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

Intracranial electroencephalographic (iEEG) recordings from patients with epilepsy provide distinct opportunities and novel data for the study of co-occurring psychiatric disorders. Comorbid psychiatric disorders are very common in drug-resistant epilepsy and their added complexity warrants careful consideration. In this review, we first discuss psychiatric comorbidities and symptoms in patients with epilepsy. We describe how epilepsy can potentially impact patient presentation and how these factors can be addressed in the experimental designs of studies focused on the electrophysiologic correlates of mood. Second, we review emerging technologies to integrate long-term iEEG recording with dense behavioral tracking in naturalistic environments. Third, we explore questions on how best to address the intersection between epilepsy and psychiatric comorbidities. Advances in ambulatory iEEG and long-term behavioral monitoring technologies will be instrumental in studying the intersection of seizures, epilepsy, psychiatric comorbidities, and their underlying circuitry.

• Klíčová slova
• SEEG (stereoelectroencephalography), biomarker, deep brain stimulation, electrocorticography (ECoG), epilepsy, major depression (MDD), neuromodulation, psychiatric disorders,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: When considering all patients with focal drug-resistant epilepsy, as high as 40-50% of patients suffer seizure recurrence after surgery. To achieve seizure freedom without side effects, accurate localization of the epileptogenic tissue is crucial before its resection. We investigate an automated, fast, objective mapping process that uses only interictal data. METHODS: We propose a novel approach based on multiple iEEG features, which are used to train a support vector machine (SVM) model for classification of iEEG electrodes as normal or pathologic using 30 min of inter-ictal recording. RESULTS: The tissue under the iEEG electrodes, classified as epileptogenic, was removed in 17/18 excellent outcome patients and was not entirely resected in 8/10 poor outcome patients. The overall best result was achieved in a subset of 9 excellent outcome patients with the area under the receiver operating curve = 0.95. CONCLUSION: SVM models combining multiple iEEG features show better performance than algorithms using a single iEEG marker. Multiple iEEG and connectivity features in presurgical evaluation could improve epileptogenic tissue localization, which may improve surgical outcome and minimize risk of side effects. SIGNIFICANCE: In this study, promising results were achieved in localization of epileptogenic regions by SVM models that combine multiple features from 30 min of inter-ictal iEEG recordings.

• Klíčová slova
• Connectivity, Drug resistant epilepsy, Epileptogenic zone localization, High frequency oscillations, Machine learning, Multi-feature approach,
• MeSH
• dospělí MeSH
• elektroencefalografie přístrojové vybavení   metody   MeSH
• epilepsie parciální diagnóza   patofyziologie   MeSH
• implantované elektrody MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Manual and semi-automatic identification of artifacts and unwanted physiological signals in large intracerebral electroencephalographic (iEEG) recordings is time consuming and inaccurate. To date, unsupervised methods to accurately detect iEEG artifacts are not available. This study introduces a novel machine-learning approach for detection of artifacts in iEEG signals in clinically controlled conditions using convolutional neural networks (CNN) and benchmarks the method's performance against expert annotations. The method was trained and tested on data obtained from St Anne's University Hospital (Brno, Czech Republic) and validated on data from Mayo Clinic (Rochester, Minnesota, U.S.A). We show that the proposed technique can be used as a generalized model for iEEG artifact detection. Moreover, a transfer learning process might be used for retraining of the generalized version to form a data-specific model. The generalized model can be efficiently retrained for use with different EEG acquisition systems and noise environments. The generalized and specialized model F1 scores on the testing dataset were 0.81 and 0.96, respectively. The CNN model provides faster, more objective, and more reproducible iEEG artifact detection compared to manual approaches.

• Klíčová slova
• Artifact probability matrix (APM), Convolutional neural networks (CNN), Intracranial EEG (iEEG), Noise detection,
• MeSH
• artefakty * MeSH
• elektroencefalografie metody   MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• neuronové sítě * MeSH
• retrospektivní studie MeSH
• strojové učení * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Brain stimulation has emerged as an effective treatment for a wide range of neurological and psychiatric diseases. Parkinson's disease, epilepsy, and essential tremor have FDA indications for electrical brain stimulation using intracranially implanted electrodes. Interfacing implantable brain devices with local and cloud computing resources have the potential to improve electrical stimulation efficacy, disease tracking, and management. Epilepsy, in particular, is a neurological disease that might benefit from the integration of brain implants with off-the-body computing for tracking disease and therapy. Recent clinical trials have demonstrated seizure forecasting, seizure detection, and therapeutic electrical stimulation in patients with drug-resistant focal epilepsy. In this paper, we describe a next-generation epilepsy management system that integrates local handheld and cloud-computing resources wirelessly coupled to an implanted device with embedded payloads (sensors, intracranial EEG telemetry, electrical stimulation, classifiers, and control policy implementation). The handheld device and cloud computing resources can provide a seamless interface between patients and physicians, and realtime intracranial EEG can be used to classify brain state (wake/sleep, preseizure, and seizure), implement control policies for electrical stimulation, and track patient health. This system creates a flexible platform in which low demand analytics requiring fast response times are embedded in the implanted device and more complex algorithms are implemented in offthebody local and distributed cloud computing environments. The system enables tracking and management of epileptic neural networks operating over time scales ranging from milliseconds to months.

