Single neuron responses underlying face recognition in the human midfusiform face-selective cortex.

Faces are critical for social interactions and their recognition constitutes one of the most important and challenging functions of the human brain. While neurons responding selectively to faces have been recorded for decades in the monkey brain, face-selective neural activations have been reported with neuroimaging primarily in the human midfusiform gyrus. Yet, the cellular mechanisms producing selective responses to faces in this hominoid neuroanatomical structure remain unknown. Here we report single neuron recordings performed in 5 human subjects (1 male, 4 females) implanted with intracerebral microelectrodes in the face-selective midfusiform gyrus, while they viewed pictures of familiar and unknown faces and places. We observed similar responses to faces and places at the single cell level, but a significantly higher number of neurons responding to faces, thus offering a mechanistic account for the face-selective activations observed in this region. Although individual neurons did not respond preferentially to familiar faces, a population level analysis could consistently determine whether or not the faces (but not the places) were familiar, only about 50 ms after the initial recognition of the stimuli as faces. These results provide insights into the neural mechanisms of face processing in the human brain.

A Bayesian approach for simultaneous spike/LFP separation and spike sorting.

Objective.The aim of this paper is to present a novel method for simultaneous spike waveforms extraction and sorting from the raw recorded signal. The objective is twofold: on the one hand, to enhance spike sorting performance by extracting the spike waveforms of each spike and, on the other hand, to improve the analysis of the multi-scale relationships between spikes and local field potentials (LFP) by offering an accurate separation of these two components constitutive of the raw micro recordings.Approach.The method, based on a Bayesian approach, is fully automated and provides a mean spike shape for each cluster, but also an estimate for each singular spike waveform, as well as the LFP signal cleaned of spiking activity.Main results.The performance of the algorithm is evaluated on simulated and real data, for which both the clustering and spike removal aspects are analyzed. Clustering performance significantly increases when compared to state-of-the-art methods, taking benefit from the separation of the spikes from the LFP handled by our model. Our method also performs better in removing the spikes from the LFP when compared to previously proposed methodologies, especially in the high frequency bands. The method is finally applied on real data (ClinicalTrials.gov Identifier: NCT02877576) and confirm the results obtained on benchmark signals.Significance.By separating more efficiently the spikes from the LFP background, our method allows both a better spike sorting and a more accurate estimate of the LFP, facilitating further analysis such as spike-LFP relationships.

Intracerebral Correlates of Scalp EEG Ictal Discharges Based on Simultaneous Stereo-EEG Recordings.

BACKGROUND AND OBJECTIVES: It remains unknown to what extent ictal scalp EEG can accurately predict the localization of the intracerebral seizure onset in presurgical evaluation of drug-resistant epilepsies. In this study, we aimed to define homogeneous ictal scalp EEG profiles (based on their first ictal abnormality) and assess their localizing value using simultaneously recorded scalp EEG and stereo-EEG. METHODS: We retrospectively included consecutive patients with drug-resistant focal epilepsy who had simultaneous stereo-EEG and scalp EEG recordings of at least 1 seizure in the epileptology unit in Nancy, France. We analyzed 1 seizure per patient and used hierarchical cluster analysis to group similar seizure profiles on scalp EEG and then performed a descriptive analysis of their intracerebral correlates. RESULTS: We enrolled 129 patients in this study. The hierarchical cluster analysis showed 6 profiles on scalp EEG first modification. None were specific to a single intracerebral localization. The "normal EEG" and "blurred EEG" clusters (early muscle artifacts) comprised only 5 patients each and corresponded to no preferential intracerebral localization. The "temporal discharge" cluster (n = 46) was characterized by theta or delta discharges on ipsilateral anterior temporal scalp electrodes and corresponded to a preferential mesial temporal intracerebral localization. The "posterior discharge" cluster (n = 42) was characterized by posterior ipsilateral or contralateral rhythmic alpha discharges or slow waves on scalp and corresponded to a preferential temporal localization. However, this profile was the statistically most frequent scalp EEG correlate of occipital and parietal seizures. The "diffuse suppression" cluster (n = 9) was characterized by a bilateral and diffuse background activity suppression on scalp and corresponded to mesial, and particularly insulo-opercular, localization. Finally, the "frontal discharge" cluster (n = 22) was characterized by bilateral frontal rhythmic fast activity or preictal spike on scalp and corresponded to preferential ventrodorsal frontal intracerebral localizations. DISCUSSION: The hierarchical cluster analysis identified 6 seizure profiles regarding the first abnormality on scalp EEG. None of them were specific of a single intracerebral localization. Nevertheless, the strong relationships between the "temporal," "frontal," "diffuse suppression," and "posterior" profiles and intracerebral discharge localizations may contribute to hierarchize hypotheses derived from ictal scalp EEG analysis regarding intracerebral seizure onset.

