Amplitude Of High-frequency Oscillations Research Articles

Central sensitization mechanisms in chronic migraine with medication overuse headache: a study of thalamocortical activation and lateral cortical inhibition.

It is unclear whether cortical hyperexcitability in chronic migraine with medication overuse headache (CM-MOH) is due to increased thalamocortical drive or aberrant cortical inhibitory mechanisms. Somatosensory evoked potentials (SSEP) were performed by electrical stimulation of the median nerve (M), ulnar nerve (U) and simultaneous stimulation of both nerves (MU) in 27 patients with CM-MOH and, for comparison, in 23 healthy volunteers (HVs) of a comparable age distribution. We calculated the degree of cortical lateral inhibition using the formula: 100 - [MU/(M + U) × 100] and the level of thalamocortical activation by analyzing the high frequency oscillations (HFOs) embedded in parietal N20 median SSEPs. Compared to HV, CM-MOH patients showed higher lateral inhibition (CM-MOH 52.2% ± 15.4 vs. HV 40.4% ± 13.3; p = 0.005), which positively correlated with monthly headache days, and greater amplitude of pre-synaptic HFOs (p = 0.010) but normal post-synaptic HFOs (p = 0.122). Our findings suggest that central neuronal circuits are highly sensitized in CM-MOH patients, at both thalamocortical and cortical levels. The observed changes could be due to the combination of dysfunctional central pain control mechanisms, hypersensitivity and hyperresponsiveness directly linked to the chronic intake of acute migraine drugs.

Single-neuron bursts encode pathological oscillations in subcortical nuclei of patients with Parkinson’s disease and essential tremor

Deep brain stimulation procedures offer an invaluable opportunity to study disease through intracranial recordings from awake patients. Here, we address the relationship between single-neuron and aggregate-level (local field potential; LFP) activities in the subthalamic nucleus (STN) and thalamic ventral intermediate nucleus (Vim) of patients with Parkinson's disease (n = 19) and essential tremor (n = 16), respectively. Both disorders have been characterized by pathologically elevated LFP oscillations, as well as an increased tendency for neuronal bursting. Our findings suggest that periodic single-neuron bursts encode both pathophysiological beta (13 to 33 Hz; STN) and tremor (4 to 10 Hz; Vim) LFP oscillations, evidenced by strong time-frequency and phase-coupling relationships between the bursting and LFP signals. Spiking activity occurring outside of bursts had no relationship to the LFP. In STN, bursting activity most commonly preceded the LFP oscillation, suggesting that neuronal bursting generated within STN may give rise to an aggregate-level LFP oscillation. In Vim, LFP oscillations most commonly preceded bursting activity, suggesting that neuronal firing may be entrained by periodic afferent inputs. In both STN and Vim, the phase-coupling relationship between LFP and high-frequency oscillation (HFO) signals closely resembled the relationships between the LFP and single-neuron bursting. This suggests that periodic single-neuron bursting is likely representative of a higher spatial and temporal resolution readout of periodic increases in the amplitude of HFOs, which themselves may be a higher resolution readout of aggregate-level LFP oscillations. Overall, our results may reconcile "rate" and "oscillation" models of Parkinson's disease and shed light on the single-neuron basis and origin of pathophysiological oscillations in movement disorders.

Improvement of urethral dysfunction by 5-HT1A receptor agonist NLX-112 in diabetic rats.

To examine the effects of the selective 5-HT1A receptor agonist, NLX-112, on urethral function in streptozotocin-induced diabetic rats. Female Sprague-Dawley rats (n = 32) were divided into two groups: rats with type 1 diabetes mellitus (T1DM) and age-matched normal control rats (NC). T1DM was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Isovolumetric cystometry and urethral perfusion pressure (UPP) were evaluated 10 weeks postinjection in rats (n = 9 per group). The selective 5-HT1A receptor antagonist, WAY-100635 maleate salt, was administered after NLX-112 hydrochloride dose-response curve was generated (intravenously). The remaining rats were used for immunofluorescence and Western blot assays. Compared to controls, type 1 diabetic rats (T1D rats) had lower maximal intravesical pressure (IP max) and UPP changes. In T1D rats, NLX-112 hydrochloride (0.003-1.0 mg/kg) induced dose-dependent decreases in UPP nadir, IP max, high-frequency oscillations (HFOs) rate; and increases in UPP change and HFOs amplitude. WAY-100635 maleate salt (0.3 mg/kg) partially or completely reversed the NLX-112-induced changes. Immunofluorescence revealed that 5-HT1A receptors were found in the L6-S1 spinal cord dorsolateral nucleus, but the expression was significantly higher in the T1D rats. Additionally, Western blot showed there were significantly more 5-HT1A receptors in the ventral L6-S1 spinal cord of T1D rats. Urethral dysfunction in T1D rats was improved by NLX-112. 5-HT1A receptors were upregulated in the dorsolateral nucleus of L6-S1 spinal cord in T1D rats. These findings suggest that NLX-112 may constitute a novel therapeutic strategy to treat diabetic urethral dysfunction.

