Prognostic Value of Complete Resection of the High-Frequency Oscillation Area in Intracranial EEG: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: High-frequency oscillations (HFOs; ripples 80-250 Hz; fast ripples [FRs] 250-500 Hz) recorded with intracranial electrodes generated excitement and debate about their potential to localize epileptogenic foci. We performed a systematic review and meta-analysis on the prognostic value of complete resection of the HFOs-area (crHFOs-area) for epilepsy surgical outcome in intracranial EEG (iEEG) accessing multiple subgroups. METHODS: We searched PubMed, Embase, and Web of Science for original research from inception to October 27, 2022. We defined favorable surgical outcome (FSO) as Engel class I, International League Against Epilepsy class 1, or seizure-free status. The prognostic value of crHFOs-area for FSO was assessed by (1) the pooled FSO proportion after crHFOs-area; (2) FSO for crHFOs-area vs without crHFOs-area; and (3) the predictive performance. We defined high combined prognostic value as FSO proportion >80% + FSO crHFOs-area >without crHFOs-area + area under the curve (AUC) >0.75 and examined this for the clinical subgroups (study design, age, diagnostic type, HFOs-identification method, HFOs-rate thresholding, and iEEG state). Temporal lobe epilepsy (TLE) was compared with extra-TLE through dichotomous variable analysis. Individual patient analysis was performed for sex, affected hemisphere, MRI findings, surgery location, and pathology. RESULTS: Of 1,387 studies screened, 31 studies (703 patients) met our eligibility criteria. Twenty-seven studies (602 patients) analyzed FRs and 20 studies (424 patients) ripples. Pooled FSO proportion after crHFOs-area was 81% (95% CI 76%-86%) for FRs and 82% (73%-89%) for ripples. Patients with crHFOs-area achieved more often FSO than those without crHFOs-area (FRs odds ratio [OR] 6.38, 4.03-10.09, p < 0.001; ripples 4.04, 2.32-7.04, p < 0.001). The pooled AUCs were 0.81 (0.77-0.84) for FRs and 0.76 (0.72-0.79) for ripples. Combined prognostic value was high in 10 subgroups: retrospective, children, long-term iEEG, threshold (FRs and ripples) and automated detection and interictal (FRs). FSO after complete resection of FRs-area (crFRs-area) was achieved less often in people with TLE than extra-TLE (OR 0.37, 0.15-0.89, p = 0.006). Individual patient analyses showed that crFRs-area was seen more in patients with FSO with than without MRI lesions (p = 0.02 after multiple correction). DISCUSSION: Complete resection of the brain area with HFOs is associated with good postsurgical outcome. Its prognostic value holds, especially for FRs, for various subgroups. The use of HFOs for extra-TLE patients requires further evidence.

Robust compression and detection of epileptiform patterns in ECoG using a real-time spiking neural network hardware framework.

Interictal Epileptiform Discharges (IED) and High Frequency Oscillations (HFO) in intraoperative electrocorticography (ECoG) may guide the surgeon by delineating the epileptogenic zone. We designed a modular spiking neural network (SNN) in a mixed-signal neuromorphic device to process the ECoG in real-time. We exploit the variability of the inhomogeneous silicon neurons to achieve efficient sparse and decorrelated temporal signal encoding. We interface the full-custom SNN device to the BCI2000 real-time framework and configure the setup to detect HFO and IED co-occurring with HFO (IED-HFO). We validate the setup on pre-recorded data and obtain HFO rates that are concordant with a previously validated offline algorithm (Spearman's ρ = 0.75, p = 1e-4), achieving the same postsurgical seizure freedom predictions for all patients. In a remote on-line analysis, intraoperative ECoG recorded in Utrecht was compressed and transferred to Zurich for SNN processing and successful IED-HFO detection in real-time. These results further demonstrate how automated remote real-time detection may enable the use of HFO in clinical practice.

Auditory prediction errors in sound frequency and duration generated different cortical activation patterns in the human brain: an ECoG study.

Sound frequency and duration are essential auditory components. The brain perceives deviations from the preceding sound context as prediction errors, allowing efficient reactions to the environment. Additionally, prediction error response to duration change is reduced in the initial stages of psychotic disorders. To compare the spatiotemporal profiles of responses to prediction errors, we conducted a human electrocorticography study with special attention to high gamma power in 13 participants who completed both frequency and duration oddball tasks. Remarkable activation in the bilateral superior temporal gyri in both the frequency and duration oddball tasks were observed, suggesting their association with prediction errors. However, the response to deviant stimuli in duration oddball task exhibited a second peak, which resulted in a bimodal response. Furthermore, deviant stimuli in frequency oddball task elicited a significant response in the inferior frontal gyrus that was not observed in duration oddball task. These spatiotemporal differences within the Parasylvian cortical network could account for our efficient reactions to changes in sound properties. The findings of this study may contribute to unveiling auditory processing and elucidating the pathophysiology of psychiatric disorders.

