Interictal epileptiform activity outside the seizure onset zone impacts cognition

Ung, Hoameng; Cazares, Christian; Nanivadekar, Ameya C.; Kini, Lohith G.; Wagenaar, Joost B.; Becker, Danielle A.; Krieger, Abba M.; Lucas, Timothy H.; Litt, Brian; Davis, Kathryn A.

doi:10.1093/brain/awx143

Cited by 120 publications

(162 citation statements)

References 54 publications

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“…There is a wide variety of interictal activity seen in human patients, and the distinction between interictal and ictal events is not always clear. For instance, similar electrographic recordings can be accompanied by different clinical manifestations, and interictal events can have a significant effect on behavior and cognitive abilities (Fisher et al 2014;Gelinas et al 2016;Ibrahim et al 2014;Ung et al 2017). In our study, polyspikes and seizures in the focus naturally separated into two groups based on the number of spikes per event, a finding that was consistent across experiments.…”

Section: Discussionsupporting

confidence: 75%

Spatiotemporal evolution of focal epileptiform activity from surface and laminar field recordings in cat neocortex

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Sedigh-Sarvestani

Fernández-Lamo

et al. 2018

Journal of Neurophysiology

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New devices that use targeted electrical stimulation to treat refractory localization-related epilepsy have shown great promise, although it is not well known which targets most effectively prevent the initiation and spread of seizures. To better understand how the brain transitions from healthy to seizing on a local scale, we induced focal epileptiform activity in the visual cortex of five anesthetized cats with local application of the GABA blocker picrotoxin while simultaneously recording local field potentials on a high-resolution electrocorticography array and laminar depth probes. Epileptiform activity appeared in the form of isolated events, revealing a consistent temporal pattern of ictogenesis across animals with interictal events consistently preceding the appearance of seizures. Based on the number of spikes per event, there was a natural separation between seizures and shorter interictal events. Two distinct spatial regions were seen: an epileptic focus that grew in size as activity progressed, and an inhibitory surround that exhibited a distinct relationship with the focus both on the surface and in the depth of the cortex. Epileptiform activity in the cortical laminae was seen concomitant with activity on the surface. Focus spikes appeared earlier on electrodes deeper in the cortex, suggesting that deep cortical layers may be integral to recruiting healthy tissue into the epileptic network and could be a promising target for interventional devices. Our study may inform more effective therapies to prevent seizure generation and spread in localization-related epilepsies. NEW & NOTEWORTHY We induced local epileptiform activity and recorded continuous, high-resolution local field potentials from the surface and depth of the visual cortex in anesthetized cats. Our results reveal a consistent pattern of ictogenesis, characterize the spatial spread of the epileptic focus and its relationship with the inhibitory surround, and show that focus activity within events appears earliest in deeper cortical layers. These findings have potential implications for the monitoring and treatment of refractory epilepsy.

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Section: Discussionsupporting

confidence: 75%

Spatiotemporal evolution of focal epileptiform activity from surface and laminar field recordings in cat neocortex

Bink

Sedigh-Sarvestani

Fernández-Lamo

et al. 2018

Journal of Neurophysiology

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“…These discharges typically occur within or around the seizure onset zone. Although IEDs are typically considered to be asymptomatic, there is some evidence that they are related to brief lapses in cognition (Aarts et al, 1984;Horak et al, 2017;Ung et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Because the extent to which IEDs originating from the hippocampus and other deep structures can be captured using scalp EEG is limited, it remains unclear how hippocampal memory processes are modulated by IEDs. More recently, work using intracranial EEG (implanted depth or subdural grid electrodes) in epilepsy patients has started to reveal a better understanding of the relationship between neural activity, cognitive processes, and their impairment by IEDs (Kleen et al, 2013;Horak et al, 2017;Ung et al, 2017). Several studies have found that the occurrence of IEDs recorded with intracranial electrodes correlates with impaired behavioral performance in working memory (Krauss et al, 1997;Ung et al, 2017) and delayed free recall tasks (Kleen et al, 2013;Horak et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans

