Afterdischarge Research Articles

Detection of after-discharges during intraoperative functional brain mapping in awake brain tumor surgery using a novel high-density circular grid

ObjectiveTo evaluate intraoperative use of a novel high-density circular grid in detecting after-discharges (AD) on electrocorticography (ECoG) during functional brain mapping (FBM). MethodsFBM during glioma surgery (10/2016 to 5/2019) recorded ADs using a 22-channel circular grid compared to conventional strip electrodes. ADs were analyzed for detection, duration, amplitude, morphology, histology, direction, and clinical signs. ResultsThirty-two patients (mean age 54.2 years; r = 30–75) with glioma (WHO grade II-IV; 20 grade IV) had surgery. ADs during FBM were more likely in patients with wild-type as opposed to IDH-1 mutants (p < 0.0001) using more contacts compared with linear strip electrodes (p = 0.0001). More sensors tended to be involved in ADs detected by the circular grid vs strips (6.61 vs 3.43; p = 0.16) at lower stimulus intensity (3.14 mA vs 4.13 mA; p = 0.09). No difference in the number of cortical stimulations before resection was present (38.9 mA vs 47.9 mA; p = 0.26). ADs longer than 10 seconds were 32.5 seconds (circular grid) vs 58.4 (strips) (p = 0.12). ConclusionsHigh-density circular grids detect ADs in 360 degrees during FBM for glioma resection. Provocation of ADs was more likely in patients with wild-type than IDH-1 mutation. SignificanceCircular grids offer high-resolution ECoG during intraoperative FBM for detection of ADs.

Electrical stimulation mapping of language with stereo-EEG

ObjectiveWe prospectively validated stereo-electroencephalography (EEG) electrical stimulation mapping (ESM) of language against a reference standard of meta-analytic functional magnetic resonance imaging (fMRI) framework (Neurosynth). MethodsLanguage ESM was performed using 50 Hz, biphasic, bipolar, stimulation at 1–8 mA, with a picture naming task. Electrode contacts (ECs) were scored as ESM+ if ESM interfered with speech/language function. For each patient, presurgical MRI was transformed to a standard space and coregistered with computed tomographic (CT) scan to obtain EC locations. After whole-brain parcellation, this fused image data were intersected with three-dimensional language fMRI (Neurosynth), and each EC was classified as lying within/outside the fMRI language parcel. Diagnostic odds ratio (DOR) and other indices were estimated. Current thresholds for language inhibition and after-discharges (ADs) were analyzed using multivariable linear mixed models. ResultsIn 10 patients (5 females), aged 5.4–21.2 years, speech/language inhibition was noted with ESM on 87/304 (29%) ECs. Stereo-EEG language ESM was a valid classifier of fMRI (Neurosynth) language sites (DOR: 9.02, p < 0.0001), with high specificity (0.87) but poor sensitivity (0.57). Similar diagnostic indices were seen for ECs in frontal or posterior regions, and gray or white matter.Language threshold (3.1 ± 1.5 mA) was lower than AD threshold (4.0 ± 2.0 mA, p = 0.0001). Language and AD thresholds decreased with age and intelligence quotient. Electrical stimulation mapping triggered seizures/auras represented patients' habitual semiology with 1 Hz stimulation. ConclusionsStereo-EEG ESM can reliably identify cerebral parcels with/without language function but may under detect all language sites. We suggest a 50-Hz stimulation protocol for language ESM with stereo-EEG.

Virtual Cortical Stimulation Mapping of Epilepsy Networks to Localize the Epileptogenic Zone.

