Daily resting-state intracranial EEG connectivity for seizure risk forecasts.

Forecasting seizure risk aims to detect proictal states in which seizures would be more likely to occur. Classical seizure prediction models are trained over long-term electroencephalographic (EEG) recordings to detect specific preictal changes for each seizure, independently of those induced by shifts in states of vigilance. A daily single measure-during a vigilance-controlled period-to estimate the risk of upcoming seizure(s) would be more convenient. Here, we evaluated whether intracranial EEG connectivity (phase-locking value), estimated from daily vigilance-controlled resting-state recordings, could allow distinguishing interictal (no seizure) from preictal (seizure within the next 24 h) states. We also assessed its relevance for daily forecasts of seizure risk using machine learning models. Connectivity in the theta band was found to provide the best prediction performances (area under the curve ≥ .7 in 80% of patients), with accurate daily and prospective probabilistic forecasts (mean Brier score and Brier skill score of .13 and .72, respectively). More efficient ambulatory clinical application could be considered using mobile EEG or chronic implanted devices.

A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials.

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.

Long-term deep intracerebral microelectrode recordings in patients with drug-resistant epilepsy: Proposed guidelines based on 10-year experience.

PURPOSE: Human neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and pathophysiological mechanisms of brain diseases, in particular epilepsy. Continuous and long-term recordings are necessary to monitor non predictable pathological and physiological activities like seizures or sleep. Because of their high impedance, microelectrodes are more sensitive to noise than macroelectrodes. Low noise levels are crucial to detect action potentials from background noise, and to further isolate single neuron activities. Therefore, long-term recordings of multi-unit activity remains a challenge. We shared here our experience with microelectrode recordings and our efforts to reduce noise levels in order to improve signal quality. We also provided detailed technical guidelines for the connection, recording, imaging and signal analysis of microelectrode recordings. RESULTS: During the last 10 years, we implanted 122 bundles of Behnke-Fried hybrid macro-microelectrodes, in 56 patients with pharmacoresistant focal epilepsy. Microbundles were implanted in the temporal lobe (74%), as well as frontal (15%), parietal (6%) and occipital (5%) lobes. Low noise levels depended on our technical setup. The noise reduction was mainly obtained after electrical insulation of the patient's recording room and the use of a reinforced microelectrode model, reaching median root mean square values of 5.8 µV. Seventy percent of the bundles could record multi-units activities (MUA), on around 3 out of 8 wires per bundle and for an average of 12 days. Seizures were recorded by microelectrodes in 91% of patients, when recorded continuously, and MUA were recorded during seizures for 75 % of the patients after the insulation of the room. Technical guidelines are proposed for (i) electrode tails manipulation and protection during surgical bandage and connection to both clinical and research amplifiers, (ii) electrical insulation of the patient's recording room and shielding, (iii) data acquisition and storage, and (iv) single-units activities analysis. CONCLUSIONS: We progressively improved our recording setup and are now able to record (i) microelectrode signals with low noise level up to 3 weeks duration, and (ii) MUA from an increased number of wires . We built a step by step procedure from electrode trajectory planning to recordings. All these delicate steps are essential for continuous long-term recording of units in order to advance in our understanding of both the pathophysiology of ictogenesis and the neuronal coding of cognitive and physiological functions.

Sleep scoring based on video-electroencephalography monitoring in an Epileptology Unit: Comparison with polysomnography.

The aim of the study was to compare the performance of video- electroencephalography (EEG) monitoring and standard polysomnography for sleep scoring in an Epileptology Unit. We calculated the level of agreement between two methods of sleep scoring, using either 27-electrode video-EEG or polysomnography for 1 night in 22 patients admitted to our Epileptology Unit. Independent experts manually scored sleep using the American Academy of Sleep Medicine 2017 guidelines. We evaluated the number of sleep cycles and their distribution on hypnogram, total sleep time, sleep efficiency, sleep and rapid eye movement sleep-onset latency, wake after sleep-onset, and sleep stages. We then extracted sub-samples of recordings to examine the agreement in microarousal and rapid eye movement scoring. We used Bland and Altman plots and Cohen's kappa test to measure agreement. Bland and Altman plots showed at least 95% agreement for all studied sleep parameters with the exception of wake after sleep onset, where there was an 11 min difference. Cohen's kappa test showed an agreement for the recognition of microarousal (0.89) and of rapid eye movements (0.96) in sub-samples. Video-EEG represents an acceptable alternative tool for sleep architecture study in patients admitted to an Epileptology Unit.

