Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program.

OBJECTIVE: Aberrant glutamate and γ-aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies. METHODS: Subjects (n = 79) were medically refractory epilepsy patients undergoing intracranial electroencephalogram evaluation. Microdialysis probes (n = 125) coupled to depth electrodes were implanted within suspected seizure onset sites and microdialysis samples were obtained during interictal periods. Glutamate, glutamine, and GABA were measured using high-performance liquid chromatography. Probe locations were subsequently classified by consensus of expert epileptologists. RESULTS: Glutamate levels were elevated in epileptogenic (p = 0.03; n = 7), nonlocalized (p < 0.001), and lesional cortical sites (p < 0.001) when compared to nonepileptogenic cortex. Glutamate was also elevated in epileptogenic (p < 0.001) compared to nonepileptogenic hippocampus. There were no statistical differences in GABA or glutamine, although GABA levels showed high variability across patients and groups. INTERPRETATION: Our findings indicate that chronically elevated extracellular glutamate is a common pathological feature among epilepsies with different etiology. Contrary to our predictions, GABA and glutamine levels were not decreased in any of the measured areas. Whereas variability in GABA levels may in part be attributed to the use of GABAergic antiepileptic drugs, the stability in glutamine across patient groups indicate that extracellular glutamine levels are under tighter metabolic regulation than previously thought. Ann Neurol 2016;80:35-45.

Influence of anxiety on memory performance in temporal lobe epilepsy.

This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 patients with temporal lobe epilepsy from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was poorer for those with high versus low levels of anxiety but was not found to be related to the TLE side. The verbal memory score on the California Verbal Learning Test (CVLT) was significantly lower for patients with left-sided TLE than for patients with right-sided TLE with low anxiety levels but equally impaired for those with high anxiety levels. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left-sided TLE for those with low anxiety levels, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety levels. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety levels. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety levels. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among patients with TLE, regardless of anxiety levels.

Impaired consciousness in temporal lobe seizures: role of cortical slow activity.

Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.

Suicide outcomes after resective epilepsy surgery.

People with epilepsy have a higher risk for suicide than people without epilepsy. The relationship between seizure control and suicide is controversial. A standardized protocol to record history, diagnostic testing, and neuropsychiatric assessments was administered. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered presurgically and yearly for up to 5 years. Among the 396 enrolled, 4 of 27 deaths were attributed to suicide. The standardized mortality ratio, compared with suicides in the U.S. population and adjusted for age and gender, was 13.3 (95% CI=3.6-34.0). Only one patient had a BDI score suggestive of severe depression (BDI=33), one had depressive symptoms that did not the meet the depressive range (BDI=7), and the other two reported no depressive symptoms. Two of the patients reported moderate to severe anxiety symptoms (BAI=17 and 21, respectively). Suicide may occur after epilepsy surgery, even when patients report excellent seizure control.

Visual memory in patients after anterior right temporal lobectomy and adult normative data for the Brown Location Test.

Several large meta-analytic studies have failed to support a consistent relationship between visual or "nonverbal" memory deficits and right mesial temporal lobe changes. The Brown Location Test (BLT), a recently developed dot location learning and memory test, uses a nonsymmetrical array and provides control over many of the confounding variables (e.g., verbal influence and drawing requirements) inherent in other measures of visual memory. In the present investigation, we evaluated the clinical utility of the BLT in patients who had undergone left or right anterior mesial temporal lobectomy. We also provide normative data of 298 healthy adults for standardized scores. Results revealed significantly worse performance on the BLT in the right as compared to the left lobectomy group and the healthy adult normative sample. The present findings support a role for the right anterior mesial temporal lobe in dot location learning and memory.

Spatial distribution of intracranially recorded spikes in medial and lateral temporal epilepsies.

PURPOSE: Although seizures and interictal spikes are not always colocalized, there may be valuable localizing information in the spatial distribution of spikes. To test this hypothesis, we studied the spatial distribution of intracranially recorded interictal spikes in patients with medial temporal (MT) and lateral temporal (LT) neocortical seizure onset. METHODS: A total of 21 patients (MT n = 12, LT n = 9) who completed intracranial monitoring were selected for this study. Two 4-h intracranial electroencephalography (icEEG) epochs were analyzed, one during wake and one during sleep, both at least 6 h removed from seizures. Spikes detected automatically in medial temporal structures [hippocampal formation (H) and entorhinal cortex (EC)], and in five cortical areas (occipital, frontal, parietal, lateral temporal, and inferior temporal) were tabulated. RESULTS: Interictal spikes occurred broadly over medial temporal structures and cortical areas in MT and LT patients. The patients differed with a greater number of spikes in medial temporal structures in the MT group (p < 0.05 for H and p < 0.001 for EC) and a greater number of spikes in parietal (p < 0.01) and frontal (p < 0.001) areas in the LT group. There were sleep-related increases in spike rates in inferomedial temporal structures in both groups. The two groups could be separated with a classifier based on medial temporal and parietal and frontal spikes (p < 0.0001). DISCUSSION: MT and LT patients have different spatial distributions of interictal spikes and can be distinguished by the relative spike rates in medial temporal and extratemporal areas during sleep and wake.

