BACKGROUND: Until now there has been no way of distinguishing between physiological and epileptic hippocampal ripples in intracranial recordings. In the present study we addressed this by investigating the effect of cognitive stimulation on interictal high frequency oscillations in the ripple range (80-250 Hz) within epileptic (EH) and non-epileptic hippocampus (NH). METHODS: We analyzed depth EEG recordings in 10 patients with intractable epilepsy, in whom hippocampal activity was recorded initially during quiet wakefulness and subsequently during a simple cognitive task. Using automated detection of ripples based on amplitude of the power envelope, we analyzed ripple rate (RR) in the cognitive and resting period, within EH and NH. RESULTS: Compared to quiet wakefulness we observed a significant reduction of RR during cognitive stimulation in EH, while it remained statistically marginal in NH. Further, we investigated the direct impact of cognitive stimuli on ripples (i.e. immediately post-stimulus), which showed a transient statistically significant suppression of ripples in the first second after stimuli onset in NH only. CONCLUSION: Our results point to a differential reactivity of ripples within EH and NH to cognitive stimulation.

• MeSH
• bdění MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• epilepsie patofyziologie   MeSH
• hipokampus patofyziologie   MeSH
• implantované elektrody MeSH
• kognice fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• neuropsychologické testy MeSH
• odpočinek MeSH
• rozpoznávání automatizované MeSH
• zraková percepce fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The dialogue between cortex and hippocampus is known to be crucial for sleep-dependent memory consolidation. During slow wave sleep, memory replay depends on slow oscillation (SO) and spindles in the (neo)cortex and sharp wave-ripples (SWRs) in the hippocampus. The mechanisms underlying interaction of these rhythms are poorly understood. We examined the interaction between cortical SO and hippocampal SWRs in a model of the hippocampo-cortico-thalamic network and compared the results with human intracranial recordings during sleep. We observed that ripple occurrence peaked following the onset of an Up-state of SO and that cortical input to hippocampus was crucial to maintain this relationship. A small fraction of ripples occurred during the Down-state and controlled initiation of the next Up-state. We observed that the effect of ripple depends on its precise timing, which supports the idea that ripples occurring at different phases of SO might serve different functions, particularly in the context of encoding the new and reactivation of the old memories during memory consolidation. The study revealed complex bidirectional interaction of SWRs and SO in which early hippocampal ripples influence transitions to Up-state, while cortical Up-states control occurrence of the later ripples, which in turn influence transition to Down-state.

• MeSH
• elektroencefalografie metody   MeSH
• hipokampus fyziologie   MeSH
• konsolidace paměti fyziologie   MeSH
• lidé MeSH
• neokortex fyziologie   MeSH
• spánek pomalých vln fyziologie   MeSH
• spánek fyziologie   MeSH
• thalamus fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Epilepsy is a very common disease affecting at least 1% of the population, comprising a number of over 50 million people. As many patients suffer from the drug-resistant version, the number of potential treatment methods is very small. However, since not only the treatment of epilepsy, but also its proper diagnosis or observation of brain signals from recordings are important research areas, in this paper, we address this very problem by developing a reliable technique for removing spikes and sharp transients from the baseline of the brain signal using a morphological filter. This allows much more precise identification of the so-called epileptic zone, which can then be resected, which is one of the methods of epilepsy treatment. We used eight patients with 5 KHz data set and depended upon the Staba 2002 algorithm as a reference to detect the ripples. We found that the average sensitivity and false detection rate of our technique are significant, and they are ∼94% and ∼14%, respectively.

• MeSH
• algoritmy MeSH
• elektroencefalografie * metody   MeSH
• epilepsie * diagnóza   MeSH
• lidé MeSH
• mapování mozku MeSH
• mozek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Pathological high-frequency oscillations are a novel marker used to improve the delineation of epileptogenic tissue and, hence, the outcome of epilepsy surgery. Their practical clinical utilization is curtailed by the inability to discriminate them from physiological oscillations due to frequency overlap. Although it is well documented that pathological HFOs are suppressed by antiepileptic drugs (AEDs), the effect of AEDs on normal HFOs is not well known. In this experimental study, we have explored whether physiological HFOs (sharp-wave ripples) of hippocampal origin respond to AED treatment. The results show that application of a single dose of levetiracetam or lacosamide does not reduce the rate of sharp-wave ripples. In addition, it seems that these new generation drugs do not negatively affect the cellular and network mechanisms involved in sharp-wave ripple generation, which may provide a plausible explanation for the absence of significant negative effects on cognitive functions of these drugs, particularly on memory.