Resting-State Neural Firing Rate Is Linked to Cardiac-Cycle Duration in the Human Cingulate and Parahippocampal Cortices.

Stimulation and functional imaging studies have revealed the existence of a large network of cortical regions involved in the regulation of heart rate. However, very little is known about the link between cortical neural firing and cardiac-cycle duration (CCD). Here, we analyze single-unit and multiunit data obtained in humans at rest, and show that firing rate covaries with CCD in 16.7% of the sample (25 of 150). The link between firing rate and CCD was most prevalent in the anterior medial temporal lobe (entorhinal and perirhinal cortices, anterior hippocampus, and amygdala), where 36% (18 of 50) of the units show the effect, and to a lesser extent in the mid-to-anterior cingulate cortex (11.1%, 5 of 45). The variance in firing rate explained by CCD ranged from 0.5 to 11%. Several lines of analysis indicate that neural firing influences CCD, rather than the other way around, and that neural firing affects CCD through vagally mediated mechanisms in most cases. These results show that part of the spontaneous fluctuations in firing rate can be attributed to the cortical control of the cardiac cycle. The fine tuning of the regulation of CCD represents a novel physiological factor accounting for spontaneous variance in firing rate. It remains to be determined whether the "noise" introduced in firing rate by the regulation of CCD is detrimental or beneficial to the cognitive information processing carried out in the parahippocampal and cingulate regions.SIGNIFICANCE STATEMENT Fluctuations in heart rate are known to be under the control of cortical structures, but spontaneous fluctuations in cortical firing rate, or "noise," have seldom been related to heart rate. Here, we analyze unit activity in humans at rest and show that spontaneous fluctuations in neural firing in the medial temporal lobe, as well as in the mid-to-anterior cingulate cortex, influence heart rate. This phenomenon was particularly pronounced in the entorhinal and perirhinal cortices, where it could be observed in one of three neurons. Our results show that part of spontaneous firing rate variability in regions best known for their cognitive role in spatial navigation and memory corresponds to precise physiological regulations.

Temporal pole epilepsy surgery-Sparing the hippocampus.

Temporal pole epilepsy (TPE) is a poorly known and difficult to individualize subtype of temporal lobe epilepsy. Consequently, in drug-resistant TPE, there is still a debate on the need for a large surgical removal of the temporal pole and mesial temporal structures or a limited resection of the temporal pole. We reviewed all patients who underwent presurgical evaluation for drug-resistant epilepsy over a 17-year period, and report here 19 patients with proven drug-resistant temporal pole epilepsy who underwent a selective temporal pole resection with respect to mesial structures. Most (15) TPE patients exhibited seizures resembling mesiotemporal seizures, whereas the others exhibited nocturnal hyperkinetic seizures or an association of both seizure types. MRI revealed a temporal pole lesion in 58% of patients. Long-term postoperative outcome after a conservative surgery was excellent: 63% of patients were seizure-free (International League Against Epilepsy [ILAE] 1) at 1-year postsurgery and 78% at 5 years. These results show that TPE has no specific electroclinical features but is a distinct type of temporal lobe epilepsy allowing a conservative surgery. Respecting the mesiotemporal structures is a valid surgical approach for drug-resistant temporal pole epilepsy.

Intracranial Recordings and Computational Modeling of Music Reveal the Time Course of Prediction Error Signaling in Frontal and Temporal Cortices.