Racial differences in patient expectations prior to resective epilepsy surgery.

We assessed the nature and frequency of preoperative expectations among patients with refractory epilepsy who were enrolled in a seven-center observational study of epilepsy surgery outcomes. At enrollment, patients responded to open-ended questions about expectations for surgical outcome. With the use of an iterative cutting-and-sorting technique, expectation themes were identified and rank-ordered. Associations of expectations with race/ethnicity were evaluated. Among 391 respondents, the two most frequently endorsed expectations (any rank order) were driving (62%) and job/school (43%). When only the most important (first-ranked) expectation was analyzed, driving (53%) and cognition (17%) were most frequently offered. Nonwhites endorsed job/school and cognition more frequently and driving less frequently than whites (all P0.05), whether expectations of any order or only first-ranked expectations were included. Elucidating the reason for these differences can aid in the clinical decision-making process for resective surgery and potentially address disparities in its utilization.

Effects of working memory load on oscillatory power in human intracranial EEG.

Studies of working memory load effects on human EEG power have indicated divergent effects in different frequency bands. Although gamma power typically increases with load, the load dependency of the lower frequency theta and alpha bands is uncertain. We obtained intracranial electroencephalography measurements from 1453 electrode sites in 14 epilepsy patients performing a Sternberg task, in order to characterize the anatomical distribution of load-related changes across the frequency spectrum. Gamma power increases occurred throughout the brain, but were most common in the occipital lobe. In the theta and alpha bands, both increases and decreases were observed, but with different anatomical distributions. Increases in theta and alpha power were most prevalent in frontal midline cortex. Decreases were most commonly observed in occipital cortex, colocalized with increases in the gamma range, but were also detected in lateral frontal and parietal regions. Spatial overlap with group functional magnetic resonance imaging results was minimal except in the precentral gyrus. These findings suggest that power in any given frequency band is not a unitary phenomenon; rather, reactivity in the same frequency band varies in different brain regions, and may relate to the engagement or inhibition of a given area in a cognitive task.

Health-related quality of life over time since resective epilepsy surgery.

OBJECTIVE: Health-related quality of life (HRQOL) improves after resective epilepsy surgery, but data are limited to short follow-up in mostly retrospective reports, with minimal consideration of other potential factors that might influence HRQOL. METHODS: In a prospective multicenter study, 396 patients underwent resective epilepsy surgery. They completed the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) before surgery, within 6 months, and at approximately yearly intervals after surgery. Seizure outcome was ascertained by phone calls every 3 months, and dates of postoperative seizures were chronicled. Overall HRQOL as measured by the QOLIE-89 was evaluated with respect to seizure outcome using logistic regression. RESULTS: QOLIE-89 scores increased significantly at the first postoperative measurement (within 6 months after surgery) in the cohort overall; subsequent changes over time were sensitive to seizure-free and aura-free status. After adjusting for baseline scores, the corresponding postsurgical QOLIE-89 overall, and four dimension scores, increased as a function of square root of time seizure-free, and independently as a function of square root of time aura free, leveling by 2 years of stable seizure (aura) status. HRQOL was not independently related to duration of epilepsy, duration of intractable epilepsy, or continuation of medications. INTERPRETATION: HRQOL improves early after surgery, regardless of seizure outcome. Subsequent changes parallel length of time seizure free or aura free, stabilize after 2 years, and are unrelated to duration of epilepsy, duration of intractable epilepsy, or continued medication use.

Interictal spikes on intracranial recording: behavior, physiology, and implications.