Cortical stimulation mapping (CSM) is a common clinical procedure for mapping eloquent cortex in epilepsy patients. Electrical responses to the stimulation, or after-discharges (ADs), that occur in response to stimulation can point to unstable regions of cortex that are more prone to spontaneous seizures. Clinicians are interested in identifying regions that start seizures, i.e., the epileptogenic zone (EZ), so that they can target treatment. However, during CSM, not all regions are stimulated, as it would be time-consuming and potentially harmful to the patient. This limits the clinician's ability to fully explore ADs to reliably localize the EZ. In this paper, we develop a virtual CSM procedure that processes pre-seizure intracranial EEG recordings obtained from epilepsy patients being treated at three different epilepsy centers. First, we identify a linear time varying network (LTVN) model from electrocorticography (ECoG) and stereo-EEG (SEEG) data using sparse least squares estimation for each patient. We then construct an virtual CSM by applying impulse perturbations to each electrode contact in the LTVN model and then measuring the ADs of the network. We summarize the l2-norm of the responses in the form of a heatmap that shows the spatio-temporal evolution of the ADs before, during, and after seizures. Finally we compute an impulse response ratio (IRR) metric from each heatmap, that measures the ratio between the mean norm of ADs of clinically annotated EZ contacts and the mean norm of ADs of the remaining contacts. We find that the IRR is higher in maps derived from patients with successful surgical outcomes and lower in failed surgical outcomes. This suggests that virtual CSM may provide valuable information to clinicians regarding EZ location.

Applying a Sensing-Enabled System for Ensuring Safe Anterior Cingulate Deep Brain Stimulation for Pain

Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) was offered to chronic pain patients who had exhausted medical and surgical options. However, several patients developed recurrent seizures. This work was conducted to assess the effect of ACC stimulation on the brain activity and to guide safe DBS programming. A sensing-enabled neurostimulator (Activa PC + S) allowing wireless recording through the stimulating electrodes was chronically implanted in three patients. Stimulation patterns with different amplitude levels and variable ramping rates were tested to investigate whether these patterns could provide pain relief without triggering after-discharges (ADs) within local field potentials (LFPs) recorded in the ACC. In the absence of ramping, AD activity was detected following stimulation at amplitude levels below those used in chronic therapy. Adjustment of stimulus cycling patterns, by slowly ramping on/off (8-s ramp duration), was able to prevent ADs at higher amplitude levels while maintaining effective pain relief. The absence of AD activity confirmed from the implant was correlated with the absence of clinical seizures. We propose that AD activity in the ACC could be a biomarker for the likelihood of seizures in these patients, and the application of sensing-enabled techniques has the potential to advance safer brain stimulation therapies, especially in novel targets.

Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats.

Objective: The adenosinergic system may influence excitability in the brain. Endogenous and exogenous adenosine has anticonvulsant activity presumably by activating A1 receptors. Adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) may thus bolster anticonvulsant effects, but its action and the number of A1 receptors at different developmental stages are not known. Methods: Hippocampal epileptic afterdischarges (ADs) were elicited in 12-, 15-, 18-, 25-, 45-, and 60-day-old rats. Stimulation and recording electrodes were implanted into the dorsal hippocampus. The A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.5 or 1 mg/kg) was administered intraperitoneally 10 min before the first stimulation. Control animals were injected with saline. All rats were stimulated with a 2-s series of 1-ms biphasic pulses delivered at 60 Hz with increasing stepwise intensity (0.05–0.6 mA). Each age and dose group contained 9–14 animals. The AD thresholds and durations were evaluated, and the A1 receptors were detected in the hippocampus in 7-, 10-, 12-, 15-, 18-, 21-, 25-, 32-, and 52-day-old rats. Results: Both CCPA doses significantly increased hippocampal AD thresholds in 12-, 15-, 18-, and 60-day-old rats compared to controls. In contrast, the higher dose significantly decreased AD threshold in the 25-day-old rats. The AD durations were significantly shortened in all age groups except for 25-day-old rats where they were significantly prolonged. A1 receptor expression in the hippocampus was highest in 10-day-old rats and subsequently decreased. Significance: The adenosine A1 receptor agonist CCPA exhibited anticonvulsant activity at all developmental stages studied here except for 25-day-old rats. Age-related differences might be due to the development of presynaptic A1 receptors in the hippocampus.

Chapter 20 - Electrocorticography and functional mapping

Brain mapping is often critical to the success of epilepsy and brain tumor surgeries. Mapping the cerebral cortex can be performed either extraoperatively or intraoperatively. When considering the optimal venue for a particular patient, a number of important considerations need to be considered including: the intended goals for the mapping, patient factors, anesthetic effects, stimulation parameters, cortical functions of interest, as well as the mapping modalities being considered. In this chapter, we will cover electrocorticography, cortical somatosensory evoked potentials, and the various neurophysiologic techniques used to map sensorimotor and cognitive functions, including language. One of the main uses of electrocorticography in epilepsy surgery is to map the cortical regions associated with epileptiform activity. This information is used to plan resection boundaries. Electrocorticography can also be used to monitor for afterdischarges (ADs) during direct cortical stimulation as well as for mapping high-frequency activity during various cognitive tasks. Cortical somatosensory evoked potentials can identify the central sulcus by mapping the dipolar activation of the primary somatosensory cortex that results from stimulation of the large fiber somatosensory pathway by peripheral nerve stimulation. Motor, sensory, and language cortex can also be identified by direct electrical cortical stimulation.