Prediction is held to be a fundamental process underpinning perception, action, and cognition. To examine the time course of prediction error signaling, we recorded intracranial EEG activity from nine presurgical epileptic patients while they listened to melodies whose information theoretical predictability had been characterized using a computational model. We examined oscillatory activity in the superior temporal gyrus (STG), the middle temporal gyrus (MTG), and the pars orbitalis of the inferior frontal gyrus, lateral cortical areas previously implicated in auditory predictive processing. We also examined activity in anterior cingulate gyrus (ACG), insula, and amygdala to determine whether signatures of prediction error signaling may also be observable in these subcortical areas. Our results demonstrate that the information content (a measure of unexpectedness) of musical notes modulates the amplitude of low-frequency oscillatory activity (theta to beta power) in bilateral STG and right MTG from within 100 and 200 msec of note onset, respectively. Our results also show this cortical activity to be accompanied by low-frequency oscillatory modulation in ACG and insula-areas previously associated with mediating physiological arousal. Finally, we showed that modulation of low-frequency activity is followed by that of high-frequency (gamma) power from approximately 200 msec in the STG, between 300 and 400 msec in the left insula, and between 400 and 500 msec in the ACG. We discuss these results with respect to models of neural processing that emphasize gamma activity as an index of prediction error signaling and highlight the usefulness of musical stimuli in revealing the wide-reaching neural consequences of predictive processing.

Probabilistic functional tractography of the human cortex revisited.

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human.

Single-unit activities during the transition to seizures in deep mesial structures.

Focal seizures are assumed to arise from a hypersynchronous activity affecting a circumscribed brain region. Using microelectrodes in seizure-generating deep mesial regions of 9 patients, we investigated the firing of hundreds of single neurons before, during, and after ictal electroencephalogram (EEG) discharges. Neuronal spiking activity at seizure initiation was highly heterogeneous and not hypersynchronous. Furthermore, groups of neurons showed significant changes in activity minutes before the seizure with no concomitant changes in the corresponding macroscopic EEG recordings. Altogether, our findings suggest that only limited subsets of neurons in epileptic depth regions initiate the seizure-onset and that ictogenic mechanisms operate in submillimeter-scale microdomains. Ann Neurol 2017 Ann Neurol 2017;82:1022-1028.

Predictive factors of long-term outcomes of surgery for mesial temporal lobe epilepsy associated with hippocampal sclerosis.

OBJECTIVE: The reasons for failure of surgical treatment for mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) remain unclear. This retrospective study analyzed seizure, cognitive, and psychiatric outcomes, searching for factors associated with seizure relapse or cognitive and psychiatric deterioration after MTLE-HS surgery. METHODS: Seizure, cognitive, and psychiatric outcomes were reviewed after 389 surgeries performed between 1990 and 2015 on patients aged 15-67 years at a tertiary center. Three surgical approaches were used: anterior temporal lobectomy (ATL; n = 209), transcortical selective amygdalohippocampectomy (SAH; n = 144), and transsylvian SAH (n = 36). RESULTS: With an average follow-up of 8.7 years (range = 1.0-25.2), seizure outcome was classified as Engel I in 83.7% and Engel Ia in 57.1% of patients. The histological classification of HS was type 1 for 75.3% of patients, type 2 for 18.7%, and type 3 for 1.2%. Two factors were significantly associated with seizure recurrence: past history of status epilepticus and preoperative intracranial electroencephalographic recording. In contrast, neither HS type, the presence of a dual pathology, nor surgical approach was associated with seizure outcome. Risk of cognitive impairment was 3.12 (95% confidence interval = 1.27-7.70), greater in patients after ATL than in patients after transcortical SAH. A presurgical psychiatric history and postoperative cognitive impairment were associated with poor psychiatric outcome. SIGNIFICANCE: The SAH and ATL approaches have similar beneficial effects on seizure control, whereas transcortical SAH tends to minimize cognitive deterioration after surgery. Variation in postsurgical outcome with the class of HS should be investigated further.

Self-induced intracerebral gamma oscillations in the human cortex.

