Inter-individual variability in dorsal stream dynamics during word production.

The current standard model of language production involves a sensorimotor dorsal stream connecting areas in the temporo-parietal junction with those in the inferior frontal gyrus and lateral premotor cortex. These regions have been linked to various aspects of word production such as phonological processing or articulatory programming, primarily through neuropsychological and functional imaging group studies. Most if not all the theoretical descriptions of this model imply that the same network should be identifiable across individual speakers. We tested this hypothesis by quantifying the variability of activation observed across individuals within each dorsal stream anatomical region. This estimate was based on electrical activity recorded directly from the cerebral cortex with millisecond accuracy in awake epileptic patients clinically implanted with intracerebral depth electrodes for pre-surgical diagnosis. Each region's activity was quantified using two different metrics-intra-cerebral evoked related potentials and high gamma activity-at the level of the group, the individual and the recording contact. The two metrics show simultaneous activation of parietal and frontal regions during a picture naming task, in line with models that posit interactive processing during word retrieval. They also reveal different levels of between-patient variability across brain regions, except in core auditory and motor regions. The independence and non-uniformity of cortical activity estimated through the two metrics push the current model towards sub-second and sub-region explorations focused on individualized language speech production. Several hypotheses are considered for this within-region heterogeneity.

An open-source toolbox for Multi-patient Intracranial EEG Analysis (MIA).

Intracranial EEG (iEEG) performed during the pre-surgical evaluation of refractory epilepsy provides a great opportunity to investigate the neurophysiology of human cognitive functions with exceptional spatial and temporal precisions. A difficulty of the iEEG approach for cognitive neuroscience, however, is the potential variability across patients in the anatomical location of implantations and in the functional responses therein recorded. In this context, we designed, implemented, and tested a user-friendly and efficient open-source toolbox for Multi-Patient Intracranial data Analysis (MIA), which can be used as standalone program or as a Brainstorm plugin. MIA helps analyzing event related iEEG signals while following good scientific practice recommendations, such as building reproducible analysis pipelines and applying robust statistics. The signals can be analyzed in the temporal and time-frequency domains, and the similarity of time courses across patients or contacts can be assessed within anatomical regions. MIA allows visualizing all these results in a variety of formats at every step of the analysis. Here, we present the toolbox architecture and illustrate the different steps and features of the analysis pipeline using a group dataset collected during a language task.

What déjà vu and the "dreamy state" tell us about episodic memory networks.

Illusions of inappropriate familiarity with the current experience or hallucinatory recall of memories are reported in temporal lobe seizures. Pathophysiological hypotheses have been proposed, involving temporal limbic regions (Hughlings-Jackson), temporal neocortex ("interpretive cortex", Penfield), or both (Bancaud). Recent data acquired from presurgical investigations using intracerebral electrode recordings, demonstrate a critical role for the sub- and para-hippocampal cortices. From this, a novel hypothesis of cortico-limbic networks emerged: déjà-vu results from an abnormal synchronization between rhinal cortices and hippocampus, and reminiscences ("dreamy state") from activation of the associational function of the hippocampus in re-assembling elements of the past experience networks. "Experiential" phenomena are better scrutinized during direct cortical stimulation than during spontaneous occurrence, because it allows precise spatiotemporal correlations to be made between the illusion/hallucination and the electrical discharge features and localization. Therefore, we present a summary of the stimulation data published since Penfield's seminal studies, review the anatomical and physiological correlations of stimulation findings, and question their functional significance. We reappraise the distinct and coactive roles of the various regions involved in perception-memory processes including the hippocampus, rhinal cortices, temporal neocortex and constituent elements of the ventral stream. Additionally, we draw insights from what is known about the perception-cognition continuum underlying the construction of episodic memories. Finally, we compare the results from cortical stimulation in the epileptogenic zone with the use of stimulation for memory enhancement and explore what this reveals about the mechanisms of stimulation.

Functional Topography of Auditory Areas Derived From the Combination of Electrophysiological Recordings and Cortical Electrical Stimulation.

