Cycles in epilepsy.

Epilepsy is among the most dynamic disorders in neurology. A canonical view holds that seizures, the characteristic sign of epilepsy, occur at random, but, for centuries, humans have looked for patterns of temporal organization in seizure occurrence. Observations that seizures are cyclical date back to antiquity, but recent technological advances have, for the first time, enabled cycles of seizure occurrence to be quantitatively characterized with direct brain recordings. Chronic recordings of brain activity in humans and in animals have yielded converging evidence for the existence of cycles of epileptic brain activity that operate over diverse timescales: daily (circadian), multi-day (multidien) and yearly (circannual). Here, we review this evidence, synthesizing data from historical observational studies, modern implanted devices, electronic seizure diaries and laboratory-based animal neurophysiology. We discuss advances in our understanding of the mechanistic underpinnings of these cycles and highlight the knowledge gaps that remain. The potential clinical applications of a knowledge of cycles in epilepsy, including seizure forecasting and chronotherapy, are discussed in the context of the emerging concept of seizure risk. In essence, this Review addresses the broad question of why seizures occur when they occur.

Human Brain Ages With Hierarchy-Selective Attenuation of Prediction Errors.

From the perspective of predictive coding, our brain embodies a hierarchical generative model to realize perception, which proactively predicts the statistical structure of sensory inputs. How are these predictive processes modified as we age? Recent research suggested that aging leads to decreased weighting of sensory inputs and increased reliance on predictions. Here we investigated whether this age-related shift from sensorium to predictions occurs at all levels of hierarchical message passing. We recorded the electroencephalography responses with an auditory local-global paradigm in a cohort of 108 healthy participants from 3 groups: seniors, adults, and adolescents. The detection of local deviancy seems largely preserved in older individuals at earlier latency (including the mismatch negativity followed by the P3a but not the reorienting negativity). In contrast, the detection of global deviancy is clearly compromised in older individuals, as they showed worse task performance and attenuated P3b. Our findings demonstrate that older brains show little decline in sensory (i.e., first-order) prediction errors but significant diminution in contextual (i.e., second-order) prediction errors. Age-related deficient maintenance of auditory information in working memory might affect whether and how lower-level prediction errors propagate to the higher level.

Neural tracking of the speech envelope in cochlear implant users.

OBJECTIVE: When listening to speech, the brain tracks the speech envelope. It is possible to reconstruct this envelope from EEG recordings. However, in people who hear using a cochlear implant (CI), the artifacts caused by electrical stimulation of the auditory nerve contaminate the EEG. The objective of this study is to develop and validate a method for assessing the neural tracking of speech envelope in CI users. APPROACH: To obtain EEG recordings free of stimulus artifacts, the electrical stimulation is periodically interrupted. During these stimulation gaps, artifact-free EEG can be sampled and used to train a linear envelope decoder. EEG recordings obtained during audible and inaudible (i.e. sub-threshold) stimulation were used to characterize the artifacts and their influence on the envelope reconstruction. MAIN RESULTS: The present study demonstrates for the first time that neural tracking of the speech envelope can be measured in response to ongoing electrical stimulation. The responses were validated to be truly neural and not affected by stimulus artifact. SIGNIFICANCE: Besides applications in audiology and neuroscience, the characterization and elimination of stimulus artifacts will enable future EEG studies involving continuous speech in CI users. Measures of neural tracking of the speech envelope reflect interesting properties of the listener's perception of speech, such as speech intelligibility or attentional state. Successful decoding of neural envelope tracking will open new possibilities to investigate the neural mechanisms of speech perception with a CI.

Changes in event-related potentials during dual task walking in aging and Parkinson's disease.

OBJECTIVE: To investigate EEG changes during an auditory odd-ball task while walking (dual-task) in young adults, older adults, and patients with Parkinson's disease. METHODS: 11 young adults, 10 older adults, and 10 patients with Parkinson's disease (PD) performed an auditory oddball task during standing and walking on a treadmill, while wearing a wireless EEG cap. The amplitude and latency of P300 were compared between groups and within conditions using linear mix model analysis. Gait was evaluated using wearable sensors and cognition was assessed using the Color Trail Test. RESULTS: P300 latency became longer during walking in all groups (p = 0.005). During walking, older adults (p = 0.005) and patients with PD (p = 0.001) showed prolonged P300 latency compared to young adults. Significant task by group interaction was found in P300 amplitude (p = 0.008). Patients with PD demonstrated reduced P300 amplitude during walking compared to standing (p = 0.023). Among all subjects, better motor and cognitive performance correlated with shorter P300 latency (r = 0.457, p = 0.014 and r = 0.431, p = 0.040, respectively). CONCLUSIONS: These findings provide direct evidence of the physiological recruitment of attentional networks during walking and their impact by ageing and disease. SIGNIFICANCE: This study is the first to report on changes in P300 latency and amplitude during dual-task oddball walking in older adults and patients with PD.

Pallidal and thalamic neural oscillatory patterns in tourette's syndrome.

OBJECTIVE: Aberrant oscillatory activity has been hypothesized to play a role in the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has recently been established as an effective treatment for severe TS. Modulation of symptom-specific oscillations may underlie the mechanism of action of DBS and could be used for adaptive neuromodulation to improve therapeutic efficacy. The objective of this study was to demonstrate a pathophysiological association of pallidal and thalamic local field potentials (LFPs) with TS. METHODS: Nine medication-refractory TS patients were included in the study. Intracerebral LFPs were recorded simultaneously from bilateral pallidal and thalamic DBS electrodes. Spectral and temporal dynamics of pallidal and thalamic oscillations were characterized and correlated with preoperative Yale Global Tic Severity Scale (YGTSS) scores. RESULTS: Peaks of activity in the theta (3-12Hz) and beta (13-35Hz) were present in pallidal and thalamic recordings from all patients (3 women/6 men; mean age, 29.8 years) and coupled through coherence across targets. Presence of prolonged theta bursts in both targets was associated with preoperative motor tic severity. Total preoperative YGTSS scores (mean, 38.1) were correlated with pallidal and thalamic LFP activity using multivariable linear regression (R² = 0.96; p = 0.02). INTERPRETATION: Our findings suggest that pallidothalamic oscillations may be implicated in the pathophysiology of TS. Furthermore, our results highlight the utility of multisite and -spectral oscillatory features in severely affected patients for future identification and clinical use of oscillatory physiomarkers for adaptive stimulation in TS. Ann Neurol 2018;84:505-514.

Extrahippocampal high-frequency oscillations during epileptogenesis.

The current study aimed to investigate the spatial and temporal patterns of high-frequency oscillations (HFOs) in the intra-/extrahippocampal areas during epileptogenesis. Local field potentials were bilaterally recorded from hippocampus (CA1), thalamus, motor cortex, and prefrontal cortex in 13 rats before and after intrahippocampal kainic acid (KA) lesions. HFOs in the ripple (100-200 Hz) and fast ripple (250-500 Hz) ranges were detected and their rates were computed during different time periods (1-5 weeks) after KA-induced status epilepticus (SE). Recurrent spontaneous seizures were observed in 7 rats after SE, and the other 6 rats did not develop epilepsy. During the latent period, the rate of hippocampal HFOs increased at the ipsilateral site of the KA lesion in both groups, and the HFO rate was significantly higher in the animals that later developed epilepsy. Animals that later developed epilepsy also demonstrated widespread appearance of HFOs, in both the ripple and the fast ripple range, whereas animals that did not develop epilepsy only exhibited changes in the ipsilateral intrahippocampal HFO rate. This study demonstrates an association between an increased rate of widespread HFOs and the later development of epilepsy, suggesting the formation of large-scale distributed pathological networks during epileptogenesis.

Effects of acute hypoxia on human cognitive processing: a study using ERPs and SEPs.

Although hypoxia has the potential to impair the cognitive function, the effects of acute hypoxia on the high-order brain function (executive and/or inhibitory processing) and somatosensory ascending processing remain unknown. We tested the hypothesis that acute hypoxia impairs both motor executive and inhibitory processing and somatosensory ascending processing. Fifteen healthy subjects performed two sessions (sessions 1 and 2), consisting of electroencephalographic event-related potentials with somatosensory Go/No-go paradigms and somatosensory-evoked potentials (SEPs) under two conditions (hypoxia and normoxia) on different days. On 1 day, participants breathed room air in the first and second sessions of the experiment; on the other day, participants breathed room air in the first session, and 12% O2 in the second session. Acute hypoxia reduced the peak amplitudes of Go-P300 and No-go-P300, and delayed the peak latency of Go-P300. However, no significant differences were observed in the peak amplitude or latency of N140, behavioral data, or the amplitudes and latencies of individual SEP components between the two conditions. These results suggest that acute hypoxia impaired neural activity in motor executive and inhibitory processing, and delayed higher cognitive processing for motor execution, whereas neural activity in somatosensory processing was not affected by acute hypoxia.NEW & NOTEWORTHY Hypoxia has the potential to impair the cognitive function, but the effects of acute hypoxia on the cognitive function remain debatable. We investigated the effects of acute hypoxia on human cognitive processing using electroencephalographic event-related potentials and somatosensory-evoked potentials. Acute normobaric hypoxia impaired neural activity in motor executive and inhibitory processing, but no significant differences were observed in neural activity in somatosensory processing.

Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks.

Introduction We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway. Methods Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1-400 Hz and 450-750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal. Results Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus. Conclusions This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype.

Variability of Post-Cardiac Arrest Care Practices Among Cardiac Arrest Centers: United States and South Korean Dual Network Survey of Emergency Physician Research Principal Investigators.

There is little consensus regarding many post-cardiac arrest care parameters. Variability in such practices could confound the results and generalizability of post-arrest care research. We sought to characterize the variability in post-cardiac arrest care practice in Korea and the United States. A 54-question survey was sent to investigators participating in one of two research groups in South Korea (Korean Hypothermia Network [KORHN]) and the United States (National Post-Arrest Research Consortium [NPARC]). Single investigators from each site were surveyed (N = 40). Participants answered questions based on local institutional protocols and practice. We calculated descriptive statistics for all variables. Forty surveys were completed during the study period with 30 having greater than 50% of questions completed (75% response rate; 24 KORHN and 6 NPARC). Most centers target either 33°C (N = 16) or vary the target based on patient characteristics (N = 13). Both bolus and continuous infusion dosing of sedation are employed. No single indication was unanimous for cardiac catheterization. Only six investigators reported having an institutional protocol for withdrawal of life-sustaining therapy (WLST). US patients with poor neurological prognosis tended to have WLST with subsequent expiration (N = 5), whereas Korean patients are transferred to a secondary care facility (N = 19). Both electroencephalography modality and duration vary between institutions. Serum biomarkers are commonly employed by Korean, but not US centers. We found significant variability in post-cardiac arrest care practices among US and Korean medical centers. These practice variations must be taken into account in future studies of post-arrest care.

Audiogenic kindling and secondary subcortico-cortical epileptogenesis: Behavioral correlates and electrographic features.

Human epilepsy is usually considered to result from cortical pathology, but animal studies show that the cortex may be secondarily involved in epileptogenesis, and cortical seizures may be triggered by extracortical mechanisms. In the audiogenic kindling model, recurrent subcortical (brainstem-driven) seizures induce secondary epileptic activation of the cortex. The present review focuses on behavioral and electrographic features of the subcortico-cortical epileptogenesis: (1) behavioral expressions of traditional and mild paradigms of audiogenic kindling produced by full-blown (generalized) and minimal (focal) audiogenic seizures, respectively; (2) electrographic manifestations of secondary epileptic activation of the cortex - cortical epileptic discharge and cortical spreading depression; and (3) persistent individual asymmetry of minimal audiogenic seizures and secondary cortical events produced by their repetition. The characteristics of audiogenic kindling suggest that this model represents a unique experimental approach to studying cortical epileptogenesis and network aspects of epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Expanding the (kaleido)scope: exploring current literature trends for translating electroencephalography (EEG) based brain-computer interfaces for motor rehabilitation in children.

Rehabilitation applications using brain-computer interfaces (BCI) have recently shown encouraging results for motor recovery. Effective BCI neurorehabilitation has been shown to exploit neuroplastic properties of the brain through mental imagery tasks. However, these applications and results are currently restricted to adults. A systematic search reveals there is essentially no literature describing motor rehabilitative BCI applications that use electroencephalograms (EEG) in children, despite advances in such applications with adults. Further inspection highlights limited literature pursuing research in the field, especially outside of neurofeedback paradigms. Then the question naturally arises, do current literature trends indicate that EEG based BCI motor rehabilitation applications could be translated to children? To provide further evidence beyond the available literature for this particular topic, we present an exploratory survey examining some of the indirect literature related to motor rehabilitation BCI in children. Our goal is to establish if evidence in the related literature supports research on this topic and if the related studies can help explain the dearth of current research in this area. The investigation found positive literature trends in the indirect studies which support translating these BCI applications to children and provide insight into potential pitfalls perhaps responsible for the limited literature. Careful consideration of these pitfalls in conjunction with support from the literature emphasize that fully realized motor rehabilitation BCI applications for children are feasible and would be beneficial. •  BCI intervention has improved motor recovery in adult patients and offer supplementary rehabilitation options to patients. •  A systematic literature search revealed that essentially no research has been conducted bringing motor rehabilitation BCI applications to children, despite advances in BCI. •  Indirect studies discovered from the systematic literature search, i.e. neurorehabilitation in children via BCI for autism spectrum disorder, provide insight into translating motor rehabilitation BCI applications to children. •  Translating BCI applications to children is a relevant, important area of research which is relatively barren.

