High Frequency Oscillations Activity Research Articles

Flexible, high-resolution cortical arrays with large coverage capture microscale high-frequency oscillations in patients with epilepsy.

Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity. In this study, we sought to characterize microscale HFO activity captured on thin, flexible microelectrocorticographic (μECoG) arrays, which provide high spatial resolution over large cortical surface areas. We used novel liquid crystal polymer thin-film μECoG arrays (.76-1.72-mm intercontact spacing) to capture HFOs in eight intraoperative recordings from seven patients with epilepsy. We identified ripple (80-250 Hz) and fast ripple (250-600 Hz) HFOs using a common energy thresholding detection algorithm along with two stages of artifact rejection. We visualized microscale subregions of HFO activity using spatial maps of HFO rate, signal-to-noise ratio, and mean peak frequency. We quantified the spatial extent of HFO events by measuring covariance between detected HFOs and surrounding activity. We also compared HFO detection rates on microcontacts to simulated macrocontacts by spatially averaging data. We found visually delineable subregions of elevated HFO activity within each μECoG recording. Forty-seven percent of HFOs occurred on single 200-μm-diameter recording contacts, with minimal high-frequency activity on surrounding contacts. Other HFO events occurred across multiple contacts simultaneously, with covarying activity most often limited to a .95-mm radius. Through spatial averaging, we estimated that macrocontacts with 2-3-mm diameter would only capture 44% of the HFOs detected in our μECoG recordings. These results demonstrate that thin-film microcontact surface arrays with both highresolution and large coverage accurately capture microscale HFO activity and may improve the utility of HFOs to localize the EZ for treatment of drug-resistant epilepsy.

Electrically evoked and spontaneous neural activity in the subthalamic nucleus under general anesthesia.

Deep brain stimulation (DBS) surgery is commonly performed with the patient awake to facilitate assessments of electrode positioning. However, awake neurosurgery can be a barrier to patients receiving DBS. Electrode implantation can be performed with the patient under general anesthesia (GA) using intraoperative imaging, although such techniques are not widely available. Electrophysiological features can also aid in the identification of target neural regions and provide functional evidence of electrode placement. Here we assess the presence and positional variation under GA of spontaneous beta and high-frequency oscillation (HFO) activity, and evoked resonant neural activity (ERNA), a novel evoked response localized to the subthalamic nucleus. ERNA, beta, and HFO were intraoperatively recorded from DBS leads comprising four individual electrodes immediately after bilateral awake implantation into the subthalamic nucleus of 21 patients with Parkinson's disease (42 hemispheres) and after subsequent GA induction deep enough to perform pulse generator implantation. The main anesthetic agent was either propofol (10 patients) or sevoflurane (11 patients). GA reduced the amplitude of ERNA, beta, and HFO activity (p < 0.001); however, ERNA amplitudes remained large in comparison to spontaneous local field potentials. Notably, a moderately strong correlation between awake ERNA amplitude and electrode distance to an "ideal" therapeutic target within dorsal STN was preserved under GA (awake: ρ = -0.73, adjusted p value [padj] < 0.001; GA: ρ = -0.69, padj < 0.001). In contrast, correlations were diminished under GA for beta (awake: ρ = -0.45, padj < 0.001; GA: ρ = -0.13, padj = 0.12) and HFO (awake: ρ = -0.69, padj < 0.001; GA: ρ = -0.33, padj < 0.001). The largest ERNA occurred at the same electrode (awake vs GA) for 35/42 hemispheres (83.3%) and corresponded closely to the electrode selected by the clinician for chronic therapy at 12 months (awake ERNA 77.5%, GA ERNA 82.5%). The largest beta amplitude occurred at the same electrode (awake vs GA) for only 17/42 (40.5%) hemispheres and 21/42 (50%) for HFO. The electrode measuring the largest awake beta and HFO amplitudes corresponded to the electrode selected by the clinician for chronic therapy at 12 months in 60% and 70% of hemispheres, respectively. However, this correspondence diminished substantially under GA (beta 20%, HFO 35%). ERNA is a robust electrophysiological signal localized to the dorsal subthalamic nucleus subregion that is largely preserved under GA, indicating it could feasibly guide electrode implantation, either alone or in complementary use with existing methods.

