Predictable and unpredictable deviance detection in the human hippocampus and amygdala.

Our brains extract structure from the environment and form predictions given past experience. Predictive circuits have been identified in wide-spread cortical regions. However, the contribution of medial temporal structures in predictions remains under-explored. The hippocampus underlies sequence detection and is sensitive to novel stimuli, sufficient to gain access to memory, while the amygdala to novelty. Yet, their electrophysiological profiles in detecting predictable and unpredictable deviant auditory events remain unknown. Here, we hypothesized that the hippocampus would be sensitive to predictability, while the amygdala to unexpected deviance. We presented epileptic patients undergoing presurgical monitoring with standard and deviant sounds, in predictable or unpredictable contexts. Onsets of auditory responses and unpredictable deviance effects were detected earlier in the temporal cortex compared with the amygdala and hippocampus. Deviance effects in 1-20 Hz local field potentials were detected in the lateral temporal cortex, irrespective of predictability. The amygdala showed stronger deviance in the unpredictable context. Low-frequency deviance responses in the hippocampus (1-8 Hz) were observed in the predictable but not in the unpredictable context. Our results reveal a distributed network underlying the generation of auditory predictions and suggest that the neural basis of sensory predictions and prediction error signals needs to be extended.

Temporal and Spatial Information Elicit Different Power and Connectivity Profiles during Working Memory Maintenance.

Working memory (WM) is the cognitive ability to store and manipulate information necessary for ongoing tasks. Although frontoparietal areas are involved in the retention of visually presented information, oscillatory neural activity differs for temporal and spatial WM processing. In this study, we corroborated previous findings describing the modulation of neural oscillations and expanded our investigation to the network organization underlying the cognitive processing of temporal and spatial information. We utilized MEG recordings during a Sternberg visual WM task. The spectral oscillatory activity in the maintenance phase revealed increased frontal theta (4-8 Hz) and parietal beta (13-30 Hz) in the temporal condition. Source level coherence analysis delineated the prominent role of parietal areas in all frequency bands during the maintenance of temporal information, whereas frontal and central areas showed major contributions in theta and beta ranges during the maintenance of spatial information. Our study revealed distinct spectral profiles of neural oscillations for separate cognitive subdomains of WM processing. The delineation of specific functional networks might have important implications for clinical applications, enabling the development of stimulation protocols targeting cognitive disabilities associated with WM impairments.

The relation between neuronal firing, local field potentials and hemodynamic activity in the human amygdala in response to aversive dynamic visual stimuli.

The amygdala is a central part of networks of brain regions underlying perception and cognition, in particular related to processing of emotionally salient stimuli. Invasive electrophysiological and hemodynamic measurements are commonly used to evaluate functions of the human amygdala, but a comprehensive understanding of their relation is still lacking. Here, we aimed at investigating the link between fast and slow frequency amygdalar oscillations, neuronal firing and hemodynamic responses. To this aim, we recorded intracranial electroencephalography (iEEG), hemodynamic responses and single neuron activity from the amygdala of patients with epilepsy. Patients were presented with dynamic visual sequences of fearful faces (aversive condition), interleaved with sequences of neutral landscapes (neutral condition). Comparing responses to aversive versus neutral stimuli across participants, we observed enhanced high gamma power (HGP, >60 â€‹Hz) during the first 2 â€‹s of aversive sequence viewing, and reduced delta power (1-4 â€‹Hz) lasting up to 18 â€‹s. In 5 participants with implanted microwires, neuronal firing rates were enhanced following aversive stimuli, and exhibited positive correlation with HGP and hemodynamic responses. Our results show that high gamma power, neuronal firing and BOLD responses from the human amygdala are co-modulated. Our findings provide, for the first time, a comprehensive investigation of amygdalar responses to aversive stimuli, ranging from single-neuron spikes to local field potentials and hemodynamic responses.

Correlation of cue-locked FRN and feedback-locked FRN in the auditory monetary incentive delay task.