Temporal and morphological characteristics of high-frequency oscillations in an acute in vivo model of epilepsy.

Approximately 30% of patients with epilepsy do not respond to anti-epileptogenic drugs. Surgical removal of the epileptogenic zone (EZ), the brain regions where the seizures originate and spread, can be a possible therapy for these patients, but localizing the EZ is challenging due to a variety of clinical factors. High-frequency oscillations (HFOs) in intracranial electroencephalography (EEG) are a promising biomarker of the EZ, but it is currently unknown whether HFO rates and HFO morphology modulate as pathological brain networks evolve in a way that gives rise to seizures. To address this question, we assessed the temporal evolution of the duration of HFO events, amplitude of HFO events, and rates of HFOs per minute. HFO events were quantified using the 4AP in vivo rodent model of epilepsy, inducing seizures in two different brain areas. We found that the duration and amplitude of HFO events were significantly increased for the cortex model when compared to the hippocampus model. Additionally, the duration and amplitude increased significantly between baseline and pre-ictal HFOs in both models. On the other hand, the two models did not display a consistent increasing or decreasing trend in amplitude, duration or rate when comparing ictal and postictal intervals. Clinical Relevance- We assessed the amplitude, duration, and rate of HFOs in two acute in vivo rodent models of epilepsy. The significant modulation of HFO morphology from baseline to pre-ictal periods suggests that these features may be a robust biomarker for pathological tissue involved in epileptogenesis. Moreover, the differences in HFO morphology observed between cortex and hippocampus animal models possibly indicate that different structural network characteristics of the EZ cause this modulation. In all, we found that HFO features modulate significantly with the onset of seizures, further highlighting the need to consider of HFO morphology in EZ-localizing studies.

Seizure Onset Zone Identification Based on Phase-Amplitude Coupling of Interictal Electrocorticogram.

Presurgical localization from interictal electrocorticogram (ECoG) and resection of seizure onset zone (SOZ) are difficult processes to achieve seizure freedom. Recently, high frequency oscillations (HFOs) have been recognized as reliable biomarkers for epilepsy surgery which has a relation with the phase of low frequency activities in ECoG. Considering the recent valid biomarker for epilepsy surgery, we hypothesize that the approach of coupling between HFOs and low frequency phases differs SOZ from non-seizure onset zone (NSOZ). This study proposes phase-amplitude coupling (PAC) method to identify SOZ by measuring whether the amplitude of HFOs is coupled with a phase at 2-34 Hz in ECoG. Besides, three machine learning models for PAC-based features are designed for SOZ detection. Four patients with focal cortical dysplasia (FCD) are examined to observe efficiency. Experimental results indicate that the mode of coupling is a potential feature to detect SOZ.Clinical relevance- This suggests the PAC feature between low frequency phase and HFO amplitude may be used as a candidate biomarker to detect SOZ.

Dynamical Analysis of Seizure in Epileptic Brain: a Dynamic Phase-Amplitude Coupling Estimation Approach.

