Fast Ripple Research Articles

High frequency activity overriding cortico-cortical evoked potentials reflects altered excitability in the human epileptic focus.

We aimed to clarify that high frequency activity (HFA) of cortico-cortical evoked potentials (CCEPs), elicited by single pulse electrical stimulation (SPES), reflects cortical excitability. We recruited 16 patients with refractory partial epilepsy who had chronic subdural electrode implantation for presurgical evaluation. A repetitive SPES was given to (1) the seizure onset zone (SOZ) and (2) the control cortices (non-seizure onset zone: nSOZ). CCEPs were recorded from the neighboring cortices within SOZ and nSOZ. We applied short-time Fourier transform to obtain the induced responses for the timing of early (<50ms after SPES) and late CCEP components and analyzed the logarithmic power change for ripple (<200Hz) and fast ripple (>200Hz) bands. Twenty-one clear CCEPs were recorded for both the SOZ and nSOZ. The HFA power of early CCEPs in SOZ significantly increased compared to that in nSOZ in both frequency bands, particularly in mesial temporal lobe epilepsy (MTLE). Similar to the features of spontaneous pathological HFOs, the power of stimulus-induced HFAs in SOZ were greater than that outside SOZ, particularly in MTLE. HFA overriding CCEPs can be a surrogate marker of cortical excitability in epileptic focus.

The glutamate receptor antagonists CNQX and MPEP decrease fast ripple events in rats treated with kainic acid.

Fast ripples (FR) are high frequency oscillations (250-600Hz) that have been associated with epilepsy. FR are assumed to be generated in small areas of the hippocampus (1mm3) that contain pathologically interconnected glutamate pyramidal cell clusters. Additionally, a relation between glutamate neurotransmission and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainite (AMPA/KA) and metabotropic mGluR5 receptors is well established. Therefore, we hypothesized that antagonism of these glutamate receptors would decrease FR activity. For this propose, we induced status epilepticus with a kainic acid injection in the posterior right hippocampus and performed intracranial EEG recordings to detect and evaluate the presence of FR 15days after the injection. The glutamate AMPA/KA receptor antagonist CNQX (10mg/kg) and the mGluR5 antagonist MPEP (20mg/kg) were administered intraperitoneally, and the effects of the drugs were evaluated for a period of three hours after their administration. The results show a decrease in the number of FR in the first hour after drug administration in both cases (CNQX, p=0.0125; MPEP, p=0.0132) and a return to basal values in the third hour of the experiment, but not significant differences in the number of oscillations per event of FR, and the frequency and duration of each event of FR. We therefore conclude that blockade of AMPA/KA and mGluR5 receptors transiently decreases the generation of FR; however, the mechanisms by which this effect is achieved are to be further analyzed in future experiments.

Correlation between resection of high frequency oscillation region and outcomes of epilepsy surgery

Objective To explore the relationship between removal of areas where high frequency oscillations (HFOs) were detected by a new automatic detector and the prognosis of epilepsy surgical. Methods In this study, 7 patients with intractable epilepsy were enrolled and their clinical data were retrospectively studied, who underwent intracranial electroencephalography (EEG) monitoring and subsequent epileptogenic zone resection from January 2013 and December 2014 at Epilepsy Center of Beijing Haidian Hospital. An automatic detector of HFOs was employed using maximum distributed peak points to calculate baseline. Then the relationship between the removal ratio of HFOs and surgical outcomes was investigated. Results Among the 7 cases of refractory epilepsy, the resection ratio of ripple area was 19.4% ~ 96.4% and that of fast ripple area was 29.3% ~ 96.0% . The surgical removal ratio of HFO areas was higher than 50% in 5 cases, 4 out of whom achieved good outcomes after surgery. In the other 2 patients whose removal ratio of HFO area was lower than 50%, poor surgical outcome was reported in 1 and good outcome was obtained in the other who had extensive area demonstrating suspicious physiological HFOs in the occipital lobe. Conclusions The automatic detector of HFOs using maximum distributed peak points to calculate baseline seems to be accurate for detection of HFOs. The ratio of resection in areas with HFOs might be closely related to the surgical outcomes. Key words: Epilepsy; Neurosurgical procedures; Maximum distributed peak points; High frequency oscillations; Prognosis

