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.

Independent Causal Contributions of Alpha- and Beta-Band Oscillations during Movement Selection.

UNLABELLED: To select a movement, specific neuronal populations controlling particular features of that movement need to be activated, whereas other populations are downregulated. The selective (dis)inhibition of cortical sensorimotor populations is governed by rhythmic neural activity in the alpha (8-12 Hz) and beta (15-25 Hz) frequency range. However, it is unclear whether and how these rhythms contribute independently to motor behavior. Building on a recent dissociation of the sensorimotor alpha- and beta-band rhythms, we test the hypothesis that the beta-band rhythm governs the disinhibition of task-relevant neuronal populations, whereas the alpha-band rhythm suppresses neurons that may interfere with task performance. Cortical alpha- and beta-band rhythms were manipulated with transcranial alternating current stimulation (tACS) while human participants selected how to grasp an object. Stimulation was applied at either 10 or 20 Hz and was imposed on the sensorimotor cortex contralaterally or ipsilaterally to the grasping hand. In line with task-induced changes in endogenous spectral power, the effect of the tACS intervention depended on the frequency and site of stimulation. Whereas tACS stimulation generally increased movement selection times, 10 Hz stimulation led to relatively faster selection times when applied to the hemisphere ipsilateral to the grasping hand, compared with other stimulation conditions. These effects occurred selectively when multiple movements were considered. These observations functionally differentiate the causal contribution of alpha- and beta-band oscillations to movement selection. The findings suggest that sensorimotor beta-band rhythms disinhibit task-relevant populations, whereas alpha-band rhythms inhibit neuronal populations that could interfere with movement selection. SIGNIFICANCE STATEMENT: This study shows dissociable effects of 10 Hz and 20 Hz tACS on the duration of movement selection. These observations have two elements of general relevance. First, the finding that alpha- and beta-band oscillations contribute independently to movement selection provides insight in how oscillations orchestrate motor behavior, which is key to understand movement selection deficits in neurodegenerative disorders. Second, the findings highlight the potential of 10 Hz stimulation as a neurophysiologically grounded intervention to enhance human performance. In particular, this intervention can potentially be exploited to boost rehabilitation after neural damage by targeting the unaffected hemisphere.

Oxytocin Modulates Semantic Integration in Speech Comprehension.

Listeners interpret utterances by integrating information from multiple sources including word level semantics and world knowledge. When the semantics of an expression is inconsistent with their knowledge about the world, the listener may have to search through the conceptual space for alternative possible world scenarios that can make the expression more acceptable. Such cognitive exploration requires considerable computational resources and might depend on motivational factors. This study explores whether and how oxytocin, a neuropeptide known to influence social motivation by reducing social anxiety and enhancing affiliative tendencies, can modulate the integration of world knowledge and sentence meanings. The study used a between-participant double-blind randomized placebo-controlled design. Semantic integration, indexed with magnetoencephalography through the N400m marker, was quantified while 45 healthy male participants listened to sentences that were either congruent or incongruent with facts of the world, after receiving intranasally delivered oxytocin or placebo. Compared with congruent sentences, world knowledge incongruent sentences elicited a stronger N400m signal from the left inferior frontal and anterior temporal regions and medial pFC (the N400m effect) in the placebo group. Oxytocin administration significantly attenuated the N400m effect at both sensor and cortical source levels throughout the experiment, in a state-like manner. Additional electrophysiological markers suggest that the absence of the N400m effect in the oxytocin group is unlikely due to the lack of early sensory or semantic processing or a general downregulation of attention. These findings suggest that oxytocin drives listeners to resolve challenges of semantic integration, possibly by promoting the cognitive exploration of alternative possible world scenarios.

Cerebral coherence between communicators marks the emergence of meaning.