High-performance prediction of epilepsy surgical outcomes based on the genetic neural networks and hybrid iEEG marker.

Accurately identification of the seizure onset zone (SOZ) is pivotal for successful surgery in patients with medically refractory epilepsy. The purpose of this study is to improve the performance of model predicting the epilepsy surgery outcomes using genetic neural network (GNN) model based on a hybrid intracranial electroencephalography (iEEG) marker. We extracted 21 SOZ related markers based on iEEG data from 79 epilepsy patients. The least absolute shrinkage and selection operator (LASSO) regression was employed to integrated seven markers, selected after testing in pairs with all 21 biomarkers and 7 machine learning models, into a hybrid marker. Based on the hybrid marker, we devised a GNN model and compared its predictive performance for surgical outcomes with six other mainstream machine-learning models. Compared to the mainstream models, underpinning the GNN with the hybrid iEEG marker resulted in a better prediction of surgical outcomes, showing a significant increase of the prediction accuracy from approximately 87% to 94.3% (P = 0.0412). This study suggests that the hybrid iEEG marker can improve the performance of model predicting the epilepsy surgical outcomes, and validates the effectiveness of the GNN in characterizing and analyzing complex relationships between clinical data variables.

Generalisability of epileptiform patterns across time and patients.

The complexity of localising the epileptogenic zone (EZ) contributes to surgical resection failures in achieving seizure freedom. The distinct patterns of epileptiform activity during interictal and ictal phases, varying across patients, often lead to suboptimal localisation using electroencephalography (EEG) features. We posed two key questions: whether neural signals reflecting epileptogenicity generalise from interictal to ictal time windows within each patient, and whether epileptiform patterns generalise across patients. Utilising an intracranial EEG dataset from 55 patients, we extracted a large battery of simple to complex features from stereo-EEG (SEEG) and electrocorticographic (ECoG) neural signals during interictal and ictal windows. Our features (n = 34) quantified many aspects of the signals including statistical moments, complexities, frequency-domain and cross-channel network attributes. Decision tree classifiers were then trained and tested on distinct time windows and patients to evaluate the generalisability of epileptogenic patterns across time and patients, respectively. Evidence strongly supported generalisability from interictal to ictal time windows across patients, particularly in signal power and high-frequency network-based features. Consistent patterns of epileptogenicity were observed across time windows within most patients, and signal features of epileptogenic regions generalised across patients, with higher generalisability in the ictal window. Signal complexity features were particularly contributory in cross-patient generalisation across patients. These findings offer insights into generalisable features of epileptic neural activity across time and patients, with implications for future automated approaches to supplement other EZ localisation methods.

High-density cortical µECoG arrays concurrently track spreading depolarizations and long-term evolution of stroke in awake rats.

Spreading depolarizations (SDs) are widely recognized as a major contributor to the progression of tissue damage from ischemic stroke even if blood flow can be restored. They are characterized by negative intracortical waveforms of up to -20 mV, propagation velocities of 3 - 6 mm/min, and massive disturbance of membrane ion homeostasis. High-density, micro-electrocorticographic (µECoG) epidural electrodes and custom, DC-coupled, multiplexed amplifiers, were used to continuously characterize and monitor SD and µECoG cortical signal evolution in awake, moving rats over days. This highly innovative approach can define these events over a large brain surface area (~ 3.4 × 3.4 mm), extending across the boundaries of the stroke, and offers sufficient electrode density (60 contacts total per array for a density of 5.7 electrodes / mm2) to measure and determine the origin of SDs in relation to the infarct boundaries. In addition, spontaneous ECoG activity can simultaneously be detected to further define cortical infarct regions. This technology allows us to understand dynamic stroke evolution and provides immediate cortical functional activity over days. Further translational development of this approach may facilitate improved treatment options for acute stroke patients.

Long-Term Home EEG Recording: Wearable and Implantable Devices.