The posterior part of the superior temporal gyrus (STG) has long been known to be a crucial hub for auditory and language processing, at the crossroad of the functionally defined ventral and dorsal pathways. Anatomical studies have shown that this "auditory cortex" is composed of several cytoarchitectonic areas whose limits do not consistently match macro-anatomic landmarks like gyral and sulcal borders. The only method to record and accurately distinguish neuronal activity from the different auditory sub-fields of primary auditory cortex, located in the tip of Heschl and deeply buried in the Sylvian fissure, is to use stereotaxically implanted depth electrodes (Stereo-EEG) for pre-surgical evaluation of patients with epilepsy. In this prospective, we focused on how anatomo-functional delineation in Heschl's gyrus (HG), Planum Temporale (PT), the posterior part of the STG anterior to HG, the posterior superior temporal sulcus (STS), and the region at the parietal-temporal boundary commonly labeled "SPT" can be achieved using data from electrical cortical stimulation combined with electrophysiological recordings during listening to pure tones and syllables. We show the differences in functional roles between the primary and non-primary auditory areas, in the left and the right hemispheres. We discuss how these findings help understanding the auditory semiology of certain epileptic seizures and, more generally, the neural substrate of hemispheric specialization for language.

Contributions of electrophysiology for identifying cortical language systems in patients with epilepsy.

A crucial element of the surgical treatment of medically refractory epilepsy is to delineate cortical areas that must be spared in order to avoid clinically relevant neurological and neuropsychological deficits postoperatively. For each patient, this typically necessitates determining the language lateralization between hemispheres and language localization within hemisphere. Understanding cortical language systems is complicated by two primary challenges: the extent of the neural tissue involved and the substantial variability across individuals, especially in pathological populations. We review the contributions made through the study of electrophysiological activity to address these challenges. These contributions are based on the techniques of magnetoencephalography (MEG), intracerebral recordings, electrical-cortical stimulation (ECS), and the electrovideo analyses of seizures and their semiology. We highlight why no single modality alone is adequate to identify cortical language systems and suggest avenues for improving current practice.

Converging intracortical signatures of two separated processing timescales in human early auditory cortex.

Neural oscillations in auditory cortex are argued to support parsing and representing speech constituents at their corresponding temporal scales. Yet, how incoming sensory information interacts with ongoing spontaneous brain activity, what features of the neuronal microcircuitry underlie spontaneous and stimulus-evoked spectral fingerprints, and what these fingerprints entail for stimulus encoding, remain largely open questions. We used a combination of human invasive electrophysiology, computational modeling and decoding techniques to assess the information encoding properties of brain activity and to relate them to a plausible underlying neuronal microarchitecture. We analyzed intracortical auditory EEG activity from 10 patients while they were listening to short sentences. Pre-stimulus neural activity in early auditory cortical regions often exhibited power spectra with a shoulder in the delta range and a small bump in the beta range. Speech decreased power in the beta range, and increased power in the delta-theta and gamma ranges. Using multivariate machine learning techniques, we assessed the spectral profile of information content for two aspects of speech processing: detection and discrimination. We obtained better phase than power information decoding, and a bimodal spectral profile of information content with better decoding at low (delta-theta) and high (gamma) frequencies than at intermediate (beta) frequencies. These experimental data were reproduced by a simple rate model made of two subnetworks with different timescales, each composed of coupled excitatory and inhibitory units, and connected via a negative feedback loop. Modeling and experimental results were similar in terms of pre-stimulus spectral profile (except for the iEEG beta bump), spectral modulations with speech, and spectral profile of information content. Altogether, we provide converging evidence from both univariate spectral analysis and decoding approaches for a dual timescale processing infrastructure in human auditory cortex, and show that it is consistent with the dynamics of a simple rate model.

Asymmetric sampling in human auditory cortex reveals spectral processing hierarchy.