How can we understand each other during communicative interactions? An influential suggestion holds that communicators are primed by each other's behaviors, with associative mechanisms automatically coordinating the production of communicative signals and the comprehension of their meanings. An alternative suggestion posits that mutual understanding requires shared conceptualizations of a signal's use, i.e., "conceptual pacts" that are abstracted away from specific experiences. Both accounts predict coherent neural dynamics across communicators, aligned either to the occurrence of a signal or to the dynamics of conceptual pacts. Using coherence spectral-density analysis of cerebral activity simultaneously measured in pairs of communicators, this study shows that establishing mutual understanding of novel signals synchronizes cerebral dynamics across communicators' right temporal lobes. This interpersonal cerebral coherence occurred only within pairs with a shared communicative history, and at temporal scales independent from signals' occurrences. These findings favor the notion that meaning emerges from shared conceptualizations of a signal's use.

Neural mechanisms of communicative innovation.

Human referential communication is often thought as coding-decoding a set of symbols, neglecting that establishing shared meanings requires a computational mechanism powerful enough to mutually negotiate them. Sharing the meaning of a novel symbol might rely on similar conceptual inferences across communicators or on statistical similarities in their sensorimotor behaviors. Using magnetoencephalography, we assess spectral, temporal, and spatial characteristics of neural activity evoked when people generate and understand novel shared symbols during live communicative interactions. Solving those communicative problems induced comparable changes in the spectral profile of neural activity of both communicators and addressees. This shared neuronal up-regulation was spatially localized to the right temporal lobe and the ventromedial prefrontal cortex and emerged already before the occurrence of a specific communicative problem. Communicative innovation relies on neuronal computations that are shared across generating and understanding novel shared symbols, operating over temporal scales independent from transient sensorimotor behavior.

Distinct roles for alpha- and beta-band oscillations during mental simulation of goal-directed actions.

Rhythmic neural activity within the alpha (8-12 Hz) and beta (15-25 Hz) frequency bands is modulated during actual and imagined movements. Changes in these rhythms provide a mechanism to select relevant neuronal populations, although the relative contributions of these rhythms remain unclear. Here we use MEG to investigate changes in oscillatory power while healthy human participants imagined grasping a cylinder oriented at different angles. This paradigm allowed us to study the neural signals involved in the simulation of a movement in the absence of signals related to motor execution and sensory reafference. Movement selection demands were manipulated by exploiting the fact that some object orientations evoke consistent grasping movements, whereas others are compatible with both overhand and underhand grasping. By modulating task demands, we show a functional dissociation of the alpha- and beta-band rhythms. As movement selection demands increased, alpha-band oscillatory power increased in the sensorimotor cortex ipsilateral to the arm used for imagery, whereas beta-band power concurrently decreased in the contralateral sensorimotor cortex. The same pattern emerged when motor imagery trials were compared with a control condition, providing converging evidence for the functional dissociation of the two rhythms. These observations call for a re-evaluation of the role of sensorimotor rhythms. We propose that neural oscillations in the alpha-band mediate the allocation of computational resources by disengaging task-irrelevant cortical regions. In contrast, the reduction of neural oscillations in the beta-band is directly related to the disinhibition of neuronal populations involved in the computations of movement parameters.

The Emerging Science of Interacting Minds.

For over a century, psychology has focused on uncovering mental processes of a single individual. However, humans rarely navigate the world in isolation. The most important determinants of successful development, mental health, and our individual traits and preferences arise from interacting with other individuals. Social interaction underpins who we are, how we think, and how we behave. Here we discuss the key methodological challenges that have limited progress in establishing a robust science of how minds interact and the new tools that are beginning to overcome these challenges. A deep understanding of the human mind requires studying the context within which it originates and exists: social interaction.

Online and offline tools for head movement compensation in MEG.

Magnetoencephalography (MEG) is measured above the head, which makes it sensitive to variations of the head position with respect to the sensors. Head movements blur the topography of the neuronal sources of the MEG signal, increase localization errors, and reduce statistical sensitivity. Here we describe two novel and readily applicable methods that compensate for the detrimental effects of head motion on the statistical sensitivity of MEG experiments. First, we introduce an online procedure that continuously monitors head position. Second, we describe an offline analysis method that takes into account the head position time-series. We quantify the performance of these methods in the context of three different experimental settings, involving somatosensory, visual and auditory stimuli, assessing both individual and group-level statistics. The online head localization procedure allowed for optimal repositioning of the subjects over multiple sessions, resulting in a 28% reduction of the variance in dipole position and an improvement of up to 15% in statistical sensitivity. Offline incorporation of the head position time-series into the general linear model resulted in improvements of group-level statistical sensitivity between 15% and 29%. These tools can substantially reduce the influence of head movement within and between sessions, increasing the sensitivity of many cognitive neuroscience experiments.

Behavioral and EEG Measures Show no Amplifying Effects of Shared Attention on Attention or Memory.

Shared attention experiments examine the potential differences in function or behavior when stimuli are experienced alone or in the presence of others, and when simultaneous attention of the participants to the same stimulus or set is involved. Previous work has found enhanced reactions to emotional stimuli in social situations, yet these changes might represent enhanced communicative or motivational purposes. This study examines whether viewing emotional stimuli in the presence of another person influences attention to or memory for the stimulus. Participants passively viewed emotionally-valenced stimuli while completing another task (counting flowers). Each participant performed this task both alone and in a shared attention condition (simultaneously with another person in the same room) while EEG signals were measured. Recognition of the emotional pictures was later measured. A significant shared attention behavioral effect was found in the attention task but not in the recognition task. Compared to event-related potential responses for neutral pictures, we found higher P3b response for task relevant stimuli (flowers), and higher Late Positive Potential (LPP) responses for emotional stimuli. However, no main effect was found for shared attention between presence conditions. To conclude, shared attention may therefore have a more limited effect on cognitive processes than previously suggested.

Beyond the Isolated Brain: The Promise and Challenge of Interacting Minds.

As scientists, we brainstorm and develop experimental designs with our colleagues and students. Paradoxically, this teamwork has produced a field focused nearly exclusively on mapping the brain as if it evolved in isolation. Here, we discuss promises and challenges in advancing our understanding of how human minds connect during social interaction.

Communicative misalignment in Autism Spectrum Disorder.

Communication deficits are a defining feature of Autism Spectrum Disorder (ASD), manifest during social interactions. Previous studies investigating communicative deficits have largely focused on the perceptual biases, social motivation, cognitive flexibility, or mentalizing abilities of isolated individuals. By embedding autistic individuals in live non-verbal interactions, we characterized a novel cause for their communication deficits. Adults with ASD matched neurotypical individuals in their ability and propensity to generate and modify intelligible behaviors for a communicative partner. However, they struggled to align the meaning of those behaviors with their partner when meaning required referencing their recent communicative history. This communicative misalignment explains why autistic individuals are vulnerable in everyday interactions, which entail fleeting ambiguities, but succeed in social cognition tests involving stereotyped contextual cues. These findings illustrate the cognitive and clinical importance of considering social interaction as a communicative alignment challenge, and how ineffective human communication is without this key interactional ingredient.

Electrocorticographic dissociation of alpha and beta rhythmic activity in the human sensorimotor system.

This study uses electrocorticography in humans to assess how alpha- and beta-band rhythms modulate excitability of the sensorimotor cortex during psychophysically-controlled movement imagery. Both rhythms displayed effector-specific modulations, tracked spectral markers of action potentials in the local neuronal population, and showed spatially systematic phase relationships (traveling waves). Yet, alpha- and beta-band rhythms differed in their anatomical and functional properties, were weakly correlated, and traveled along opposite directions across the sensorimotor cortex. Increased alpha-band power in the somatosensory cortex ipsilateral to the selected arm was associated with spatially-unspecific inhibition. Decreased beta-band power over contralateral motor cortex was associated with a focal shift from relative inhibition to excitation. These observations indicate the relevance of both inhibition and disinhibition mechanisms for precise spatiotemporal coordination of movement-related neuronal populations, and illustrate how those mechanisms are implemented through the substantially different neurophysiological properties of sensorimotor alpha- and beta-band rhythms.

Task switching in autism: An EEG study on intentions and actions.

One of the main symptoms of Autism Spectrum Conditions (ASC) is experiencing cognitive inflexibility when adjustments of behaviour are required. While this so-called behavioural rigidity is broadly recognised in ASC, finding evidence for the underlying neurocognitive mechanisms remains challenging. In this electroencephalographic (EEG) study, participants with ASC and matched controls were instructed to choose between two cognitive tasks in each trial, and to respond to the subsequently presented target stimulus according to their task choice. While doing so, we tracked the frontally distributed contingent negative variation (CNV) during the task preparation interval as a measure of intentional control, and the posteriorly measured P3 during the task execution interval to monitor the translation of intentions into actions. The results support the notion of intentional control difficulties in ASC, where the CNV was attenuated in the ASC group compared to the control group. Furthermore, the CNV was differentiated between the tasks and transition types in the control group only, suggesting that the ASC group was less fine-tuning the required amount of intentional control to contextual circumstances. In contrast, the P3 showed no significant differences between the groups. Together, these findings highlight the importance of intentional control mechanisms as a crucial future route for a better understanding of cognitive flexibility and behavioural rigidity in ASC.

Encoding of Multiple Reward-Related Computations in Transient and Sustained High-Frequency Activity in Human OFC.

Human orbitofrontal cortex (OFC) has long been implicated in value-based decision making. In recent years, convergent evidence from human and model organisms has further elucidated its role in representing reward-related computations underlying decision making. However, a detailed description of these processes remains elusive due in part to (1) limitations in our ability to observe human OFC neural dynamics at the timescale of decision processes and (2) methodological and interspecies differences that make it challenging to connect human and animal findings or to resolve discrepancies when they arise. Here, we sought to address these challenges by conducting multi-electrode electrocorticography (ECoG) recordings in neurosurgical patients during economic decision making to elucidate the electrophysiological signature, sub-second temporal profile, and anatomical distribution of reward-related computations within human OFC. We found that high-frequency activity (HFA) (70-200 Hz) reflected multiple valuation components grouped in two classes of valuation signals that were dissociable in temporal profile and information content: (1) fast, transient responses reflecting signals associated with choice and outcome processing, including anticipated risk and outcome regret, and (2) sustained responses explicitly encoding what happened in the immediately preceding trial. Anatomically, these responses were widely distributed in partially overlapping networks, including regions in the central OFC (Brodmann areas 11 and 13), which have been consistently implicated in reward processing in animal single-unit studies. Together, these results integrate insights drawn from human and animal studies and provide evidence for a role of human OFC in representing multiple reward computations.

Integrated analysis of anatomical and electrophysiological human intracranial data.

Human intracranial electroencephalography (iEEG) recordings provide data with much greater spatiotemporal precision than is possible from data obtained using scalp EEG, magnetoencephalography (MEG), or functional MRI. Until recently, the fusion of anatomical data (MRI and computed tomography (CT) images) with electrophysiological data and their subsequent analysis have required the use of technologically and conceptually challenging combinations of software. Here, we describe a comprehensive protocol that enables complex raw human iEEG data to be converted into more readily comprehensible illustrative representations. The protocol uses an open-source toolbox for electrophysiological data analysis (FieldTrip). This allows iEEG researchers to build on a continuously growing body of scriptable and reproducible analysis methods that, over the past decade, have been developed and used by a large research community. In this protocol, we describe how to analyze complex iEEG datasets by providing an intuitive and rapid approach that can handle both neuroanatomical information and large electrophysiological datasets. We provide a worked example using an example dataset. We also explain how to automate the protocol and adjust the settings to enable analysis of iEEG datasets with other characteristics. The protocol can be implemented by a graduate student or postdoctoral fellow with minimal MATLAB experience and takes approximately an hour to execute, excluding the automated cortical surface extraction.

Oxytocin modulates human communication by enhancing cognitive exploration.

