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Article ; Online: Passive and active markers of cortical excitability in epilepsy.

Ramantani, Georgia / Westover, M Brandon / Gliske, Stephen / Sarnthein, Johannes / Sarma, Sridevi / Wang, Yujiang / Baud, Maxime O / Stacey, William C / Conrad, Erin C

Epilepsia

2023 Volume 64 Suppl 3, Page(s) S25–S36

Abstract: Electroencephalography (EEG) has been the primary diagnostic tool in clinical epilepsy for nearly a century. Its review is performed using qualitative clinical methods that have changed little over time. However, the intersection of higher resolution ... ...

Abstract	Electroencephalography (EEG) has been the primary diagnostic tool in clinical epilepsy for nearly a century. Its review is performed using qualitative clinical methods that have changed little over time. However, the intersection of higher resolution digital EEG and analytical tools developed in the past decade invites a re-exploration of relevant methodology. In addition to the established spatial and temporal markers of spikes and high-frequency oscillations, novel markers involving advanced postprocessing and active probing of the interictal EEG are gaining ground. This review provides an overview of the EEG-based passive and active markers of cortical excitability in epilepsy and of the techniques developed to facilitate their identification. Several different emerging tools are discussed in the context of specific EEG applications and the barriers we must overcome to translate these tools into clinical practice.
MeSH term(s)	Humans ; Epilepsy/diagnosis ; Electroencephalography/methods ; Cortical Excitability
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17578
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Article ; Online: Attitudes Toward Cognitive Enhancement: The Role of Metaphor and Context.

Conrad, Erin C / Humphries, Stacey / Chatterjee, Anjan

AJOB neuroscience

2019 Volume 10, Issue 1, Page(s) 35–47

Abstract: The widespread use of stimulants among healthy individuals to improve cognition has received growing attention; however, public attitudes toward this practice are not well understood. We determined the effect of framing metaphors and context of use on ... ...

Abstract	The widespread use of stimulants among healthy individuals to improve cognition has received growing attention; however, public attitudes toward this practice are not well understood. We determined the effect of framing metaphors and context of use on public opinion toward cognitive enhancement. We recruited 3,727 participants from the United States to complete three surveys using Amazon's Mechanical Turk between April and July 2017. Participants read vignettes describing an individual using cognitive enhancement, varying framing metaphors (fuel versus steroid), and context of use (athletes versus students versus employees). The main outcome measure was the difference in respondent-assigned level of acceptability of the use of cognitive enhancement by others and by themselves between the contrasting vignettes. Participants were more likely to support the use of cognitive enhancement by others than by themselves and more when the use of enhancement by others was framed with a fuel metaphor than with a steroid metaphor. Metaphoric framing did not affect participants' attitudes toward their own use. Participants supported the use of enhancement by employees more than by students or athletes. These results are discussed in relation to existing ethical and policy literature.
MeSH term(s)	Attitude ; Cognition/drug effects ; Comprehension/drug effects ; Female ; Humans ; Male ; Metaphor ; Morals ; Nootropic Agents/pharmacology ; Public Opinion ; United States
Chemical Substances	Nootropic Agents
Language	English
Publishing date	2019-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2576262-X
ISSN	2150-7759 ; 2150-7740
ISSN (online)	2150-7759
ISSN	2150-7740
DOI	10.1080/21507740.2019.1595771
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Article ; Online: Addressing spatial bias in intracranial EEG functional connectivity analyses for epilepsy surgical planning.

Conrad, Erin C / Bernabei, John M / Sinha, Nishant / Ghosn, Nina J / Stein, Joel M / Shinohara, Russell T / Litt, Brian

Journal of neural engineering

2022 Volume 19, Issue 5

Abstract: Objective. ...