Evidence of degraded representation of speech in noise, in the aging midbrain and cortex.

Humans have a remarkable ability to track and understand speech in unfavorable conditions, such as in background noise, but speech understanding in noise does deteriorate with age. Results from several studies have shown that in younger adults, low-frequency auditory cortical activity reliably synchronizes to the speech envelope, even when the background noise is considerably louder than the speech signal. However, cortical speech processing may be limited by age-related decreases in the precision of neural synchronization in the midbrain. To understand better the neural mechanisms contributing to impaired speech perception in older adults, we investigated how aging affects midbrain and cortical encoding of speech when presented in quiet and in the presence of a single-competing talker. Our results suggest that central auditory temporal processing deficits in older adults manifest in both the midbrain and in the cortex. Specifically, midbrain frequency following responses to a speech syllable are more degraded in noise in older adults than in younger adults. This suggests a failure of the midbrain auditory mechanisms needed to compensate for the presence of a competing talker. Similarly, in cortical responses, older adults show larger reductions than younger adults in their ability to encode the speech envelope when a competing talker is added. Interestingly, older adults showed an exaggerated cortical representation of speech in both quiet and noise conditions, suggesting a possible imbalance between inhibitory and excitatory processes, or diminished network connectivity that may impair their ability to encode speech efficiently.

Electroencephalographic Motor Imagery Brain Connectivity Analysis for BCI: A Review.

Recent research has reached a consensus on the feasibility of motor imagery brain-computer interface (MI-BCI) for different applications, especially in stroke rehabilitation. Most MI-BCI systems rely on temporal, spectral, and spatial features of single channels to distinguish different MI patterns. However, no successful communication has been established for a completely locked-in subject. To provide more useful and informative features, it has been recommended to take into account the relationships among electroencephalographic (EEG) sensor/source signals in the form of brain connectivity as an efficient tool of neuroscience. In this review, we briefly report the challenges and limitations of conventional MI-BCIs. Brain connectivity analysis, particularly functional and effective, has been described as one of the most promising approaches for improving MI-BCI performance. An extensive literature on EEG-based MI brain connectivity analysis of healthy subjects is reviewed. We subsequently discuss the brain connectomes during left and right hand, feet, and tongue MI movements. Moreover, key components involved in brain connectivity analysis that considerably affect the results are explained. Finally, possible technical shortcomings that may have influenced the results in previous research are addressed and suggestions are provided.

Tracking EEG changes during the exposure to hyperbaric oxygen.

OBJECTIVE: The aim was to investigate and define possible alterations in cerebral activity during prolonged hyperbaric oxygen exposure and decompression as compared to baseline activity. METHODS: Thirty-two channel electroencephalography (EEG) was recorded with a Bluetooth EEG system in 11 subjects. A 20-min EEG recording was carried out under three different conditions: breathing air inside a hyperbaric chamber at sea level; breathing oxygen at a simulated depth of 18 msw; breathing air at sea level after decompression. Relative EEG power was estimated in frequency ranges. RESULTS: During oxygen breathing, brain activity showed an early fast delta decrease in the posterior regions, with a synchronous and significant increase in alpha in the same regions. After decompression, the delta relative power decrease was uniformly distributed over the cerebral cortex until minute 8, and the alpha relative power was maximal in the posterior regions during the first 2 min. CONCLUSIONS: These results may be relevant for establishing a reference point in future studies on oxygen-sensitive subjects who reported problems during oxygen diving. SIGNIFICANCE: Significant changes in EEG relative power suggest that it may be possible to define and recognize landmarks of oxygen-induced brain activity, which would be useful in the medical treatment of subjects reporting "oxygen-toxicity diving-related problems".

Holistic approach for automated background EEG assessment in asphyxiated full-term infants.