Extracting the Invisible: Mesial Temporal Source Detection in Simultaneous EEG and SEEG Recordings.

Epileptic source detection relies mainly on visual expertise of scalp EEG signals, but it is recognised that epileptic discharges can escape to this expertise due to a deep localization of the brain sources that induce a very low, even negative, signal to noise ratio. In this methodological study, we aimed to investigate the feasibility of extracting deep mesial temporal sources that were invisible in scalp EEG signals using blind source separation (BSS) methods (infomax ICA, extended infomax ICA, and JADE) combined with a statistical measure (kurtosis). We estimated the effect of different methodological and physiological parameters that could alter or improve the extraction. Using nine well-defined mesial epileptic networks (1949 spikes) obtained from seven patients and simultaneous EEG-SEEG recordings, the first independent component extracted from the scalp EEG signals was validated in mean from 46 to 80% according to the different parameters. The three BSS methods equally performed (no significant difference) and no influence of the number of scalp electrodes used was found. At the opposite, the number and amplitude of spikes included in the averaging before the extraction modified the performance. Anyway, despite their invisibility in scalp EEG signals, this study demonstrates that deep source extraction is feasible under certain conditions and with the use of common signal analysis toolboxes. This finding confirms the crucial need to continue the signal analysis of scalp EEG recordings which contains subcortical signals that escape to expert visual analysis but could be found by signal processing.

Transcranial Electrical Stimulation generates electric fields in deep human brain structures.

BACKGROUND: Transcranial electrical stimulation (TES) efficiency is related to the electric field (EF) magnitude delivered on the target. Very few studies (n = 4) have estimated the in-vivo intracerebral electric fields in humans. They have relied mainly on electrocorticographic recordings, which require a craniotomy impacting EF distribution, and did not investigate deep brain structures. OBJECTIVE: To measure the electric field in deep brain structures during TES in humans in-vivo. Additionally, to investigate the effects of TES frequencies, intensities, and montages on the intracerebral EF. METHODS: Simultaneous bipolar transcranial alternating current stimulation and intracerebral recordings (SEEG) were performed in 8 drug-resistant epileptic patients. TES was applied using small high-definition (HD) electrodes. Seven frequencies, two intensities and 15 montages were applied on one, six and one patients, respectively. RESULTS: At 1 mA intensity, we found mean EF magnitudes of 0.21, 0.17 and 0.07 V·m-1 in the amygdala, hippocampus, and cingulate gyrus, respectively. An average of 0.14 ± 0.07 V·m-1 was measured in these deep brain structures. Mean EF magnitudes in these structures at 1Hz were 11% higher than at 300Hz (+0.03 V·m-1). The EF was correlated with the TES intensities. The TES montages that yielded the maximum EF in the amygdalae were T7-T8 and in the cingulate gyri were C3-FT10 and T7-C4. CONCLUSION: TES at low intensities and with small HD electrodes can generate an EF in deep brain structures, irrespective of stimulation frequency. EF magnitude is correlated to the stimulation intensity and depends upon the stimulation montage.

Respective Contribution of Ictal and Inter-ictal Electrical Source Imaging to Epileptogenic Zone Localization.