Abstract	Objective.
MeSH term(s)	Bias ; Brain ; Electrocorticography/methods ; Electroencephalography/methods ; Epilepsy/diagnosis ; Epilepsy/surgery ; Humans ; Seizures
Language	English
Publishing date	2022-09-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2170901-4
ISSN	1741-2552 ; 1741-2560
ISSN (online)	1741-2552
ISSN	1741-2560
DOI	10.1088/1741-2552/ac90ed
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Article ; Online: Quantitative artifact reduction and pharmacologic paralysis improve detection of EEG epileptiform activity in critically ill patients.

Kulick-Soper, Catherine V / Shinohara, Russell T / Ellis, Colin A / Ganguly, Taneeta M / Raghupathi, Ramya / Pathmanathan, Jay S / Conrad, Erin C

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

2022 Volume 145, Page(s) 89–97

Abstract: Objective: Epileptiform activity is common in critically ill patients, but movement-related artifacts-including electromyography (EMG) and myoclonus-can obscure EEG, limiting detection of epileptiform activity. We sought to determine the ability of ... ...

Abstract	Objective: Epileptiform activity is common in critically ill patients, but movement-related artifacts-including electromyography (EMG) and myoclonus-can obscure EEG, limiting detection of epileptiform activity. We sought to determine the ability of pharmacologic paralysis and quantitative artifact reduction (AR) to improve epileptiform discharge detection. Methods: Retrospective analysis of patients who underwent continuous EEG monitoring with pharmacologic paralysis. Four reviewers read each patient's EEG pre- and post- both paralysis and AR, and indicated the presence of epileptiform discharges. We compared the interrater reliability (IRR) of identifying discharges at baseline, post-AR, and post-paralysis, and compared the performance of AR and paralysis according to artifact type. Results: IRR of identifying epileptiform discharges at baseline was slight (N = 30; κ = 0.10) with a trend toward increase post-AR (κ = 0.26, p = 0.053) and a significant increase post-paralysis (κ = 0.51, p = 0.001). AR was as effective as paralysis at improving IRR of identifying discharges in those with high EMG artifact (N = 15; post-AR κ = 0.63, p = 0.009; post-paralysis κ = 0.62, p = 0.006) but not with primarily myoclonus artifact (N = 15). Conclusions: Paralysis improves detection of epileptiform activity in critically ill patients when movement-related artifact obscures EEG features. AR improves detection as much as paralysis when EMG artifact is high, but is ineffective when the primary source of artifact is myoclonus. Significance: In the appropriate setting, both AR and paralysis facilitate identification of epileptiform activity in critically ill patients.
MeSH term(s)	Humans ; Electroencephalography ; Artifacts ; Critical Illness ; Retrospective Studies ; Myoclonus/diagnosis ; Reproducibility of Results ; Paralysis/diagnosis
Language	English
Publishing date	2022-11-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1463630-x
ISSN	1872-8952 ; 0921-884X ; 1388-2457
ISSN (online)	1872-8952
ISSN	0921-884X ; 1388-2457
DOI	10.1016/j.clinph.2022.11.007
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Article: Resting-state background features demonstrate multidien cycles in long-term EEG device recordings.

Ojemann, William K S / Scheid, Brittany H / Mouchtaris, Sofia / Lucas, Alfredo / LaRocque, Joshua J / Aguila, Carlos / Ashourvan, Arian / Caciagli, Lorenzo / Davis, Kathryn A / Conrad, Erin C / Litt, Brian

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Longitudinal EEG recorded by implanted devices is critical for understanding and managing epilepsy. Recent research reports patient-specific, multi-day cycles in device-detected epileptiform events that coincide with increased likelihood of ... ...