PURPOSE: The physiological, pathological, and clinical meaning of interictal spikes (IISs) remains controversial. We systematically analyzed the frequency, occurrence, and distribution of IISs recorded from multiple intracranial electrodes in 34 refractory epileptic patients with respect to seizures and antiepileptic drug (AED) changes. METHODS: Continuous spike counts from all recorded contacts of all implanted electrodes, and also separately for the subset of contacts involved at seizure onset, were tabulated for every hour of every day of recording, and expressed as spikes per hour in six preselected, 24-h intervals (defined to exclude seizures): (1) on medications; (2) prepreseizure; (3) preseizure; (4) postseizure; (5) off meds; and (6) resumed meds. Mean spike rates were analyzed for differences between designated 24-h intervals. RESULTS: Spike rate in all recorded contacts consistently and significantly decreased after AED withdrawal, despite variability in initial spike rate, diurnal occurrence, seizure character/number/localization of onset, and type(s) of AED continued or withdrawn (p < 0.0001). A significant increase in spike rate was noted in the 24 h after seizures of medial temporal origin, in the medial temporal lobe contacts; neocortical onset seizures did not show any increase. CONCLUSIONS: These observations confirm and extend previous reports, suggesting a general effect of AED withdrawal, and a more specific effect of medial temporal lobe seizures, on IIS rate. AED mechanisms and efficacy might be demonstrated by quantifying IIS with changes in AEDs. Furthermore, variability in IIS rate after seizures distinguishes localization of seizure onset in medial temporal versus neocortical locations.

Local spatial effect of 50 Hz cortical stimulation in humans.

PURPOSE: Cortical stimulation to abort seizures is under human investigation. Ideal electrode placement and stimulating parameters are unknown with poor understanding of tissue volume affected by stimulation or duration and nature of its effect on cortical activity. To help characterize this effect, we analyzed electrocorticography (ECoG) recorded adjacent to stimulated contacts during and after bipolar stimulation in patients undergoing functional cortical mapping with subdural electrodes. METHODS: We analyzed four functional mapping procedures in three patients. One row of contacts was chosen for bipolar stimulation at sequential distances. Stimulation parameters were those used for functional mapping. Pooled Teager energy (TE) and band power were calculated for: (1) baseline, (2) 5 s during stimulation, and (3) 5-15 s after the stimulus. RESULTS: Average TE increased during stimulation, falling with distance from the stimulus. Average poststimulus TE increased (284-905%) compared to baseline. Increased TE was observed: (1) up to 10 s after stimulation, (2) stimulation amplitudes of 4 mA or greater, and (3) up to 2 cm from the stimulus. There was no difference in poststimulus TE between the stimulated pair of contacts and outside the pair. Greatest increase in poststimulus signal power occurred in beta and gamma bands. CONCLUSIONS: Human cortical stimulation of 50 Hz resulted in elevated ECoG energy measurements up to 10 s poststimulation. Contacts >2 cm from stimulated electrodes did not show significant response to stimulation. Separating contacts >2 cm on the cortical surface may not result in efficacious treatment of seizure activity using common stimulation amplitudes (2-10 mA).

Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients.

PURPOSE: Temporal lobe epilepsy (TLE) is associated with smaller hippocampal volume and with elevated extracellular (EC) glutamate levels. We investigated the relationship between the hippocampal volume and glutamate in refractory TLE patients. METHODS: We used quantitative MRI volumetrics to measure the hippocampal volume and zero-flow microdialysis to measure the interictal glutamate, glutamine, and GABA levels in the epileptogenic hippocampus of 17 patients with medication-resistant epilepsy undergoing intracranial EEG evaluation. The relationships between hippocampal volume, neurochemical levels, and relevant clinical factors were examined. RESULTS: Increased EC glutamate in the epileptogenic hippocampus was significantly related to smaller ipsilateral (R(2)= 0.75, p < 0.0001), but not contralateral hippocampal volume when controlled for glutamine and GABA levels, and for clinical factors known to influence hippocampal volume. Glutamate in the atrophic hippocampus was significantly higher (p = 0.008, n = 9), with the threshold for hippocampal atrophy estimated as 5 microM. GABA and glutamine levels in the atrophic and nonatrophic hippocampus were comparable. Decreased hippocampal volume was related to higher seizure frequency (p = 0.008), but not to disease duration or febrile seizure history. None of these clinical factors were related to the neurochemical levels. CONCLUSIONS: We provide evidence for a significant association between increased EC glutamate and decreased ipsilateral epileptogenic hippocampal volume in TLE. Future work will be needed to determine whether the increase in glutamate has a causal relationship with hippocampal atrophy, or whether another, yet unknown factor results in both. This work has implications for the understanding and treatment of epilepsy as well as other neurodegenerative disorders associated with hippocampal atrophy.

Expanding CERC beyond public health: sharing best practices with healthcare managers via virtual learning.

