Cross-frequency coupling in cortico-hippocampal networks supports the maintenance of sequential auditory information in short-term memory.

It has been suggested that cross-frequency coupling in cortico-hippocampal networks enables the maintenance of multiple visuo-spatial items in working memory. However, whether this mechanism acts as a global neural code for memory retention across sensory modalities remains to be demonstrated. Intracranial EEG data were recorded while drug-resistant patients with epilepsy performed a delayed matched-to-sample task with tone sequences. We manipulated task difficulty by varying the memory load and the duration of the silent retention period between the to-be-compared sequences. We show that the strength of theta-gamma phase amplitude coupling in the superior temporal sulcus, the inferior frontal gyrus, the inferior temporal gyrus, and the hippocampus (i) supports the short-term retention of auditory sequences; (ii) decodes correct and incorrect memory trials as revealed by machine learning analysis; and (iii) is positively correlated with individual short-term memory performance. Specifically, we show that successful task performance is associated with consistent phase coupling in these regions across participants, with gamma bursts restricted to specific theta phase ranges corresponding to higher levels of neural excitability. These findings highlight the role of cortico-hippocampal activity in auditory short-term memory and expand our knowledge about the role of cross-frequency coupling as a global biological mechanism for information processing, integration, and memory in the human brain.

Decoding the neural dynamics of free choice in humans.

How do we choose a particular action among equally valid alternatives? Nonhuman primate findings have shown that decision-making implicates modulations in unit firing rates and local field potentials (LFPs) across frontal and parietal cortices. Yet the electrophysiological brain mechanisms that underlie free choice in humans remain ill defined. Here, we address this question using rare intracerebral electroencephalography (EEG) recordings in surgical epilepsy patients performing a delayed oculomotor decision task. We find that the temporal dynamics of high-gamma (HG, 60-140 Hz) neural activity in distinct frontal and parietal brain areas robustly discriminate free choice from instructed saccade planning at the level of single trials. Classification analysis was applied to the LFP signals to isolate decision-related activity from sensory and motor planning processes. Compared with instructed saccades, free-choice trials exhibited delayed and longer-lasting HG activity during the delay period. The temporal dynamics of the decision-specific sustained HG activity indexed the unfolding of a deliberation process, rather than memory maintenance. Taken together, these findings provide the first direct electrophysiological evidence in humans for the role of sustained high-frequency neural activation in frontoparietal cortex in mediating the intrinsically driven process of freely choosing among competing behavioral alternatives.

Advances in human intracranial electroencephalography research, guidelines and good practices.

Since the second-half of the twentieth century, intracranial electroencephalography (iEEG), including both electrocorticography (ECoG) and stereo-electroencephalography (sEEG), has provided an intimate view into the human brain. At the interface between fundamental research and the clinic, iEEG provides both high temporal resolution and high spatial specificity but comes with constraints, such as the individual's tailored sparsity of electrode sampling. Over the years, researchers in neuroscience developed their practices to make the most of the iEEG approach. Here we offer a critical review of iEEG research practices in a didactic framework for newcomers, as well addressing issues encountered by proficient researchers. The scope is threefold: (i) review common practices in iEEG research, (ii) suggest potential guidelines for working with iEEG data and answer frequently asked questions based on the most widespread practices, and (iii) based on current neurophysiological knowledge and methodologies, pave the way to good practice standards in iEEG research. The organization of this paper follows the steps of iEEG data processing. The first section contextualizes iEEG data collection. The second section focuses on localization of intracranial electrodes. The third section highlights the main pre-processing steps. The fourth section presents iEEG signal analysis methods. The fifth section discusses statistical approaches. The sixth section draws some unique perspectives on iEEG research. Finally, to ensure a consistent nomenclature throughout the manuscript and to align with other guidelines, e.g., Brain Imaging Data Structure (BIDS) and the OHBM Committee on Best Practices in Data Analysis and Sharing (COBIDAS), we provide a glossary to disambiguate terms related to iEEG research.