• Publikační typ
• časopisecké články MeSH

High-frequency oscillations (HFOs) represent an electrographic biomarker of endogenous epileptogenicity and seizure-generating tissue that proved clinically useful in presurgical planning and delineating the resection area. In the neocortex, the clinical observations on HFOs are not sufficiently supported by experimental studies stemming from a lack of realistic neocortical epilepsy models that could provide an explanation of the pathophysiological substrates of neocortical HFOs. In this study, we explored pathological epileptiform network phenomena, particularly HFOs, in a highly realistic murine model of neocortical epilepsy due to focal cortical dysplasia (FCD) type II. FCD was induced in mice by the expression of the human pathogenic mTOR gene mutation during embryonic stages of brain development. Electrographic recordings from multiple cortical regions in freely moving animals with FCD and epilepsy demonstrated that the FCD lesion generates HFOs from all frequency ranges, i.e., gamma, ripples, and fast ripples up to 800 Hz. Gamma-ripples were recorded almost exclusively in FCD animals, while fast ripples occurred in controls as well, although at a lower rate. Gamma-ripple activity is particularly valuable for localizing the FCD lesion, surpassing the utility of fast ripples that were also observed in control animals, although at significantly lower rates. Propagating HFOs occurred outside the FCD, and the contralateral cortex also generated HFOs independently of the FCD, pointing to a wider FCD network dysfunction. Optogenetic activation of neurons carrying mTOR mutation and expressing Channelrhodopsin-2 evoked fast ripple oscillations that displayed spectral and morphological profiles analogous to spontaneous oscillations. This study brings experimental evidence that FCD type II generates pathological HFOs across all frequency bands and provides information about the spatiotemporal properties of each HFO subtype in FCD. The study shows that mutated neurons represent a functionally interconnected and active component of the FCD network, as they can induce interictal epileptiform phenomena and HFOs.

• MeSH
• elektroencefalografie MeSH
• epilepsie * MeSH
• fokální kortikální dysplazie * MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• TOR serin-threoninkinasy MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Interictal high-frequency oscillations (HFO) were recently identified in recordings from depth macroelectrodes in epileptic patients. StereoEEG (SEEG) recordings were analyzed in four patients with medically intractable partial seizures due to focal cortical dysplasia type IIA. Characteristics of HFO within seizure onset zone (SOZ), irritative zone, and remote brain areas were investigated. Whilst the rate of occurrence for ripples (80-200 Hz) was significantly higher in recordings from within than outside the SOZ, the rate of fast ripples (200-450 Hz) was less reliable index of SOZ. Interestingly, the mean powers across subjects were significantly higher within than outside the SOZ in both ripple and fast ripple frequency ranges. Our study demonstrates a capacity of interictal HFO to detect the SOZ in focal cortical dysplasias.

• MeSH
• analýza rozptylu MeSH
• dospělí MeSH
• elektrody MeSH
• elektroencefalografie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• malformace mozkové kůry komplikace   patologie   MeSH
• mapování mozku MeSH
• mladiství MeSH
• mozek patofyziologie   MeSH
• počítačové zpracování signálu MeSH
• spektrální analýza MeSH
• záchvaty etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: In the present study, we aimed to investigate depth electroencephalographic (EEG) recordings in a large cohort of patients with drug-resistant epilepsy and to focus on interictal very high-frequency oscillations (VHFOs) between 500Hz and 2kHz. We hypothesized that interictal VHFOs are more specific biomarkers for epileptogenic zone compared to traditional HFOs. METHODS: Forty patients with focal epilepsy who underwent presurgical stereo-EEG (SEEG) were included in the study. SEEG data were recorded with a sampling rate of 25kHz, and a 30-minute resting period was analyzed for each patient. Ten patients met selected criteria for analyses of correlations with surgical outcome: detection of interictal ripples (Rs), fast ripples (FRs), and VHFOs; resective surgery; and at least 1 year of postoperative follow-up. Using power envelope computation and visual inspection of power distribution matrixes, electrode contacts with HFOs and VHFOs were detected and analyzed. RESULTS: Interictal very fast ripples (VFRs; 500-1,000Hz) were detected in 23 of 40 patients and ultrafast ripples (UFRs; 1,000-2,000Hz) in almost half of investigated subjects (n = 19). VFRs and UFRs were observed only in patients with temporal lobe epilepsy and were recorded exclusively from mesiotemporal structures. The UFRs were more spatially restricted in the brain than lower-frequency HFOs. When compared to R oscillations, significantly better outcomes were observed in patients with a higher percentage of removed contacts containing FRs, VFRs, and UFRs. INTERPRETATION: Interictal VHFOs are relatively frequent abnormal phenomena in patients with epilepsy, and appear to be more specific biomarkers for epileptogenic zone when compared to traditional HFOs. Ann Neurol 2017;82:299-310.

• MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• endofenotypy * MeSH
• epilepsie parciální patofyziologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozkové vlny fyziologie   MeSH
• refrakterní epilepsie patofyziologie   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The main aim of this study was to investigate the potential differences in terms of interictal high frequency oscillations (HFOs) between both hippocampi in unilateral (U-MTLE) and bilateral mesial temporal lobe epilepsy (B-MTLE). METHODS: Sixteen patients with MTLE underwent bilateral hippocampal depth electrode implantation as part of epilepsy surgery evaluation. Interictal HFOs were detected automatically. The analyses entail comparisons of the rates and spatial distributions of ripples and fast ripples (FR) in hippocampi and amygdalae, with respect to the eventual finding of hippocampal sclerosis (HS). RESULTS: In U-MTLE, higher ripple and FR rates were found in the hippocampi ipsilateral to the seizure onset than in the contralateral hippocampi. Non-epileptic hippocampi in U-MTLE were distinguished by significantly lower ripple rate than in the remaining analyzed hippocampi. There were not differences between the hippocampi in B-MTLE. In the hippocampi with proven HS, higher FR rates were observed in the ventral than in the dorsal parts. CONCLUSIONS: Non-epileptic hippocampi in U-MTLE demonstrated significantly lower ripple rates than those epileptic in U-MTLE and B-MTLE. SIGNIFICANCE: Low interictal HFO occurrence might be considered as a marker of the non-epileptic hippocampi in MTLE.

• MeSH
• amygdala patofyziologie   MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• epilepsie temporálního laloku patologie   patofyziologie   MeSH
• hipokampus patologie   patofyziologie   MeSH
• implantované elektrody MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• retrospektivní studie MeSH
• spánkový lalok patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hippocampal high-frequency electrographic activity (HFOs) represents one of the major discoveries not only in epilepsy research but also in cognitive science over the past few decades. A fundamental challenge, however, has been the fact that physiological HFOs associated with normal brain function overlap in frequency with pathological HFOs. We investigated the impact of a cognitive task on HFOs with the aim of improving differentiation between epileptic and non-epileptic hippocampi in humans. Hippocampal activity was recorded with depth electrodes in 15 patients with focal epilepsy during a resting period and subsequently during a cognitive task. HFOs in ripple and fast ripple frequency ranges were evaluated in both conditions, and their rate, spectral entropy, relative amplitude and duration were compared in epileptic and non-epileptic hippocampi. The similarity of HFOs properties recorded at rest in epileptic and non-epileptic hippocampi suggests that they cannot be used alone to distinguish between hippocampi. However, both ripples and fast ripples were observed with higher rates, higher relative amplitudes and longer durations at rest as well as during a cognitive task in epileptic compared with non-epileptic hippocampi. Moreover, during a cognitive task, significant reductions of HFOs rates were found in epileptic hippocampi. These reductions were not observed in non-epileptic hippocampi. Our results indicate that although both hippocampi generate HFOs with similar features that probably reflect non-pathological phenomena, it is possible to differentiate between epileptic and non-epileptic hippocampi using a simple odd-ball task.

• MeSH
• dospělí MeSH
• elektroencefalografie přístrojové vybavení   MeSH
• epilepsie temporálního laloku diagnóza   patofyziologie   terapie   MeSH
• hipokampus patofyziologie   MeSH
• implantované elektrody MeSH
• kognice fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mozkové vlny fyziologie   MeSH
• neuropsychologické testy MeSH
• refrakterní epilepsie diagnóza   patofyziologie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH