Yield of non-invasive imaging in MRI-negative focal epilepsy.

OBJECTIVE: The absence of MRI-lesion reduces considerably the probability of having an excellent outcome (International League Against Epilepsies [ILAE] class I-II) after epilepsy surgery. Surgical success in magnetic-resonance imaging (MRI)-negative cases relies therefore mainly on non-invasive techniques such as positron-emission tomography (PET), subtraction ictal/inter-ictal single-photon-emission-computed-tomography co-registered to MRI (SISCOM), electric source imaging (ESI) and morphometric MRI analysis (MAP). We were interested in identifying the optimal imaging technique or combination to achieve post-operative class I-II in patients with MRI-negative focal epilepsy. METHODS: We identified 168 epileptic patients without MRI lesion. Thirty-three (19.6%) were diagnosed with unifocal epilepsy, underwent surgical resection and follow-up ⩾ 2 years. Sensitivity, specificity, predictive values, and diagnostic odds ratio (OR) were calculated for each technique individually and in combination (after co-registration). RESULTS: 23/33 (70%) were free of disabling seizures (75.0% with temporal and 61.5% extratemporal lobe epilepsy). None of the individual modalities presented an OR > 1.5, except ESI if only patients with interictal epileptiform discharges (IEDs) were considered (OR 3.2). On a dual combination, SISCOM with ESI presented the highest outcome (OR = 6). MAP contributed to detecting indistinguishable focal cortical dysplasia in particular in extratemporal epilepsies with a sensitivity of 75%. Concordance of PET, ESI on interictal epileptic discharges, and SISCOM was associated with the highest chance for post-operative seizure control (OR = 11). CONCLUSION: If MRI is negative, the chances to benefit from epilepsy surgery are almost as high as in lesional epilepsy, provided that multiple established non-invasive imaging tools are rigorously applied and co-registered together.

Implantation and reimplantation of intracranial EEG electrodes in patients considering epilepsy surgery.

In patients with drug-resistant epilepsy who are considering surgery, intracranial EEG (iEEG) helps delineate the putative epileptogenic zone. In a minority of patients, iEEG fails to identify seizure onsets. In such cases, it might be worthwhile to reimplant more iEEG electrodes. The consequences of such a strategy for the patient are unknown. We matched 12 patients in whom the initially implanted iEEG electrodes did not delineate the seizure onset zone precisely enough to offer resective surgery, and in whom additional iEEG electrodes were implanted during the same inpatient stay, to controls who did not undergo reimplantation. Seven cases and eight controls proceeded to resective surgery. No intracranial infection occurred. One control suffered an intracranial hemorrhage. Three cases and two controls suffered from a post-operative neurological or neuropsychological deficit. We found no difference in post-operative seizure control between cases and controls. Compared to an ILAE score of 5 (ie, stable seizure frequency in the absence of resective surgery), cases showed significant improvement. Reimplantation of iEEG electrodes can offer the possibility of resective epilepsy surgery to patients in whom the initial iEEG investigation was inconclusive, without compromising on the risk of complications or seizure control.

Asymmetry of sleep electrophysiological markers in patients with focal epilepsy.

Sleep can modulate epileptic activities, but our knowledge of sleep perturbation by epilepsy remains sparse. Interestingly, epilepsy and sleep both present with defining electrophysiological features in the form of specific graphoelements on EEG. This raises the possibility to identify, within ongoing EEG activity, how epilepsy impacts and disrupts sleep. Here, we asked whether the presence of a lateralized epileptic focus interferes with the expression of the dominant electrophysiological hallmarks of sleep: slow oscillations, slow waves and spindles. To this aim, we conducted a cross-sectional study and analysed sleep recordings with surface EEG from 69 patients with focal epilepsy (age range at EEG: 17-61 years, 29 females, 34 left focal epilepsy). Comparing patients with left and right focal epilepsy, we assessed inter-hemispheric asymmetry of sleep slow oscillations power (delta range, 0.5-4 Hz); sleep slow wave density; amplitude, duration and slope; and spindle density, amplitude, duration as well as locking to slow oscillations. We found significantly different asymmetries in slow oscillation power (P < 0.01); slow wave amplitude (P < 0.05) and slope (P < 0.01); and spindle density (P < 0.0001) and amplitude (P < 0.05). To confirm that these population-based differences reflect actual patient-by-patient differences, we then tested whether asymmetry of sleep features can classify laterality of the epileptic focus using a decision tree and a 5-fold cross-validation. We show that classification accuracy is above chance level (accuracy of 65%, standard deviation: 5%) and significantly outperforms a classification based on a randomization of epileptic lateralization (randomization data accuracy: 50%, standard deviation 7%, unpaired t-test, P < 0.0001). Importantly, we show that classification of epileptic lateralization by the canonical epileptic biomarker, i.e. interictal epileptiform discharges, improves slightly but significantly when combined with electrophysiological hallmarks of physiological sleep (from 75% to 77%, P < 0.0001, one-way ANOVA + Sidak's multiple comparisons test). Together, we establish that epilepsy is associated with inter-hemispheric perturbation of sleep-related activities and provide an in-depth multi-dimensional profile of the main sleep electrophysiological signatures in a large cohort of patients with focal epilepsy. We provide converging evidence that the underlying epileptic process interacts with the expression of sleep markers, in addition to triggering well-known pathological activities, such as interictal epileptiform discharges.

Prestimulus amygdala spectral activity is associated with visual face awareness.

Alpha cortical oscillations have been proposed to suppress sensory processing in the visual, auditory, and tactile domains, influencing conscious stimulus perception. However, it is unknown whether oscillatory neural activity in the amygdala, a subcortical structure involved in salience detection, has a similar impact on stimulus awareness. Recording intracranial electroencephalography (EEG) from 9 human amygdalae during face detection in a continuous flash suppression task, we found increased spectral prestimulus power and phase coherence, with most consistent effects in the alpha band, when faces were undetected relative to detected, similarly as previously observed in cortex with this task using scalp-EEG. Moreover, selective decreases in the alpha and gamma bands preceded face detection, with individual prestimulus alpha power correlating negatively with detection rate in patients. These findings reveal for the first time that prestimulus subcortical oscillations localized in human amygdala may contribute to perceptual gating mechanisms governing subsequent face detection and offer promising insights on the role of this structure in visual awareness.

Semiautomatic interictal electric source localization based on long-term electroencephalographic monitoring: A prospective study.

OBJECTIVE: Electric source imaging (ESI) of interictal epileptiform discharges (IEDs) has shown significant yield in numerous studies; however, its implementation at most centers is labor- and cost-intensive. Semiautomatic ESI analysis (SAEA) has been proposed as an alternative and has previously shown benefit. Computer-assisted automatic spike cluster retrieval, averaging, and source localization are carried out for each cluster and are then reviewed by an expert neurophysiologist, to determine their relevance for the individual case. Here, we examine its yield in a prospective single center study. METHOD: Between 2017 and 2022, 122 patients underwent SAEA. Inclusion criteria for the current study were unifocal epilepsy disorder, epilepsy surgery with curative purpose, and postoperative follow-up of 2 years or more. All patients (N=40) had continuous video-electroencephalographic (EEG) monitoring with 37 scalp electrodes, which underwent SAEA. Forty patients matched our inclusion criteria. RESULTS: Twenty patients required intracranial monitoring; 13 were magnetic resonance imaging (MRI)-negative. Mean duration of analyzed EEG was 4.3 days (±3.1 days), containing a mean of 12 749 detected IEDs (±22 324). The sensitivity, specificity, and accuracy of SAEA for localizing the epileptogenic focus of the entire group were 74.3%, 80%, and 75%, respectively, leading to an odds ratio (OR) of 11.5 to become seizure-free if the source was included in the resection volume (p < .05). In patients with extratemporal lobe epilepsy, our results indicated an accuracy of 68% (OR=11.7). For MRI-negative patients (n = 13) and patients requiring intracranial EEG (n = 20), we found a similarly high accuracy of 84.6% (OR=19) and 75% (OR = 15.9), respectively. SIGNIFICANCE: In this prospective study of SAEA of long-term video-EEG, spanning several days, we found excellent localizing information and a high yield, even in difficult patient groups. This compares favorably to high-density ESI, most likely due to marked improved signal-to-noise ratio of the averaged IEDs. We propose including ESI, or SAEA, in the workup of all patients who are referred for epilepsy surgery.

High density electric source imaging in childhood-onset epilepsy due to focal cortical dysplasia.

Objective: The goal of this study was to investigate the diagnostic utility of electric source imaging (ESI) in the presurgical evaluation of children with focal cortical dysplasia (FCD) and to compare it with other imaging techniques. Methods: Twenty patients with epilepsy onset before 18 years, surgically treated focal epilepsy with a minimal follow-up of 2 years, and histologically proven FCD were retrospectively selected. All patients underwent MRI, positron emission tomography (PET), and 16 patients also had ictal single-photon emission computed tomography (iSPECT). ESI, using EEG with 64 electrodes or more (HD-ESI), was performed in all 20 patients. We determined sensitivity, specificity and accuracy of ESI, and compared its yield to that of other imaging techniques. Results: Twelve patients were seizure-free post-operatively (60%). Among all patients, highest localization accuracy (80%) was obtained with ESI, followed by PET and iSPECT (75%). When results from ESI and SPECT were concordant 100% of patients achieved Engel I outcome. If ESI and PET showed concordant localization, 90% of patients achieved postoperative seizure freedom. Conclusions: Our findings demonstrate that HD-ESI allows accurate localization of the epileptogenic zone in patients with FCD. Significance: In combination with other imaging modalities, ESI helps with planning a more accurate surgery and therefore, the chances of postoperative seizure control are higher. Since it is based on EEG recordings, it does not require sedation, which is particularly interesting in pediatric patients. ESI represents an important imaging tool in focal epilepsies due to cortical dysplasia, which might be difficult to detect on standard imaging.

Increased delta power as a scalp marker of epileptic activity: a simultaneous scalp and intracranial electroencephalography study.

BACKGROUND AND PURPOSE: The purpose was to evaluate whether intracranial interictal epileptiform discharges (IEDs) that are not visible on the scalp are associated with changes in the frequency spectrum on scalp electroencephalograms (EEGs). METHODS: Simultaneous scalp high-density EEG and intracranial EEG recordings were recorded in nine patients undergoing pre-surgical invasive recordings for pharmaco-resistant temporal lobe epilepsy. Epochs with hippocampal IED visible on intracranial EEG (ic-IED) but not on scalp EEG were selected, as well as control epochs without ic-IED. Welch's power spectral density was computed for each scalp electrode and for each subject; the power spectral density was further averaged across the canonical frequency bands and compared between the two conditions with and without ic-IED. For each patient the peak frequency in the delta band (the significantly strongest frequency band in all patients) was determined during periods of ic-IED. The five electrodes showing strongest power at the peak frequency were also determined. RESULTS: It was found that intracranial IEDs are associated with an increase in delta power on scalp EEGs, in particular at a frequency ≥1.4 Hz. Electrodes showing slow frequency power changes associated with IEDs were consistent with the hemispheric lateralization of IEDs. Electrodes with maximum power of slow activity were not limited to temporal regions but also involved frontal (bilateral or unilateral) regions. CONCLUSIONS: In patients with a clinical picture suggestive of temporal lobe epilepsy, the presence of delta slowing ≥1.4 Hz in anterior temporal regions can represent a scalp marker of hippocampal IEDs. To our best knowledge this is the first study that demonstrates the co-occurrence of ic-IED and increased delta power.

Insular Stimulation Produces Mental Clarity and Bliss.

For the first time, an ecstatic aura has been evoked through the electrical stimulation of the dorsal anterior insula during presurgical invasive intracerebral monitoring in a patient who did not suffer from an ecstatic form of epilepsy. This case provides more evidence that the anterior insula is the major generator of such a mystical-type experience even in individuals with no underlying brain network changes related to a preexisting ecstatic epilepsy. ANN NEUROL 2022;91:289-292.

Automated interictal source localisation based on high-density EEG.

PURPOSE: To study the accuracy of automated interictal EEG source localisation based on high-density EEG, and to compare it to low-density EEG. METHODS: Thirty patients operated for pharmacoresistant focal epilepsy were retrospectively examined. Twelve months after resective brain surgery, 18 were seizure-free or had 'auras' only, while 12 had persistence of disabling seizures. Presurgical 257-channel EEG lasting 3-20 h was down-sampled to 25, 40, and 204 channels for separate analyses. For each electrode setup, interictal spikes were detected, clustered, and averaged automatically before validation by an expert reviewer. An individual 6-layer finite difference head model and the standardised low-resolution electromagnetic tomography were used to localise the maximum source activity of the most prevalent spike. Sublobar concordance with the resected brain area was visually assessed and related to favourable vs. unfavourable postsurgical outcome. RESULTS: Depending on the EEG setup, epileptic spikes were detected in 21-24 patients (70-80%). The median number of single spikes per average was 470 (range 17-15,066). Diagnostic sensitivity of EEG source localisation was 58-75%, specificity was 50-67%, and overall accuracy was 55-71%. There were no significant differences between low- and high-density EEG setups with 25 to 257 electrodes. CONCLUSION: Automated high-density EEG source localisation provides meaningful information in the majority of cases. With hundreds of single spikes averaged, diagnostic accuracy is similar in high- and low-density EEG. Therefore, low-density EEG may be sufficient for interictal EEG source localisation if high numbers of spikes are available.

Extracting seizure onset from surface EEG with independent component analysis: Insights from simultaneous scalp and intracerebral EEG.

The success of stereoelectroencephalographic (SEEG) investigations depends crucially on the hypotheses on the putative location of the seizure onset zone. This information is derived from non-invasive data either based on visual analysis or advanced source localization algorithms. While source localization applied to interictal spikes recorded on scalp is the classical method, it does not provide unequivocal information regarding the seizure onset zone. Raw ictal activity contains a mixture of signals originating from several regions of the brain as well as EMG artifacts, hampering direct input to the source localization algorithms. We therefore introduce a methodology that disentangles the various sources contributing to the scalp ictal activity using independent component analysis and uses equivalent current dipole localization as putative locus of ictal sources. We validated the results of our analysis pipeline by performing long-term simultaneous scalp - intracerebral (SEEG) recordings in 14 patients and analyzing the wavelet coherence between the independent component encoding the ictal discharge and the SEEG signals in 8 patients passing the inclusion criteria. Our results show that invasively recorded ictal onset patterns, including low-voltage fast activity, can be captured by the independent component analysis of scalp EEG. The visibility of the ictal activity strongly depends on the depth of the sources. The equivalent current dipole localization can point to the seizure onset zone (SOZ) with an accuracy that can be as high as 10 mm for superficially located sources, that gradually decreases for deeper seizure generators, averaging at 47 mm in the 8 analyzed patients. Independent component analysis is therefore shown to have a promising SOZ localizing value, indicating whether the seizure onset zone is neocortical, and its approximate location, or located in mesial structures. That may contribute to a better crafting of the hypotheses used as basis of the stereo-EEG implantations.

Slow oscillations open susceptible time windows for epileptic discharges.