Reflecting the discrepancy between received and predicted outcomes, the reward prediction error (RPE) plays an important role in learning in a dynamic environment. A number of studies suggested that the feedback-related negativity (FRN) component of an event-related potential, known to be associated with unexpected outcomes, encodes RPEs. While FRN was clearly shown to be sensitive to the probability of outcomes, the effect of outcome magnitude on FRN remains to be further clarified. In studies on the neural underpinnings of reward anticipation and outcome evaluation, a monetary incentive delay (MID) task proved to be particularly useful. We investigated whether feedback-locked FRN and cue-locked dN200 responses recorded during an auditory MID task were sensitive to the probability and magnitude of outcomes. The cue-locked dN200 is associated with the update of information about the magnitude of prospective outcomes. Overall, we showed that feedback-locked FRN was modulated by both the magnitude and the probability of outcomes during an auditory version of MID task, whereas no such effect was found for cue-locked dN200. Furthermore, the cue-locked dN200, which is associated with the update of information about the magnitude of prospective outcomes, correlated with the standard feedback-locked FRN, which is associated with a negative RPE. These results further expand our knowledge on the interplay between the processing of predictive cues that forecast future outcomes and the subsequent revision of these predictions during outcome delivery.

Non-invasive single-trial EEG detection of evoked human neocortical population spikes.

QUESTION: Human high-frequency (>400 Hz) components of somatosensory evoked potentials (hf-SEPs), which can be recorded non-invasively at the scalp, are generated by cortical population spikes, as inferred from microelectrode recordings in non-human primates. It is a critical limitation to broader neurophysiological study of hf-SEPs in that hundreds of responses have to be averaged to detect hf-SEPs reliably. Here, we establish a framework for detecting human hf-SEPs non-invasively in single trials. METHODS: Spatio-temporal features were extracted from band-pass filtered (400-900 Hz) hf-SEPs by bilinear Common Spatio-Temporal Patterns (bCSTP) and then classified by a weighted Extreme Learning Machine (w-ELM). The effect of varying signal-to-noise ratio (SNR), number of trials, and degree of w-ELM re-weighting was characterized using surrogate data. For practical demonstration of the algorithm, median nerve hf-SEPs were recorded inside a shielded room in four subjects, spanning the hf-SEP signal-to-noise ratio characteristic for a larger population, utilizing a custom-built 29-channel low-noise EEG amplifier. RESULTS: Using surrogate data, the SNR proved to be pivotal to detect hf-SEPs in single trials efficiently, with the trade-off between sensitivity and specificity of the algorithm being obtained by the w-ELM re-weighting parameter. In practice, human hf-SEPs were detected non-invasively in single trials with a sensitivity of up to 99% and a specificity of up to 97% in two subjects, even without any recourse to knowledge of stimulus timing. Matching with the results of the surrogate data analysis, these rates dropped to 62-79% sensitivity and 18-31% specificity in two subjects with lower SNR. CONCLUSIONS: Otherwise buried in background noise, human high-frequency EEG components can be extracted from low-noise recordings. Specifically, refined supervised filter optimization and classification enables the reliable detection of single-trial hf-SEPs, representing non-invasive correlates of cortical population spikes. SIGNIFICANCE: While low-frequency EEG reflects summed postsynaptic potentials, and thereby neuronal input, we suggest that high-frequency EEG (>400 Hz) can provide non-invasive access to the unaveraged output of neuronal computation, i.e., single-trial population spike activity evoked in the responsive neuronal ensemble.

Monochromatic ultra-slow (~0.1 Hz) oscillations in the human electroencephalogram and their relation to hemodynamics.

Previous studies demonstrated the presence of Monochromatic Ultra-Slow Oscillations (MUSO) in human EEG. In the present study we explored the biological origin of MUSO by simultaneous recordings of EEG, Near-Infrared Spectroscopy (NIRS), arterial blood pressure, respiration and Laser Doppler flowmetry. We used a head-up tilt test in order to check whether MUSO might relate to Mayer waves in arterial blood pressure, known to be enhanced by the tilting procedure. MUSO were detected in 8 out of 10 subjects during rest and showed a striking monochromatic spectrum (0.07-0.14 Hz). The spatial topography of MUSO was complex, showing multiple foci variable across subjects. While the head-up tilt test increased the relative power of Mayer waves, it had no effect on MUSO. On the other hand, the relative spectral power of 0.1 Hz oscillations in EEG, NIRS and blood pressure signals were positively correlated across subjects in the tilted condition. Eight subjects showed a coherence between MUSO and NIRS/arterial blood pressure. Moreover, MUSO at different electrode sites demonstrated coherence not reducible to volume conduction, thus indicating that MUSO are unlikely to be generated by one source. We related our experimental findings to known biological phenomena being generated at about 0.1 Hz, i.e.: arterial blood pressure, cerebral and skin vasomotion, respiration and neuronal activity. While no definite conclusion can yet be drawn as to an exact physiological mechanism of MUSO, we suggest that these oscillations might be of a rather extraneuronal origin reflecting cerebral vasomotion.