Cross-frequency coupling in general and phase-amplitude coupling (PAC) as a particular form of it, provides an opportunity to investigate the complex interactions between neural oscillations in the human brain and neurological disorders such as epilepsy. Using PAC detection methods on temporal sliding windows, we developed a map of dynamic PAC evolution to investigate the spatiotemporal changes occurring during ictal transitions in a patient with intractable mesial temporal lobe epilepsy. The map is built by computing the modulation index between the amplitude of high frequency oscillations and the phase of lower frequency rhythms from the intracranial stereoelectroencephalography recordings during seizure. Our preliminary results show early abnormal PAC changes occurring in the preictal state prior to the occurrence of clinical or visible electrographic seizure onset, and suggest that dynamic PAC measures may serve as a potential clinical technique for analyzing seizure dynamics.Clinical Relevance-Application of a dynamic temporal PAC map as a new tool may provide novel insights into the neurophysiology of epileptic seizure activity and its spatio-temporal dynamics.

Study on combustion oscillation characteristics of micron aluminum particles

Aluminum (Al) particles are regarded as general addictive into solid propellants not only as an extra energy source but also as a metallic damping-carrier on combustion instability. It is possible that the stability in propellant can be improved through partial Al substitution. However, knowledge of unsteady combustion characteristics of Al particles has been insufficient. In order to explore the unsteady combustion and attenuation characteristics of Al particle, a methane micro-combustor is designed. The acoustic oscillation of combustor is found to be excited, regardless of the Al particles mass of diameter. Moreover, the effects of 1) particle size and 2) mass are examined in detail. The burning of micro-sized Al particles in present experiment is attributed to melt dispersion mechanism. The rupture time is in the range of 2.18 ms to 2.81 ms for Al particles with mean diameter of 10 μm, 20 μm and 30 μm. With the increasing of particle size, the sound level of high-frequency oscillation increases from 65 dB to 85 dB. However, the attenuation effect for high-frequency oscillation is weakened for larger particle size. Finally, it is found that the pressure growth rate can be dramatically increased from 1000 Pa/s to 11,000 Pa/s and the peak amplitude of high frequency oscillation is augmented, as the Al particles mass ratio is increased. The present research sheds lights on an effective evaluation of unsteady Al combustion by considering particles parameters.

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS. MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis. ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively). ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival. SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.

A Novel Analysis, Design, and Optimal Methodology of High-Frequency Oscillation for Dual Active Bridge Converters With WBG Switching Devices and Nanocrystalline Transformer Cores

With the fast development of advanced switches and magnetic cores, high-frequency oscillation (HFO) caused by high dv/dt of fast switching devices and stray capacitances of transformer in dual active bridge (DAB) presents a significantly challenge. In this article, a comprehensive analysis, design, and optimal methodology of HFO for DAB with wideband gap (WBG) switching devices and nanocrystalline transformer cores is proposed. The stray parameters equivalent circuit of DAB is built and the key influencing factors to mitigated the HFO are identified by establishing a time-domain analytical model. Based on the theoretical analysis, this article points out for the first time that the traditional method of decreasing the stray capacitance of the transformer to eliminate HFO is not suitable for high dv/dt occasions when using WBG switching devices. Correspondingly, a novel elimination method of HFO by equating the voltage changing time of dv/dt to the oscillation cycle is proposed, through which the minimum voltage spike amplitude (VSA) of HFO can be achieved mathematically. A 6.6-kW DAB prototype with three different transformers is developed and an approximately 95% reduction of the VSA can be achieved when the proposed HFO elimination method is adopted, which verifies the effectiveness of the proposed method.

Role of High Frequency Oscillations of Somatosensory Evoked Potentials in Deciphering Pathophysiology of Migraine.

Background Habituation deficit is considered as a neurophysiological abnormality among migraineurs in the interictal period. For clear comprehension and clarity about the mechanism underlying habituation in migraine, a sophisticated method, i.e., high frequency oscillations (HFOs) evoked potentials, have been utilized. However, studies pertaining to this in the Indian context are rare. Objective The aim of the study is to determine the utility of HFO of somatosensory evoked potential (SSEP) in deciphering the pathophysiology of migraine. Materials and Methods Sixty subjects including 30 migraineurs in the interictal period and 30 healthy controls were considered for the study. Median nerve SSEP was recorded in patients and controls by standard protocols. HFO was extracted offline using the Digital zero-phase shift band-pass filtering at 450 and 750 Hz. The early and late HFOs were determined with respect to the N20 peak and were compared between the groups. Results Of total 30 migraineurs, 18 had hemicranial headache and 12 had holocranial headache. N20 latency, P25 latency, N20 onset to peak amplitude, and N20 onset to P25 amplitude were comparable in migraineurs and controls. The intraburst frequency of early HFOs in migraineurs was significantly higher ( p = 0.04), whereas the peak-to-peak amplitude was significantly lower ( p = 0.001). Conclusion Early HFOs on SSEP represent the thalamocortical excitatory drive in migraineurs. Overall, the study reports that reduced amplitude of early HFOs in the interictal period suggest reduced thalamocortical drive in migraineurs.