OBJECTIVE: To develop an automated algorithm to quantify background EEG abnormalities in full-term neonates with hypoxic ischemic encephalopathy. APPROACH: The algorithm classifies 1 h of continuous neonatal EEG (cEEG) into a mild, moderate or severe background abnormality grade. These classes are well established in the literature and a clinical neurophysiologist labeled 272 1 h cEEG epochs selected from 34 neonates. The algorithm is based on adaptive EEG segmentation and mapping of the segments into the so-called segments' feature space. Three features are suggested and further processing is obtained using a discretized three-dimensional distribution of the segments' features represented as a 3-way data tensor. Further classification has been achieved using recently developed tensor decomposition/classification methods that reduce the size of the model and extract a significant and discriminative set of features. MAIN RESULTS: Effective parameterization of cEEG data has been achieved resulting in high classification accuracy (89%) to grade background EEG abnormalities. SIGNIFICANCE: For the first time, the algorithm for the background EEG assessment has been validated on an extensive dataset which contained major artifacts and epileptic seizures. The demonstrated high robustness, while processing real-case EEGs, suggests that the algorithm can be used as an assistive tool to monitor the severity of hypoxic insults in newborns.

T-type Ca2+ channels in absence epilepsy.

Absence epilepsy accompanies the paroxysmal oscillations in the thalamocortical circuit referred as spike and wave discharges (SWDs). Low-threshold burst firing mediated by T-type Ca(2+) channels highly expressed in both inhibitory thalamic reticular nuclei (TRN) and excitatory thalamocortical (TC) neurons has been correlated with the generation of SWDs. A generally accepted view has been that rhythmic burst firing mediated by T-type channels in both TRN and TC neurons are equally critical in the generation of thalamocortical oscillations during sleep rhythms and SWDs. This review examined recent studies on the T-type channels in absence epilepsy which leads to an idea that even though both TRN and TC nuclei are required for thalamocortical oscillations, the contributions of T-type channels to TRN and TC neurons are not equal in the genesis of sleep spindles and SWDs. Accumulating evidence revealed a crucial role of TC T-type channels in SWD generation. However, the role of TRN T-type channels in SWD generation remains controversial. Therefore, a deeper understanding of the functional consequences of modulating each T-type channel subtype could guide the development of therapeutic tools for absence seizures while minimizing side effects on physiological thalamocortical oscillations.

Towards passive brain-computer interfaces: applying brain-computer interface technology to human-machine systems in general.

Cognitive monitoring is an approach utilizing realtime brain signal decoding (RBSD) for gaining information on the ongoing cognitive user state. In recent decades this approach has brought valuable insight into the cognition of an interacting human. Automated RBSD can be used to set up a brain-computer interface (BCI) providing a novel input modality for technical systems solely based on brain activity. In BCIs the user usually sends voluntary and directed commands to control the connected computer system or to communicate through it. In this paper we propose an extension of this approach by fusing BCI technology with cognitive monitoring, providing valuable information about the users' intentions, situational interpretations and emotional states to the technical system. We call this approach passive BCI. In the following we give an overview of studies which utilize passive BCI, as well as other novel types of applications resulting from BCI technology. We especially focus on applications for healthy users, and the specific requirements and demands of this user group. Since the presented approach of combining cognitive monitoring with BCI technology is very similar to the concept of BCIs itself we propose a unifying categorization of BCI-based applications, including the novel approach of passive BCI.

Critical issues in state-of-the-art brain-computer interface signal processing.

This paper reviews several critical issues facing signal processing for brain-computer interfaces (BCIs) and suggests several recent approaches that should be further examined. The topics were selected based on discussions held during the 4th International BCI Meeting at a workshop organized to review and evaluate the current state of, and issues relevant to, feature extraction and translation of field potentials for BCIs. The topics presented in this paper include the relationship between electroencephalography and electrocorticography, novel features for performance prediction, time-embedded signal representations, phase information, signal non-stationarity, and unsupervised adaptation.

Optimizing the P300-based brain-computer interface: current status, limitations and future directions.

This paper summarizes the presentations and discussions at a workshop held during the Fourth International BCI Meeting charged with reviewing and evaluating the current state, limitations and future development of P300-based brain-computer interface (P300-BCI) systems. We reviewed such issues as potential users, recording methods, stimulus presentation paradigms, feature extraction and classification algorithms, and applications. A summary of the discussions and the panel's recommendations for each of these aspects are presented.