Intraoperative fast ripples independently predict postsurgical epilepsy outcome: Comparison with other electrocorticographic phenomena

In the surgical management of epilepsy, the resection of cortex exhibiting interictal fast ripples (250–500Hz) on electrocorticography has been linked to postoperative seizure-freedom. Although fast ripples appear to accurately identify the epileptogenic zone—the minimum tissue that must be removed at surgery to achieve seizure-freedom—it has not been established that fast ripples are a superior biomarker in comparison with multimodal presurgical neuroimaging and other electrocorticography abnormalities. Hence, in the prediction of postoperative seizure-freedom, we compared the value of fast ripples with other intraoperative electocorticography abnormalities including focal slowing, paroxysmal fast activity, intermittent spike discharges, continuous epileptiform discharges, focal attenuation, and intraoperative seizures, as well as complete resection of the lesion defined by MRI and other neuroimaging. In a cohort of 60 children with lesional epilepsy and median postsurgical follow-up exceeding 4 years, who underwent resective epilepsy surgery with intraoperative electrocorticography, we evaluated the extent to which removal of each intraoperative electrocorticography abnormality impacts time to first postoperative seizure using the Kaplan-Meier method and Cox proportional hazards regression. Secondly, we contrasted the predictive value of resection of each competing electrocorticography abnormality using standard test metrics (sensitivity, specificity, positive predictive value, and negative predictive value). In contrast with all other intraoperative electrocorticography abnormalities, fast ripples demonstrated the most favorable combination of positive predictive value (100%) and negative predictive value (76%) in the prediction of postoperative seizures. Among all candidate electrocorticography features, time to first postoperative seizure was most strongly associated with incomplete resection of fast ripples (hazard ratio=19.8, p<0.001). In multivariate survival analyses, postoperative seizures were independently predicted by incomplete resection of cortex generating fast ripples (hazard ratio=25.4, 95%CI 6.71–96.0, p<0.001) and focal slowing (hazard ratio=5.79, 95%CI 1.76–19.0, p=0.004), even after adjustment for the impact of an otherwise complete resection. All children with incomplete resection of interictal FR-generating cortex exhibited postoperative seizures within six months. Notably, this cohort included many patients with large resections and thus limited opportunity to exhibit unresected fast ripples. Future study in a cohort with small resection volume, or a clinical trial in which resection margins are guided by fast ripple distribution, would likely yield a more precise estimate of the risk posed by unresected fast ripples. With a high detection rate during brief intraoperative electrocorticography and favorable positive and negative predictive value, interictal fast ripple characterization during surgery is a feasible and useful adjunct to standard methods for epilepsy surgery planning, and represents a valuable spatially-localizing biomarker of the epileptogenic zone, without the need for prolonged extraoperative electrocorticography.

1-1-06. Repeated, cortical stimulation can modify the wideband cortical activity correlates of interictal epileptiform discharge

Electric cortical stimulation (ECS) is known to have suppressive effects on epileptic focus. However, the inhibitory mechanism remains to be elucidated. We investigated the effect of ECS on human epileptic focus by evaluating wideband cortical activities accompanied with interictal epileptiform discharges (IEDs). We recruited 9 patients with intractable partial epilepsy who underwent invasive pre-surgical evaluation with subdural electrodes. 50-Hz stimulation (0.3 ms pulse, 1–15 mA, 1–5 s) was applied at seizure onset zone (SOZ) as a part of functional cortical mapping. By performing Hilbert transform, we calculated the power of 4 frequency bands: fast ripple (200–300 Hz), ripple (80–200 Hz), low gamma (30–50 Hz) and beta (15–30 Hz). We compared them between pre- and post ECS at the timing of spike peak of IEDs. 2 patients were excluded due to artifacts or no examinations. In 3 patients, the power decreased after ECS in all frequency bands. The power did not change in 1, and the power change varied depending on the frequency band or the time after ECS in 3. We demonstrated that 50-Hz ECS on epileptic focus can suppress wide-band activities accompanied with IEDs, suggesting its potential ability to modulate cortical excitability toward less excitation and more inhibition.