SUMMARY: Electroencephalography (EEG) monitoring has served as a cornerstone in the diagnostic and therapeutic evaluation of epilepsy since its development. This has been accomplished with short-term inpatient video-EEG hospitalization enabling observation of both the semiological and the electrographic features of seizures or with short-term home ambulatory EEG or video-EEG. The advantages of inpatient video-EEG monitoring are limited by high cost, inconvenience, and inability to monitor patients for long periods (weeks or months) as might be done in the outpatient setting. This limitation has impelled the development of wearable EEG devices, which aim to capture high-quality long-term EEG data in a user-friendly and unobtrusive manner. This review article aims to summarize three broad categories of wearable EEG devices, including scalp, subcutaneous, and intracranial EEG. In this review, we will discuss the features of each type of device and the implications for the management of epilepsy. This review does not aim to describe every wearable EEG device on the market but instead seeks to provide a broad overview of the various categories of device that are available, giving examples of each and those in development (with no intention to recommend or advocate for any particular product).

Intracerebral Dynamics of Sleep Arousals: A Combined Scalp-Intracranial EEG Study.

As an intrinsic component of sleep architecture, sleep arousals represent an intermediate state between sleep and wakefulness and are important for sleep-wake regulation. They are defined in an all-or-none manner, whereas they actually present a wide range of scalp-electroencephalography (EEG) activity patterns. It is poorly understood how these arousals differ in their mechanisms. Stereo-EEG (SEEG) provides the unique opportunity to record intracranial activities in superficial and deep structures in humans. Using combined polysomnography and SEEG, we quantitatively categorized arousals during nonrapid eye movement sleep into slow wave (SW) and non-SW arousals based on whether they co-occurred with a scalp-EEG SW event. We then investigated their intracranial correlates in up to 26 brain regions from 26 patients (12 females). Across both arousal types, intracranial theta, alpha, sigma, and beta activities increased in up to 25 regions (p < 0.05; d = 0.06-0.63), while gamma and high-frequency (HF) activities decreased in up to 18 regions across the five brain lobes (p < 0.05; d = 0.06-0.44). Intracranial delta power widely increased across five lobes during SW arousals (p < 0.05 in 22 regions; d = 0.10-0.39), while it widely decreased during non-SW arousals (p < 0.05 in 19 regions; d = 0.10-0.30). Despite these main patterns, unique activities were observed locally in some regions such as the hippocampus and middle cingulate cortex, indicating spatial heterogeneity of arousal responses. Our results suggest that non-SW arousals correspond to a higher level of brain activation than SW arousals. The decrease in HF activities could potentially explain the absence of awareness and recollection during arousals.

Patient experiences of resection versus responsive neurostimulation for drug-resistant epilepsy.

This study explored illness experiences and decision-making among patients with epilepsy who underwent two different types of surgical interventions: resection versus implantation of the NeuroPace Responsive Neurostimulation System (RNS). We recruited 31 participants from a level four epilepsy center in an academic medical institution. We observed 22 patient clinic visits (resection: n = 10, RNS: n = 12) and conducted 18 in-depth patient interviews (resection: n = seven, RNS: n = 11); most visits and interviews included patient caregivers. Using an applied ethnographic approach, we identified three major themes in the experiences of resection versus RNS patients. First, for patients in both cohorts, the therapeutic journey was circuitous in ways that defied standardized first-, second-, and third- line of care models. Second, in conceptualizing risk, resection patients emphasized the permanent loss of "taking out" brain tissue whereas RNS patients highlighted the reversibility of "putting in" a device. Lastly, in considering benefit, resection patients perceived their surgery as potentially curative while RNS patients understood implantation as primarily palliative with possible additional diagnostic benefit from chronic electrocorticography. Insight into the perspectives of patients and caregivers may help identify key topics for counseling and exploration by clinicians.

The impact of simultaneous intracranial recordings on scalp EEG: A finite element analysis.