High frequency oscillations in relation to interictal spikes in predicting postsurgical seizure freedom.

We evaluate whether interictal spikes, epileptiform HFOs and their co-occurrence (Spike + HFO) were included in the resection area with respect to seizure outcome. We also characterise the relationship between high frequency oscillations (HFOs) and propagating spikes. We analysed intracranial EEG of 20 patients that underwent resective epilepsy surgery. The co-occurrence of ripples and fast ripples was considered an HFO event; the co-occurrence of an interictal spike and HFO was considered a Spike + HFO event. HFO distribution and spike onset were compared in cases of spike propagation. Accuracy in predicting seizure outcome was 85% for HFO, 60% for Spikes, and 79% for Spike + HFO. Sensitivity was 57% for HFO, 71% for Spikes and 67% for Spikes + HFO. Specificity was 100% for HFO, 54% for Spikes and 85% for Spikes + HFO. In 2/2 patients with spike propagation, the spike onset included the HFO area. Combining interictal spikes with HFO had comparable accuracy to HFO. In patients with propagating spikes, HFO rate was maximal at the onset of spike propagation.

Anterior cingulate and medial prefrontal cortex oscillations underlie learning alterations in trait anxiety in humans.

Anxiety has been linked to altered belief formation and uncertainty estimation, impacting learning. Identifying the neural processes underlying these changes is important for understanding brain pathology. Here, we show that oscillatory activity in the medial prefrontal, anterior cingulate and orbitofrontal cortex (mPFC, ACC, OFC) explains anxiety-related learning alterations. In a magnetoencephalography experiment, two groups of human participants pre-screened with high and low trait anxiety (HTA, LTA: 39) performed a probabilistic reward-based learning task. HTA undermined learning through an overestimation of volatility, leading to faster belief updating, more stochastic decisions and pronounced lose-shift tendencies. On a neural level, we observed increased gamma activity in the ACC, dmPFC, and OFC during encoding of precision-weighted prediction errors in HTA, accompanied by suppressed ACC alpha/beta activity. Our findings support the association between altered learning and belief updating in anxiety and changes in gamma and alpha/beta activity in the ACC, dmPFC, and OFC.

Scalp high-frequency oscillations differentiate neonates with seizures from healthy neonates.

OBJECTIVE: We aimed to investigate (1) whether an automated detector can capture scalp high-frequency oscillations (HFO) in neonates and (2) whether scalp HFO rates can differentiate neonates with seizures from healthy neonates. METHODS: We considered 20 neonates with EEG-confirmed seizures and four healthy neonates. We applied a previously validated automated HFO detector to determine scalp HFO rates in quiet sleep. RESULTS: Etiology in neonates with seizures included hypoxic-ischemic encephalopathy in 11 cases, structural vascular lesions in 6, and genetic causes in 3. The HFO rates were significantly higher in neonates with seizures (0.098 ± 0.091 HFO/min) than in healthy neonates (0.038 ± 0.025 HFO/min; P = 0.02) with a Hedge's g value of 0.68 indicating a medium effect size. The HFO rate of 0.1 HFO/min/ch yielded the highest Youden index in discriminating neonates with seizures from healthy neonates. In neonates with seizures, etiology, status epilepticus, EEG background activity, and seizure patterns did not significantly impact HFO rates. SIGNIFICANCE: Neonatal scalp HFO can be detected automatically and differentiate neonates with seizures from healthy neonates. Our observations have significant implications for neuromonitoring in neonates. This is the first step in establishing neonatal HFO as a biomarker for neonatal seizures.

Epileptogenic high-frequency oscillations present larger amplitude both in mesial temporal and neocortical regions.