Interictal electrical source imaging (ESI) encompasses a risk of false localization due to complex relationships between irritative and epileptogenic networks. This study aimed to compare the localizing value of ESI derived from ictal and inter-ictal EEG discharges and to evaluate the localizing value of ESI according to three different subgroups: MRI lesion, presumed etiology and morphology of ictal EEG pattern. We prospectively analyzed 54 of 78 enrolled patients undergoing pre-surgical investigation for refractory epilepsy. Ictal and inter-ictal ESI results were interpreted blinded to- and subsequently compared with stereoelectroencephalography as a reference method. Anatomical concordance was assessed at a sub-lobar level. Sensitivity and specificity of ictal, inter-ictal and ictal plus inter-ictal ESI were calculated and compared according to the different subgroups. Inter-ictal and ictal ESI sensitivity (84% and 75% respectively) and specificity (38% and 50% respectively) were not statistically different. Regarding the sensitivity, ictal ESI was never higher than inter-ictal ESI. Regarding the specificity, ictal ESI was higher than inter-ictal ESI in malformations of cortical development (MCD) (60% vs. 43%) and in MRI positive patients (49% vs. 30%). Within the ictal ESI analysis, we showed a higher specificity for ictal spikes (59%) and rhythmic discharges > 13 Hz (50%) than rhythmic discharges < 13 Hz (37%) and (ii) for MCD (60%) than in other etiologies (29%). This prospective study demonstrates the relevance of a combined interpretation of distinct inter-ictal and ictal analysis. Inter-ictal analysis gave the highest sensitivity. Ictal analysis gave the highest specificity especially in patients with MCD or a lesion on MRI.

Fast periodic visual stimulation to highlight the relationship between human intracerebral recordings and scalp electroencephalography.

Despite being of primary importance for fundamental research and clinical studies, the relationship between local neural population activity and scalp electroencephalography (EEG) in humans remains largely unknown. Here we report simultaneous scalp and intracerebral EEG responses to face stimuli in a unique epileptic patient implanted with 27 intracerebral recording contacts in the right occipitotemporal cortex. The patient was shown images of faces appearing at a frequency of 6 Hz, which elicits neural responses at this exact frequency. Response quantification at this frequency allowed to objectively relate the neural activity measured inside and outside the brain. The patient exhibited typical 6 Hz responses on the scalp at the right occipitotemporal sites. Moreover, there was a clear spatial correspondence between these scalp responses and intracerebral signals in the right lateral inferior occipital gyrus, both in amplitude and in phase. Nevertheless, the signal measured on the scalp and inside the brain at nearby locations showed a 10-fold difference in amplitude due to electrical insulation from the head. To further quantify the relationship between the scalp and intracerebral recordings, we used an approach correlating time-varying signals at the stimulation frequency across scalp and intracerebral channels. This analysis revealed a focused and right-lateralized correspondence between the scalp and intracerebral recordings that were specific to the face stimulation is more broadly distributed in various control situations. These results demonstrate the interest of a frequency tagging approach in characterizing the electrical propagation from brain sources to scalp EEG sensors and in identifying the cortical sources of brain functions from these recordings.

A unified weighted minimum norm solution for the reference inverse problem in EEG.

A well known problem in EEG recordings deals with the unknown potential of the reference electrode. In the last years several authors presented comparisons among the most popular solutions, the global conclusion being that the traditional Average Reference (AR) and the Reference Standardization Technique (REST) are the best approximations (Nunez, 2010; Kayser and Tenke, 2010; Liu et al., 2015; Chella et al., 2016). In this work we do not aim to further compare these techniques but to support the fact that both solutions can be derived from a general inverse problem formalism for reference estimation (Hu et al., 2019; Hu et al., 2018; Salido-Ruiz et al., 2011). Using the alternative approach of least squares, our findings are consistent with the theoretical findings in Hu et al. (2019) and Hu et al. (2018) showing that the AR is the minimum norm solution, while REST is a weighted minimum norm including some approximate propagation model. AR is thus a particular case of REST, which itself uses a particular formulation of the source estimation inverse problem. With a different derivation, we provide the additional powerful evidences to reinforce the cited findings.

