Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60-150 Hz), ripple (80-250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.

• Klíčová slova
• cognition, intracranial EEG, local field potential, memory consolidation, network oscillations, sharp-wave ripples,
• MeSH
• elektroencefalografie MeSH
• kognice * fyziologie   MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• mozkové vlny fyziologie   MeSH
• paměť fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Sleep manifests itself by the spontaneous emergence of characteristic oscillatory rhythms, which often time-lock and are implicated in memory formation. Here, we analyze a neural mass model of the thalamocortical loop in which the cortical node can generate slow oscillations (approximately 1 Hz) while its thalamic component can generate fast sleep spindles of σ-band activity (12-15 Hz). We study the dynamics for different coupling strengths between the thalamic and cortical nodes, for different conductance values of the thalamic node's potassium leak and hyperpolarization-activated cation-nonselective currents, and for different parameter regimes of the cortical node. The latter are listed as follows: (1) a low activity (DOWN) state with noise-induced, transient excursions into a high activity (UP) state, (2) an adaptation induced slow oscillation limit cycle with alternating UP and DOWN states, and (3) a high activity (UP) state with noise-induced, transient excursions into the low activity (DOWN) state. During UP states, thalamic spindling is abolished or reduced. During DOWN states, the thalamic node generates sleep spindles, which in turn can cause DOWN to UP transitions in the cortical node. Consequently, this leads to spindle-induced UP state transitions in parameter regime (1), thalamic spindles induced in some but not all DOWN states in regime (2), and thalamic spindles following UP to DOWN transitions in regime (3). The spindle-induced σ-band activity in the cortical node, however, is typically the strongest during the UP state, which follows a DOWN state "window of opportunity" for spindling. When the cortical node is parametrized in regime (3), the model well explains the interactions between slow oscillations and sleep spindles observed experimentally during Non-Rapid Eye Movement sleep. The model is computationally efficient and can be integrated into large-scale modeling frameworks to study spatial aspects like sleep wave propagation.

• Klíčová slova
• cross-frequency coupling, neural mass model, sleep spindles, slow oscillations, thalamocortical loop,
• Publikační typ
• časopisecké články 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

BACKGROUND: High frequency oscillations (HFOs) are emerging as potentially clinically important biomarkers for localizing seizure generating regions in epileptic brain. These events, however, are too frequent, and occur on too small a time scale to be identified quickly or reliably by human reviewers. Many of the deficiencies of the HFO detection algorithms published to date are addressed by the CS algorithm presented here. NEW METHOD: The algorithm employs novel methods for: 1) normalization; 2) storage of parameters to model human expertise; 3) differentiating highly localized oscillations from filtering phenomena; and 4) defining temporal extents of detected events. RESULTS: Receiver-operator characteristic curves demonstrate very low false positive rates with concomitantly high true positive rates over a large range of detector thresholds. The temporal resolution is shown to be +/-∼5ms for event boundaries. Computational efficiency is sufficient for use in a clinical setting. COMPARISON WITH EXISTING METHODS: The algorithm performance is directly compared to two established algorithms by Staba (2002) and Gardner (2007). Comparison with all published algorithms is beyond the scope of this work, but the features of all are discussed. All code and example data sets are freely available. CONCLUSIONS: The algorithm is shown to have high sensitivity and specificity for HFOs, be robust to common forms of artifact in EEG, and have performance adequate for use in a clinical setting.

• Klíčová slova
• Detection algorithm, Frequency dominance, HFO, High frequency oscillations, Ripples,
• MeSH
• algoritmy * MeSH
• artefakty MeSH
• časové faktory MeSH
• elektroencefalografie metody   MeSH
• epilepsie diagnóza   patofyziologie   MeSH
• falešně pozitivní reakce MeSH
• hlodavci MeSH
• lidé MeSH
• mozek fyziologie   patofyziologie   MeSH
• počítačové zpracování signálu MeSH
• psi MeSH
• ROC křivka MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• zvířata 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.