Spectral performance of SKA Log-periodic Antennas I: mitigating spectral artefacts in SKA1-LOW 21 cm cosmology experiments

This paper is the first in a series of papers describing the impact of antenna instrumental artefacts on the 21-cm cosmology experiments to be carried out by the low frequency instrument (SKA1-LOW) of the Square Kilometre Array telescope (SKA), i.e., the Cosmic Dawn (CD) and the Epoch of Reionization (EoR). The smoothness of the passband response of the current log-periodic antenna being developed for the SKA1-LOW is analyzed using numerical electromagnetic simulations. The amplitude variations over the frequency range are characterized using low-order polynomials defined locally, in order to study the impact of the passband smoothness in the instrument calibration and CD/EoR Science. A solution is offered to correct a fast ripple found at 60~MHz during a test campaign at the SKA site at the Murchison Radio-astronomy Observatory, Western Australia in September 2015 with a minor impact on the telescope's performance and design. A comparison with the Hydrogen Epoch of Reionization Array antenna is also shown demonstrating the potential use of the SKA1-LOW antenna for the Delay Spectrum technique to detect the EoR.

Behavioral state classification in epileptic brain using intracranial electrophysiology

Objective. Automated behavioral state classification can benefit next generation implantable epilepsy devices. In this study we explored the feasibility of automated awake (AW) and slow wave sleep (SWS) classification using wide bandwidth intracranial EEG (iEEG) in patients undergoing evaluation for epilepsy surgery. Approach. Data from seven patients (age , 4 women) who underwent intracranial depth electrode implantation for iEEG monitoring were included. Spectral power features (0.1–600 Hz) spanning several frequency bands from a single electrode were used to train and test a support vector machine classifier. Main results. Classification accuracy of 97.8 ± 0.3% (normal tissue) and 89.4 ± 0.8% (epileptic tissue) across seven subjects using multiple spectral power features from a single electrode was achieved. Spectral power features from electrodes placed in normal temporal neocortex were found to be more useful (accuracy 90.8 ± 0.8%) for sleep-wake state classification than electrodes located in normal hippocampus (87.1 ± 1.6%). Spectral power in high frequency band features (Ripple (80–250 Hz), Fast Ripple (250–600 Hz)) showed comparable performance for AW and SWS classification as the best performing Berger bands (Alpha, Beta, low Gamma) with accuracy ⩾90% using a single electrode contact and single spectral feature. Significance. Automated classification of wake and SWS should prove useful for future implantable epilepsy devices with limited computational power, memory, and number of electrodes. Applications include quantifying patient sleep patterns and behavioral state dependent detection, prediction, and electrical stimulation therapies.

Prediction of antiepileptic drug treatment outcomes using machine learning

Objective. Antiepileptic drug (AED) treatments produce inconsistent outcomes, often necessitating patients to go through several drug trials until a successful treatment can be found. This study proposes the use of machine learning techniques to predict epilepsy treatment outcomes of commonly used AEDs. Approach. Machine learning algorithms were trained and evaluated using features obtained from intracranial electroencephalogram (iEEG) recordings of the epileptiform discharges observed in Mecp2-deficient mouse model of the Rett Syndrome. Previous work have linked the presence of cross-frequency coupling (ICFC) of the delta (2–5 Hz) rhythm with the fast ripple (400–600 Hz) rhythm in epileptiform discharges. Using the ICFC to label post-treatment outcomes we compared support vector machines (SVMs) and random forest (RF) machine learning classifiers for providing likelihood scores of successful treatment outcomes. Main results. (a) There was heterogeneity in AED treatment outcomes, (b) machine learning techniques could be used to rank the efficacy of AEDs by estimating likelihood scores for successful treatment outcome, (c) ICFC features yielded the most effective a priori identification of appropriate AED treatment, and (d) both classifiers performed comparably. Significance. Machine learning approaches yielded predictions of successful drug treatment outcomes which in turn could reduce the burdens of drug trials and lead to substantial improvements in patient quality of life.