High-frequency oscillations (HFO) are a promising biomarker for the identification of epileptogenic tissue. While HFO rates have been shown to predict seizure outcome, it is not yet clear whether their morphological features might improve this prediction. We validated HFO rates against seizure outcome and delineated the distribution of HFO morphological features. We collected stereo-EEG recordings from 20 patients (231 electrodes; 1,943 contacts). We computed HFO rates (the co-occurrence of ripples and fast ripples) through a validated automated detector during non-rapid eye movement sleep. Applying machine learning, we delineated HFO morphological features within and outside epileptogenic tissue across mesial temporal lobe (MTL) and Neocortex. HFO rates predicted seizure outcome with 85% accuracy, 79% specificity, 100% sensitivity, 100% negative predictive value, and 67% positive predictive value. The analysis of HFO features showed larger amplitude in the epileptogenic tissue, similar morphology for epileptogenic HFO in MTL and Neocortex, and larger amplitude for physiological HFO in MTL. We confirmed HFO rates as a reliable biomarker for epilepsy surgery and characterized the potential clinical relevance of HFO morphological features. Our results support the prospective use of HFO in epilepsy surgery and contribute to the anatomical mapping of HFO morphology.

Data-driven approach for the delineation of the irritative zone in epilepsy in MEG.

The reliable identification of the irritative zone (IZ) is a prerequisite for the correct clinical evaluation of medically refractory patients affected by epilepsy. Given the complexity of MEG data, visual analysis of epileptiform neurophysiological activity is highly time consuming and might leave clinically relevant information undetected. We recorded and analyzed the interictal activity from seven patients affected by epilepsy (Vectorview Neuromag), who successfully underwent epilepsy surgery (Engel > = II). We visually marked and localized characteristic epileptiform activity (VIS). We implemented a two-stage pipeline for the detection of interictal spikes and the delineation of the IZ. First, we detected candidate events from peaky ICA components, and then clustered events around spatio-temporal patterns identified by convolutional sparse coding. We used the average of clustered events to create IZ maps computed at the amplitude peak (PEAK), and at the 50% of the peak ascending slope (SLOPE). We validated our approach by computing the distance of the estimated IZ (VIS, SLOPE and PEAK) from the border of the surgically resected area (RA). We identified 25 spatiotemporal patterns mimicking the underlying interictal activity (3.6 clusters/patient). Each cluster was populated on average by 22.1 [15.0-31.0] spikes. The predicted IZ maps had an average distance from the resection margin of 8.4 ± 9.3 mm for visual analysis, 12.0 ± 16.5 mm for SLOPE and 22.7 ±. 16.4 mm for PEAK. The consideration of the source spread at the ascending slope provided an IZ closer to RA and resembled the analysis of an expert observer. We validated here the performance of a data-driven approach for the automated detection of interictal spikes and delineation of the IZ. This computational framework provides the basis for reproducible and bias-free analysis of MEG recordings in epilepsy.

Dataset of spiking and LFP activity invasively recorded in the human amygdala during aversive dynamic stimuli.

We present an electrophysiological dataset collected from the amygdalae of nine participants attending a visual dynamic stimulation of emotional aversive content. The participants were patients affected by epilepsy who underwent preoperative invasive monitoring in the mesial temporal lobe. Participants were presented with dynamic visual sequences of fearful faces (aversive condition), interleaved with sequences of neutral landscapes (neutral condition). The dataset contains the simultaneous recording of intracranial EEG (iEEG) and neuronal spike times and waveforms, and localization information for iEEG electrodes. Participant characteristics and trial information are provided. We technically validated this dataset and provide here the spike sorting quality metrics and the spectra of iEEG signals. This dataset allows the investigation of amygdalar response to dynamic aversive stimuli at multiple spatial scales, from the macroscopic EEG to the neuronal firing in the human brain.

Publisher Correction: High-frequency oscillations in scalp EEG mirror seizure frequency in pediatric focal epilepsy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dataset of human medial temporal lobe neurons, scalp and intracranial EEG during a verbal working memory task.