Abstract	Background: Longitudinal EEG recorded by implanted devices is critical for understanding and managing epilepsy. Recent research reports patient-specific, multi-day cycles in device-detected epileptiform events that coincide with increased likelihood of clinical seizures. Understanding these cycles could elucidate mechanisms generating seizures and advance drug and neurostimulation therapies. Objective/hypothesis: We hypothesize that seizure-correlated cycles are present in background neural activity, independent of interictal epileptiform spikes, and that neurostimulation may disrupt these cycles. Methods: We analyzed regularly-recorded seizure-free data epochs from 20 patients implanted with a responsive neurostimulation (RNS) device for at least 1.5 years, to explore the relationship between cycles in device-detected interictal epileptiform activity (dIEA), clinician-validated interictal spikes, background EEG features, and neurostimulation. Results: Background EEG features tracked the cycle phase of dIEA in all patients (AUC: 0.63 [0.56 - 0.67]) with a greater effect size compared to clinically annotated spike rate alone (AUC: 0.55 [0.53-0.61], p < 0.01). After accounting for circadian variation and spike rate, we observed significant population trends in elevated theta and beta band power and theta and alpha connectivity features at the cycle peaks (sign test, p < 0.05). In the period directly after stimulation we observe a decreased association between cycle phase and EEG features compared to background recordings (AUC: 0.58 [0.55-0.64]). Conclusions: Our findings suggest that seizure-correlated dIEA cycles are not solely due to epileptiform discharges but are associated with background measures of brain state; and that neurostimulation may disrupt these cycles. These results may help elucidate mechanisms underlying seizure generation, provide new biomarkers for seizure risk, and facilitate monitoring, treating, and managing epilepsy with implantable devices.
Language	English
Publishing date	2023-07-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.05.23291521
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Article ; Online: Resting-state background features demonstrate multidien cycles in long-term EEG device recordings.

Brain stimulation

2023 Volume 16, Issue 6, Page(s) 1709–1718

Abstract	Background: Longitudinal EEG recorded by implanted devices is critical for understanding and managing epilepsy. Recent research reports patient-specific, multi-day cycles in device-detected epileptiform events that coincide with increased likelihood of clinical seizures. Understanding these cycles could elucidate mechanisms generating seizures and advance drug and neurostimulation therapies. Objective/hypothesis: We hypothesize that seizure-correlated cycles are present in background neural activity, independent of interictal epileptiform spikes, and that neurostimulation may temporarily interrupt these cycles. Methods: We analyzed regularly-recorded seizure-free data epochs from 20 patients implanted with a responsive neurostimulation (RNS) device for at least 1.5 years, to explore the relationship between cycles in device-detected interictal epileptiform activity (dIEA), clinician-validated interictal spikes, background EEG features, and neurostimulation. Results: Background EEG features tracked the cycle phase of dIEA in all patients (AUC: 0.63 [0.56-0.67]) with a greater effect size compared to clinically annotated spike rate alone (AUC: 0.55 [0.53-0.61], p < 0.01). After accounting for circadian variation and spike rate, we observed significant population trends in elevated theta and beta band power and theta and alpha connectivity features at the cycle peaks (sign test, p < 0.05). In the period directly after stimulation we observe a decreased association between cycle phase and EEG features compared to background recordings (AUC: 0.58 [0.55-0.64]). Conclusions: Our findings suggest that seizure-correlated dIEA cycles are not solely due to epileptiform discharges but are associated with background measures of brain state; and that neurostimulation may temporarily interrupt these cycles. These results may help elucidate mechanisms underlying seizure generation, provide new biomarkers for seizure risk, and facilitate monitoring, treating, and managing epilepsy with implantable devices.
MeSH term(s)	Humans ; Electroencephalography/methods ; Epilepsy/therapy ; Seizures/therapy ; Brain
Chemical Substances	N,N-diisopropylethylamine (5SIQ15721L)
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2394410-9
ISSN	1876-4754 ; 1935-861X
ISSN (online)	1876-4754
ISSN	1935-861X
DOI	10.1016/j.brs.2023.11.005
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Article ; Online: The seizure severity score: a quantitative tool for comparing seizures and their response to therapy.

Pattnaik, Akash R / Ghosn, Nina J / Ong, Ian Z / Revell, Andrew Y / Ojemann, William K S / Scheid, Brittany H / Georgostathi, Georgia / Bernabei, John M / Conrad, Erin C / Sinha, Saurabh R / Davis, Kathryn A / Sinha, Nishant / Litt, Brian

Journal of neural engineering

2023 Volume 20, Issue 4

Abstract: Objective. ...