A New Approach of Modified Submerged Patch Clamp Recording Reveals Interneuronal Dynamics during Epileptiform Oscillations.

Highlights Simultaneous epileptiform LFPs and single-cell activity can be recorded in the membrane chamber.Interneuron firing can be linked to epileptiform high frequency activity.Fast ripples, unique to chronic epilepsy, can be modeled in ex vivo tissue from TeNT-treated rats.Traditionally, visually-guided patch clamp in brain slices using submerged recording conditions has been required to characterize the activity of individual neurons. However, due to limited oxygen availability, submerged conditions truncate fast network oscillations including epileptiform activity. Thus, it is technically challenging to study the contribution of individual identified neurons to fast network activity. The membrane chamber is a submerged-style recording chamber, modified to enhance oxygen supply to the slice, which we use to demonstrate the ability to record single-cell activity during in vitro epilepsy. We elicited epileptiform activity using 9 mM potassium and simultaneously recorded from fluorescently labeled interneurons. Epileptiform discharges were more reliable than in standard submerged conditions. During these synchronous discharges interneuron firing frequency increased and action potential amplitude progressively decreased. The firing of 15 interneurons was significantly correlated with epileptiform high frequency activity (HFA; ~100–500 Hz) cycles. We also recorded epileptiform activity in tissue prepared from chronically epileptic rats, treated with intrahippocampal tetanus neurotoxin. Four of these slices generated fast ripple activity, unique to chronic epilepsy. We showed the membrane chamber is a promising new in vitro environment facilitating patch clamp recordings in acute epilepsy models. Further, we showed that chronic epilepsy can be better modeled using ex vivo brain slices. These findings demonstrate that the membrane chamber facilitates previously challenging investigations into the neuronal correlates of epileptiform activity in vitro.

Prospective and “live” fast ripple detection and localization in the operating room: Impact on epilepsy surgery outcomes in children

ObjectiveFast ripples (FR, 250–500Hz) are proposed biomarkers of the epileptogenic zone on the basis of several retrospective reports linking postoperative seizure freedom to their complete resection. There are no clinical trials or prospective reports validating the use of FR as characterized by electrocorticography (ECoG), to guide the scope of epilepsy surgery, and to inform prognosis thereafter. We set out to prospectively evaluate the utility of FR resection to predict postoperative epilepsy outcomes, and examine the feasibility of “live” intraoperative FR ascertainment. MethodsFR were prospectively reviewed in 30 consecutive pediatric cases including 11 reviewed “live” during surgery. Intraoperative ECoG studies were recorded at 2000Hz sampling rate, interpreted conventionally to guide surgical resection, and visually inspected for FR. Seizure outcome was tallied for all 30 children. ResultsMedian age at surgery was 9.1 years (interquartile range [IQR] 4.7–13.2), median ECoG duration was 10.5min (IQR 8.0–13.2), and median postoperative follow-up was 58.4 months (IQR 25.7–79.0). FR were identified in 24 of 30 ECoG studies. The incomplete resection of FR was strongly linked to postoperative seizures (hazard ratio 11.6, p=0.005). “Live” ECoG review in the operating room to ascertain FR proved feasible and did not differ from conventional FR ascertainment. Significance:In a prospective fashion, including “live” review, FR were detected in 80% of pediatric ECoG studies, and incomplete resection of FR cortex predicted postoperative seizures. These findings extend the notion that interictal FR are surrogate markers of the epileptogenic zone, and that their intraoperative localization could be used to inform prognosis and guide surgical resections in children.

Load estimator-based hybrid controller design for two-interleaved boost converter dedicated to renewable energy and automotive applications

This paper is devoted to the development of a hybrid controller for a two-interleaved boost converter dedicated to renewable energy and automotive applications. The control requirements, resumed in fast transient and low input current ripple, are formulated as a problem of fast stabilization of a predefined optimal limit cycle, and solved using hybrid automaton formalism. In addition, a real time estimation of the load is developed using an algebraic approach for online adjustment of the hybrid controller. Mathematical proofs are provided with simulations to illustrate the effectiveness and the robustness of the proposed controller despite different disturbances. Furthermore, a fuel cell system supplying a resistive load through a two-interleaved boost converter is also highlighted.