Generalized seizures evoked by nucleus accumbens stimulation induced an opiate-mediated suppression of psychosis relevant behaviors

We have previously demonstrated that kindling of the nucleus accumbens (NAc) induced psychosis relevant behaviors only after one, but not after five, stage-5 seizures, suggesting that five stage-5 NAc-evoked seizures antagonized psychosis relevant behaviors in rats. We hypothesized that brain opioid receptors are responsible for seizure-induced reduction of psychosis relevant behaviors in NAc kindled rats. Rats received NAc kindling until a stage-4 seizure was induced, after which naloxone, a non-specific opioid receptor antagonist, at dose of 1 or 10 mg/kg i.p., or saline (0.3 mL) i.p., was injected 15 min before each kindled seizure. Duration of afterdischarge (AD) was not significantly different among naloxone- and saline-treated groups. However, duration of postictal behavioral depression induced by a stage-5 seizure was significantly shorter in 10 mg/kg naloxone-treated than saline-treated rats, for long (>36 s) AD duration. When tested 3–4 days after five stage-5 seizures, 10 mg/kg naloxone-treated rats, as compared to saline-treated rats, showed a statistically significant loss of gating of hippocampal auditory evoked potentials, and significant reduction of startle response amplitude, but non-significant differences in prepulse inhibition and methamphetamine-induced locomotion. It is inferred that stage-5 seizures, by releasing endogenous opiates, contribute to postictal behavioral depression, and some long-term seizure-induced antipsychotic effects.

Threshold and distribution of afterdischarges with electrical cortical stimulation

ObjectiveThe present study aimed to investigate the threshold and distribution of afterdischarges (ADs) with cortical electrical stimulation for functional brain mapping. MethodWe retrospectively analyzed data from 11 patients with medically intractable epilepsy who underwent 50-Hz cortical electrical stimulation for functional mapping followed by resection. These patients became seizure free for more than six months. The threshold and distribution of ADs induced by the stimulation were evaluated. ResultsThe median threshold was 6 mA (range: 2–15 mA) for the frontal lobe, 8 mA (3–15 mA) for the temporal lobe, 6 mA (2–15 mA) for the parietal lobe, and 6 mA (4–12 mA) for the occipital lobe. No significant interlobar differences were observed in AD thresholds. No significant differences were noted between within and outside epileptogenic zones. The distribution of ADs, remote spread was observed in all patients, reflecting fronto-parieto-temporal connections, as well as contiguous spread. The stimulation of premotor areas, the inferior parietal lobule, supplementary motor area, and basal temporal areas appeared to induce ADs in remote cortices. ConclusionWhile no locational differences were observed in AD thresholds, each brain region showed a characteristic pattern for AD spread. Remote AD spread needs to be considered for safe functional mapping.

Quantitative Analysis of the Antiepileptogenic Effects of Low Frequency Stimulation Applied Prior or After Kindling Stimulation in Rats.

Background and Objective: Developing quantitative measures based on spectral analysis of electroencephalograph (EEG) recordings of neural activities plays an important role in developing efficient treatments for epilepsy. Such biomarkers can be used for developing open or closed loop approaches for seizure prediction or prevention. This study aims to quantitatively evaluate antiepileptogenic effects of low frequency stimulation (LFS) applied immediately before or after kindling stimulations using spectral power analysis of extracellular EEG in rat.Methods: Nineteen adult rats were used: seven for kindle, six for LFS+Kindle (LFSK) and six for Kindle+LFS (KLFS). Four packages of LFS (1Hz) were applied immediately before or after rapid kindling stimulations. The power spectral densities of afterdischarge (AD) sections of EEG corresponding to different stages of kindling for delta (0–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–28 Hz), gamma (28–40 Hz) sub-bands, and theta/alpha ratio were comparatively investigated. Moreover, correlation between AD duration (ADD) and its different frequency components was calculated.Results: Both LFSK and KLFS significantly increased delta and reduced beta and gamma oscillations, compared with kindle group. However, just the reduction in LFSK group was significant. Both protocols increased theta/alpha ratio, but just LFSK showed significant increase (p < 0.05). Although LFSK enhanced theta/alpha ratio more than KLFS, the difference was not statistically significant. Furthermore, strong correlation between each frequency sub band and ADD was not observed in kindle and LFS treated groups (both LFSK and KLFS).Conclusion: Although behavioral assessments showed relatively the same level of antiepileptogenic effects for KLFS and LFSK, quantitative assessments showed more significant differences in the quantitative measures between the two protocols. Developing more quantitative EEG based measures correlated with LFS-induced effects can facilitate developing open or closed loop seizure prevention modalities.

BS25. Language inhibition and motor response thresholds during extra-operative cortical stimulation mapping

Introduction Electrical cortical stimulation (ECS) is the clinical standard for brain mapping to define the functionally eloquent cortex in patients undergoing pre-surgical evaluation with intracranial electrodes. This study evaluated thresholds for language inhibition and motor response during ECS and their determinants. Methods A retrospective review of clinical information and extra-operative electrocorticography (ECoG) recordings was performed. The thresholds for functional responses were determined and compared with after-discharge (AD) thresholds. Multivariate models were used to evaluate predictors of functional thresholds. Results A total of 122 children were included. The mean language threshold was 7.4 ( ± 3.0) mA. 40/47 (85%) of patients with language response during ECS also had ADs. Language thresholds were found to be equal to or higher than AD thresholds in 34/40 (85%) patients. The mean motor threshold was 5.4 ( ± 2.8) mA. 71/85(83.5%) of patients with motor response during ECS also had ADs. Motor thresholds were found to be equal to or higher than AD thresholds in 47/71 (66%) patients. Minimum AD threshold was a significant determinant of minimum language threshold (regression co-efficient 0.446, 95% CI −0.001 to 0.892, p = 0.050) and minimum motor threshold (regression co-efficient 0.664, 95%CI 0.058 to 1.270, p = 0.034). Conclusion AD threshold was a significant determinant of language and motor thresholds. Most children with functional response during ECS also had ADs, with the functional thresholds being equal to or higher than AD thresholds. These findings underscore a potential pitfall in functional cortex localization with ECS findings and emphasize the need for a functional mapping method with improved neurophysiologic validity, especially in children.

T149. After-discharges and seizures during functional brain mapping with extra-operative electrical cortical stimulation

Electrical cortical stimulation (ECS) is the clinical standard for brain mapping to define the relationship between seizure-onset zone and functionally eloquent cortex in patients undergoing presurgical evaluation with intracranial electrodes. ECS-induced after-discharges (ADs) and seizures contribute to the morbidity and compromise the validity of ECS results. This study examines the incidence, thresholds, and determinants of ECS-induced ADs and seizures. A retrospective review of clinical information and extra-operative electrocorticography (ECoG) recordings was performed in pediatric patients to determine incidence and thresholds of ECS-induced Ads and seizures. Multivariate models were used to evaluate predictors of AD and seizure occurrence and their thresholds. A total of 122 children were included. The incidence of ADs and seizures were 77% (94/122) and 35% (43/122) respectively. Males (OR 2.92, 95% CI 1.21–7.38, p = 0.02) and patients with MRI-negative epilepsy (OR 3.69, 95% CI 1.24–13.7, p = 0.03) had increased odds of ECS-induced ADs. A significant trend for decreasing AD thresholds with age was seen (regression co-efficient 0.151, p = 0.011). ECSinduced seizures were more likely to occur in patients with lateralized positron emission tomography (OR 6.62, 95% CI 1.36–55.56, p = 0.036) and presence of ADs (OR 3.50, 95% CI 1.12–13.36, p = 0.043). ECS functional brain mapping is associated with a high incidence of ADs and seizures. Increasing age is significantly associated with decreasing current thresholds and increased probability of occurrence of ADs and seizures. These findings underscore the need to develop safer method(s) for mapping brain function, particularly in children.