• Klíčová slova
• antiepileptic drugs, high-frequency oscillations, hippocampus, in vivo, lacosamide, levetiracetam, ripples, sharp-wave ripples,
• Publikační typ
• časopisecké články MeSH

Modern electroencephalographic (EEG) technology contributed to the appreciation that the EEG signal outside the classical Berger frequency band contains important information. In epilepsy, research of the past decade focused particularly on interictal high-frequency oscillations (HFOs) > 80 Hz. The first large application of HFOs was in the context of epilepsy surgery. This is now followed by other applications such as assessment of epilepsy severity and monitoring of antiepileptic therapy. This article reviews the evidence on the clinical use of HFOs in epilepsy with an emphasis on the latest developments. It highlights the growing literature on the association between HFOs and postsurgical seizure outcome. A recent meta-analysis confirmed a higher resection ratio for HFOs in seizure-free versus non-seizure-free patients. Residual HFOs in the postoperative electrocorticogram were shown to predict epilepsy surgery outcome better than preoperative HFO rates. The review further discusses the different attempts to separate physiological from epileptic HFOs, as this might increase the specificity of HFOs. As an example, analysis of sleep microstructure demonstrated a different coupling between HFOs inside and outside the epileptogenic zone. Moreover, there is increasing evidence that HFOs are useful to measure disease activity and assess treatment response using noninvasive EEG and magnetoencephalography. This approach is particularly promising in children, because they show high scalp HFO rates. HFO rates in West syndrome decrease after adrenocorticotropic hormone treatment. Presence of HFOs at the time of rolandic spikes correlates with seizure frequency. The time-consuming visual assessment of HFOs, which prevented their clinical application in the past, is now overcome by validated computer-assisted algorithms. HFO research has considerably advanced over the past decade, and use of noninvasive methods will make HFOs accessible to large numbers of patients. Prospective multicenter trials are awaited to gather information over long recording periods in large patient samples.

• Klíčová slova
• Biomarker, Scalp EEG, Seizure, Sleep, Surgical outcome,
• MeSH
• biologické hodiny fyziologie   MeSH
• biomedicínský výzkum * MeSH
• elektroencefalografie MeSH
• epilepsie diagnóza   patofyziologie   MeSH
• lidé MeSH
• mapování mozku MeSH
• mozkové vlny fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

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

High frequency oscillations are associated with normal brain function, but also increasingly recognized as potential biomarkers of the epileptogenic brain. Their role in human cognition has been predominantly studied in classical gamma frequencies (30-100 Hz), which reflect neuronal network coordination involved in attention, learning and memory. Invasive brain recordings in animals and humans demonstrate that physiological oscillations extend beyond the gamma frequency range, but their function in human cognitive processing has not been fully elucidated. Here we investigate high frequency oscillations spanning the high gamma (50-125 Hz), ripple (125-250 Hz) and fast ripple (250-500 Hz) frequency bands using intracranial recordings from 12 patients (five males and seven females, age 21-63 years) during memory encoding and recall of a series of affectively charged images. Presentation of the images induced high frequency oscillations in all three studied bands within the primary visual, limbic and higher order cortical regions in a sequence consistent with the visual processing stream. These induced oscillations were detected on individual electrodes localized in the amygdala, hippocampus and specific neocortical areas, revealing discrete oscillations of characteristic frequency, duration and latency from image presentation. Memory encoding and recall significantly modulated the number of induced high gamma, ripple and fast ripple detections in the studied structures, which was greater in the primary sensory areas during the encoding (Wilcoxon rank sum test, P = 0.002) and in the higher-order cortical association areas during the recall (Wilcoxon rank sum test, P = 0.001) of memorized images. Furthermore, the induced high gamma, ripple and fast ripple responses discriminated the encoded and the affectively charged images. In summary, our results show that high frequency oscillations, spanning a wide range of frequencies, are associated with memory processing and generated along distributed cortical and limbic brain regions. These findings support an important role for fast network synchronization in human cognition and extend our understanding of normal physiological brain activity during memory processing.

• Klíčová slova
• cognitive processing, gamma oscillations, high frequency oscillations, memory, neural networks,
• MeSH
• afekt fyziologie   MeSH
• amygdala fyziologie   chirurgie   MeSH
• dospělí MeSH
• elektroencefalografie přístrojové vybavení   metody   MeSH
• funkční zobrazování neurálních procesů MeSH
• hipokampus fyziologie   chirurgie   MeSH
• implantované elektrody MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mozková kůra fyziologie   MeSH
• mozkové vlny fyziologie   MeSH
• nervová síť fyziologie   MeSH
• paměť fyziologie   MeSH
• rozpomínání fyziologie   MeSH
• rozpoznávání (psychologie) fyziologie   MeSH
• somatosenzorické korové centrum fyziologie   MeSH
• velký mozek fyziologie   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
• Research Support, N.I.H., Extramural MeSH