PD24-05 OXIDATIVE STRESS INDUCES DETRUSOR UNDERACTIVITY AND URETHRAL DYSFUNCTION IN AGING RATS

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II (PD24)1 Apr 2020PD24-05 OXIDATIVE STRESS INDUCES DETRUSOR UNDERACTIVITY AND URETHRAL DYSFUNCTION IN AGING RATS Asato Ohtsubo*, Takuma Oshiro, Ryu Kimura, Minoru Miyazato, Tomohiro Matsuo, Yasuyoshi Miyata, and Hideki Sakai Asato Ohtsubo*Asato Ohtsubo* More articles by this author , Takuma OshiroTakuma Oshiro More articles by this author , Ryu KimuraRyu Kimura More articles by this author , Minoru MiyazatoMinoru Miyazato More articles by this author , Tomohiro MatsuoTomohiro Matsuo More articles by this author , Yasuyoshi MiyataYasuyoshi Miyata More articles by this author , and Hideki SakaiHideki Sakai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000881.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Age-related symptoms, such as urinary retention and a poor urinary stream have been attributed to detrusor underactivity. Our recent studies showed that by simultaneously recording intravesical pressure and urethral perfusion pressure (UPP), urethral relaxation during bladder contractions was diminished in aged rats. Nevertheless, L-arginine (a substrate of nitric oxide (NO) synthase) could not restore a diminished urethral relaxation. Thus, we hypothesized that age-associated oxidative stress would impair NO/soluble guanylyl cyclase (sGC) system which induces urethral relaxation. This hypothesis was tested by measuring an oxidative stress marker in the bladder and also by simultaneously recording intravesical pressure and UPP using BAY 41-2272 as a novel NO-independent stimulator of sGC. METHODS: Female Sprague Dawley rats (young rats aged 3 months and old rats aged 12–15 months) were used. 1) Oxidative stress marker staining for 8-hydroxy-2’-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) in the bladder was performed in both groups. 2) Urethral activity was evaluated by simultaneously recording the intravesical pressure under isovolumetric conditions and UPP under urethane anesthesia. 3) BAY 41-2272 (1 mg/kg) was administered intravenously in both groups under isovolumetric conditions. RESULTS: 1) Oxidative marker staining revealed that 8-OHdG and MDA levels were higher in aging rats than those in young rats. 2) UPP nadir during urethral relaxation was significantly higher (38%) in aging rats than in young rats (p < 0.05). The mean amplitude of high frequency oscillation (HFO) of the urethral striated muscle was also significantly lower (49%) in aging rats than in normal rats (p < 0.05). 3) BAY 41-2272 increased urethral relaxation in young rats while restoring impaired urethral relaxation in aged rats. CONCLUSIONS: These results indicate that aging induces a dysfunction in urethral relaxation during voiding, as evidenced by a decrease in HFO activity of the urethral striated muscle as well as NO mediated urethral relaxation of the urethral smooth muscle. Because NO-independent stimulator could restore impaired urethral relaxation in the aged bladder, age-associated oxidative stress in the NO/sGC system might be correlated with an age associated impairment in bladder and urethral coordination. This novel study coupled with physiological and morphological changes in the aged bladder would contribute to elucidating the process of aging in bladders. Source of Funding: This work was supported by a Grant-in-Aid for Scientific Research (18K17752, 18K10714 and 18K10749 ). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e533-e534 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Asato Ohtsubo* More articles by this author Takuma Oshiro More articles by this author Ryu Kimura More articles by this author Minoru Miyazato More articles by this author Tomohiro Matsuo More articles by this author Yasuyoshi Miyata More articles by this author Hideki Sakai More articles by this author Expand All Advertisement PDF downloadLoading ...

The Ambiguous Nature of Fast Ripples in Epilepsy Surgery.