We present an electrophysiological dataset recorded from nine subjects during a verbal working memory task. Subjects were epilepsy patients undergoing intracranial monitoring for the localization of epileptic seizures. Subjects performed a modified Sternberg task in which the encoding of memory items, maintenance, and recall were temporally separated. The dataset includes simultaneously recorded scalp EEG with the 10-20 system, intracranial EEG (iEEG) recorded with depth electrodes, waveforms and spike times of neurons recorded in the medial temporal lobe, and localization information on the depth electrodes. Subject characteristics and information on each trial (set size, match/mismatch, correct/incorrect, response, and response time) are given. For technical validation of data, we provide spike sorting quality metrics and the spectra of iEEG and scalp EEG signals. This dataset enables the investigation of working memory by providing simultaneous scalp EEG and iEEG recordings, which can be used for connectivity analysis, along with hard-to-obtain neuronal recordings from humans.

High-frequency oscillations in scalp EEG mirror seizure frequency in pediatric focal epilepsy.

High-frequency oscillations (HFO) are promising EEG biomarkers of epileptogenicity. While the evidence supporting their significance derives mainly from invasive recordings, recent studies have extended these observations to HFO recorded in the widely accessible scalp EEG. Here, we investigated whether scalp HFO in drug-resistant focal epilepsy correspond to epilepsy severity and how they are affected by surgical therapy. In eleven children with drug-resistant focal epilepsy that underwent epilepsy surgery, we prospectively recorded pre- and postsurgical scalp EEG with a custom-made low-noise amplifier (LNA). In four of these children, we also recorded intraoperative electrocorticography (ECoG). To detect clinically relevant HFO, we applied a previously validated automated detector. Scalp HFO rates showed a significant positive correlation with seizure frequency (R2 = 0.80, p < 0.001). Overall, scalp HFO rates were higher in patients with active epilepsy (19 recordings, p = 0.0066, PPV = 86%, NPV = 80%, accuracy = 84% CI [62% 94%]) and decreased following successful epilepsy surgery. The location of the highest HFO rates in scalp EEG matched the location of the highest HFO rates in ECoG. This study is the first step towards using non-invasively recorded scalp HFO to monitor disease severity in patients affected by epilepsy.

The Monetary Incentive Delay (MID) Task Induces Changes in Sensory Processing: ERP Evidence.

Numerous cognitive studies have demonstrated experience-induced plasticity in the primary sensory cortex, indicating that repeated decisions could modulate sensory processing. In this context, we investigated whether an auditory version of the monetary incentive delay (MID) task could change the neural processing of the incentive cues that code expected monetary outcomes. To study sensory plasticity, we presented the incentive cues as deviants during oddball sessions recorded before and after training in the two MID task sessions. We found that after 2 days of training in the MID task, incentive cues evoked a larger P3a (compared with the baseline condition), indicating there was an enhancement of the involuntary attention to the stimuli that predict rewards. At the individual level, the training-induced change of mismatch-related negativity was correlated with the amplitude of the feedback-related negativity (FRN) recorded during the first MID task session. Our results show that the MID task evokes plasticity changes in the auditory system associated with better passive discrimination of incentive cues and with enhanced involuntary attention switching towards these cues. Thus, the sensory processing of incentive cues is dynamically modulated by previous outcomes.

High-density ECoG improves the detection of high frequency oscillations that predict seizure outcome.

OBJECTIVES: Residual fast ripples (FR) in the intraoperative ECoG are highly specific predictors of postsurgical seizure recurrence. However, a FR is generated by a small patch of cortical tissue. Spatial sampling with standard electrodes may thus miss clinically relevant information. METHODS: We analyzed FR rates in the intraoperative ECoG of 22 patients that underwent resective epilepsy surgery. We used standard electrodes with 10 mm inter-contact spacing (standard ECoG) in 14 surgeries and high-density grid electrodes with 5 mm spacing (hd-ECoG) in 8 surgeries. We detected FR using a previously validated automatic detector. RESULTS: Postoperative seizure freedom was achieved in 14/22 (64%) cases. Across all 42 ECoG recordings, FR rates were higher for hd-ECoG than for standard ECoG. In the 14 seizure free patients (ILAE 1), no residual FR were detected (specificity = 100%). In the 8 patients with seizure recurrence (ILAE > 1), residual FR were detected in 1/7 standard ECoG and 1/1 hd-ECoG (Accuracy ACCstandard ECoG = 57%, CI [29% 82%], ACChd-ECoG = 100%, CI [63% 100%]). CONCLUSION: Denser spatial sampling by hd-ECoG improved FR detection compared to standard ECoG. SIGNIFICANCE: Hd-ECoG may advance seizure freedom after epilepsy surgery.