Amplitude of high frequency oscillations as a biomarker of the seizure onset zone

ObjectiveStudies of high frequency oscillations (HFOs) in epilepsy have primarily tested the HFO rate as a biomarker of the seizure onset zone (SOZ), but the rate varies over time and is not robust for all individual subjects. As an alternative, we tested the performance of HFO amplitude as a potential SOZ biomarker using two automated detection algorithms. MethodHFOs were detected in intracranial electroencephalogram (iEEG) from 11 patients using a machine learning algorithm and a standard amplitude-based algorithm. For each detector, SOZ and non-SOZ channels were classified using the rate and amplitude of high frequency events, and performance was compared using receiver operating characteristic curves. ResultsThe amplitude of detected events was significantly higher in SOZ. Across subjects, amplitude more accurately classified SOZ/non-SOZ than rate (higher values of area under the ROC curve and sensitivity, and lower false positive rates). Moreover, amplitude was more consistent across segments of data, indicated by lower coefficient of variation. ConclusionAs an SOZ biomarker, HFO amplitude offers advantages over HFO rate: it exhibits higher classification accuracy, more consistency over time, and robustness to parameter changes. SignificanceThis biomarker has the potential to increase the generalizability of HFOs and facilitate clinical implementation as a tool for SOZ localization.

Detection of anomalous high-frequency events in human intracranial EEG.

ObjectiveHigh‐frequency oscillations (HFOs) are a promising biomarker for the epileptogenic zone. However, no physiological definition of an HFO has been established, so detection relies on the empirical definition of an HFO derived from visual observation. This can bias estimates of HFO features such as amplitude and duration, thereby hindering their utility as biomarkers. Therefore, we set out to develop an algorithm that detects high‐frequency events in the intracranial EEG that are morphologically distinct from background without requiring assumptions about event amplitude or shape.MethodWe propose the anomaly detection algorithm (ADA), which uses unsupervised machine learning to identify segments of data that are distinct from the background. We apply ADA and a standard HFO detector using a root mean square amplitude threshold to intracranial EEG from 11 patients undergoing evaluation for epilepsy surgery. The rate, amplitude, and duration of the detected events and the percent overlap between the two detectors are compared.ResultIn the seizure onset zone (SOZ), ADA detected a subset of conventional HFOs. In non‐SOZ channels, ADA detected at least twice as many events as the standard approach, including some conventional HFOs; however, ADA also identified many low and intermediate amplitude events missed by the standard amplitude‐based method. The rate of ADA events was similar across all channels; however, the amplitude of ADA events was significantly higher in SOZ channels (P < .0045), and the amplitude measurement was more stable over time than the HFO rate, as indicated by a lower coefficient of variation (P < .0125).SignificanceADA does not require human supervision, parameter optimization, or prior assumptions about event shape, amplitude, or duration. Our results suggest that the algorithm's estimate of event amplitude may differentiate SOZ and non‐SOZ channels. Further studies will examine the utility of HFO amplitude as a biomarker for epilepsy surgical outcome.

Short-latency afferent inhibition and somato-sensory evoked potentials during the migraine cycle: surrogate markers of a cycling cholinergic thalamo-cortical drive?

BackgroundShort-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features.MethodsSAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation.ResultsCompared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI.ConclusionsThe migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.

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 ...