Removing High-Frequency Oscillations: A Prospective Multicenter Study on Seizure Outcome Jacobs J, Wu JY, Perucca P, et al. Neurology. 2018;91(11):e1040-e1052. doi:10.1212/WNL.0000000000006158Objective:To evaluate the use of interictal high-frequency oscillations (HFOs) in epilepsy surgery for prediction of postsurgical seizure outcome in a prospective multicenter trial.Methods:We hypothesized that a seizure-free outcome could be expected in patients in whom the surgical planning included the majority of HFO-generating brain tissue, while a poor seizure outcome could be expected in patients in whom only a few such areas were planned to be resected. Fifty-two patients were included from 3 tertiary epilepsy centers during a 1-year period. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were automatically detected during slow-wave sleep with chronic intracranial EEG in 2 centers and acute intraoperative electrocorticography in 1 patient.Results:There was a correlation between the removal of HFO-generating regions and seizure-free outcome at the group level for all patients. No correlation was found, however, for the center-specific analysis, and an individual prognostication of seizure outcome was true in only 36 (67%) patients. Moreover, some patients became seizure-free without removal of the majority of HFO-generating tissue. The investigation of influencing factors, including comparisons of visual and automatic analysis, using a threshold analysis for areas with high HFO activity, and excluding contacts bordering the resection, did not result in improved prognostication.Conclusions:On an individual patient level, a prediction of outcome was not possible in all patients. This may be due to the analysis techniques used. Alternatively, HFOs may be less specific for epileptic tissue than earlier studies have indicated.

Effect of 5-HT2A receptor antagonist ketanserin on micturition in male rats

ObjectivesThis study aimed to investigate the effects of ketanserin on micturition mediated via the 5-HT2A receptor in the motoneuron nucleus of the Lumbosacral cord, as reflected in high frequency oscillations (HFOs) of intravesical pressure and the external urethral sphincter electromyogram (EUS-EMG) in anesthetized male rats. Methods：Male Sprague-Dawley rats were used. Cystometry and EUS-EMG were performed in all rats under urethane anesthesia to examine the variations after successive intrathecal (i.t.) administration of various doses of ketanserin into the lumbosacral cord. Immunofluorescence staining and Western blotting were made to observe the distribution of 5-HT2 A and −2C receptors in the lumbosacral cord motor neurons. ResultsCompared to the controls, ketanserin-treated rats showed a declined trend of dose-dependent manner in the HFOs, in accordance with the variation of EUS-EMG, while decreased micturition volume, voiding efficiency, and increased post-void residual volume was only observed at the dose of 0.1 mg/kg. The effects of ketanserin on the HFO and EUS-EMG activity were partially or completely reversed by the 5-HT2A/2C receptor agonist, DOI. Meanwhile, immunofluorescence staining and Western blot analysis showed that immunoreactivity of 5-HT2A receptor was higher than that of 5-HT2C, labeling in the lumbosacral cord motoneurons. ConclusionsThe intrathecally administrated 5-HT2A receptor antagonist ketanserin can weaken the EUS bursting activity, decrease HFOs, and reduce voiding efficiency as dose dependently. The effects of ketanserin on micturition may be mainly mediated via the 5-HT2A receptors in the motoneuron nucleus of the lumbosacral cord.

Spatial variation in high-frequency oscillation rates and amplitudes in intracranial EEG.

To assess the variation in baseline and seizure onset zone interictal high-frequency oscillation (HFO) rates and amplitudes across different anatomic brain regions in a large cohort of patients. Seventy patients who had wide-bandwidth (5 kHz) intracranial EEG (iEEG) recordings during surgical evaluation for drug-resistant epilepsy between 2005 and 2014 who had high-resolution MRI and CT imaging were identified. Discrete HFOs were identified in 2-hour segments of high-quality interictal iEEG data with an automated detector. Electrode locations were determined by coregistering the patient's preoperative MRI with an X-ray CT scan acquired immediately after electrode implantation and correcting electrode locations for postimplant brain shift. The anatomic locations of electrodes were determined using the Desikan-Killiany brain atlas via FreeSurfer. HFO rates and mean amplitudes were measured in seizure onset zone (SOZ) and non-SOZ electrodes, as determined by the clinical iEEG seizure recordings. To promote reproducible research, imaging and iEEG data are made freely available (msel.mayo.edu). Baseline (non-SOZ) HFO rates and amplitudes vary significantly in different brain structures, and between homologous structures in left and right hemispheres. While HFO rates and amplitudes were significantly higher in SOZ than non-SOZ electrodes when analyzed regardless of contact location, SOZ and non-SOZ HFO rates and amplitudes were not separable in some lobes and structures (e.g., frontal and temporal neocortex). The anatomic variation in SOZ and non-SOZ HFO rates and amplitudes suggests the need to assess interictal HFO activity relative to anatomically accurate normative standards when using HFOs for presurgical planning.