The inferior occipital gyrus is a major cortical source of the face-evoked N170: Evidence from simultaneous scalp and intracerebral human recordings.

The sudden onset of a face image leads to a prominent face-selective response in human scalp electroencephalographic (EEG) recordings, peaking 170 ms after stimulus onset at occipito-temporal (OT) scalp sites: the N170 (or M170 in magnetoencephalography). According to a widely held view, the main cortical source of the N170 lies in the fusiform gyrus (FG), whereas the posteriorly located inferior occipital gyrus (IOG) would rather generate earlier face-selective responses. Here, we report neural responses to upright and inverted faces recorded in a unique patient using multicontact intracerebral electrodes implanted in the right IOG and in the OT sulcus above the right lateral FG (LFG). Simultaneous EEG recordings on the scalp identified the N170 over the right OT scalp region. The latency and amplitude of this scalp N170 were correlated at the single-trial level with the N170 recorded in the lateral IOG, close to the scalp lateral occipital surface. In addition, a positive component maximal around the latency of the N170 (a P170) was prominent above the internal LFG, whereas this region typically generates an N170 (or "N200") over its external/ventral surface. This suggests that electrophysiological responses in the LFG manifest as an equivalent dipole oriented mostly along the vertical axis with likely minimal projection to the lateral OT scalp region. Altogether, these observations provide evidence that the IOG is a major cortical generator of the face-selective scalp N170, qualifying the potential contribution of the FG and questioning a strict serial spatiotemporal organization of the human cortical face network.

sEEG is a Safe Procedure for a Comprehensive Anatomic Exploration of the Insula: A Retrospective Study of 108 Procedures Representing 254 Transopercular Insular Electrodes.

BACKGROUND: The exploration of the insula in pre-surgical evaluation of epilepsy is considered to be associated with a high vascular risk resulting in an incomplete exploration of the insular cortex. OBJECTIVE: To report a retrospective observational study of insular exploration using stereoelectroencephalography (sEEG) with transopercular and parasagittal oblique intracerebral electrodes from January 2008 to January 2016. The first purpose of this study was to evaluate the surgical risks of insular cortex sEEG exploration. The second purpose was to define the ability of placing intracerebral contacts in the whole insular cortex. METHODS: Ninety-nine patients underwent 108 magnetic resonance imaging (MRI)-guided stereotactic implantations of intracerebral electrodes in the context of preoperative assessment of drug-resistant epilepsy, including at least 1 electrode placed in the insular cortex. On postoperative computed tomography images co-registered with MRI, followed by MRI segmentation and application of a transformation matrix, intracerebral contact coordinates of the insular electrodes' contacts were anatomically localized in the Talairach space. Finally, dispersion and clustering analysis was performed. RESULTS: There was no morbidity, in particular hemorrhagic complications, or mortality related to insular electrodes. Statistical comparison of intracerebral contact positions demonstrated that whole insula exploration is possible on the left and right sides. In addition, the clustering analysis showed the homogeneous distribution of the electrodes within the insular cortex. CONCLUSION: In the presurgical evaluation of drug-resistant epilepsy, the insular cortex can be explored safely and comprehensively using transopercular sEEG electrodes. Parasagittal oblique trajectories may also be associated to achieve an optimal exploration.

Localizing value of electrical source imaging: Frontal lobe, malformations of cortical development and negative MRI related epilepsies are the best candidates.