Dynamic interaction of local and transhemispheric networks is necessary for progressive intensification of hippocampal seizures

The detailed mechanisms of progressive intensification of seizures often occurring in epilepsy are not well understood. Animal models of kindling, with progressive intensification of stimulation-induced seizures, have been previously used to investigate alterations in neuronal networks, but has been obscured by limited recording capabilities during electrical stimulations. Remote networks in kindling have been studied by physical deletions of the connected structures or pathways, inevitably leading to structural reorganisations and related adverse effects. We used optogenetics to circumvent the above-mentioned problems inherent to electrical kindling, and chemogenetics to temporarily inhibit rather than ablate the remote interconnected networks. Progressively intensifying afterdischarges (ADs) were induced by repetitive photoactivation of principal neurons in the hippocampus of anaesthetized transgenic mice expressing ChR2. This allowed, during the stimulation, to reveal dynamic increases in local field potentials (LFPs), which coincided with the start of AD intensification. Furthermore, chemogenetic functional inhibition of contralateral hippocampal neurons via hM4D(Gi) receptors abrogated AD progression. These findings demonstrate that, during repeated activation, local circuits undergo acute plastic changes with appearance of additional network discharges (LFPs), leading to transhemispheric recruitment of contralateral dentate gyrus, which seems to be necessary for progressive intensification of ADs.

Role of β2/3-specific GABA-A receptor isoforms in the development of hippocampus kindling epileptogenesis

ObjectiveSubunit-specific positive allosteric modulators (PAMs) of gamma-aminobutyric acid-A (GABA-A) receptors are commonly used to uncover the role of GABA-A receptor isoforms in brain function. Recently, we have designed novel PAMs selective for β2/3-subunit containing GABA-A receptors (β2/3-selective PAMs) that are nonbenzodiazepine site-mediated and do not show an α-subunit isoform selectivity, yet exhibit anxiolytic efficacy with reduced potential for sedation, cognitive impairment, and tolerance. In this study, we used three novel β2/3-selective PAMs (2-261, 2-262, and 10029) with differential β2/3-subunit potency to identify the role of β2/3-selective receptor isoforms in limbic epileptogenesis. MethodsExperimental epileptogenesis was induced in mice by daily hippocampus stimulations until each mouse showed generalized (stage 5) seizures. Patch-clamp electrophysiology was used to record GABA-gated currents. Brain levels of β2/3-selective PAMs were determined for mechanistic correlations. ResultsTreatment with the β2/3-selective PAMs 2-261 (30mg/kg), 2-262 (10mg/kg), and 10029 (30mg/kg), 30min prior to stimulations, significantly suppressed the rate of development of kindled seizure activity without affecting the afterdischarge (AD) signal, indicating their disease-modifying activity. The β2/3-selective agents suppressed chemical epileptogenesis in the pentylenetetrazol model. Test doses of these agents were devoid of acute antiseizure activity in the kindling model. ConclusionThese findings demonstrate that β2/3-selective PAMs can moderately retard experimental epileptogenesis, indicating the protective role of β2/3-subunit GABA-A receptor isoforms in the development of epilepsy.

08-Development of cortical evoked potentials and epileptic after discharges in rats

Cortical interhemispheric responses in rats may serve as an index of maturation. The first two waves monosynaptically elicited by callosal fibres can be reliably evoked since the postnatal day (PD) five. The latency and duration of these evoked potentials markedly shorten after PD7. Paired-pulse stimulations demonstrate fatiguability of immature cortex; potentiation of the second response takes place since the third week. Frequency potentiation appears in the fourth postnatal week. Epileptic afterdischarges (ADs) can be elicited by low-frequency rhythmic stimulation since PD9. Their duration is longest at PD12, then it shortens. If stimulation is repeated, adult animals exhibit postictal refractoriness, i.e. an inability to elicit the second AD. This refractoriness lasting up to 3 min appeared in the fourth postnatal week, animals at PD12 and 15 exhibit marked postictal potentiation – the second, testing AD is significantly longer than the first conditioning AD. The results demonstrate that electrical stimulation induces a purely cortical phenomenon (interhemispheric responses) earlier than the complex cortico-thalamo-cortical epileptic AD. Paired stimulations demonstrate that potentiation appeared earlier in epileptic ADs than in more simple cortical evoked potentials. This study was supported by US-Czech collaborative grants No. LH11015 and LH15032 and a project of Czech Academy of Sciences No. RVO 67985823.