Automated Detector of High Frequency Oscillations in Epilepsy Based on Maximum Distributed Peak Points.

High frequency oscillations (HFOs) are considered as biomarker for epileptogenicity. Reliable automation of HFOs detection is necessary for rapid and objective analysis, and is determined by accurate computation of the baseline. Although most existing automated detectors measure baseline accurately in channels with rare HFOs, they lose accuracy in channels with frequent HFOs. Here, we proposed a novel algorithm using the maximum distributed peak points method to improve baseline determination accuracy in channels with wide HFOs activity ranges and calculate a dynamic baseline. Interictal ripples (80-200[Formula: see text]Hz), fast ripples (FRs, 200-500[Formula: see text]Hz) and baselines in intracerebral EEGs from seven patients with intractable epilepsy were identified by experienced reviewers and by our computer-automated program, and the results were compared. We also compared the performance of our detector to four well-known detectors integrated in RIPPLELAB. The sensitivity and specificity of our detector were, respectively, 71% and 75% for ripples and 66% and 84% for FRs. Spearman's rank correlation coefficient comparing automated and manual detection was [Formula: see text] for ripples and [Formula: see text] for FRs ([Formula: see text]). In comparison to other detectors, our detector had a relatively higher sensitivity and specificity. In conclusion, our automated detector is able to accurately calculate a dynamic iEEG baseline in different HFO activity channels using the maximum distributed peak points method, resulting in higher sensitivity and specificity than other available HFO detectors.

MP26-18 TIME-DEPENDENT BLADDER AND URETHRAL DYSFUNCTIONS IN AGING RATS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2017MP26-18 TIME-DEPENDENT BLADDER AND URETHRAL DYSFUNCTIONS IN AGING RATS Takuma Oshiro, Minoru Miyazato, Asuka Ashikari, and Seiich Saito Takuma OshiroTakuma Oshiro More articles by this author , Minoru MiyazatoMinoru Miyazato More articles by this author , Asuka AshikariAsuka Ashikari More articles by this author , and Seiich SaitoSeiich Saito More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.789AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Age-related symptoms such as urinary retention, poor urine flow, and/or incontinence have been attributed to detrusor underactivity (DU). Our recent data showed that in continuous cystometry, bladder contractility did not diminish but post-void residual urine volume was higher in aging rats than in young rats. Thus, the assumption that bladder and urethral dysfunction occur simultaneously in aging rats seems reasonable. Therefore, we investigated this possibility by measuring time-dependent changes of bladder and urethral functions in rats. METHODS Female Sprague-Dawley rats (young rats aged 3 months and rats aged 12 and 24 months) were used. 1) Continuous cystometry was performed under awake condition in each group. 2) Urethral activity was evaluated by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) under urethane anesthesia in 3-month-old and 12-month-old rats. 3) Masson's trichrome staining in the bladder was performed in each group. RESULTS 1) Cystometric evaluations revealed that the intercontraction intervals in the 24-month-old rats were prolonged (p < 0.01) when compared with those in the 3-month-old or 12-month-old rats. In the 24-month-old rats, residual urine volume was significantly higher than in the 3-month-old or 12-month-old rats, and non-voiding contractions were prominent. However, the amplitude of bladder contraction did not differ among the three groups. 2) UPP relaxation (baseline UPP minus nadir UPP) was more significantly diminished (64%) in the 12-month-old rats than in the 3-month-old rats (p < 0.05). The mean rate and amplitude of high-frequency oscillation (HFO) of urethral striated muscle were also significantly lower (12% and 41%, respectively) in the 12-month-old rats than in the 3-month-old rats. 3) In the bladders of the 24-month-old rats, increases in smooth muscle cell hypertrophy and fibrous tissue were observed. CONCLUSIONS 1) Our aging model that focused on bladder function showed increased intercontraction intervals and non-voiding bladder contractions with increased residual urine volume, suggesting detrusor hyperactivity with impaired contractility bladder activity. 2) Our aging model that focused on urethral function indicates urethral dysfunction, as evident from the reduction in HFO activity of the urethral striated muscle and the urethral relaxation. Thus, age-associated bladder and urethral dysfunction seem likely to occur simultaneously, which leads to DU with a vicious cycle. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e326-e327 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Takuma Oshiro More articles by this author Minoru Miyazato More articles by this author Asuka Ashikari More articles by this author Seiich Saito More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat.