BACKGROUND: In this study, we examined the utility of simultaneous scalp and stereotactic intracranial electroencephalography (SSIEEG) in epilepsy patients. Although SSIEEG offers valuable insights into epilepsy and cognitive function, its routine use is uncommon. Challenges include interpreting post-craniotomy scalp EEG due to surgically implanted electrodes. NEW METHOD: We describe our methodology for conducting SSIEEG recordings. To simulate the potential impact on EEG interpretation, we computed the leadfield of scalp electrodes with and without burrholes using Finite Element Analysis to compare the resulting sensitivity volume and waveforms of simulated intracranial signals between skulls with and without burrholes. RESULTS: The presence of burr holes in the skull layer of the leadfield models did not discernibly modify simulated waveforms or scalp EEG topology. Using realistic SEEG burr hole diameter, the difference in the average leadfield of scalp electrodes was 0.12% relative to the effect of switching two nearby electrodes, characterized by the cosine similarity difference. No patients experienced adverse events related to SSIEEG. COMPARISON WITH EXISTING METHODS: Although there is increasing acceptance and interest in SSIEEG, few studies have characterized the technical feasibility. Here, we demonstrate through modelling that scalp recordings from SSIEEG are comparable to that through an intact skull. CONCLUSION: The placement and simultaneous acquisition of scalp EEG during invasive monitoring through stereotactically inserted EEG electrodes is routinely performed at the Hospital for Sick Children. Scalp EEG recordings may assist with clinical interpretation. Burr holes in the skull layer did not discernibly alter EEG waveforms or topology.

A personalized earbud for non-invasive long-term EEG monitoring.

Objective. The primary objective of this study was to evaluate the reliability, comfort, and performance of a custom-fit, non-invasive long-term electrophysiologic headphone, known as Aware Hearable, for the ambulatory recording of brain activities. These recordings play a crucial role in diagnosing neurological disorders such as epilepsy and in studying neural dynamics during daily activities.Approach.The study uses commercial manufacturing processes common to the hearing aid industry, such as 3D scanning, computer-aided design modeling, and 3D printing. These processes enable the creation of the Aware Hearable with a personalized, custom-fit, thereby ensuring complete and consistent contact with the inner surfaces of the ear for high-quality data recordings. Additionally, the study employs a machine learning data analysis approach to validate the recordings produced by Aware Hearable, by comparing them to the gold standard intracranial electroencephalography recordings in epilepsy patients.Main results.The results indicate the potential of Aware Hearable to expedite the diagnosis of epilepsy by enabling extended periods of ambulatory recording.Significance.This offers significant reductions in burden to patients and their families. Furthermore, the device's utility may extend to a broader spectrum, making it suitable for other applications involving neurophysiological recordings in real-world settings.

A biophysically constrained brain connectivity model based on stimulation-evoked potentials.

BACKGROUND: Single-pulse electrical stimulation (SPES) is an established technique used to map functional effective connectivity networks in treatment-refractory epilepsy patients undergoing intracranial-electroencephalography monitoring. While the connectivity path between stimulation and recording sites has been explored through the integration of structural connectivity, there are substantial gaps, such that new modeling approaches may advance our understanding of connectivity derived from SPES studies. NEW METHOD: Using intracranial electrophysiology data recorded from a single patient undergoing stereo-electroencephalography (sEEG) evaluation, we employ an automated detection method to identify early response components, C1, from pulse-evoked potentials (PEPs) induced by SPES. C1 components were utilized for a novel topology optimization method, modeling 3D electrical conductivity to infer neural pathways from stimulation sites. Additionally, PEP features were compared with tractography metrics, and model results were analyzed with respect to anatomical features. RESULTS: The proposed optimization model resolved conductivity paths with low error. Specific electrode contacts displaying high error correlated with anatomical complexities. The C1 component strongly correlated with additional PEP features and displayed stable, weak correlations with tractography measures. COMPARISON WITH EXISTING METHOD: Existing methods for estimating neural signal pathways are imaging-based and thus rely on anatomical inferences. CONCLUSIONS: These results demonstrate that informing topology optimization methods with human intracranial SPES data is a feasible method for generating 3D conductivity maps linking electrical pathways with functional neural ensembles. PEP-estimated effective connectivity is correlated with but distinguished from structural connectivity. Modeled conductivity resolves connectivity pathways in the absence of anatomical priors.

Multimodal single-neuron, intracranial EEG, and fMRI brain responses during movie watching in human patients.

We present a multimodal dataset of intracranial recordings, fMRI, and eye tracking in 20 participants during movie watching. Recordings consist of single neurons, local field potential, and intracranial EEG activity acquired from depth electrodes targeting the amygdala, hippocampus, and medial frontal cortex implanted for monitoring of epileptic seizures. Participants watched an 8-min long excerpt from the video "Bang! You're Dead" and performed a recognition memory test for movie content. 3 T fMRI activity was recorded prior to surgery in 11 of these participants while performing the same task. This NWB- and BIDS-formatted dataset includes spike times, field potential activity, behavior, eye tracking, electrode locations, demographics, and functional and structural MRI scans. For technical validation, we provide signal quality metrics, assess eye tracking quality, behavior, the tuning of cells and high-frequency broadband power field potentials to familiarity and event boundaries, and show brain-wide inter-subject correlations for fMRI. This dataset will facilitate the investigation of brain activity during movie watching, recognition memory, and the neural basis of the fMRI-BOLD signal.