• Klíčová slova
• Epilepsy, deep brain stimulation, distributed computing, implantable devices, seizure detection, seizure prediction,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: This study investigates high-frequency oscillations (HFOs; 65-600 Hz) as a biomarker of epileptogenic brain and explores three barriers to their clinical translation: (1) Distinguishing pathological HFOs (pathHFO) from physiological HFOs (physHFO). (2) Classifying tissue under individual electrodes as epileptogenic (3) Reproducing results across laboratories. METHODS: We recorded HFOs using intracranial EEG (iEEG) in 90 patients with focal epilepsy and 11 patients without epilepsy. In nine patients with epilepsy putative physHFOs were induced by cognitive or motor tasks. HFOs were identified using validated detectors. A support vector machine (SVM) using HFO features was developed to classify tissue under individual electrodes as normal or epileptogenic. RESULTS: There was significant overlap in the amplitude, frequency, and duration distributions for spontaneous physHFO, task induced physHFO, and pathHFO, but the amplitudes of the pathHFO were higher (P < 0.0001). High gamma pathHFO had the strongest association with seizure onset zone (SOZ), and were elevated on SOZ electrodes in 70% of epilepsy patients (P < 0.0001). Failure to resect tissue generating high gamma pathHFO was associated with poor outcomes (P < 0.0001). A SVM classified individual electrodes as epileptogenic with 63.9% sensitivity and 73.7% specificity using SOZ as the target. INTERPRETATION: A broader range of interictal pathHFO (65-600 Hz) than previously recognized are biomarkers of epileptogenic brain, and are associated with SOZ and surgical outcome. Classification of HFOs into physiological or pathological remains challenging. Classification of tissue under individual electrodes was demonstrated to be feasible. The open source data and algorithms provide a resource for future studies.

• Publikační typ
• časopisecké články MeSH

Pupil responses are known to indicate brain processes involved in perception, attention and decision-making. They can provide an accessible biomarker of human memory performance and cognitive states in general. Here we investigated changes in the pupil size during encoding and recall of word lists. Consistent patterns in the pupil response were found across and within distinct phases of the free recall task. The pupil was most constricted in the initial fixation phase and was gradually more dilated through the subsequent encoding, distractor and recall phases of the task, as the word items were maintained in memory. Within the final recall phase, retrieving memory for individual words was associated with pupil dilation in absence of visual stimulation. Words that were successfully recalled showed significant differences in pupil response during their encoding compared to those that were forgotten - the pupil was more constricted before and more dilated after the onset of word presentation. Our results suggest pupil size as a potential biomarker for probing and modulation of memory processing.

• MeSH
• dospělí MeSH
• kognice fyziologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• pupila fyziologie   MeSH
• rozpomínání fyziologie   MeSH
• světelná stimulace MeSH
• velikost orgánu fyziologie   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

• MeSH
• elektrokortikografie * MeSH
• kohortové studie MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mozek diagnostické zobrazování   patofyziologie   MeSH
• periodicita MeSH
• počítačová rentgenová tomografie MeSH
• počítačové zpracování signálu MeSH
• předoperační péče MeSH
• refrakterní epilepsie diagnostické zobrazování   patofyziologie   terapie   MeSH
• záchvaty diagnostické zobrazování   patofyziologie   terapie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62-118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with "poor" memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation.

• Klíčová slova
• ECoG, brain stimulation, cognitive enhancement, high-frequency oscillations, intracranial EEG, γ-activity,
• MeSH
• dospělí MeSH
• elektrická stimulace * MeSH
• elektrokortikografie * MeSH
• gama rytmus EEG fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mozková kůra fyziologie   MeSH
• paměť fyziologie   MeSH
• refrakterní epilepsie 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
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

High-frequency oscillations (HFOs: 100 - 600 Hz) have been widely proposed as biomarkers of epileptic brain tissue. In addition, HFOs over a broader range of frequencies spanning 30 - 2000 Hz are potential biomarkers of both physiological and pathological brain processes. The majority of the results from humans with focal epilepsy have focused on HFOs recorded directly from the brain with intracranial EEG (iEEG) in the high gamma (65 - 100 Hz), ripple (100 - 250 Hz), and fast ripple (250 - 600 Hz) frequency ranges. These results are supplemented by reports of HFOs recorded with iEEG in the low gamma (30 - 65Hz) and very high frequency (500 - 2000 Hz) ranges. Visual detection of HFOs is laborious and limited by poor inter-rater agreement; and the need for accurate, reproducible automated HFOs detection is well recognized. In particular, the clinical translation of HFOs as a biomarker of the epileptogenic brain has been limited by the ability to reliably detect and accurately classify HFOs as physiological or pathological. Despite these challenges, there has been significant progress in the field, which is the subject of this review. Furthermore, we provide data and corresponding analytic code in an effort to promote reproducible research and accelerate clinical translation.

• Publikační typ
• časopisecké články MeSH