Reed¹,

Mosher²,

Chandravadia³

et al. 2019

J. Neurosci.

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Memory deficits are common in epilepsy patients. In these patients, the interictal EEG commonly shows interictal epileptiform discharges (IEDs). While IEDs are associated with transient cognitive impairments, it remains poorly understood why this is. We investigated the effects of human (male and female) hippocampal IEDs on single-neuron activity during a memory task in patients with medically refractory epilepsy undergoing depth electrode monitoring. We quantified the effects of hippocampal IEDs on single-neuron activity and the impact of this modulation on subjectively declared memory strength. Across all recorded neurons, the activity of 50 of 728 neurons were significantly modulated by IEDs, with the strongest modulation in the medial temporal lobe (33 of 416) and in particular the right hippocampus (12 of 58). Putative inhibitory neurons, as identified by their extracellular signature, were more likely to be modulated by IEDs than putative excitatory neurons (19 of 157 vs 31 of 571). Behaviorally, the occurrence of hippocampal IEDs was accompanied by a disruption of recognition of familiar images only if they occurred up to 2 s before stimulus onset. In contrast, IEDs did not impair encoding or recognition of novel images, indicating high temporal and task specificity of the effects of IEDs. The degree of modulation of individual neurons by an IED correlated with the declared confidence of a retrieval trial, with higher firing rates indicative of reduced confidence. Together, these data link the transient modulation of individual neurons by IEDs to specific declarative memory deficits in specific cell types, thereby revealing a mechanism by which IEDs disrupt medial temporal lobe-dependent declarative memory retrieval processes.

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“…Lastly, apart from signal processing implications, it is worth mentioning that IEDs can also transiently disrupt the local neural dysfunction of the region in which they occur (Krauss et al, 1997;Kleen et al, 2013;Horak et al, 2017;Ung et al, 2017). This could lead to cognitive errors that could influence trial-based and other analyses, posing a separate argument for the exclusion of trials with IEDs when making conclusions regarding ''normal'' cognitive processing.…”

Section: Further Considerationsmentioning

confidence: 99%

Interictal Epileptiform Discharges and the Quality of Human Intracranial Neurophysiology Data

Ammanuel

Kleen

Leonard

et al. 2020

Front. Hum. Neurosci.

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Intracranial electroencephalography (IEEG) involves recording from electrodes placed directly onto the cortical surface or deep brain locations. It is performed on patients with medically refractory epilepsy, undergoing pre-surgical seizure localization. IEEG recordings, combined with advancements in computational capacity and analysis tools, have accelerated cognitive neuroscience. This Perspective describes a potential pitfall latent in many of these recordings by virtue of the subject population-namely interictal epileptiform discharges (IEDs), which can cause spurious results due to the contamination of normal neurophysiological signals by pathological waveforms related to epilepsy. We first discuss the nature of IED hazards, and why they deserve the attention of neurophysiology researchers. We then describe four general strategies used when handling IEDs (manual identification, automated identification, manual-automated hybrids, and ignoring by leaving them in the data), and discuss their pros, cons, and contextual factors. Finally, we describe current practices of human neurophysiology researchers worldwide based on a cross-sectional literature review and a voluntary survey. We put these results in the context of the listed strategies and make suggestions on improving awareness and clarity of reporting to enrich both data quality and communication in the field.

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Interictal epileptiform activity outside the seizure onset zone impacts cognition

Cited by 120 publications

References 54 publications

Spatiotemporal evolution of focal epileptiform activity from surface and laminar field recordings in cat neocortex

Spatiotemporal evolution of focal epileptiform activity from surface and laminar field recordings in cat neocortex

Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans

Interictal Epileptiform Discharges and the Quality of Human Intracranial Neurophysiology Data

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