Abstract	Objective.
MeSH term(s)	Humans ; Seizures/diagnosis ; Seizures/therapy ; Epilepsy ; Electroencephalography/methods ; Brain/surgery ; Electrocorticography
Language	English
Publishing date	2023-08-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2170901-4
ISSN	1741-2552 ; 1741-2560
ISSN (online)	1741-2552
ISSN	1741-2560
DOI	10.1088/1741-2552/aceca1
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Article ; Online: Quantifying trial-by-trial variability during cortico-cortical evoked potential mapping of epileptogenic tissue.

Cornblath, Eli J / Lucas, Alfredo / Armstrong, Caren / Greenblatt, Adam S / Stein, Joel M / Hadar, Peter N / Raghupathi, Ramya / Marsh, Eric / Litt, Brian / Davis, Kathryn A / Conrad, Erin C

Epilepsia

2023 Volume 64, Issue 4, Page(s) 1021–1034

Abstract: Objective: Measuring cortico-cortical evoked potentials (CCEPs) is a promising tool for mapping epileptic networks, but it is not known how variability in brain state and stimulation technique might impact the use of CCEPs for epilepsy localization. We ... ...

Abstract	Objective: Measuring cortico-cortical evoked potentials (CCEPs) is a promising tool for mapping epileptic networks, but it is not known how variability in brain state and stimulation technique might impact the use of CCEPs for epilepsy localization. We test the hypotheses that (1) CCEPs demonstrate systematic variability across trials and (2) CCEP amplitudes depend on the timing of stimulation with respect to endogenous, low-frequency oscillations. Methods: We studied 11 patients who underwent CCEP mapping after stereo-electroencephalography electrode implantation for surgical evaluation of drug-resistant epilepsy. Evoked potentials were measured from all electrodes after each pulse of a 30 s, 1 Hz bipolar stimulation train. We quantified monotonic trends, phase dependence, and standard deviation (SD) of N1 (15-50 ms post-stimulation) and N2 (50-300 ms post-stimulation) amplitudes across the 30 stimulation trials for each patient. We used linear regression to quantify the relationship between measures of CCEP variability and the clinical seizure-onset zone (SOZ) or interictal spike rates. Results: We found that N1 and N2 waveforms exhibited both positive and negative monotonic trends in amplitude across trials. SOZ electrodes and electrodes with high interictal spike rates had lower N1 and N2 amplitudes with higher SD across trials. Monotonic trends of N1 and N2 amplitude were more positive when stimulating from an area with higher interictal spike rate. We also found intermittent synchronization of trial-level N1 amplitude with low-frequency phase in the hippocampus, which did not localize the SOZ. Significance: These findings suggest that standard approaches for CCEP mapping, which involve computing a trial-averaged response over a .2-1 Hz stimulation train, may be masking inter-trial variability that localizes to epileptogenic tissue. We also found that CCEP N1 amplitudes synchronize with ongoing low-frequency oscillations in the hippocampus. Further targeted experiments are needed to determine whether phase-locked stimulation could have a role in localizing epileptogenic tissue.
MeSH term(s)	Humans ; Electric Stimulation/methods ; Evoked Potentials/physiology ; Electroencephalography/methods ; Epilepsy/diagnosis ; Brain ; Brain Mapping/methods
Language	English
Publishing date	2023-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17528
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Article ; Online: Spike patterns surrounding sleep and seizures localize the seizure-onset zone in focal epilepsy.

Conrad, Erin C / Revell, Andrew Y / Greenblatt, Adam S / Gallagher, Ryan S / Pattnaik, Akash R / Hartmann, Nicole / Gugger, James J / Shinohara, Russell T / Litt, Brian / Marsh, Eric D / Davis, Kathryn A

Epilepsia

2023 Volume 64, Issue 3, Page(s) 754–768

Abstract: Objective: Interictal spikes help localize seizure generators as part of surgical planning for drug-resistant epilepsy. However, there are often multiple spike populations whose frequencies change over time, influenced by brain state. Understanding ... ...