Intracranial EEG seizure onset-patterns correlate with high-frequency oscillations in patients with drug-resistant epilepsy

ObjectiveHigh-frequency oscillations (80–500Hz; HFOs) have been shown to be a specific biomarker of the seizure-onset zone. The relationship of HFOs with seizures having different intracranial electroencephalography (iEEG) morphological onsets, however, has shown significant relationships in experimental animals but has not been studied in humans. We investigated how interictal and ictal HFOs relate to different seizure-onset morphological patterns. MethodsWe analyzed the most representative seizure type of 37 patients with drug-resistant focal epilepsy who underwent iEEG for diagnostic evaluation. According to the morphology, 211 seizure-onset zone channels were classified in six patterns (low-voltage fast activity; sharp activity at ≤13Hz; low-frequency high-amplitude periodic spikes; burst of high-amplitude polyspikes; spike-and-wave activity; and delta brush). Interictal and ictal HFOs were compared between the six seizure-onset patterns. ResultsInterictal ripple and fast ripple rates differed significantly across seizure-onset patterns (p<0.001). Significant differences were also found for ictal HFOs density across the different seizure-onset patterns (p<0.001). Sharp activity at ≤13Hz was associated with the lowest interictal HFO rate suggesting either that the mechanism that generates this type of EEG morphology do not generate HFOs or possibly that this pattern is more likely to be generated in a region of seizure spread. Regarding the difference in HFO density between pre-ictal baseline and seizure-onset section across the six patterns, burst of high-amplitude polyspikes and delta brushes had the highest densities of both ripples and fast ripples (p<0.001). SignificanceWe demonstrated that distinct seizure-onset patterns correlate specific interictal and ictal HFO profiles confirming that seizures with different morphological patterns likely have different mechanisms of generation. This study emphazises that, in clinical practice, seizure-onset patterns should be distinguished and specified when analyzing HFOs, particularly if they are used in presurgical evaluation to better localize the seizure-onset zone.

Computational modeling of high frequency oscillations recorded with clinical intracranial macroelectrodes.

High Frequency Oscillations (HFOs) are a potential biomarker of epileptogenic regions. They have been extensively investigated in terms of automatic detection, classification and feature extraction. However, the mechanisms governing the generation of HFOs as well as the observability conditions on clinical intracranial macroelectrodes remain elusive. In this paper, we propose a novel physiologically-relevant macroscopic model for accurate simulation of HFOs as invasively recorded in epileptic patients. This model accounts for both the temporal and spatial properties of the cortical patch at the origin of epileptiform activity. Indeed, neuronal populations are combined with a 3D geometrical representation to simulate an extended epileptic source. Then, by solving the forward problem, the contributions of neuronal population signals are projected onto intracerebral electrode contacts. The obtained signals are qualitatively and quantitatively compared to real HFOs, and a relationship is drawn between macroscopic model parameters such as synchronization and spatial extent on the one hand, and HFO features such as the wave and fast ripple (200-600 Hz) components, on the other hand.

Resection of ictal high frequency oscillations is associated with favorable surgical outcome in pediatric drug resistant epilepsy secondary to tuberous sclerosis complex

Resective epilepsy surgery can improve seizures when the epileptogenic zone (EZ) is limited to a well-defined region. High frequency oscillations (HFO) have been recognized as having a high association with the seizure onset zone. Therefore, we retrospectively identified ictal HFOs and determined their relationship to specific intracranial features of cortical tubers in children with TSC who underwent resective surgery. We identified 14 patients with drug resistant epilepsy secondary to TSC who underwent subdural grid and strip implantation for presurgical evaluation and subsequent resection with adequate post-surgical follow-up. We aimed to determine the relationship between ictal HFOs, post-resection outcome and neuroimaging features in this population.The largest tuber was identified in all 14 patients (100%). Four patients (29%) had unusual tubers. HFOs were observed at ictal onset in all 14 patients. Seven of 10 patients with complete resection of HFOs were seizure free. The better seizure outcome (ILAE=1–3) was achieved with complete HFO resection regardless of the unique TSC structural features (p=0.0140).Our study demonstrates the presence of ripple and fast ripple range HFOs at ictal onset in children with TSC. Our study showed that complete HFO resection led to the better surgical outcome, independent of MR imaging findings.