Speech perception is mediated by both left and right auditory cortices but with differential sensitivity to specific acoustic information contained in the speech signal. A detailed description of this functional asymmetry is missing, and the underlying models are widely debated. We analyzed cortical responses from 96 epilepsy patients with electrode implantation in left or right primary, secondary, and/or association auditory cortex (AAC). We presented short acoustic transients to noninvasively estimate the dynamical properties of multiple functional regions along the auditory cortical hierarchy. We show remarkably similar bimodal spectral response profiles in left and right primary and secondary regions, with evoked activity composed of dynamics in the theta (around 4-8 Hz) and beta-gamma (around 15-40 Hz) ranges. Beyond these first cortical levels of auditory processing, a hemispheric asymmetry emerged, with delta and beta band (3/15 Hz) responsivity prevailing in the right hemisphere and theta and gamma band (6/40 Hz) activity prevailing in the left. This asymmetry is also present during syllables presentation, but the evoked responses in AAC are more heterogeneous, with the co-occurrence of alpha (around 10 Hz) and gamma (>25 Hz) activity bilaterally. These intracranial data provide a more fine-grained and nuanced characterization of cortical auditory processing in the 2 hemispheres, shedding light on the neural dynamics that potentially shape auditory and speech processing at different levels of the cortical hierarchy.

Neural processes of auditory perception in Heschl's gyrus for upcoming acoustic stimuli in humans.

In the natural environment, attended sounds tend to be perceived much better than unattended sounds. However, the physiological mechanism of how our neural systems direct the state of perceptual attention to prepare for the detection of upcoming acoustic stimuli before auditory stream segregation remains elusive. In this study, based on the direct intracerebral recordings from the auditory cortex in eight epileptic patients with refractory focal seizures, we investigated the neural processing of auditory attention by comparing the local field potentials before 'attentional' and 'distracted' conditions. Here we first showed a distinct build-up of slow, negative cortical potential in Heschl's gyrus. The amplitude increased steadily, starting from 600 to 800 ms before presentation of the tone until the onset of the evoked component P/N 60-80 when the patients were in the attentional condition. Because of their specific topographical distribution and modality-specific properties, we named these 'auditory preparatory potentials', which are also associated with increased gamma oscillations (30-150 Hz) and desynchronized low frequency activity (below 30 Hz). Thus, our findings suggest that the auditory cortex is pre-activated to facilitate the perception of forthcoming sound events, and contribute to the understanding of the neurophysiological mechanisms of auditory perception from a new perspective.

Cortical Dynamics of Semantic Priming and Interference during Word Production: An Intracerebral Study.

Language production requires that semantic representations are mapped to lexical representations on the basis of the ongoing context to select the appropriate words. This mapping is thought to generate two opposing phenomena, "semantic priming," where multiple word candidates are activated, and "interference," where these word activities are differentiated to make a goal-relevant selection. In previous neuroimaging and neurophysiological research, priming and interference have been associated to activity in regions of a left frontotemporal network. Most of such studies relied on recordings that either have high temporal or high spatial resolution, but not both. Here, we employed intracerebral EEG techniques to explore with both high resolutions, the neural activity associated with these phenomena. The data came from nine epileptic patients who were stereotactically implanted for presurgical diagnostics. They performed a cyclic picture-naming task contrasting semantically homogeneous and heterogeneous contexts. Of the 84 brain regions sampled, 39 showed task-evoked activity that was significant and consistent across two patients or more. In nine of these regions, activity was significantly modulated by the semantic manipulation. It was reduced for semantically homogeneous contexts (i.e., priming) in eight of these regions, located in the temporal ventral pathway as well as frontal areas. Conversely, it was increased only in the pre-SMA, notably at an early poststimulus temporal window (200-300 msec) and a preresponse temporal window (700-800 msec). These temporal effects respectively suggest the pre-SMA's role in initial conflict detection (e.g., increased response caution) and in preresponse control. Such roles of the pre-SMA are traditional from a history of neural evidence in simple perceptual tasks, yet are also consistent with recent cognitive lexicosemantic theories that highlight top-down processes in language production. Finally, although no significant semantic modulation was found in the ACC, future intracerebral EEG work should continue to inspect ACC with the pre-SMA.

An intracerebral exploration of functional connectivity during word production.