Developed by the Center for Disease Control and Prevention in 2002, the Crisis Emergency and Risk Communication (CERC) training module is a nationally and internationally recognized communication model. With the looming threat of a pandemic and the potential for a protracted ongoing siege, a valuable opportunity exists to introduce crisis and emergency preparedness communication best practices to a new population--health care managers and administrators. The CERC toolkit and resources, provide an easy, turn-key solution and a validated template for educators who are not directly involved in public health education but desire to share this content. In this example, graduate students enrolled in an Master of Health Administration program, used a Play2Train scenario, located in the virtual learning environment of SecondLife (2007), to incorporate concepts from the CERC model. By applying the CERC best practices in a real-time virtual learning scenario, students learned collaboration and the leadership competencies necessary to help implement Joint Commission on Accreditation of Health Organizations emergency communication protocols and community collaboration requirements. By expanding the impact of the CERC model and developing unified risk communication responses and information sharing, all health professionals can enhance the effectiveness of their emergency preparedness plans so that the public can be better served.

On the use of bipolar montages for time-series analysis of intracranial electroencephalograms.

OBJECTIVE: Bipolar montages are routinely employed for the interpretation of scalp and intracranial EEGs (icEEGs). In this manuscript we consider the assumptions that support the use of a bipolar montage and question the universal appropriateness of bipolar representation of icEEGs for the time-series analysis of these signals. Bipolar montages introduce an element of spatial processing into the observed time-series. In the case of icEEGs, we argue ambiguity may be introduced in some settings through this operation because of a lack of certifiability of local differentiability and continuity of the spatial structure of icEEGs, and their suboptimal spatial sampling. METHODS: Example icEEGs were collected from three patients being studied for possible resective epilepsy surgery. Referential and bipolar representations of these signals were subjected to different visual and time-series analysis. The time-series measures calculated were the power spectral density and magnitude squared coherence. RESULTS: Visual analysis and time-series measures revealed that the icEEG time-series was altered by the use of a bipolar montage. The changes resulted from either the introduction of unrelated information from the two referential time-series into the bipolar time-series, or from the removal or alteration of information common to the two referential time-series in the bipolar time-series. The changes could not be predicted without prior knowledge of the relationship between measurement sites that form the bipolar montage. CONCLUSIONS: In certain settings, bipolar montages alter icEEGs and can confound the time-series analysis of these signals. In such settings, bipolar montages should be used with caution in the time-series analysis of icEEGs. SIGNIFICANCE: This manuscript addresses the representation of the intracranial EEG for time-series analysis. There may be contexts where the assumptions underpinning correct application of the bipolar montage to the intracranial EEG are not satisfied.

The relationship between seizures, interictal spikes and antiepileptic drugs.

OBJECTIVE: A considerable decrease in spike rate accompanies antiepileptic drug (AED) taper during intracranial EEG (icEEG) monitoring. Since spike rate during icEEG monitoring can be influenced by surgery to place intracranial electrodes, we studied spike rate during long-term scalp EEG monitoring to further test this observation. METHODS: We analyzed spike rate, seizure occurrence and AED taper in 130 consecutive patients over an average of 8.9days (range 5-17days). RESULTS: We observed a significant relationship between time to the first seizure, spike rate, AED taper and seizure occurrence (F (3,126)=19.77, p<0.0001). A high spike rate was related to a longer time to the first seizure. Further, in a subset of 79 patients who experienced seizures on or after day 4 of monitoring, spike rate decreased initially from an on- to off-AEDs epoch (from 505.0 to 382.3 spikes per hour, p<0.00001), and increased thereafter with the occurrence of seizures. CONCLUSIONS: There is an interplay between seizures, spikes and AEDs such that spike rate decreases with AED taper and increases after seizure occurrence. SIGNIFICANCE: The direct relationship between spike rate and AEDs and between spike rate and time to the first seizure suggests that spikes are a marker of inhibition rather than excitation.

When should temporal-lobe epilepsy be treated surgically?

Our current knowledge of mesial-temporal-lobe epilepsy (MTLE) is extensive, yet still insufficient to draw final conclusions on the optimal approach to its therapy. MTLE has been well characterised and can usually be identified with noninvasive studies including scalp electroencephalography (EEG) and video monitoring with ictal recording, magnetic resonance imaging, single-photon-emission computed tomography, positron emission tomography, neuropsychological assessment, and historical and clinical data. Sometimes, invasive EEG is needed to confirm mesial-temporal-lobe seizure onset, which, combined with the underlying pathological abnormality (the substrate) of mesial temporal sclerosis (hippocampal neuronal loss and gliosis), defines MTLE. This disorder is the most common refractory partial epilepsy, and also the one most often treated surgically, because medical treatment fails in 75% of cases, and surgical treatment succeeds in a similar percentage. Despite the recent publication of the first randomised trial of surgical treatment for MTLE, questions remain about the neurological consequences of both medical and surgical treatment, the ultimate gains in quality of life parameters, and the precise predictors of success. Long-term follow-up and analyses of multiple factors in large groups of contemporary patient populations will be necessary to fully answer the question, "is temporal lobe epilepsy a surgical disease?" Right now it should be considered one in most cases.