To examine the effects of the serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) on micturition in rats with diabetes mellitus (DM). Female Sprague-Dawley rats (n = 16) were divided into two groups: rats with Type 1 DM and age-matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram (CMG) studies were performed 8 weeks post-injection in all rats under urethane anaesthesia. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve was plotted. All drugs were administered i.v. Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post-void residual urine volume (PVR), and a markedly lower voiding efficiency. In DM rats, DOI (0.01-0.3 mg/kg) induced significant dose-dependent increases in micturition volume and reductions in PVR, resulting in greater voiding efficiency. CMG measurements showed a dose-dependent increase in high-frequency oscillation (HFO) activity, evidenced by an increased duration of HFOs per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI-induced changes. The HFOs observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5-HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies.

Identification of seizure onset zone and preictal state based on characteristics of high frequency oscillations

ObjectiveWe investigate the relevance of high frequency oscillations (HFO) for biomarkers of epileptogenic tissue and indicators of preictal state before complex partial seizures in humans. MethodsWe introduce a novel automated HFO detection method based on the amplitude and features of the HFO events. We examined intracranial recordings from 33 patients and compared HFO rates and characteristics between channels within and outside the seizure onset zone (SOZ). We analyzed changes of HFO activity from interictal to preictal and to ictal periods. ResultsThe average HFO rate is higher for SOZ channels compared to non-SOZ channels during all periods. Amplitudes and durations of HFO are higher for events within the SOZ in all periods compared to non-SOZ events, while their frequency is lower. All analyzed HFO features increase for the ictal period. ConclusionsHFO may occur in all channels but their rate is significantly higher within SOZ and HFO characteristics differ from HFO outside the SOZ, but the effect size of difference is small. SignificanceThe present results show that based on accumulated dataset it is possible to distinguish HFO features different for SOZ and non-SOZ channels, and to show changes in HFO characteristics during the transition from interictal to preictal and to ictal periods.

The effect of the 5‐HT7 serotonin receptor agonist, LP44, on micturition in rats with chronic spinal cord injury

To better understand the effects of the selective 5-HT7 receptor agonist 4-[2-(Methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-piperazinehexanamide hydrochloride (LP44) on micturition in spinal cord injury (SCI) rats. Female Sprague-Dawley rats weighing 200-275 g were used. SCI was produced in 8 of the 16 rats by transection at the T10 level; cystometric study occurred 8-12 weeks post-transection. Intravesical pressure was monitored in urethane-anesthetized animals via a transvesical catheter. The selective 5-HT7 antagonist (R)-3-[2-[2-(4-Methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl] phenol hydrochloride (SB-269970) was administered after each LP44 dose-response curve (all drugs were administered intravenously, i.v). Compared to controls, SCI rats had a higher bladder capacity and residual volume, and a lower voiding efficiency. In SCI rats, LP44 (0.003-0.3 mg/kg, i.v) induced significant dose-dependent increases in micturition volume, significant dose-dependent decreases in residual volume, resulting in significant increases in voiding efficiency. CMG measurements showed a dose-dependent increase of the high-frequency oscillation (HFO) activity, including the number of small oscillation per voiding. This was correlated with the improved voiding efficiency. SB-269970 (0.1 mg/kg, i.v) partially or completely reversed all LP44-induced changes. HFOs seems to be correlated with external urethral sphincter (EUS) bursting activity during voiding. Both the bladder voiding efficiency and the periodic EUS activity were decreased in SCI rats. 5-HT7 receptor agonist can enhance HFO activity, thereby improving voiding efficiency. Whether or not these results may have implications for the future treatment of voiding dysfunction in SCI patients remains to be studied.

The Effect of the 5-HT2A/2C Receptor Agonist DOI on Micturition in Rats with Chronic Spinal Cord Injury