Gamma oscillations play a pivotal role in multiple cognitive functions. They enable coordinated activity and communication of local assemblies, while abnormalities in gamma oscillations exist in different neurological and psychiatric diseases. Thus, a specific rectification of gamma synchronization could potentially compensate the deficits in pathological conditions. Previous experiments have shown that animals can voluntarily modulate their gamma power through operant conditioning. Using a closed-loop experimental setup, we show in six intracerebrally recorded epileptic patients undergoing presurgical evaluation that intracerebral power spectrum can be increased in the gamma frequency range (30-80 Hz) at different fronto-temporal cortical sites in human subjects. Successful gamma training was accompanied by increased gamma power at other cortical locations and progressively enhanced cross-frequency coupling between gamma and slow oscillations (3-12 Hz). Finally, using microelectrode targets in two subjects, we report that upregulation of gamma activities is possible also in spatial micro-domains, without the spread to macroelectrodes. Overall, our findings indicate that intracerebral gamma modulation can be achieved rapidly, beyond the motor system and with high spatial specificity, when using micro targets. These results are especially significant because they pave the way for use of high-resolution therapeutic approaches for future clinical applications.

An Intracranial EEG Study of the Neural Dynamics of Musical Valence Processing.

The processing of valence is known to recruit the amygdala, orbitofrontal cortex, and relevant sensory areas. However, how these regions interact remains unclear. We recorded cortical electrical activity from 7 epileptic patients implanted with depth electrodes for presurgical evaluation while they listened to positively and negatively valenced musical chords. Time-frequency analysis suggested a specific role of the orbitofrontal cortex in the processing of positively valenced stimuli while, most importantly, Granger causality analysis revealed that the amygdala tends to drive both the orbitofrontal cortex and the auditory cortex in theta and alpha frequency bands, during the processing of valenced stimuli. Results from the current study show the amygdala to be a critical hub in the emotion processing network: specifically one that influences not only the higher order areas involved in the evaluation of a stimulus's emotional value but also the sensory cortical areas involved in the processing of its low-level acoustic features.

Event-Related Potential, Time-frequency, and Functional Connectivity Facets of Local and Global Auditory Novelty Processing: An Intracranial Study in Humans.

Auditory novelty detection has been associated with different cognitive processes. Bekinschtein et al. (2009) developed an experimental paradigm to dissociate these processes, using local and global novelty, which were associated, respectively, with automatic versus strategic perceptual processing. They have mostly been studied using event-related potentials (ERPs), but local spiking activity as indexed by gamma (60-120 Hz) power and interactions between brain regions as indexed by modulations in beta-band (13-25 Hz) power and functional connectivity have not been explored. We thus recorded 9 epileptic patients with intracranial electrodes to compare the precise dynamics of the responses to local and global novelty. Local novelty triggered an early response observed as an intracranial mismatch negativity (MMN) contemporary with a strong power increase in the gamma band and an increase in connectivity in the beta band. Importantly, all these responses were strictly confined to the temporal auditory cortex. In contrast, global novelty gave rise to a late ERP response distributed across brain areas, contemporary with a sustained power decrease in the beta band (13-25 Hz) and an increase in connectivity in the alpha band (8-13 Hz) within the frontal lobe. We discuss these multi-facet signatures in terms of conscious access to perceptual information.

Characterization of seizure-induced syncopes: EEG, ECG, and clinical features.