Fosphenytoin pre-medication for pediatric extra-operative electrical stimulation brain mapping

PurposeWe studied the effect of fosphenytoin (FOS) pre-medication on the incidence and thresholds of after-discharges (ADs), seizures, and functional responses during electrical stimulation mapping (ESM). MethodsAs individualized by the attending epileptologist, FOS was given intravenously at 2 mg-phenytoin-equivalents (PE)/kg/min or 150 mg-PE/min (whichever slower). Patients who received and did not receive FOS were compared for the incidence and thresholds of ADs, seizures, and functional responses. ResultsBefore ESM, 40 and 82 patients respectively were pre-medicated/not pre-medicated with FOS. The incidence of ESM-induced seizures was significantly lower in FOS pre-medicated patients (22.5% vs. 42.7%, p = 0.044), whereas temporal language threshold was higher (9.2 vs. 6.5 mA, p = 0.032). FOS was more efficacious in preventing ESM-induced seizures in patients with symptomatogenic zone ipsilateral to the side of ESM.Although FOS dose had no significant effect on minimum language, minimum motor, or AD thresholds; seizure and temporal language thresholds showed trends approaching significance, intersecting at 12.2 mg-PE/kg. The incidence of ESM-induced seizures was significantly lower in those who received FOS at a dose of ≤12 mg/kg (9.1%) compared to those who did not receive any FOS (42.7%, p = 0.046), while the temporal language thresholds were not significantly different (6.3 vs. 6.5 mA, p = 0.897). ConclusionsThis study provides class III evidence that FOS pre-medication before ESM decreases the incidence of ESM-induced seizures, but increases temporal language threshold. FOS pre-medication may thus be considered before ESM. Future studies should prospectively verify these observations and characterize dose-response relationships.

Locally stable brain states predict suppression of epileptic activity by enhanced cognitive effort.

Cognitive effort is known to play a role in healthy brain state organization, but little is known about its effects on pathological brain dynamics. When cortical stimulation is used to map functional brain areas prior to surgery, a common unwanted side effect is the appearance of afterdischarges (ADs), epileptiform and potentially epileptogenic discharges that can progress to a clinical seizure. It is therefore desirable to suppress this activity. Here, we analyze electrocorticography recordings from 15 patients with epilepsy. We show that a cognitive intervention in the form of asking an arithmetic question can be effective in suppressing ADs, but that its effectiveness is dependent upon the brain state at the time of intervention. By applying novel techniques from network analysis to quantify brain states, we find that the spatial organization of ADs with respect to coherent brain regions relates to the success of the cognitive intervention: if ADs are mainly localized within a single stable brain region, a cognitive intervention is likely to suppress the ADs. These findings show that cognitive effort is a useful tactic to modify unstable pathological activity associated with epilepsy, and suggest that the success of therapeutic interventions to alter activity may depend on an individual's brain state at the time of intervention.

Participation of GABAB receptors in cortical postictal excitability in immature rats

Arrest of seizures is due to an active inhibition and is followed in mature brain by period of refractoriness markedly present one min after the end of seizures. To study changes in cortical excitability after epileptic seizures we used electrical stimulation of sensorimotor cortical area in immature rats – 25-day-old ones with mature postictal refractoriness and 12-day-old where postictal potentiation of afterdischarges (ADs) is present instead of refractoriness at one minute after the end of the conditioning AD. GABAB receptor antagonist CGP35348 was found to partly suppress postictal refractoriness. In present study not only an antagonist CGP46381 (3 and 10mg/kg i.p.) but also positive allosteric modulator of GABAB receptors CGP7930 (20 and 40mg/kg i.p.) were used to study the role of GABAB receptors in both age groups. They were injected immediately after testing AD and 10min later the two stimulations were repeated. CGP46381 partly antagonized postictal refractoriness in 25-day-old rats but did not significantly affect ADs in 12-day-old animals. CGP7930 did not significantly change ADs duration in either age group.GABAB receptors participate in mechanism of postictal refractoriness but did not play an important role in 12-day-old rats where potentiation instead of refractoriness is present.