Surgical management of parietal lobe epilepsy.

Parietal lobe seizure foci are difficult to localize unless there is an MRI lesion or contralateral sensory aura. Rapid network projection often makes scalp EEG and semiology misleading. However, seizure control can be achieved with reasonable success when concordant information guides the physician to a parietal ictal onset. Perhaps the most important messages that this small surgical series provides is that of neurologic outcome. The parietal lobe is a highly convergent cortical region and a major network way station. Except for primary sensory phenomena and language, one cannot temporarily ablate parietal cortical association area within a presumed epileptogenic region and predict the visuospatial, cognitive, and neurologic outcome. Therefore, data demonstrating that one can resect regions of parietal cortex and not cause serious dysfunction are helpful. The mild morbidity encountered in this group of patients would not be necessarily predicted if the same region of normal parietal lobe was resected. Therefore, one must consider cortical plasticity and functional redistribution as possible reasons for this, particularly when most of these substrates are of developmental origin.

An approach to the evaluation of a patient for seizures and epilepsy.

Epilepsy affects approximately 1 percent of the population and is characterized by recurrent unprovoked seizures. A careful clinical history is often helpful in diagnosis, classification of seizure and epilepsy types, selection of appropriate ancillary studies, selection of anti-epileptic drugs, and formulation of a long-term management plan. This article provides directions and guidelines both for the family practice physician and the specialist in evaluating this patient population in the clinics.

Intracranially recorded interictal spikes: relation to seizure onset area and effect of medication and time of day.

OBJECTIVE: The relationship between seizures and interictal spikes remains undetermined. We analyzed intracranial EEG (icEEG) recordings to examine the relationship between the seizure onset area and interictal spikes. METHODS: 80 unselected patients were placed into 5 temporal, 4 extratemporal, and one unlocalized groups based on the location of the seizure onset area. We studied 4-h icEEG epochs, removed from seizures, from day-time and night-time during both on- and off-medication periods. Spikes were detected automatically from electrode contacts sampling the hemisphere ipsilateral to the seizure onset area. RESULTS: There was a widespread occurrence of spikes over the hemisphere ipsilateral to the seizure onset area. The spatial distributions of spike rates for the different patient groups were different (p<0.0001, chi-square test). The area with the highest spike rate coincided with the seizure onset area only in half of the patients. CONCLUSION: The spatial distribution of spike rates is strongly associated with the location of the seizure onset area, suggesting the presence of a distributed spike generation network, which is related to the seizure onset area. SIGNIFICANCE: The spatial distribution of spike rates, but not the area with the highest spike rate, may hold value for the localization of the seizure onset area.

Background intracranial EEG spectral changes with anti-epileptic drug taper.

OBJECTIVE: Previous studies have revealed a surprising decrease in spike counts and Teager energy between on- and off-AEDs states during intracranial EEG (icEEG) monitoring. Here, we expand the measures evaluated to icEEG power and frequency band power. METHODS: Two icEEG epochs, on- and off-AEDs, each 1h in duration, were studied for each of 21 unselected adult patients. Spike counts, Teager energy and total power were evaluated for each electrode contact. Power was also evaluated for delta (0-4Hz), theta (4-8Hz), alpha (8-13Hz), beta (13-25Hz), gamma (25-55Hz) and high (65-128Hz) frequency bands. RESULTS: A decrease in power accompanies AED taper and the previously reported decrease in spike counts and Teager energy. The decrease in power was underpinned by a spatially widespread and broadband decrease in power in delta through gamma frequency bands with maximum decrease in the lowest frequency bands. An increase in high-frequency power was observed in some patients. CONCLUSIONS: There is a decrease in spike counts, Teager energy and power from on- to off-AEDs state during intracranial monitoring. The decrease in power is spatially widespread and broadband including power in the delta through gamma frequency bands. SIGNIFICANCE: The decrease in cortical activity with AED taper suggests that seizure generation during intracranial monitoring may not be mediated solely by poorly regulated cortical excitation.