OBJECTIVE: Ictal bradycardia and ictal asystole (IA) are rare but severe complications of epileptic seizures. They are difficult to recognize within a seizure and their consequences remain unclear. Herein we aimed to extend the description of electrical and clinical features of seizures with IA and/or syncope. METHODS: Among 828 patients with epilepsy who were admitted for presurgical video-electroencephalogram (EEG) monitoring evaluation between 2003 and 2012, we selected those presenting IA and/or syncope. We studied the electroclinical sequence of these manifestations and their correlation with electrocardiogram (ECG), and we compared seizures with or without IA among the same patients. RESULTS: Nine (1.08%) of 828 patients (four men, mean age 43 ± 6 years) showed IA. Six patients had temporal lobe epilepsy and the others had frontal, temporooccipital, or occipital epilepsy, demonstrated by intracranial EEG in two. In these patients, 59 of 103 recorded seizures induced a reduction of heart rate (HR), leading to IA in 26. IAs were mostly (80%) symptomatic, whereas ictal HR decreases alone were not. In seizures with IA, we identified usual ictal symptoms, and then symptoms related primarily to cerebral hypoperfusion (pallor, atonia, early myoclonic jerks, loss of consciousness, hypertonia, and fall) and secondarily to cerebral reperfusion (skin flushing, late myoclonic jerks). At 32 ± 18 s after the onset of the seizure, the HR decreased progressively during 11 ± 6 s, reaching a sinusal pause for 13 ± 7 s. The duration of the IA was strongly correlated with electroclinical consequences. IA was longer in patients with atonia (14.8 ± 7 vs. 5.7 ± 3 s), late myoclonic jerks (15.8 ± 7 vs. 8 ± 6 s), hypertonia (19 ± 4.5 vs. 8.3 ± 5 s), and EEG hypoperfusion changes (16 ± 5.6 vs. 6.9 ± 5.5 s). IA may induce a fall during atonia or hypertonia. Surface and intracerebral EEG recordings showed that ictal HR decrease and IA often occurred when seizure activity became bilateral. Finally, we identified one patient with ictal syncopes but without IA, presumably related to vasoplegia. SIGNIFICANCE: We provide a more complete description of the electroclinical features of seizures with IA, of the mechanism of falls, and distinguish between hypoperfusion and reperfusion symptoms of syncope. Identification of the mechanisms of syncope may improve management of patients with epilepsy. A pacemaker can be proposed, when parasympathetic activation provokes a negative chronotropic effect that leads to asystole. It is less likely to be useful when vasoplegic effects predominate.

Intracortical recordings reveal vision-to-action cortical gradients driving human exogenous attention.

Exogenous attention, the process that makes external salient stimuli pop-out of a visual scene, is essential for survival. How attention-capturing events modulate human brain processing remains unclear. Here we show how the psychological construct of exogenous attention gradually emerges over large-scale gradients in the human cortex, by analyzing activity from 1,403 intracortical contacts implanted in 28 individuals, while they performed an exogenous attention task. The timing, location and task-relevance of attentional events defined a spatiotemporal gradient of three neural clusters, which mapped onto cortical gradients and presented a hierarchy of timescales. Visual attributes modulated neural activity at one end of the gradient, while at the other end it reflected the upcoming response timing, with attentional effects occurring at the intersection of visual and response signals. These findings challenge multi-step models of attention, and suggest that frontoparietal networks, which process sequential stimuli as separate events sharing the same location, drive exogenous attention phenomena such as inhibition of return.

Intracranial study in humans: Neural spectral changes during watching comedy movie of Charlie Chaplin.

Humor plays a prominent role in our lives. Thus, understanding the cognitive and neural mechanisms of humor is particularly important. Previous studies that investigated neural substrates of humor used functional MRI and to a lesser extent EEG. In the present study, we conducted intracranial recording in human patients, enabling us to obtain the signal with high temporal precision from within specific brain locations. Our analysis focused on the temporal lobe and the surrounding areas, the temporal lobe was most densely covered in our recording. Thirteen patients watched a fragment of a Charlie Chaplin movie. An independent group of healthy participants rated the same movie fragment, helping us to identify the most funny and the least funny frames of the movie. We compared neural activity occurring during the most funny and least funny frames across frequencies in the range of 1-170 Hz. The most funny compared to least funny parts of the movie were associated with activity modulation in the broadband high-gamma (70-170 Hz; mostly activation) and to a lesser extent gamma band (40-69Hz; activation) and low frequencies (1-12 Hz, delta, theta, alpha bands; mostly deactivation). With regard to regional specificity, we found three types of brain areas: (I) temporal pole, middle and inferior temporal gyrus (both anterior and posterior) in which there was both activation in the high-gamma/gamma bands and deactivation in low frequencies; (II) ventral part of the temporal lobe such as the fusiform gyrus, in which there was mostly deactivation the low frequencies; (III) posterior temporal cortex and its environment, such as the middle occipital and the temporo-parietal junction, in which there was activation in the high-gamma/gamma band. Overall, our results suggest that humor appreciation might be achieved by neural activity across the frequency spectrum.