Effect of sampling rate and filter settings on High Frequency Oscillation detections.

High Frequency Oscillations (HFOs) are being studied as a biomarker of epilepsy, yet it is unknown how various acquisition parameters at different centers affect detection and analysis of HFOs. This paper specifically quantifies effects of sampling rate (FS) and anti-aliasing filter (AAF) positions on automated HFO detection. HFOs were detected on intracranial EEG recordings (17 patients) with 5kHz FS. HFO detection was repeated on downsampled and/or filtered copies of the EEG data, mimicking sampling rates and low-pass filter settings of various acquisition equipment. For each setting, we compared the HFO detection sensitivity, HFO features, and ability to identify the ictal onset zone. The relative sensitivity remained above 80% for either FS ⩾2kHz or AAF ⩾500Hz. HFO feature distributions were consistent (AUROC<0.7) down to 1kHz FS or 200Hz AAF. HFO rate successfully identified ictal onset zone over most settings. HFO peak frequency was highly variable under most parameters (Spearman correlation<0.5). We recommend at least FS ⩾2kHz and AAF ⩾500Hz to detect HFOs. Additionally, HFO peak frequency is not robust at any setting: the same HFO event can be variably classified either as a ripple (<200Hz) or fast ripple (>250Hz) under different acquisition settings. These results inform clinical centers on requirements to analyze HFO rates and features.

Interaction with slow waves during sleep improves discrimination of physiologic and pathologic high-frequency oscillations (80-500 Hz).

To characterize the interaction between physiologic and pathologic high-frequency oscillations (HFOs) and slow waves during sleep, and to evaluate the practical significance of these interactions by automatically classifying channels as recording from normal or epileptic brain regions. We automatically detected HFOs in intracerebral electroencephalography (EEG) recordings of 45 patients. We characterized the interaction between the HFOs and the amplitude and phase of automatically detected slow waves during sleep. We computed features associated with HFOs, and compared classic features such as rate, amplitude, duration, and frequency to novel features related to the interaction between HFOs and slow waves. To quantify the practical significance of the difference in these features we classified the channels as recording from normal/epileptic regions using logistic regression. We assessed the results in different brain regions to study differences in the HFO characteristics at the lobar level. We found a clear difference in the coupling between the phase of slow waves during sleep and the occurrence of HFOs. In channels recording physiologic activity, the HFOs tend to occur after the peak of the deactivated state of the slow wave, and in channels with epileptic activity, the HFOs occur more often before this peak. This holds for HFOs in the ripple (80-250 Hz) and fast ripple (250-500 Hz) bands, and different regions of the brain. When using this interaction to automatically classify channels as recording from normal/epileptic brain regions, the performance is better than when using other HFO characteristics. We confirmed differences in the HFO characteristics in mesiotemporal structures and in the occipital lobe. We found the association between slow waves and HFOs to be different in normal and epileptic brain regions, emphasizing their different origin. This is also of practical significance, since it improves the separation between channels recording from normal and epileptic brain regions.

Activation of specific neuronal networks leads to different seizure onset types.

Ictal events occurring in temporal lobe epilepsy patients and in experimental models mimicking this neurological disorder can be classified, based on their onset pattern, into low-voltage, fast versus hypersynchronous onset seizures. It has been suggested that the low-voltage, fast onset pattern is mainly contributed by interneuronal (γ-aminobutyric acidergic) signaling, whereas the hypersynchronous onset involves the activation of principal (glutamatergic) cells. Here, we tested this hypothesis using the optogenetic control of parvalbumin-positive or somatostatin-positive interneurons and of calmodulin-dependent, protein kinase-positive, principal cells in the mouse entorhinal cortex in the in vitro 4-aminopyridine model of epileptiform synchronization. We found that during 4-aminopyridine application, both spontaneous seizure-like events and those induced by optogenetic activation of interneurons displayed low-voltage, fast onset patterns that were associated with a higher occurrence of ripples than of fast ripples. In contrast, seizures induced by the optogenetic activation of principal cells had a hypersynchronous onset pattern with fast ripple rates that were higher than those of ripples. Our results firmly establish that under a similar experimental condition (ie, bath application of 4-aminopyridine), the initiation of low-voltage, fast and of hypersynchronous onset seizures in the entorhinal cortex depends on the preponderant involvement of interneuronal and principal cell networks, respectively.