Language is mediated by pathways connecting distant brain regions that have diverse functional roles. For word production, the network includes a ventral pathway, connecting temporal and inferior frontal regions, and a dorsal pathway, connecting parietal and frontal regions. Despite the importance of word production for scientific and clinical purposes, the functional connectivity underlying this task has received relatively limited attention, and mostly from techniques limited in either spatial or temporal resolution. Here, we exploited data obtained from depth intra-cerebral electrodes stereotactically implanted in eight epileptic patients. The signal was recorded directly from various structures of the neocortex with high spatial and temporal resolution. The neurophysiological activity elicited by a picture naming task was analyzed in the time-frequency domain (10-150 Hz), and functional connectivity between brain areas among ten regions of interest was examined. Task related-activities detected within a network of the regions of interest were consistent with findings in the literature, showing task-evoked desynchronization in the beta band and synchronization in the gamma band. Surprisingly, long-range functional connectivity was not particularly stronger in the beta than in the high-gamma band. The latter revealed meaningful sub-networks involving, notably, the temporal pole and the inferior frontal gyrus (ventral pathway), and parietal regions and inferior frontal gyrus (dorsal pathway). These findings are consistent with the hypothesized network, but were not detected in every patient. Further research will have to explore their robustness with larger samples.

The different patterns of seizure-induced aphasia in temporal lobe epilepsies.

OBJECTIVES: Ictal language disturbances may occur in dominant hemisphere temporal lobe epilepsy (TLE), but little is known about the precise anatomoelectroclinical correlations. This study investigated the different facets of ictal aphasia in intracerebrally recorded TLE. METHODS: Video-stereoelectroencephalography (SEEG) recordings of 37 seizures in 17 right-handed patients with drug-resistant TLE were analyzed; SEEG electroclinical correlations between language disturbance and involvement of temporal lobe structures were assessed. In the clinical analysis, we separated speech disturbance from loss of consciousness. RESULTS: According to the region involved, different patterns of ictal aphasia in TLE were identified. Impaired speech comprehension was associated with posterior lateral involvement, anomia and reduced verbal fluency with anterior mediobasal structures, and jargonaphasia with basal temporal involvement. The language production deficits, such as anomia and low fluency, cannot be simply explained by an involvement of Broca's area, since this region was not affected by seizure discharge. SIGNIFICANCE: Assessment of language function in the early ictal state can be successfully performed and provides valuable information on seizure localization within the temporal lobe as well as potentially useful information for guiding surgery.

The Role of Associative Cortices and Hippocampus during Movement Perturbations.

Although motor control has been extensively studied, most research involving neural recordings has focused on primary motor cortex, pre-motor cortex, supplementary motor area, and cerebellum. These regions are involved during normal movements, however, associative cortices and hippocampus are also likely involved during perturbed movements as one must detect the unexpected disturbance, inhibit the previous motor plan, and create a new plan to compensate. Minimal data is available on these brain regions during such "robust" movements. Here, epileptic patients implanted with intracerebral electrodes performed reaching movements while experiencing occasional unexpected force perturbations allowing study of the fronto-parietal, limbic and hippocampal network at unprecedented high spatial, and temporal scales. Areas including orbitofrontal cortex (OFC) and hippocampus showed increased activation during perturbed trials. These results, coupled with a visual novelty control task, suggest the hippocampal MTL-P300 novelty response is modality independent, and that the OFC is involved in modifying motor plans during robust movement.

Estimating Parallel Processing in a Language Task Using Single-Trial Intracerebral Electroencephalography.

We provide a quantitative assessment of the parallel-processing hypothesis included in various language-processing models. First, we highlight the importance of reasoning about cognitive processing at the level of single trials rather than using averages. Then, we report the results of an experiment in which the hypothesis was tested at an unprecedented level of granularity with intracerebral data recorded during a picture-naming task. We extracted patterns of significant high-gamma activity from multiple patients and combined them into a single analysis framework that identified consistent patterns. Average signals from different brain regions, presumably indexing distinct cognitive processes, revealed a large degree of concurrent activity. In comparison, at the level of single trials, the temporal overlap of detected significant activity was unexpectedly low, with the exception of activity in sensory cortices. Our novel methodology reveals some limits on the degree to which word production involves parallel processing.