Fronto-parietal networks shape human conscious report through attention gain and reorienting.

How do attention and consciousness interact in the human brain? Rival theories of consciousness disagree on the role of fronto-parietal attentional networks in conscious perception. We recorded neural activity from 727 intracerebral contacts in 13 epileptic patients, while they detected near-threshold targets preceded by attentional cues. Clustering revealed three neural patterns: first, attention-enhanced conscious report accompanied sustained right-hemisphere fronto-temporal activity in networks connected by the superior longitudinal fasciculus (SLF) II-III, and late accumulation of activity (>300 ms post-target) in bilateral dorso-prefrontal and right-hemisphere orbitofrontal cortex (SLF I-III). Second, attentional reorienting affected conscious report through early, sustained activity in a right-hemisphere network (SLF III). Third, conscious report accompanied left-hemisphere dorsolateral-prefrontal activity. Task modeling with recurrent neural networks revealed multiple clusters matching the identified brain clusters, elucidating the causal relationship between clusters in conscious perception of near-threshold targets. Thus, distinct, hemisphere-asymmetric fronto-parietal networks support attentional gain and reorienting in shaping human conscious experience.

Gamma amplitude is coupled to opposed hippocampal theta-phase states during the encoding and retrieval of episodic memories in humans.

Computational models and in vivo studies in rodents suggest that the emergence of gamma activity (40-140 Hz) during memory encoding and retrieval is coupled to opposed-phase states of the underlying hippocampal theta rhythm (4-9 Hz).1,2,3,4,5,6,7,8,9,10 However, direct evidence for whether human hippocampal gamma-modulated oscillatory activity in memory processes is coupled to opposed-phase states of the ongoing theta rhythm remains elusive. Here, we recorded local field potentials (LFPs) directly from the hippocampus of 10 patients with epilepsy, using depth electrodes. We used a memory encoding and retrieval task whereby trial unique sequences of pictures depicting real-life episodes were presented, and 24 h later, participants were asked to recall them upon the appearance of the first picture of the encoded episodic sequence. We found theta-to-gamma cross-frequency coupling that was specific to the hippocampus during both the encoding and retrieval of episodic memories. We also revealed that gamma was coupled to opposing theta phases during both encoding and recall processes. Additionally, we observed that the degree of theta-gamma phase opposition between encoding and recall was associated with participants' memory performance, so gamma power was modulated by theta phase for both remembered and forgotten trials, although only for remembered trials the dominant theta phase was different for encoding and recall trials. The current results offer direct empirical evidence in support of hippocampal theta-gamma phase opposition models in human long-term memory and provide fundamental insights into mechanistic predictions derived from computational and animal work, thereby contributing to establishing similarities and differences across species.

The EPILEPSIAE database: an extensive electroencephalography database of epilepsy patients.

From the very beginning the seizure prediction community faced problems concerning evaluation, standardization, and reproducibility of its studies. One of the main reasons for these shortcomings was the lack of access to high-quality long-term electroencephalography (EEG) data. In this article we present the EPILEPSIAE database, which was made publicly available in 2012. We illustrate its content and scope. The EPILEPSIAE database provides long-term EEG recordings of 275 patients as well as extensive metadata and standardized annotation of the data sets. It will adhere to the current standards in the field of prediction and facilitate reproducibility and comparison of those studies. Beyond seizure prediction, it may also be of considerable benefit for studies focusing on seizure detection, basic neurophysiology, and other fields.

Converging intracranial markers of conscious access.

We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms), accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access.