin ( December 2017 , Epilepsia)

   Identification of patient‐specific epileptogenic networks is critical to designing successful treatment strategies. Multiple noninvasive methods have been used to characterize epileptogenic networks. However, these methods lack the spatiotemporal resolution to allow precise localization of epileptiform activity. We used intracranial recordings, at much higher spatiotemporal resolution, across a cohort of patients with mesial temporal lobe epilepsy (MTLE) to delineate features common to their epileptogenic networks. We used interictal rather than seizure data because interictal spikes occur more frequently, providing us greater power for analyzing variances in the network.

   Intracranial recordings from 10 medically refractoryMTLEpatients were analyzed. In each patient, hour‐long recordings were selected for having frequent interictal discharges and no ictal events. For all possible pairs of electrodes, conditional probability of the occurrence of interictal spikes within a 150‐millisecond bin was computed. These probabilities were used to construct a weighted graph between all electrodes, and the node degree was estimated. To assess the relationship of the highly connected regions in this network to the clinically identified seizure network, logistic regression was used to model the regions that were surgically resected using weighted node degree and number of spikes in each channel as factors. Lastly, the conditional spike probability was normalized and averaged across patients to visualize theMTLEnetwork at group level.

   We generated the first graph of connectivity across a cohort ofMTLEpatients using interictal activity. The most consistent connections were hippocampus to amygdala, anterior fusiform cortex to hippocampus, and parahippocampal gyrus projections to amygdala. Additionally, the weighted node degree and number of spikes modeled the brain regions identified as seizure networks by clinicians.

   Apart from identifying interictal measures that can model patient‐specific epileptogenic networks, we also produce a group map of network connectivity from a cohort ofMTLEpatients.

    

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