Human Anterior Insula Encodes Performance Feedback and Relays Prediction Error to the Medial Prefrontal Cortex.

Adaptive behavior requires the comparison of outcome predictions with actual outcomes (e.g., performance feedback). This process of performance monitoring is computed by a distributed brain network comprising the medial prefrontal cortex (mPFC) and the anterior insular cortex (AIC). Despite being consistently co-activated during different tasks, the precise neuronal computations of each region and their interactions remain elusive. In order to assess the neural mechanism by which the AIC processes performance feedback, we recorded AIC electrophysiological activity in humans. We found that the AIC beta oscillations amplitude is modulated by the probability of performance feedback valence (positive or negative) given the context (task and condition difficulty). Furthermore, the valence of feedback was encoded by delta waves phase-modulating the power of beta oscillations. Finally, connectivity and causal analysis showed that beta oscillations relay feedback information signals to the mPFC. These results reveal that structured oscillatory activity in the anterior insula encodes performance feedback information, thus coordinating brain circuits related to reward-based learning.

BLAST paradigm: A new test to assess brief attentional fluctuations in children with epilepsy, ADHD, and normally developing children.

BACKGROUND: Pure attentional deficits are still underdiagnosed in children with epilepsy. While attention-deficit hyperactivity disorder (ADHD) is historically the most studied cause of attentional disorders, an important number of children with epilepsy and attentional complaints do not fully meet the DSM-V (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition) criteria for ADHD and may be excluded from specific care. Clinical tools currently available are insufficient to detect more subtle but clinically relevant attentional fluctuations. OBJECTIVE/METHODS: The recently developed Bron-Lyon Attention Stability Test (BLAST) was used to evaluate brief attentional fluctuations with a high temporal precision. Drawing on two new attentional indices, we evaluated spontaneous fluctuations of response accuracy and timing, underlying attentional stability. The main objective was to assess attentional stability in children with i) epilepsy with comorbid ADHD, ii) epilepsy without comorbid ADHD, iii) ADHD not medicated and without epilepsy, and iv) normal development. Further objectives were to assess the main determinants of attentional stability in those groups, including the effect of factors related to the epileptic condition. RESULTS: In 122 children with epilepsy (67 with comorbid ADHD), 52 children with ADHD, and 53 healthy controls, we demonstrated lower attentional stability in both the groups with epilepsy and ADHD compared with healthy children. In children with epilepsy, BLAST scores were negatively associated with earlier seizure onset and AED (antiepileptic drug) polytherapy, while the seizure frequency, epilepsy duration, or type did not influence BLAST scores. CONCLUSIONS: This study demonstrates that attentional stability is impaired in children with epilepsy and/or ADHD. Bron-Lyon Attention Stability Test seems to be a sensitive test to detect attentional stability deficit in children with epilepsy and with attentional complaints who did not meet all criteria of ADHD. We propose that BLAST could be a useful clinical neuropsychological tool to assess attentional disorders in children.

Task-induced gamma band effect in type II focal cortical dysplasia: An exploratory study.

OBJECTIVE: Few data are available about the functionality of type II focal cortical dysplasia (FCD). Identification of high-frequency activities (HFAs) induced by cognitive tasks has been proposed as an additional way to map cognitive functions in patients undergoing presurgical evaluation using stereoelectroencephalography (SEEG). However, the repetitive subcontinuous spiking pattern which characterizes type II FCD might limit the reliability of this approach, and its feasibility in these patients remains to be evaluated. METHODS: Seven patients whose magnetic resonance imaging (MRI) data, SEEG data, and/or pathological data were consistent with the diagnosis of type II FCD were included. All patients performed standardized cognitive tasks specifically designed to map task-induced increase of HFA (50 Hz to 150 Hz) at the recorded sites. Electrode contacts which showed an interictal SEEG pattern typical of type II FCD were considered to be localized within the FCD. A site was considered responsive if it was significantly different from baseline in at least one cognitive task. RESULTS: Three of the seven patients (43%) had significant task-induced increase of HFA in the FCD for a total of 15 sites with an interictal SEEG pattern typical of type II FCD. These sites were always localized at the external border of the FCD whereas no HFA response was in the core of FCD. In three of the four other patients, a significant task-induced increase of HFA was observed in a cortical site immediately adjacent to the dysplastic cortex. SIGNIFICANCE: Detection of task-induced HFA remains feasible despite the repetitive subcontinuous spiking pattern which characterizes type II FCD. Depending on the localization of the FCD, some sites of the dysplastic cortex were included in large-scale functional networks. However, these sites were always those closest to the nondysplastic cortex suggesting that persistence of cortical functions might be restricted to a limited part of the FCD.