OBJECTIVE: We aimed to prospectively assess the anatomical concordance of electric source localizations of interictal discharges with the epileptogenic zone (EZ) estimated by stereo-electroencephalography (SEEG) according to different subgroups: the type of epilepsy, the presence of a structural MRI lesion, the aetiology and the depth of the EZ. METHODS: In a prospective multicentric observational study, we enrolled 85 consecutive patients undergoing pre-surgical SEEG investigation for focal drug-resistant epilepsy. Electric source imaging (ESI) was performed before SEEG. Source localizations were obtained from dipolar and distributed source methods. Anatomical concordance between ESI and EZ was defined according to 36 predefined sublobar regions. ESI was interpreted blinded to- and subsequently compared with SEEG estimated EZ. RESULTS: 74 patients were finally analyzed. 38 patients had temporal and 36 extra-temporal lobe epilepsy. MRI was positive in 52. 41 patients had malformation of cortical development (MCD), 33 had another or an unknown aetiology. EZ was medial in 27, lateral in 13, and medio-lateral in 34. In the overall cohort, ESI completely or partly localized the EZ in 85%: full concordance in 13 cases and partial concordance in 50 cases. The rate of ESI full concordance with EZ was significantly higher in (i) frontal lobe epilepsy (46%; p = 0.05), (ii) cases of negative MRI (36%; p = 0.01) and (iii) MCD (27%; p = 0.03). The rate of ESI full concordance with EZ was not statistically different according to the depth of the EZ. SIGNIFICANCE: We prospectively demonstrated that ESI more accurately estimated the EZ in subgroups of patients who are often the most difficult cases in epilepsy surgery: frontal lobe epilepsy, negative MRI and the presence of MCD.

Discrimination of a medial functional module within the temporal lobe using an effective connectivity model: A CCEP study.

The temporal lobe is classically divided in two functional systems: the ventral visual pathway and the medial temporal memory system. However, their functional separation has been challenged by studies suggesting that the medial temporal lobe could be best understood as an extension of the hierarchically organized ventral visual pathway. Our purpose was to investigate (i) whether cerebral regions within the temporal lobe could be grouped into distinct functional assemblies, and (ii) which regions were central within these functional assemblies. We studied low intensity and low frequency electrical stimulations (0.5 mA, 1 Hz, 4 ms) performed during sixteen pre-surgical intracerebral EEG investigations in patients with medically intractable temporal or temporo-occipital lobe epilepsies. Eleven regions of interest were delineated per anatomical landmarks such as gyri and sulci. Effective connectivity based on electrophysiological feature (amplitude) of cortico-cortical evoked potentials (CCEPs) was evaluated and subjected to graph metrics. The amplitudes discriminated one medial module where the hippocampus could act as a signal amplifier. Mean amplitudes of CCEPs in regions of the temporal lobe showed a generalized Pareto distribution of probability suggesting neural synchronies to be self-organized critically. Our description of effective interactions within the temporal lobe provides a regional electrophysiological model of effective connectivity which is discussed in the context of the current hypothesis of pattern completion.

The standardized EEG electrode array of the IFCN.

Standardized EEG electrode positions are essential for both clinical applications and research. The aim of this guideline is to update and expand the unifying nomenclature and standardized positioning for EEG scalp electrodes. Electrode positions were based on 20% and 10% of standardized measurements from anatomical landmarks on the skull. However, standard recordings do not cover the anterior and basal temporal lobes, which is the most frequent source of epileptogenic activity. Here, we propose a basic array of 25 electrodes including the inferior temporal chain, which should be used for all standard clinical recordings. The nomenclature in the basic array is consistent with the 10-10-system. High-density scalp EEG arrays (64-256 electrodes) allow source imaging with even sub-lobar precision. This supplementary exam should be requested whenever necessary, e.g. search for epileptogenic activity in negative standard EEG or for presurgical evaluation. In the near future, nomenclature for high density electrodes arrays beyond the 10-10 system needs to be defined, to allow comparison and standardized recordings across centers. Contrary to the established belief that smaller heads needs less electrodes, in young children at least as many electrodes as in adults should be applied due to smaller skull thickness and the risk of spatial aliasing.

Stereo-electroencephalography identifies N2 sleep and spindles in human hippocampus.