Abstract	Objective: Interictal spikes help localize seizure generators as part of surgical planning for drug-resistant epilepsy. However, there are often multiple spike populations whose frequencies change over time, influenced by brain state. Understanding state changes in spike rates will improve our ability to use spikes for surgical planning. Our goal was to determine the effect of sleep and seizures on interictal spikes, and to use sleep and seizure-related changes in spikes to localize the seizure-onset zone (SOZ). Methods: We performed a retrospective analysis of intracranial electroencephalography (EEG) data from patients with focal epilepsy. We automatically detected interictal spikes and we classified different time periods as awake or asleep based on the ratio of alpha to delta power, with a secondary analysis using the recently published SleepSEEG algorithm. We analyzed spike rates surrounding sleep and seizures. We developed a model to localize the SOZ using state-dependent spike rates. Results: We analyzed data from 101 patients (54 women, age range 16-69). The normalized alpha-delta power ratio accurately classified wake from sleep periods (area under the curve = .90). Spikes were more frequent in sleep than wakefulness and in the post-ictal compared to the pre-ictal state. Patients with temporal lobe epilepsy had a greater wake-to-sleep and pre- to post-ictal spike rate increase compared to patients with extra-temporal epilepsy. A machine-learning classifier incorporating state-dependent spike rates accurately identified the SOZ (area under the curve = .83). Spike rates tended to be higher and better localize the seizure-onset zone in non-rapid eye movement (NREM) sleep than in wake or REM sleep. Significance: The change in spike rates surrounding sleep and seizures differs between temporal and extra-temporal lobe epilepsy. Spikes are more frequent and better localize the SOZ in sleep, particularly in NREM sleep. Quantitative analysis of spikes may provide useful ancillary data to localize the SOZ and improve surgical planning.
MeSH term(s)	Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Epilepsy, Temporal Lobe ; Retrospective Studies ; Seizures/surgery ; Epilepsies, Partial ; Epilepsy/surgery ; Sleep ; Electroencephalography
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17482
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Article ; Online: Long-term epilepsy outcome dynamics revealed by natural language processing of clinic notes.

Xie, Kevin / Gallagher, Ryan S / Shinohara, Russell T / Xie, Sharon X / Hill, Chloe E / Conrad, Erin C / Davis, Kathryn A / Roth, Dan / Litt, Brian / Ellis, Colin A

Epilepsia

2023 Volume 64, Issue 7, Page(s) 1900–1909

Abstract: Objective: Electronic medical records allow for retrospective clinical research with large patient cohorts. However, epilepsy outcomes are often contained in free text notes that are difficult to mine. We recently developed and validated novel natural ... ...

Abstract	Objective: Electronic medical records allow for retrospective clinical research with large patient cohorts. However, epilepsy outcomes are often contained in free text notes that are difficult to mine. We recently developed and validated novel natural language processing (NLP) algorithms to automatically extract key epilepsy outcome measures from clinic notes. In this study, we assessed the feasibility of extracting these measures to study the natural history of epilepsy at our center. Methods: We applied our previously validated NLP algorithms to extract seizure freedom, seizure frequency, and date of most recent seizure from outpatient visits at our epilepsy center from 2010 to 2022. We examined the dynamics of seizure outcomes over time using Markov model-based probability and Kaplan-Meier analyses. Results: Performance of our algorithms on classifying seizure freedom was comparable to that of human reviewers (algorithm F Significance: Our findings demonstrate that epilepsy outcome measures can be extracted accurately from unstructured clinical note text using NLP. At our tertiary center, the disease course often followed a remitting and relapsing pattern. This method represents a powerful new tool for clinical research with many potential uses and extensions to other clinical questions.
MeSH term(s)	Humans ; Retrospective Studies ; Natural Language Processing ; Epilepsy/epidemiology ; Seizures ; Electronic Health Records
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17633
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