Pediatric Intraoperative Neurophysiologic Mapping and Monitoring in Brain Surgery.

SUMMARY: Similar to adults, children undergoing brain surgery can significantly benefit from intraoperative neurophysiologic mapping and monitoring. Although young brains present the advantage of increased plasticity, during procedures in close proximity to eloquent regions, the risk of irreversible neurological compromise remains and can be lowered further by these techniques. More so, pathologies specific to the pediatric population, such as neurodevelopmental lesions, often result in medically refractory epilepsy. Thus, their successful surgical treatment also relies on accurate demarcation and resection of the epileptogenic zone, processes in which intraoperative electrocorticography is often employed. However, stemming from the development and maturation of the central and peripheral nervous systems as the child grows, intraoperative neurophysiologic testing in this population poses methodologic and interpretative challenges even to experienced clinical neurophysiologists. For example, it is difficult to perform awake craniotomies and language testing in the majority of pediatric patients. In addition, children may be more prone to intraoperative seizures and exhibit afterdischarges more frequently during functional mapping using electrical cortical stimulation because of high stimulation thresholds needed to depolarize immature cortex. Moreover, choice of anesthetic regimen and doses may be different in pediatric patients, as is the effect of these drugs on immature brain; these factors add additional complexity in terms of interpretation and analysis of neurophysiologic recordings. Below, we are describing the modalities commonly used during intraoperative neurophysiologic testing in pediatric brain surgery, with emphasis on age-specific clinical indications, methodology, and challenges.

Multi-night cortico-basal recordings reveal mechanisms of NREM slow-wave suppression and spontaneous awakenings in Parkinson's disease.

Sleep disturbance is a prevalent and disabling comorbidity in Parkinson's disease (PD). We performed multi-night (n = 57) at-home intracranial recordings from electrocorticography and subcortical electrodes using sensing-enabled Deep Brain Stimulation (DBS), paired with portable polysomnography in four PD participants and one with cervical dystonia (clinical trial: NCT03582891). Cortico-basal activity in delta increased and in beta decreased during NREM (N2 + N3) versus wakefulness in PD. DBS caused further elevation in cortical delta and decrease in alpha and low-beta compared to DBS OFF state. Our primary outcome demonstrated an inverse interaction between subcortical beta and cortical slow-wave during NREM. Our secondary outcome revealed subcortical beta increases prior to spontaneous awakenings in PD. We classified NREM vs. wakefulness with high accuracy in both traditional (30 s: 92.6 ± 1.7%) and rapid (5 s: 88.3 ± 2.1%) data epochs of intracranial signals. Our findings elucidate sleep neurophysiology and impacts of DBS on sleep in PD informing adaptive DBS for sleep dysfunction.

Benchmarking signal quality and spatiotemporal distribution of interictal spikes in prolonged human iEEG recordings using CorTec wireless brain interchange.

Neuromodulation through implantable pulse generators (IPGs) represents an important treatment approach for neurological disorders. While the field has observed the success of state-of-the-art interventions, such as deep brain stimulation (DBS) or responsive neurostimulation (RNS), implantable systems face various technical challenges, including the restriction of recording from a limited number of brain sites, power management, and limited external access to the assessed neural data in a continuous fashion. To the best of our knowledge, for the first time in this study, we investigated the feasibility of recording human intracranial EEG (iEEG) using a benchtop version of the Brain Interchange (BIC) unit of CorTec, which is a portable, wireless, and externally powered implant with sensing and stimulation capabilities. We developed a MATLAB/SIMULINK-based rapid prototyping environment and a graphical user interface (GUI) to acquire and visualize the iEEG captured from all 32 channels of the BIC unit. We recorded prolonged iEEG (~ 24 h) from three human subjects with externalized depth leads using the BIC and commercially available clinical amplifiers simultaneously in the epilepsy monitoring unit (EMU). The iEEG signal quality of both streams was compared, and the results demonstrated a comparable power spectral density (PSD) in all the systems in the low-frequency band (< 80 Hz). However, notable differences were primarily observed above 100 Hz, where the clinical amplifiers were associated with lower noise floor (BIC-17 dB vs. clinical amplifiers < - 25 dB). We employed an established spike detector to assess and compare the spike rates in each iEEG stream. We observed over 90% conformity between the spikes rates and their spatial distribution captured with BIC and clinical systems. Additionally, we quantified the packet loss characteristic in the iEEG signal during the wireless data transfer and conducted a series of simulations to compare the performance of different interpolation methods for recovering the missing packets in signals at different frequency bands. We noted that simple linear interpolation has the potential to recover the signal and reduce the noise floor with modest packet loss levels reaching up to 10%. Overall, our results indicate that while tethered clinical amplifiers exhibited noticeably better noise floor above 80 Hz, epileptic spikes can still be detected successfully in the iEEG recorded with the externally powered wireless BIC unit opening the road for future closed-loop neuromodulation applications with continuous access to brain activity.