Persistent hippocampal neural firing and hippocampal-cortical coupling predict verbal working memory load.

The maintenance of items in working memory relies on persistent neural activity in a widespread network of brain areas. To investigate the influence of load on working memory, we asked human subjects to maintain sets of letters in memory while we recorded single neurons and intracranial encephalography (EEG) in the medial temporal lobe and scalp EEG. Along the periods of a trial, hippocampal neural firing differentiated between success and error trials during stimulus encoding, predicted workload during memory maintenance, and predicted the subjects' behavior during retrieval. During maintenance, neuronal firing was synchronized with intracranial hippocampal EEG. On the network level, synchronization between hippocampal and scalp EEG in the theta-alpha frequency range showed workload dependent oscillatory coupling between hippocampus and cortex. Thus, we found that persistent neural activity in the hippocampus participated in working memory processing that is specific to memory maintenance, load sensitive and synchronized to the cortex.

Machine Learning Algorithm Identifies Patients at High Risk for Early Complications After Intracranial Tumor Surgery: Registry-Based Cohort Study.

INTRODUCTION: Reliable preoperative identification of patients at high risk for early postoperative complications occurring within 24 h (EPC) of intracranial tumor surgery can improve patient safety and postoperative management. Statistical analysis using machine learning algorithms may generate models that predict EPC better than conventional statistical methods. OBJECTIVE: To train such a model and to assess its predictive ability. METHODS: This cohort study included patients from an ongoing prospective patient registry at a single tertiary care center with an intracranial tumor that underwent elective neurosurgery between June 2015 and May 2017. EPC were categorized based on the Clavien-Dindo classification score. Conventional statistical methods and different machine learning algorithms were used to predict EPC using preoperatively available patient, clinical, and surgery-related variables. The performance of each model was derived from examining classification performance metrics on an out-of-sample test dataset. RESULTS: EPC occurred in 174 (26%) of 668 patients included in the analysis. Gradient boosting machine learning algorithms provided the model best predicting the probability of an EPC. The model scored an accuracy of 0.70 (confidence interval [CI] 0.59-0.79) with an area under the curve (AUC) of 0.73 and a sensitivity and specificity of 0.80 (CI 0.58-0.91) and 0.67 (CI 0.53-0.77) on the test set. The conventional statistical model showed inferior predictive power (test set: accuracy: 0.59 (CI 0.47-0.71); AUC: 0.64; sensitivity: 0.76 (CI 0.64-0.85); specificity: 0.53 (CI 0.41-0.64)). CONCLUSION: Using gradient boosting machine learning algorithms, it was possible to create a prediction model superior to conventional statistical methods. While conventional statistical methods favor patients' characteristics, we found the pathology and surgery-related (histology, anatomical localization, surgical access) variables to be better predictors of EPC.

Intraoperative subdural low-noise EEG recording of the high frequency oscillation in the somatosensory evoked potential.

OBJECTIVE: The detectability of high frequency oscillations (HFO, >200Hz) in the intraoperative ECoG is restricted by their low signal-to-noise ratio (SNR). Using the somatosensory evoked HFO, we quantify how HFO detectability can benefit from a custom-made low-noise amplifier (LNA). METHODS: In 9 patients undergoing tumor surgery in the central region, subdural strip electrodes were placed for intraoperative neurophysiological monitoring. We recorded the somatosensory evoked potential (SEP) simultaneously by custom-made LNA and by a commercial device (CD). We varied the stimulation rate between 1.3 and 12.7Hz to tune the SNR of the N20 component and the evoked HFO and quantified HFO detectability at the single trial level. In three patients we compared Propofol® and Sevoflurane® anesthesia. RESULTS: In the average, amplitude decreased in both in N20 and evoked HFO amplitude with increasing stimulation rate (p<0.05). We detected a higher percentage of single trial evoked HFO with the LNA (p<0.001) for recordings with low impedance (<5kΩ). Average amplitudes were indistinguishable between anesthesia compounds. CONCLUSION: Low-noise amplification improves the detection of the evoked HFO in recordings with subdural electrodes with low impedance. SIGNIFICANCE: Low-noise EEG might critically improve the detectability of interictal spontaneous HFO in subdural and possibly in scalp recordings.