Direct Recordings from Human Anterior Insula Reveal its Leading Role within the Error-Monitoring Network.

The ability to monitor our own errors is mediated by a network that includes dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI). However, the dynamics of the underlying neurophysiological processes remain unclear. In particular, whether AI is on the receiving or driving end of the error-monitoring network is unresolved. Here, we recorded intracerebral electroencephalography signals simultaneously from AI and dmPFC in epileptic patients while they performed a stop-signal task. We found that errors selectively modulated broadband neural activity in human AI. Granger causality estimates revealed that errors were immediately followed by a feedforward influence from AI onto anterior cingulate cortex and, subsequently, onto presupplementary motor area. The reverse pattern of information flow was observed on correct responses. Our findings provide the first direct electrophysiological evidence indicating that the anterior insula rapidly detects and conveys error signals to dmPFC, while the latter might use this input to adapt behavior following inappropriate actions.

From intentions to actions: Neural oscillations encode motor processes through phase, amplitude and phase-amplitude coupling.

Goal-directed motor behavior is associated with changes in patterns of rhythmic neuronal activity across widely distributed brain areas. In particular, movement initiation and execution are mediated by patterns of synchronization and desynchronization that occur concurrently across distinct frequency bands and across multiple motor cortical areas. To date, motor-related local oscillatory modulations have been predominantly examined by quantifying increases or suppressions in spectral power. However, beyond signal power, spectral properties such as phase and phase-amplitude coupling (PAC) have also been shown to carry information with regards to the oscillatory dynamics underlying motor processes. Yet, the distinct functional roles of phase, amplitude and PAC across the planning and execution of goal-directed motor behavior remain largely elusive. Here, we address this question with unprecedented resolution thanks to multi-site intracerebral EEG recordings in human subjects while they performed a delayed motor task. To compare the roles of phase, amplitude and PAC, we monitored intracranial brain signals from 748 sites across six medically intractable epilepsy patients at movement execution, and during the delay period where motor intention is present but execution is withheld. In particular, we used a machine-learning framework to identify the key contributions of various neuronal responses. We found a high degree of overlap between brain network patterns observed during planning and those present during execution. Prominent amplitude increases in the delta (2-4Hz) and high gamma (60-200Hz) bands were observed during both planning and execution. In contrast, motor alpha (8-13Hz) and beta (13-30Hz) power were suppressed during execution, but enhanced during the delay period. Interestingly, single-trial classification revealed that low-frequency phase information, rather than spectral power change, was the most discriminant feature in dissociating action from intention. Additionally, despite providing weaker decoding, PAC features led to statistically significant classification of motor states, particularly in anterior cingulate cortex and premotor brain areas. These results advance our understanding of the distinct and partly overlapping involvement of phase, amplitude and the coupling between them, in the neuronal mechanisms underlying motor intentions and executions.

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.

Selective modulation of auditory cortical alpha activity in an audiovisual spatial attention task.

Despite substantial research on attentional modulations of visual alpha activity, doubts remain as to the existence and functional relevance of auditory cortical alpha-band oscillations. It has been argued that auditory cortical alpha does not exist, cannot be measured noninvasively, or that it is dependent on visual alpha generators. This study aimed to address these remaining doubts concerning auditory cortical alpha. A magnetoencephalography study was conducted using a combined audiovisual spatial cueing paradigm. In each trial, a cue indicated the side (left or right) and the modality (auditory or visual) to attend, followed by a short lateralized auditory or visual stimulus. Participants were instructed to respond to the stimuli by a button press. Results show that auditory cortical alpha power is selectively modulated by the audiospatial, but not the visuospatial, attention task. These findings provide further evidence for a distinct auditory cortical alpha generator, which can be measured noninvasively.