Irregularity of instantaneous gamma frequency in the motor control network characterize visuomotor and proprioceptive information processing.

Objective.The study aims to characterize movements with different sensory goals, by contrasting the neural activity involved in processing proprioceptive and visuo-motor information. To accomplish this, we have developed a new methodology that utilizes the irregularity of the instantaneous gamma frequency parameter for characterization.Approach.In this study, eight essential tremor patients undergoing an awake deep brain stimulation implantation surgery repetitively touched the clinician's finger (forward visually-guided/FV movement) and then one's own chin (backward proprioceptively-guided/BP movement). Neural electrocorticographic recordings from the motor (M1), somatosensory (S1), and posterior parietal cortex (PPC) were obtained and band-pass filtered in the gamma range (30-80 Hz). The irregularity of the inter-event intervals (IEI; inverse of instantaneous gamma frequency) were examined as: (1) auto-information of the IEI time series and (2) correlation between the amplitude and its proceeding IEI. We further explored the network connectivity after segmenting the FV and BP movements by periods of accelerating and decelerating forces, and applying the IEI parameter to transfer entropy methods.Main results.Conceptualizing that the irregularity in IEI reflects active new information processing, we found the highest irregularity in M1 during BP movement, highest in PPC during FV movement, and the lowest during rest at all sites. Also, connectivity was the strongest from S1 to M1 and from S1 to PPC during FV movement with accelerating force and weakest during rest.Significance. We introduce a novel methodology that utilize the instantaneous gamma frequency (i.e. IEI) parameter in characterizing goal-oriented movements with different sensory goals, and demonstrate its use to inform the directional connectivity within the motor cortical network. This method successfully characterizes different movement types, while providing interpretations to the sensory-motor integration processes.

The value of additional electrodes when stereo-electroencephalography is inconclusive.

OBJECTIVE: Stereo-electroencephalography (SEEG) is the preferred method for intracranial localization of the seizure-onset zone (SOZ) in drug-resistant focal epilepsy. Occasionally SEEG evaluation fails to confirm the pre-implantation hypothesis. This leads to a decision tree regarding whether the addition of SEEG electrodes (two-step SEEG - 2sSEEG) or placement of subdural electrodes (SDEs) after SEEG (SEEG2SDE) would help. There is a dearth of literature encompassing this scenario, and here we aimed to characterize outcomes following unplanned two-step intracranial EEG (iEEG). METHODS: All 225 adult SEEG cases over 8 years at our institution were reviewed to extract patient data and outcomes following a two-step evaluation. Three raters independently quantified benefits of additional intracranial electrodes. The relationship between two-step iEEG benefit and clinical outcome was then analyzed. RESULTS: Fourteen patients underwent 2sSEEG and nine underwent SEEG2SDE. In the former cohort, the second SEEG procedure was performed for these reasons-precise localization of the SOZ (36%); defining margins of eloquent cortex (21%); and broadening coverage in the setting of non-localizable seizure onsets (43% of cases). Sixty-four percent of 2sSEEG cases were consistently deemed beneficial (Light's κ = 0.80). 2sSEEG performed for the first two indications was much more beneficial than when onsets were not localizable (100% vs 17%, p = .02). In the SEEG2SDE cohort, SDEs identified the SOZ and enabled delineation of margins relative to eloquent cortex in all cases. SIGNIFICANCE: The two-step iEEG is useful if the initial evaluation is broadly concordant with the original electroclinical hypothesis, where it can clarify onset zones or delineate safe surgical margins; however, it provides minimal benefit when the implantation hypothesis is erroneous, and we recommend that 2sSEEG not be generally utilized in such cases. SDE implantation after SEEG minimizes the need for SDEs and is helpful in delineating surgical boundaries relative to ictal-onset zones and eloquent cortex.