Hippocampus duality: Memory and novelty detection are subserved by distinct mechanisms.

The hippocampus plays a pivotal role both in novelty detection and in long-term memory. The physiological mechanisms underlying these behaviors have yet to be understood in humans. We recorded intracerebral evoked potentials within the hippocampus of epileptic patients (n = 10) during both memory and novelty detection tasks (targets in oddball tasks). We found that memory and detection tasks elicited late local field potentials in the hippocampus during the same period, but of opposite polarity (negative during novelty detection tasks, positive during memory tasks, ∼260-600 ms poststimulus onset, P < 0.05). Critically, these potentials had maximal amplitude on the same contact in the hippocampus for each patient. This pattern did not depend on the task as different types of memory and novelty detection tasks were used. It did not depend on the novelty of the stimulus or the difficulty of the task either. Two different hypotheses are discussed to account for this result: it is either due to the activation of CA1 pyramidal neurons by two different pathways such as the monosynaptic and trisynaptic entorhinal-hippocampus pathways, or to the activation of different neuronal populations, that is, differing either functionally (e.g., novelty/familiarity neurons) or located in different regions of the hippocampus (e.g., CA1/subiculum). In either case, these activities may integrate the activity of two distinct large-scale networks implementing externally or internally oriented, mutually exclusive, brain states. © 2017 Wiley Periodicals, Inc.

High frequency gamma activity in the left hippocampus predicts visual object naming performance.

Access to an object's name requires the retrieval of an arbitrary association between it's identity and a word-label. The hippocampus is essential in retrieving arbitrary associations, and thus could be involved in retrieving the link between an object and its name. To test this hypothesis we recorded the iEEG signal from epileptic patients, directly implanted in the hippocampus, while they performed a picture naming task. High-frequency broadband gamma (50-150 Hz) responses were computed as an index of population-level spiking activity. Our results show, for the first time, single-trial hippocampal dynamics between visual confrontation and naming. Remarkably, the latency of the hippocampal response predicts naming latency, while inefficient hippocampal activation is associated with "tip-of-the-tongue" states (a failure to retrieve the name of a recognized object) suggesting that the hippocampus is an active component of the naming network and that its dynamics are closely related to efficient word production.

How functional coupling between the auditory cortex and the amygdala induces musical emotion: a single case study.

Music is a sound structure of remarkable acoustical and temporal complexity. Although it cannot denote specific meaning, it is one of the most potent and universal stimuli for inducing mood. How the auditory and limbic systems interact, and whether this interaction is lateralized when feeling emotions related to music, remains unclear. We studied the functional correlation between the auditory cortex (AC) and amygdala (AMY) through intracerebral recordings from both hemispheres in a single patient while she listened attentively to musical excerpts, which we compared to passive listening of a sequence of pure tones. While the left primary and secondary auditory cortices (PAC and SAC) showed larger increases in gamma-band responses than the right side, only the right side showed emotion-modulated gamma oscillatory activity. An intra- and inter-hemisphere correlation was observed between the auditory areas and AMY during the delivery of a sequence of pure tones. In contrast, a strikingly right-lateralized functional network between the AC and the AMY was observed to be related to the musical excerpts the patient experienced as happy, sad and peaceful. Interestingly, excerpts experienced as angry, which the patient disliked, were associated with widespread de-correlation between all the structures. These results suggest that the right auditory-limbic interactions result from the formation of oscillatory networks that bind the activities of the network nodes into coherence patterns, resulting in the emergence of a feeling.

Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition.

Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal resolution of functional brain studies. However, this method usually suffers from poor EEG quality, especially for evoked potentials (ERPs), due to specific artifacts. As such, the use of EEG-informed fMRI analysis in the context of cognitive studies has particularly focused on optimizing narrow ERP time windows of interest, which ignores the rich diverse temporal information of the EEG signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural cascade occurring during face recognition in 14 healthy volunteers by using the successive ERP peaks recorded during the cognitive part of this process. N170, N400 and P600 peaks, commonly associated with face recognition, were successfully and reproducibly identified for each trial and each subject by using a group independent component analysis (ICA). For the first time we use this group ICA to extract several independent components (IC) corresponding to the sequence of activation and used single-trial peaks as modulation parameters in a general linear model (GLM) of fMRI data. We obtained an occipital-temporal-frontal stream of BOLD signal modulation, in accordance with the three successive IC-ERPs providing an unprecedented spatio-temporal characterization of the whole cognitive process as defined by BOLD signal modulation. By using this approach, the pattern of EEG-informed BOLD modulation provided improved characterization of the network involved than the fMRI-only analysis or the source reconstruction of the three ERPs; the latter techniques showing only two regions in common localized in the occipital lobe.

How familiarization and repetition modulate the picture naming network.

A common strategy to reveal the components of the speech production network is to use psycholinguistic manipulations previously tested in behavioral protocols. This often disregards how implementation aspects that are nonessential for interpreting behavior may affect the neural response. We compared the electrophysiological (EEG) signature of two popular picture naming protocols involving either unfamiliar pictures without repetitions or repeated familiar pictures. We observed significant semantic interference effects in behavior but not in the EEG, contrary to some previous findings. Remarkably, the two protocols elicited clearly distinct EEG responses. These were not due to naming latency differences nor did they reflect a homogeneous modulation of amplitude over the trial time-window. The effect of protocol is attributed to the familiarization induced by the first encounter with the materials. Picture naming processes can be substantially modulated by specific protocol requirements controlled by familiarity and, to a much lesser degree, the repetition of materials.

Simultaneous recording of MEG, EEG and intracerebral EEG during visual stimulation: from feasibility to single-trial analysis.

Electroencephalography (EEG), magnetoencephalography (MEG), and intracerebral stereotaxic EEG (SEEG) are the three neurophysiological recording techniques, which are thought to capture the same type of brain activity. Still, the relationships between non-invasive (EEG, MEG) and invasive (SEEG) signals remain to be further investigated. In early attempts at comparing SEEG with either EEG or MEG, the recordings were performed separately for each modality. However such an approach presents substantial limitations in terms of signal analysis. The goal of this technical note is to investigate the feasibility of simultaneously recording these three signal modalities (EEG, MEG and SEEG), and to provide strategies for analyzing this new kind of data. Intracerebral electrodes were implanted in a patient with intractable epilepsy for presurgical evaluation purposes. This patient was presented with a visual stimulation paradigm while the three types of signals were simultaneously recorded. The analysis started with a characterization of the MEG artifact caused by the SEEG equipment. Next, the average evoked activities were computed at the sensor level, and cortical source activations were estimated for both the EEG and MEG recordings; these were shown to be compatible with the spatiotemporal dynamics of the SEEG signals. In the average time-frequency domain, concordant patterns between the MEG/EEG and SEEG recordings were found below the 40 Hz level. Finally, a fine-grained coupling between the amplitudes of the three recording modalities was detected in the time domain, at the level of single evoked responses. Importantly, these correlations have shown a high level of spatial and temporal specificity. These findings provide a case for the ability of trimodal recordings (EEG, MEG, and SEEG) to reach a greater level of specificity in the investigation of brain signals and functions.

Action monitoring and medial frontal cortex: leading role of supplementary motor area.

The capacity to evaluate the outcomes of our actions is fundamental for adapting and optimizing behavior and depends on an action-monitoring system that assesses ongoing actions and detects errors. The neuronal network underlying this executive function, classically attributed to the rostral cingulate zone, is poorly characterized in humans, owing to the limited number of direct neurophysiological data. Using intracerebral recordings, we show that the leading role is played by the supplementary motor area (SMA), which rapidly evaluates successful and erroneous actions. The rostral part of medial prefrontal cortex, driven by the SMA, was activated later and exclusively in the case of errors. This suggests a hierarchical organization of the different frontal regions involved in implementation of action monitoring and error processing.