Oxytocin is a neuropeptide known to influence how humans share material resources. Here we explore whether oxytocin influences how we share knowledge. We focus on two distinguishing features of human communication, namely the ability to select communicative signals that disambiguate the many-to-many mappings that exist between a signal's form and meaning, and adjustments of those signals to the presumed cognitive characteristics of the addressee ("audience design"). Fifty-five males participated in a randomized, double-blind, placebo controlled experiment involving the intranasal administration of oxytocin. The participants produced novel non-verbal communicative signals towards two different addressees, an adult or a child, in an experimentally-controlled live interactive setting. We found that oxytocin administration drives participants to generate signals of higher referential quality, i.e. signals that disambiguate more communicative problems; and to rapidly adjust those communicative signals to what the addressee understands. The combined effects of oxytocin on referential quality and audience design fit with the notion that oxytocin administration leads participants to explore more pervasively behaviors that can convey their intention, and diverse models of the addressees. These findings suggest that, besides affecting prosocial drive and salience of social cues, oxytocin influences how we share knowledge by promoting cognitive exploration.

Communicative knowledge pervasively influences sensorimotor computations.

Referential pointing is a characteristically human behavior, which involves moving a finger through space to direct an addressee towards a desired mental state. Planning this type of action requires an interface between sensorimotor and conceptual abilities. A simple interface could supplement spatially-guided motor routines with communicative-ostensive cues. For instance, a pointing finger held still for an extended period of time could aid the addressee's understanding, without altering the movement's trajectory. A more complex interface would entail communicative knowledge penetrating the sensorimotor system and directly affecting pointing trajectories. We compare these two possibilities using motion analyses of referential pointing during multi-agent interactions. We observed that communicators produced ostensive cues that were sensitive to the communicative context. Crucially, we also observed pervasive adaptations to the pointing trajectories: they were tailored to the communicative context and to partner-specific information. These findings indicate that human referential pointing is planned and controlled on the basis of partner-specific knowledge, over and above the tagging of motor routines with ostensive cues.

Conceptual Alignment: How Brains Achieve Mutual Understanding.

We share our thoughts with other minds, but we do not understand how. Having a common language certainly helps, but infants' and tourists' communicative success clearly illustrates that sharing thoughts does not require signals with a pre-assigned meaning. In fact, human communicators jointly build a fleeting conceptual space in which signals are a means to seek and provide evidence for mutual understanding. Recent work has started to capture the neural mechanisms supporting those fleeting conceptual alignments. The evidence suggests that communicators and addressees achieve mutual understanding by using the same computational procedures, implemented in the same neuronal substrate, and operating over temporal scales independent from the signals' occurrences.

Altered communicative decisions following ventromedial prefrontal lesions.

Damage to the human ventromedial prefrontal cortex (vmPFC) leads to profound changes in everyday social interactions [1, 2]. Yet, in the lab, vmPFC patients show surprising proficiency in reasoning about other agents [3-8]. These conflicting observations suggest that what vmPFC patients lack in everyday social interactions might be the ability to guide their decisions with knowledge about a social partner [9-13], despite preserved access to that knowledge [2, 14]. Quantification of socially relevant decisions during live interaction with different partners offers the possibility of testing this hypothesis. Eight patients with vmPFC damage, eight patients with brain damage elsewhere, and 15 healthy participants were asked to communicate non-verbally with two different addressees, an adult or a child, in an experimentally controlled interactive setting [15, 16]. In reality, a confederate blindly performed the role of both adult and child addressee, with matched performance and response times, such that the two addressees differed only in terms of the communicator's beliefs. Patients with vmPFC damage were able-and motivated-to generate communicatively effective behaviors. However, unlike patient and healthy controls, vmPFC patients failed to adjust their communicative decisions to the presumed abilities of their addressee. These findings indicate that the human vmPFC is necessarily involved in social interactions, insofar as those interactions need to be tailored toward knowledge about a social partner. In this perspective, the known contribution of this region to disparate domains like value-based decision-making [17-19], schema-based memory-processing [20-22], and person-specific mentalizing [11-13] might be instances of decisions based on contingently updated conceptual knowledge.