Research Article -Somatosensory Evoked High Frequency Oscillations in a Homogeneous Population of Drug Naive Migraineurs

Introduction: High band pass filtering of evoked potentials have produced the results of decreased early High frequency oscillations (HFOs) in previous studies of migraine patients. However, in most of these studies, the study population has been heterogeneous. The only study till date which used homogenous drug naive group of patients has actually produced contradictory results to the previous studies showing. Aim: We aimed to clarify the status of HFO amplitudes and latencies in drug-naive newly diagnosed patients. Methods: In the present study, we evaluated the 20 newly diagnosed and drug naive migraine patients using electrophysiological assessments using Somatosensory evoked potentials (SSEPs) and compared their SSEP parameters with those of the healthy age and gender matched normal controls. Median nerve SSEP was obtained by standard protocols. High frequency oscillations were extracted from the broad-band evoked potentials by digitally filtering using high pass filtering at 450Hz-1KHz. Early HFOs were identified when occurred before the N20 peak. Results: No differences were observed in the broad-band SSEPs i.e., N20 amplitudes and latencies. The maximal peak to peak amplitudes in the drug naïve migraineurs in between the attacks for the early HFOs (occurring before the N20 peak) were significantly smaller than the normal controls (p=0.046). The number of negative peaks were also fewer in the migraineurs in a statistically nonsignificant way. Discussion: This is the first HFO study on a homogenous population of migraineurs which shows decreased early HFOs, thus implicating weaker thalamocortical activity and contradicting the results by Lai et al1.

Assessing Epileptogenicity Using Phase-Locked High Frequency Oscillations: A Systematic Comparison of Methods.

High frequency oscillations (HFOs) are traditional biomarkers to identify the epileptogenic tissue during presurgical evaluation in pharmacoresistant epileptic patients. Recently, the resection of brain tissue exhibiting coupling between the amplitude of HFOs and the phase of low frequencies demonstrated a more favorable surgical outcome. Here we compare the predictive value of ictal HFOs and four methods for quantifying the ictal phase-amplitude coupling, namely mean vector length, phase-locked high gamma, phase locking value, and modulation index (MI). We analyzed 32 seizures from 16 patients to identify the channels that exhibit HFOs and phase-locked HFOs during seizures. We compared the resection ratio, defined as the percentage of channels exhibiting coupling located in the resected tissue, with the postsurgical outcome. We found that the MI is the only method to show a significant difference between the resection ratios of patients with good and poor outcomes. We further show that the whole seizure, not only the onset, is critical to assess epileptogenicity using the phase-locked HFOs. We postulate that the superiority of MI stems from its capacity to assess coupling of discrete HFO events and its independence from the HFO power. These results confirm that quantitative analysis of HFOs can boost presurgical evaluation and indicate the paramount importance of algorithm selection for clinical applications.

Strong coupling between slow oscillations and wide fast ripples in children with epileptic spasms: Investigation of modulation index and occurrence rate.

Epileptic spasms (ES) often become drug-resistant. To reveal the electrophysiological difference between children with ES (ES+) and without ES (ES-), we compared the occurrence rate (OR) of high-frequency oscillations (HFOs) and the modulation index (MI) of coupling between slow and fast oscillations. In ES+, we hypothesized that (1) pathological HFOs are more widely distributed and (2) slow oscillations show stronger coupling with pathological HFOs than in ES-. We retrospectively reviewed 24 children with drug-resistant multilobar onset epilepsy, who underwent intracranial video electroencephalography prior to multilobar resections. We measured the OR of HFOs and determined the electrodes with a high rate of HFOs by cluster analysis. We calculated MI, which reflects the degree of coupling between HFO (ripple/fast ripple [FR]) amplitude and 5 different frequency bands of delta and theta activities (0.5-1 Hz, 1-2 Hz, 2-3 Hz, 3-4 Hz, 4-8 Hz). In ES+ (n = 10), the OR(FRs) , the number of electrodes with high-rate FRs, and the MI(FRs & 3-4 Hz) in all electrodes were significantly higher than in ES- (n = 14). In both the ES+ and ES- groups, MI(ripples/FRs & 3-4 Hz) was the highest among the 5 frequency bands. Within the good seizure outcome group, the OR(FRs) and the MI(FRs & 3-4 Hz) in the resected area in ES+ were significantly higher than in ES- (OR[FRs] , P = .04; MI[FRs & 3-4 Hz] , P = .04). In ES+, the larger number of high-rate FR electrodes indicates more widespread epileptogenicity than in ES-. High values of OR(FRs) and MI(FRs & 3-4 Hz) in ES+ compared to ES- are a signature of the severity of epileptogenicity. We proved that ES+ children who achieved seizure freedom following multilobar resections exhibited strong coupling between slow oscillations and FRs.