The Influence of Vagus Nerve and Spinal Cord Stimulation on the Ictal Fast Ripple Activity in a Spike-and-Wave Rat Model of Seizures.

Fast ripple (FR) activity has received increasing attention as a potential epileptic marker. The current knowledge on how neurostimulation affects FRs is, however, very limited. In this study, we assess the influence of the vagus nerve stimulation (VNS) and spinal cord stimulation (SCS) frequency on ictal FRs associated with spike-and-wave (SW) seizures. SW discharges were induced and maintained by an infusion of pentylenetetrazol in rat. During ongoing SW seizures, SCS was conducted at 30, 80, 130, and 180 Hz and VNS at 10, 30, 80, 130, and 180 Hz. The FRs were derived from intracortical recordings and the FR rate was used for quantifying the level of FR activity. The FR rate was significantly correlated (r = 0.81) with the level of total pentylenetetrazol dose. Compared with no stimulation intervals, SCS conducted at 80, 130, and 180 Hz significantly reduced the normalized FR rate by 24, 38, and 44%, respectively. Similarly, VNS conducted at 30, 80, 130, and 180 Hz significantly reduced the normalized FR rate by 23, 40, 61, and 65%, respectively. In the present model of sustained SW seizures, the FR rate was proportional with the severity of the SW seizures. Both SCS and VNS attenuated the FR rate and this attenuation was consistently strongest at the higher stimulation frequencies. Our results suggest that SCS may induce some of the same antiepileptic effects as VNS.

The Harmonic Analysis of RMP Coil Power Supply in EAST TOKAMAK

In EAST TOKAMAK, resonant magnetic perturbation (RMP) coils, which are powered by RMP coil power supply (PS), are set to research edge localized mode, resistive wall mode and error field correction. In order to meet the requirements of fast response and output voltage ripple proposed by physical experimenters, the structure of multiple modules using cascaded carrier phase-shifted PWM H-bridges is adopted, which enhances the equal switch-frequency of the PS and improves the quality of output voltage. In the paper, theoretical calculation applying Fourier analysis is given to analyze its harmonics. Both simulation results on Matlab and test results of output voltage ripple show that the RMP coil PS can meet the requirements.

Serotonin receptor antagonists increase fast ripple activity in rats treated with kainic acid.

Fast ripples (FR, 250-600 Hz) are field potentials that occur only in those areas capable of generating seizures, such as the hippocampus, and modulation of FR by serotonin has been reported. Therefore, we hypothesized that the receptor antagonists 5HT1A and 5HT2A, B, C will increase FR in rats treated with kainic acid (KA, 0.8 μg/0.5 μl). For this purpose, the intracranial EEG recordings of the hippocampus from animals treated with KA and the serotonin antagonists WAY100135 and ritanserin (dose 0.2mg/Kg, i.p) were analyzed. In addition, morphologic parameters were analyzed after staining samples with cresyl violet, Timm stain, NeuN and GFAP and observing immunofluorescence. The results showed an increase in the number of events of FR (p<0.0001) and duration of each FR event after the administration of WAY100135 (p<0.030). Additionally, there was an increase in the number of events of FR (p<0.0001) and amplitude of FR after ritanserin administration (p<0.014). In relation to changes in unspecified cells, there was a significant decrement in the width of the CA3 pyramidal layer of the hippocampus (p<0.001), and there were no significant changes in reactive glia and fiber sprouting. However, a slight gain of astrocytes marked with GFAP and larger astrocytes with more projections were observed. In conclusion, these results support the modulation of FR by serotonin with participation of the 5HT1A receptor as a possible mediator of the effect. However the exact mechanisms resulting in such effect is not known.