We examined the effects of the 5-HT2A/2C receptor agonist DOI on micturition in chronic spinal cord injured rats. Female Sprague-Dawley® rats were used. Spinal cord injury was produced by transection at the T10 level. A cystometric study was performed 8 to 12 weeks after transection. Cystometrograms were done using urethane anesthesia in all rats. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve. All drugs were administered intravenously. Compared to controls, spinal cord injured rats had higher bladder capacity and post-void residual urine volume, and lower voiding efficiency. In spinal cord injured rats DOI (0.01 to 0.3 mg/kg) induced significant dose dependent increases in micturition volume and decreases in residual volume, resulting in increased voiding efficiency. Cystometrogram measurements showed a dose dependent increase in high frequency oscillation activity, evident as an increased number of small oscillation per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI induced changes. High frequency oscillation seems to reflect external urethral sphincter burst activity during voiding. Bladder voiding efficiency and high frequency oscillation activity were decreased in spinal cord injured rats. High frequency oscillation activity can be enhanced by 5-HT2A receptor agonism, improving voiding efficiency. To our knowledge it remains to be studied whether these results may have implications for the future treatment of voiding dysfunction in patients with spinal cord injury.

Automatic 80–250 Hz “ripple” high frequency oscillation detection in invasive subdural grid and strip recordings in epilepsy by a radial basis function neural network

ObjectiveRecent studies give evidence that high frequency oscillations (HFOs) in the range between 80Hz and 500Hz in invasive recordings of epilepsy patients have the potential to serve as reliable markers of epileptogenicity. This study presents an algorithm for automatic HFO detection. MethodsThe presented HFO detector uses a radial basis function neural network. Input features of the detector were energy, line length and instantaneous frequency. Visual marked “ripple” HFOs (80–250Hz) of 3 patients were used to train the neural network, and a further 8 patients served for the detector evaluation. ResultsDetector sensitivity and specificity were 49.1% and 36.3%. The linear and rank correlation between visual and automatic marked “ripple” HFO counts over the channels were significant for all recordings. A reference detector based on the line length achieved a sensitivity of 35.4% and a specificity of 46.8%. ConclusionsAutomatic detections corresponded only partly to visual markings for single events but the relative distribution of brain regions displaying “ripple” HFO activity is reflected by the automated system. SignificanceThe detector allows the automatic evaluation of brain areas with high HFO frequency, which is of high relevance for the demarcation of the epileptogenic zone.

Characterization of fast oscillatory rhythms in multiple respiratory‐related motor outputs during eupnea in decerebrate adult rat in vivo

Respiratory motor discharges exhibit both slow and fast oscillatory rhythms. The slow rhythms correspond to inspiratory (I), expiratory (E), or phase‐spanning behaviors while the fast rhythms appear to be exclusive to motor outputs exhibiting inspiratory‐related discharges. To further evaluate these respiratory‐related rhythms, we examined basal phrenic (PHR), hypoglossal (XII), and recurrent laryngeal (RLN) nerve bursts recorded simultaneously from decerebrate (unanesthetized) paralyzed mechanically‐ventilated adult rats in vivo. PHR discharge served as an index of I activity, and burst duration (TI) and the duration between bursts (TE) were determined from PHR traces. XII activity exhibited pre‐I and I phase discharge and RLN activity exhibited pre‐I, I, and E phase discharge. In each respiratory‐related motor output, high frequency oscillations (HFO) were identified but they were restricted to the I phase of each burst (i.e., no significant HFO activity was seen during pre‐I or E phases). PHR and RLN HFO peaks were located between 100‐150 Hz, and XII activity exhibited several distinct peaks with a broadband power distribution. HFO onset occurred at ~50% TI for PHR activity and somewhat earlier for XII and RLN activities; RLN HFO activity spanned most of the TI period. These data suggest that fast oscillatory rhythms in respiratory‐related motor discharges underlie only the I phase. Supported by NS049310.