OBJECTIVES: To describe the hippocampal stereo-electroencephalogram during sleep according to sleep stages (including N2 sleep) and cycles, together with the hippocampal spindles. METHODS: All patients with drug-resistant focal epilepsy undergoing intra-hippocampal implantation between August 2012 and June 2013 at Nancy University Hospital were screened. Six patients with explored hippocampus devoid of pathological features were analyzed. During one night, we identified continuous periods of successive N2, N3 and REM sleep for two full cycles. We performed a spectral analysis of the hippocampal signal for each labeled sleep period. RESULTS: N2, N3 and REM sleeps were individualized according to their spectral powers, for each frequency band and sleep cycle. Hippocampal spindles showed dynamic intrinsic properties, the 11.5-16Hz frequency band being mainly dominant, whereas the 9-11.5Hz frequency band heightening during the beginning and the end of the transient. For N3 and REM sleep stages, the power of the hippocampal signal was significantly decreased between the first and the second sleep cycle. CONCLUSION: Distinct N2 sleep, fast spindles and homeostatic profile are all common properties shared by hippocampus and cortex during sleep. SIGNIFICANCE: The close functional link between hippocampus and cortex may have various sleep-related substrates.

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation.

To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation.

In-vivo measurements of human brain tissue conductivity using focal electrical current injection through intracerebral multicontact electrodes.

In-vivo measurements of human brain tissue conductivity at body temperature were conducted using focal electrical currents injected through intracerebral multicontact electrodes. A total of 1,421 measurements in 15 epileptic patients (age: 28 ± 10) using a radiofrequency generator (50 kHz current injection) were analyzed. Each contact pair was classified as being from healthy (gray matter, n = 696; white matter, n = 530) or pathological (epileptogenic zone, n = 195) tissue using neuroimaging analysis of the local tissue environment and intracerebral EEG recordings. Brain tissue conductivities were obtained using numerical simulations based on conductivity estimates that accounted for the current flow in the local brain volume around the contact pairs (a cube with a side length of 13 mm). Conductivity values were 0.26 S/m for gray matter and 0.17 S/m for white matter. Healthy gray and white matter had statistically different median impedances (P < 0.0001). White matter conductivity was found to be homogeneous as normality tests did not find evidence of multiple subgroups. Gray matter had lower conductivity in healthy tissue than in the epileptogenic zone (0.26 vs. 0.29 S/m; P = 0.012), even when the epileptogenic zone was not visible in the magnetic resonance image (MRI) (P = 0.005). The present in-vivo conductivity values could serve to create more accurate volume conduction models and could help to refine the identification of relevant intracerebral contacts, especially when located within the epileptogenic zone of an MRI-invisible lesion. Hum Brain Mapp 38:974-986, 2017. © 2016 Wiley Periodicals, Inc.

Correlation of invasive EEG and scalp EEG.

Ever since the implementation of invasive EEG recordings in the clinical setting, it has been perceived that a considerable proportion of epileptic discharges present at a cortical level are missed by routine scalp EEG recordings. Several in vitro, in vivo, and simulation studies have been performed in the past decades aiming to clarify the interrelations of cortical sources with their scalp and invasive EEG correlates. The amplitude ratio of cortical potentials to their scalp EEG correlates, the extent of the cortical area involved in the discharge, as well as the localization of the cortical source and its geometry have been each independently linked to the recording of the cortical discharge with scalp electrodes. The need to elucidate these interrelations has been particularly imperative in the field of epilepsy surgery with its rapidly growing EEG-based localization technologies. Simultaneous multiscale EEG recordings with scalp, subdural and/or depth electrodes, applied in presurgical epilepsy workup, offer an excellent opportunity to shed some light to this fundamental issue. Whereas past studies have considered predominantly neocortical sources in the context of temporal lobe epilepsy, current investigations have included deep sources, as in mesial temporal epilepsy, as well as extratemporal sources. Novel computational tools may serve to provide surrogates for the shortcomings of EEG recording methodology and facilitate further developments in modern electrophysiology.