Ten years of Nature Reviews Neuroscience: insights from the highly cited.

To celebrate the first 10 years of Nature Reviews Neuroscience, we invited the authors of the most cited article of each year to look back on the state of their field of research at the time of publication and the impact their article has had, and to discuss the questions that might be answered in the next 10 years. This selection of highly cited articles provides interesting snapshots of the progress that has been made in diverse areas of neuroscience. They show the enormous influence of neuroimaging techniques and highlight concepts that have generated substantial interest in the past decade, such as neuroimmunology, social neuroscience and the 'network approach' to brain function. These advancements will pave the way for further exciting discoveries that lie ahead.

Proceedings of the Seventh International Workshop on Advances in Electrocorticography.

The Seventh International Workshop on Advances in Electrocorticography (ECoG) convened in Washington, DC, on November 13-14, 2014. Electrocorticography-based research continues to proliferate widely across basic science and clinical disciplines. The 2014 workshop highlighted advances in neurolinguistics, brain-computer interface, functional mapping, and seizure termination facilitated by advances in the recording and analysis of the ECoG signal. The following proceedings document summarizes the content of this successful multidisciplinary gathering.

Temporal components in the parahippocampal place area revealed by human intracerebral recordings.

Many high-level visual regions exhibit complex patterns of stimulus selectivity that make their responses difficult to explain in terms of a single cognitive mechanism. For example, the parahippocampal place area (PPA) responds maximally to environmental scenes during fMRI studies but also responds strongly to nonscene landmark objects, such as buildings, which have a quite different geometric structure. We hypothesized that PPA responses to scenes and buildings might be driven by different underlying mechanisms with different temporal profiles. To test this, we examined broadband γ (50-150 Hz) responses from human intracerebral electroencephalography recordings, a measure that is closely related to population spiking activity. We found that the PPA distinguished scene from nonscene stimuli in ∼80 ms, suggesting the operation of a bottom-up process that encodes scene-specific visual or geometric features. In contrast, the differential PPA response to buildings versus nonbuildings occurred later (∼170 ms) and may reflect a delayed processing of spatial or semantic features definable for both scenes and objects, perhaps incorporating signals from other cortical regions. Although the response preferences of high-level visual regions are usually interpreted in terms of the operation of a single cognitive mechanism, these results suggest that a more complex picture emerges when the dynamics of recognition are considered.

Subthalamic nucleus activity dissociates proactive and reactive inhibition in patients with Parkinson's disease.

Models of action selection postulate the critical involvement of the subthalamic nucleus (STN), especially in reactive inhibition processes when inappropriate responses to a sudden stimulus must be overridden. The STN could also play a key role during proactive inhibition, when subjects prepare to potentially suppress their actions. Here, we hypothesized that STN responses to reactive and proactive inhibitory control might be driven by different underlying mechanisms with specific temporal profiles. Direct neural recordings in twelve Parkinson's disease patients during a modified stop signal task (SST) revealed a decrease of beta band activity (ßA, 13-35Hz) in the STN during reactive inhibition of smaller amplitude and shorter duration than during motor execution. Crucially, the onset latency of this relative increase of ßA took place before the stop signal reaction time. It could thus be thought of as a "stop" signal inhibiting thalamo-cortical activity that would have supported motor execution. Finally, results also revealed a higher level of ßA in the STN during proactive inhibition, which correlated with patient's inhibitory performances. We propose that ßA in the STN would here participate in the implementation of a "hold your horse" signal to delay motor responses, thus prioritizing accuracy as compared to speed. In brief, our results provide strong electrophysiological support for the hypothesized role of the STN during executive control underlying proactive and reactive response suppression.