Evoked potentials and evoked ripples in the human hippocampal formation

Event Abstract Back to Event Evoked potentials and evoked ripples in the human hippocampal formation Daniel Fabo1, 2*, Z. Magloczky3, E. Toth4, L. Eross2, A. Solyom2, S. Czirjak2, G. Rasonyi2, P. Halasz4, T. F. Freund3, G. Karmos1, 4 and I. Ulbert1, 2, 4 1 Institute for Psychology, Hungarian Academy of Sciences, Hungary 2 National Institute of Neurosurgery, Hungary 3 Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary 4 Peter Pazmany Catholic University, Hungary Intracranial electrical stimulation (IES) is a main candidate for future therapy of drug resistant epilepsies. However, the current knowledge on the effect of IES is poorly understood. Under general anesthesia we inserted laminar multielectrodes into the hippocampal formation (HF) of five temporal lobe epilepsy (TLE) patients to record local field potential (LFP), multiple unit activity (MUA), current source density (CSD) and spectral activation of evoked potentials (EPs) elicited by brief, singe pulse, subdural cortical electrical stimuli (0.1ms; 5- 15mA; 0.5Hz). LFP based ripple detection algorhythm was developed. The EPs started with a 10-50ms spike, and ended with a 100-500ms slow wave. The spike was characterized by CSD sink and MUA increase. In one case, the onset latency was less than 5ms. The fastest responses were elicited from a 2-4cm cortical region. The CSD pattern at a particular recording site varied with stimulus site and strength. High frequency oscillation activity was measured during the initial sink. Ripple activity was elicited with 60-98% probability preferably from more anterior sites. Both ripples and fast ripples could be evoked both in the subiculum and the dentate gyrus. During the slow wave, high frequency activity was depressed. We conclude that the HF’s response amplitude is stimulus strength dependent, while the time course of the EP depends on the location of the stimulation site suggesting differently activated afferent fiber systems. Since IES evokes increased ripple/fast ripple activity, it is of utmost importance to further investigate different stimulation paradigms to expose the most beneficial anti-epileptic stimulation parameters. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Research on the cerebral cortex and related structures Citation: Fabo D, Magloczky Z, Toth E, Eross L, Solyom A, Czirjak S, Rasonyi G, Halasz P, Freund TF, Karmos G and Ulbert I (2009). Evoked potentials and evoked ripples in the human hippocampal formation. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.191 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 Mar 2009; Published Online: 06 Mar 2009. * Correspondence: Daniel Fabo, Institute for Psychology, Hungarian Academy of Sciences, Budapest, Hungary, fabo.daniel@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Daniel Fabo Z. Magloczky E. Toth L. Eross A. Solyom S. Czirjak G. Rasonyi P. Halasz T. F Freund G. Karmos I. Ulbert Google Daniel Fabo Z. Magloczky E. Toth L. Eross A. Solyom S. Czirjak G. Rasonyi P. Halasz T. F Freund G. Karmos I. Ulbert Google Scholar Daniel Fabo Z. Magloczky E. Toth L. Eross A. Solyom S. Czirjak G. Rasonyi P. Halasz T. F Freund G. Karmos I. Ulbert PubMed Daniel Fabo Z. Magloczky E. Toth L. Eross A. Solyom S. Czirjak G. Rasonyi P. Halasz T. F Freund G. Karmos I. Ulbert Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Interictal high‐frequency oscillations (80–500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain

High-frequency oscillations (HFOs) known as ripples (80-250 Hz) and fast ripples (250-500 Hz) can be recorded from macroelectrodes inserted in patients with intractable focal epilepsy. They are most likely linked to epileptogenesis and have been found in the seizure onset zone (SOZ) of human ictal and interictal recordings. HFOs occur frequently at the time of interictal spikes, but were also found independently. This study analyses the relationship between spikes and HFOs and the occurrence of HFOs in nonspiking channels. Intracerebral EEGs of 10 patients with intractable focal epilepsy were studied using macroelectrodes. Rates of HFOs within and outside spikes, the overlap between events, event durations, and the percentage of spikes carrying HFOs were calculated and compared according to anatomical localization, spiking activity, and relationship to the SOZ. HFOs were found in all patients, significantly more within mesial temporal lobe structures than in neocortex. HFOs could be seen in spiking as well as nonspiking channels in all structures. Rates and durations of HFOs were significantly higher in the SOZ than outside. It was possible to establish a rate of HFOs to identify the SOZ with better sensitivity and specificity than with the rate of spikes. HFOs occurred to a large extent independently of spikes. They are most frequent in mesial temporal structures. They are prominent in the SOZ and provide additional information on epileptogenicity independently of spikes. It was possible to identify the SOZ with a high specificity by looking at only 10 min of HFO activity.