Properties of afterdischarges from electrical stimulation in patients with epilepsy

ObjectiveTo investigate the properties of afterdischarges (ADs) from intracerebral electrical stimulation (ES) in patients with epilepsy who underwent stereotactic electroencephalography (SEEG) and determine the relationship between epileptogenic zone (EZ) or irritative zone (IZ) and ADs. MethodsWe retrospectively analyzed 10 patients with intractable epilepsy who underwent SEEG. ESs were delivered following the given parameters: bipolar, biphasic, 50Hz, 0.2ms pulse duration, 0.5–10mA. The properties of ADs were documented, including their incidence, location, threshold, morphology and evolution. ResultsA total of 213 ADs (5%) were elicited by 4701 trains of ES. Stimulation through contacts implanted in the hippocampus (59%) generally evoked more ADs than contacts elsewhere (19%). AD thresholds for hippocampal stimulation were significantly lower than those for stimulation in grey matter. Polyspikes (58%) were the most common AD morphology. Evolution occurred more commonly with sequential spikes (47%) than with other AD morphologies (14%). There was no significant correlation between the location of ADs and EZ. However, ADs were significantly more frequently localized to IZ than areas outside IZ (P<0.05). ConclusionsThere seemed to be a lack of correlation between the location of ADs and EZ. However, ADs were more likely to be elicited in IZ.

After-discharges and seizures during pediatric extra-operative electrical cortical stimulation functional brain mapping: Incidence, thresholds, and determinants

ObjectiveThis study examined the incidence, thresholds, and determinants of electrical cortical stimulation (ECS)-induced after-discharges (ADs) and seizures. MethodsElectrocorticograph recordings were reviewed to determine incidence of ECS-induced ADs and seizures. Multivariable analyses for predictors of AD/seizure occurrence and their thresholds were performed. ResultsIn 122 patients, the incidence of ADs and seizures was 77% (94/122) and 35% (43/122) respectively. Males (odds ratio [OR] 2.92, 95% CI 1.21–7.38, p=0.02) and MRI-negative patients (OR 3.69, 95% CI 1.24–13.7, p=0.03) were found to have higher odds of ECS-induced ADs. A significant trend for decreasing AD thresholds with age was seen (regression co-efficient −0.151, 95% CI −0.267 to −0.035, p=0.011). ECS-induced seizures were more likely in patients with lateralized functional imaging (OR 6.62, 95% CI 1.36–55.56, p=0.036, for positron emission tomography) and presence of ADs (OR 3.50, 95% CI 1.12–13.36, p=0.043). ConclusionsECS is associated with a high incidence of ADs and seizures. With age, current thresholds decrease and the probability for AD/seizure occurrence increases. SignificanceADs and seizures during ECS brain mapping are potentially hazardous and affect its functional validity. Thus, safer method(s) for brain mapping with improved neurophysiologic validity are desirable.

Language and motor function thresholds during pediatric extra-operative electrical cortical stimulation brain mapping

ObjectiveTo examine current thresholds and their determinants for language and motor mapping with extra-operative electrical cortical stimulation (ECS). MethodsECS electrocorticograph recordings were reviewed to determine functional thresholds. Predictors of functional thresholds were found with multivariable analyses. ResultsIn 122 patients (age 11.9±5.4years), average minimum, frontal, and temporal language thresholds were 7.4 (± 3.0), 7.8 (± 3.0), and 7.4 (± 3.1) mA respectively. Average minimum, face, upper and lower extremity motor thresholds were 5.4 (± 2.8), 6.1 (± 2.8), 4.9 (± 2.3), and 5.3 (± 3.3) mA respectively.Functional and after-discharge (AD)/seizure thresholds were significantly related. Minimum, frontal, and temporal language thresholds were higher than AD thresholds at all ages. Minimum motor threshold was higher than minimum AD threshold up to 8.0years of age, face motor threshold was higher than frontal AD threshold up to 11.8years age, and lower subsequently. UE motor thresholds remained below frontal AD thresholds throughout the age range. ConclusionsFunctional thresholds are frequently above AD thresholds in younger children. SignificanceThese findings raise concerns about safety and neurophysiologic validity of ECS mapping. Functional and AD/seizure thresholds relationships suggest individual differences in cortical excitability which cannot be explained by clinical variables.