Neural repetition suppression in ventral occipito-temporal cortex occurs during conscious and unconscious processing of frequent stimuli.

Stimulus repetition can produce neural response attenuation in stimulus-category selective networks within the occipito-temporal lobe. It is hypothesized that this neural suppression reflects the functional sharpening of local neuronal assemblies which boosts information processing efficiency. This neural suppression phenomenon has been mainly reported during conditions of conscious stimulus perception. The question remains whether frequent stimuli processed in the absence of conscious perception also induce repetition suppression in those specialized networks. Using rare intracranial EEG recordings in the ventral occipito-temporal cortex (VOTC) of human epileptic patients we investigated neural repetition suppression in conditions of conscious and unconscious visual processing of words. To this end, we used an orthogonal design manipulating respectively stimulus repetition (frequent vs. unique stimuli) and conscious perception (masked vs. unmasked stimuli). By measuring the temporal dynamics of high-frequency broadband gamma activity in VOTC and testing for main and interaction effects, we report that early processing of words in word-form selective networks exhibits a temporal cascade of modulations by stimulus repetition and masking: neuronal attenuation initially is observed in response to repeated words (irrespective of consciousness), that is followed by a second modulation contingent upon word reportability (irrespective of stimulus repetition). Later on (>300ms post-stimulus), a significant effect of conscious perception on the extent of repetition suppression was observed. The temporal dynamics of consciousness, the recognition memory processes and their interaction revealed in this study advance our understanding of their contributions to the neural mechanisms of word processing in VOTC.

Functional selectivity in the human occipitotemporal cortex during natural vision: evidence from combined intracranial EEG and eye-tracking.

Eye movements are a constant and essential component of natural vision, yet, most of our knowledge about the human visual system comes from experiments that restrict them. This experimental constraint is mostly in place to control visual stimuli presentation and to avoid artifacts in non-invasive measures of brain activity, however, this limitation can be overcome with intracranial EEG (iEEG) recorded from epilepsy patients. Moreover, the high-frequency components of the iEEG signal (between about 50 and 150Hz) can provide a proxy of population-level spiking activity in any cortical area during free-viewing. We combined iEEG with high precision eye-tracking to study fine temporal dynamics and functional specificity in the fusiform face (FFA) and visual word form area (VWFA) while patients inspected natural pictures containing faces and text. We defined the first local measure of visual (electrophysiological) responsiveness adapted to free-viewing in humans: amplitude modulations in the high-frequency activity range (50-150Hz) following fixations (fixation-related high-frequency response). We showed that despite the large size of receptive fields in the ventral occipito-temporal cortex, neural activity during natural vision of realistic cluttered scenes is mostly dependent upon the category of the foveated stimulus - suggesting that category-specificity is preserved during free-viewing and that attention mechanisms might filter out the influence of objects surrounding the fovea.

The Reflective Mind of the Anxious in Action: Metacognitive Beliefs and Maladaptive Emotional Regulation Strategies Constrain Working Memory Efficiency.

The Attentional Control Theory (ACT) posits that, while trait anxiety may not directly impact performance, it can influence processing efficiency by prompting the use of compensatory mechanisms. The specific nature of these mechanisms, which might be reflective, is not detailed by the ACT. In a study involving 110 students (M = 20.12; SD = 2.10), surveys were administered to assess the students' metacognitive beliefs, trait anxiety, and emotion regulation strategies (ERSs). The participants engaged in two working memory exercises: the digit span task from the WAIS-IV and an emotional n-back task. The findings indicated that anxiety, metacognitive beliefs, and maladaptive ERSs did not affect task performance but were correlated with increased response times. Several regression analyses demonstrated that a lack of confidence in one's cognitive abilities and maladaptive ERSs predict higher reaction times (RT) in the n-back task. Additionally, maladaptive ERSs also predict an increased use of strategies in the digit span task. Finally, two mediation analyses revealed that anxiety increases processing efficiency, and this relation is mediated by the use of maladaptive ERSs. These results underscore the importance of the reflective level in mediating the effects of trait anxiety on efficiency. They highlight the necessity of incorporating metacognitive beliefs and maladaptive emotion regulation strategies for a thorough comprehension of the Attentional Control Theory. Recognizing these factors offers valuable perspectives for enhancing cognitive capabilities and fostering academic achievement.