Modulation of high-frequency oscillations associated with NMDA receptor hypofunction in the rodent nucleus accumbens by lamotrigine

We reported recently that ketamine can increase the power of high-frequency oscillations (HFO) in the rodent nucleus accumbens (NAc), a region implicated in the pathophysiology of schizophrenia. Lamotrigine is known to reduce several of the abnormal behaviors induced by NMDA receptor antagonists in humans and rodents. This prompted us to examine whether lamotrigine would disrupt ketamine-enhanced HFO. Local field potentials (LFPs) and locomotor activity were recorded from male Wistar rats chronically implanted with electrodes in the NAc. Rats were pretreated with either saline or lamotrigine for 60min followed by injection of ketamine (25mg/kg). A separate group received a unilateral intra-NAc infusion of lamotrigine immediately followed by systemic injection of ketamine. We found systemic injection of a high dose of lamotrigine (20.1mg/kg) reduced the power and frequency of ketamine-enhanced HFO. This dose of lamotrigine was also associated with a decrease in both spontaneous HFO and locomotor activity, but did not significantly reduce locomotor activity induced by ketamine. In contrast, a low dose of lamotrigine (2.0mg/kg) produced a small, but significant increase of both ketamine-enhanced HFO and locomotor activity. Local infusion of lamotrigine into the NAc did not significantly affect ketamine-induced HFO, suggesting lamotrigine produces its effect on structures afferent to the NAc, and effects on HFO most likely result from modulating excitatory transmission to the NAc.

Influence of extracellular [K+] on inspiratory‐phase synchronization in arterially‐perfused adult rat

Studies examining central respiratory control using reduced preparations commonly increase the K+ concentration ([K+]o) in the artificial cerebral spinal fluid (aCSF) supplied to the preparation in order to increase excitability and maintain stable respiratory output. Although studies have evaluated the influence of varying the [K+]o on temporal and spectral characteristics of inspiratory motor discharge in the in vitro transverse slice preparation, much less is know about the influence of [K+]o on these parameters in the arterially‐perfused adult rat preparation. Therefore, using this preparation, we examined the effects of perfusion with aCSF containing either 3 mM (n=9; low) or the typically used 6.25 mM (n=8; control) [K+]o on phrenic nerve discharge. During perfusion with low [K+]o, phrenic burst frequency was 16.6± 1.4 bpm, TI was 904±145 ms, and TE was 2.9±0.2 s; during perfusion with control [K+]o, phrenic burst frequency was 17.7± 1.7 bpm, TI was 741±47 ms, and TE was 2.9±0.3 s. Perfusion with low [K+]o also resulted in a broadening of the high frequency oscillation (HFO) spectral peak and HFO activity was dispersed across much of the inspiratory burst, with a shift in the onset of spectral activity to an earlier point in inspiration. These findings suggest that low [K+]o reduces inspiratory‐phase synchronization. Supported by NS045321 and NS049310

High-frequency oscillations after status epilepticus: epileptogenesis and seizure genesis.

To investigate the temporal relation between high-frequency oscillations (HFOs) in the dentate gyrus and recurrent spontaneous seizures after intrahippocampal kainite-induced status epilepticus. Recording microelectrodes were implanted bilaterally in different regions of hippocampus and entorhinal cortex. A guide cannula for microinjection of kainic acid (KA) was implanted above the right posterior CA3 area of hippocampus. After recording baseline electrical activity, KA (0.4 microg/0.2 microl) was injected. Beginning on the next day, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for > or = 30 days. Of the 26 rats studied, 19 revealed the appearance of sharp-wave activity and HFOs in the frequency range of 80 to 500 Hz in the dentate gyrus ipsilateral to the KA injection. In the remaining seven rats, no appreciable activity was noted in this frequency range. In some rats with recurrent seizures, HFOs were in the ripple frequency range (100-200 Hz); in others, HFOs were in the fast ripple frequency range (200-500 Hz), or a mixture of both oscillation frequencies was found. The time of detection of the first HFOs after status epilepticus varied between 1 and 30 days, with a mean of 6.3 +/- 2.0 (SEM). Of the 19 rats in which HFO activity appeared, all later developed recurrent spontaneous seizures, whereas none of the rats without HFOs developed seizures. The sooner HFO activity was detected after status epilepticus, the sooner the first spontaneous seizure occurred. A significant inverse relation was found between the time to the first HFO detection and the subsequent rate of spontaneous seizures. A strong correlation was found between a decreased time to detection of HFOs and an increased rate of spontaneous seizures, as well as with a decrease in the duration of the latent period between KA injection and the detection of spontaneous seizures. Two types of HFOs were found after KA injection, one in the frequency range of 100 to 200 Hz, and the other, in the frequency range of 200 to 500 Hz, and both should be considered pathological, suggesting that both are epileptogenic.