Power and coherence of cortical high-frequency oscillations during wakefulness and sleep.

Recently, a novel type of fast cortical oscillatory activity that occurs between 110 and 160Hz (high-frequency oscillations (HFO)) was described. HFO are modulated by the theta rhythm in hippocampus and neocortex during active wakefulness and REM sleep. As theta-HFO coupling increases during REM, a role for HFO in memory consolidation has been proposed. However, global properties such as the cortex-wide topographic distribution and the cortico-cortical coherence remain unknown. In this study, we recorded the electroencephalogram during sleep and wakefulness in the rat and analyzed the spatial extent of the HFO band power and coherence. We confirmed that the HFO amplitude is phase-locked to theta oscillations and is modified by behavioral states. During active wakefulness, HFO power was relatively higher in the neocortex and olfactory bulb compared to sleep. HFO power decreased during non-REM and had an intermediate level during REM sleep. Furthermore, coherence was larger during active wakefulness than non-REM, while REM showed a complex pattern in which coherence increased only in intra and decreased in inter-hemispheric combination of electrodes. This coherence pattern is different from gamma (30-100Hz) coherence, which is reduced during REM sleep. This data show an important HFO cortico-cortical dialog during active wakefulness even when the level of theta comodulation is lower than in REM. In contrast, during REM, this dialog is highly modulated by theta and restricted to intra-hemispheric medial-posterior cortical regions. Further studies combining behavior, electrophysiology and new analytical tools are needed to plunge deeper into the functional significance of the HFO.

Pallidal low β-low γ phase-amplitude coupling inversely correlates with Parkinson disease symptoms

ObjectiveRecent discoveries suggest that it is most likely the coupling of β oscillations (13–30Hz) and not merely their power that relates to Parkinson disease (PD) pathophysiology. MethodsWe analyzed power and phase amplitude coupling (PAC) in local field potentials (LFP) recorded from Pallidum after placement of deep brain stimulation (DBS) leads in nineteen PD patients and three patients with dystonia. ResultsWithin GPi, we identified PAC between phase of β and amplitude of high frequency oscillations (200–300Hz) and distinct β-low γ (40–80Hz) PAC both modulated by contralateral movement. Resting β-low γ PAC, also present in dystonia patients, inversely correlated with severity of rigidity and bradykinesia (R=−0.44, P=0.028). These findings were specific to the low β band, suggesting a differential role for the two β sub-bands. ConclusionsPAC is present across distinct frequency bands within the GPi. Given the presence of low β-low γ PAC in dystonia and the inverse correlation with symptom severity, we propose that this PAC may be a normal pallidal signal. SignificanceThis study provides new evidence on the pathophysiological contribution of local pallidal coupling and suggests similar and distinct patterns of coupling within GPi and STN in PD.

73. Transcutaneous supraorbital nerve stimulation increases thalamocortical activity in migraine between attacks

In a recent randomized double-blind sham-controlled study the Cefaly®, a novel transcutaneous supraorbital electrostimulation device, has been successfully used as a prophylactic treatment for episodic migraine. The possible mechanisms of action through which the device is able to induce clinical improvement in migraine are not known. Here, we investigated whether Cefaly® may act centrally at the thalamocortical/cortical level. We have recorded the somatosensory evoked potentials (SSEPs) before and two times after one session of supraorbital stimulation with Cefaly® lasting 20 min in 10 migraine without aura patients between attacks. We measured the N20-P25 amplitudes on the low-frequency SSEP, and, after applying a band-pass filter (450–750 Hz), maximal peak-to-peak amplitudes of the pre-synaptic, reflecting thalamocortical activity, and post-synaptic, reflecting primary cortical activation, high-frequency oscillations (HFOs). Pre-synaptic HFO amplitudes, reflecting somatosensory thalamocortical activity, significantly increased after the stimulation (from 0.035 microV to 0.058 microV, p Present data might support the hypothesis that Cefaly® acts centrally through increased thalamocortical activity induced by the neurostimulation. It is of obvious interest to verify whether these device-induced changes might persist at long-term after 3-month daily preventive stimulation, and if they follow clinical improvement.