Trait Anxiety, Emotion Regulation, and Metacognitive Beliefs: An Observational Study Incorporating Separate Network and Correlation Analyses to Examine Associations with Executive Functions and Academic Achievement.

Trait anxiety, emotion regulation strategies, and metacognitive beliefs influence executive functions (EFs) and academic achievement. This study examines their interplay and impact on academic success. In total, 275 adolescents (10-17 years) and parents completed an online questionnaire assessing trait anxiety, emotion regulation strategies, metacognition, parent-reported behaviors related to executive functioning, and overall school average. Preliminary analyses confirmed consistency with the existing literature for each variable and their interaction. Furthermore, we conducted a network analysis among the main variables. This analysis supports the need to pay more attention to reflective variables-maladaptive emotion regulation strategies and metacognitive beliefs about worry-when studying trait anxiety. These variables were linked to problematic executive functioning in adolescents, and the latter was negatively linked to academic achievement. This study offers innovative insights by investigating relationships less explored in the scientific literature. It reveals high and significant correlations between metacognitive beliefs, maladaptive emotion regulation strategies, and trait anxiety (r > 0.500, p < 0.001) but also between these variables and both executive functioning and academic achievement. These findings offer new perspectives for research and underscore the importance of holistically examining the psychological factors related to academic success.

Human local field potentials in motor and non-motor brain areas encode upcoming movement direction.

Limb movement direction can be inferred from local field potentials in motor cortex during movement execution. Yet, it remains unclear to what extent intended hand movements can be predicted from brain activity recorded during movement planning. Here, we set out to probe the directional-tuning of oscillatory features during motor planning and execution, using a machine learning framework on multi-site local field potentials (LFPs) in humans. We recorded intracranial EEG data from implanted epilepsy patients as they performed a four-direction delayed center-out motor task. Fronto-parietal LFP low-frequency power predicted hand-movement direction during planning while execution was largely mediated by higher frequency power and low-frequency phase in motor areas. By contrast, Phase-Amplitude Coupling showed uniform modulations across directions. Finally, multivariate classification led to an increase in overall decoding accuracy (>80%). The novel insights revealed here extend our understanding of the role of neural oscillations in encoding motor plans.

Introducing HiBoP: a Unity-based visualization software for large iEEG datasets.

BACKGROUND: Intracranial EEG data offer a unique spatio-temporal precision to investigate human brain functions. Large datasets have become recently accessible thanks to new iEEG data-sharing practices and tighter collaboration with clinicians. Yet, the complexity of such datasets poses new challenges, especially regarding the visualization and anatomical display of iEEG. NEW METHOD: We introduce HiBoP, a multi-modal visualization software specifically designed for large groups of patients and multiple experiments. Its main features include the dynamic display of iEEG responses induced by tasks/stimulations, the definition of Regions and electrodes Of Interest, and the shift between group-level and individual-level 3D anatomo-functional data. RESULTS: We provide a use-case with data from 36 patients to reveal the global cortical dynamics following tactile stimulation. We used HiBoP to visualize high-gamma responses [50-150 Hz], and define three major response components in primary somatosensory and premotor cortices and parietal operculum. COMPARISON WITH EXISTING METHODS(S): Several iEEG softwares are now publicly available with outstanding analysis features. Yet, most were developed in languages (Python/Matlab) chosen to facilitate the inclusion of new analysis by users, rather than the quality of the visualization. HiBoP represents a visualization tool developed with videogame standards (Unity/C#), and performs detailed anatomical analysis rapidly, across multiple conditions, patients, and modalities with an easy export toward third-party softwares. CONCLUSION: HiBoP provides a user-friendly environment that greatly facilitates the exploration of large iEEG datasets, and helps users decipher subtle structure/function relationships.