OBJECTIVE: In patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so-called "irritative" activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression. METHODS: We used multisite intracortical recordings from patients who underwent intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the existence of proepileptogenic windows before interictal epileptic discharges. We tested whether the amplitude and phase synchronization of slow oscillations (.5-4 Hz and 4-7 Hz) increase before epileptic discharges and whether the latter are phase-locked to slow oscillations. Then, we tested whether the phase-locking of neuronal activity (assessed by high-gamma activity, 60-160 Hz) to slow oscillations increases before epileptic discharges to provide a potential mechanism linking slow oscillations to interictal activities. RESULTS: Changes in widespread slow oscillations anticipate upcoming epileptic discharges. The network extends beyond the irritative zone, but the increase in amplitude and phase synchronization is rather specific to the irritative zone. In contrast, epileptic discharges are phase-locked to widespread slow oscillations and the degree of phase-locking tends to be higher outside the irritative zone. Then, within the irritative zone only, we observe an increased coupling between slow oscillations and neuronal discharges before epileptic discharges. SIGNIFICANCE: Our results show that epileptic discharges occur during vulnerable time windows set up by a specific phase of slow oscillations. The specificity of these permissive windows is further reinforced by the increased coupling of neuronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodulation strategies aiming at disrupting proepileptic mechanisms.

High-density Electric Source Imaging of interictal epileptic discharges: How many electrodes and which time point?

OBJECTIVE: To assess the value of caudal EEG electrodes over cheeks and neck for high-density electric source imaging (ESI) in presurgical epilepsy evaluation, and to identify the best time point during averaged interictal epileptic discharges (IEDs) for optimal ESI accuracy. METHODS: We retrospectively examined presurgical 257-channel EEG recordings of 45 patients with pharmacoresistant focal epilepsy. By stepwise removal of cheek and neck electrodes, averaged IEDs were downsampled to 219, 204, and 156 EEG channels. Additionally, ESI at the IED's half-rise was compared to other time points. The respective sources of maximum activity were compared to the resected brain area and postsurgical outcome. RESULTS: Caudal channels had disproportionately more artefacts. In 30 patients with favourable outcome, the 204-channel array yielded the most accurate results with ESI maxima < 10 mm from the resection in 67% and inside affected sublobes in 83%. Neither in temporal nor in extratemporal cases did the full 257-channel setup improve ESI accuracy. ESI was most accurate at 50% of the IED's rising phase. CONCLUSION: Information from cheeks and neck electrodes did not improve high-density ESI accuracy, probably due to higher artefact load and suboptimal biophysical modelling. SIGNIFICANCE: Very caudal EEG electrodes should be used for ESI with caution.

Temporal dynamics of amygdala response to emotion- and action-relevance.

It has been proposed that the human amygdala may not only encode the emotional value of sensory events, but more generally mediate the appraisal of their relevance for the individual's goals, including relevance for action or task-based needs. However, emotional and non-emotional/action-relevance might drive amygdala activity through distinct neural signals, and the relative timing of both kinds of responses remains undetermined. Here, we recorded intracranial event-related potentials from nine amygdalae of patients undergoing epilepsy surgery, while they performed variants of a Go/NoGo task with faces and abstract shapes, where emotion- and action-relevance were orthogonally manipulated. Our results revealed early amygdala responses to emotion facial expressions starting ~ 130 ms after stimulus-onset. Importantly, the amygdala responded to action-relevance not only with face stimuli but also with abstract shapes (squares), and these relevance effects consistently occurred in later time-windows (starting ~ 220 ms) for both faces and squares. A similar dissociation was observed in gamma activity. Furthermore, whereas emotional responses habituated over time, the action-relevance effect increased during the course of the experiment, suggesting progressive learning based on the task needs. Our results support the hypothesis that the human amygdala mediates a broader relevance appraisal function, with the processing of emotion-relevance preceding temporally that of action-relevance.

Visual analysis of high density EEG: As good as electrical source imaging?

OBJECTIVE: In this study, we sought to determine whether visual analysis of high density EEG (HD-EEG) would provide similar localizing information comparable to electrical source imaging (ESI). METHODS: HD-EEG (256 electrodes) recordings from 20 patients suffering from unifocal, drug-resistant epilepsy (13 women, mean age 29.1 ±â€¯2.62 years, 11 with temporal lobe epilepsy) were examined. In the visual analysis condition, we identified the 5 contacts with maximal spike amplitude and determined their localization with respect to the underlying cortex. ESI was computed using the LAURA algorithm of the averaged spikes in the patient's individual MRI. We considered the localization "correct" if all 5 contacts were concordant with the resection volume underneath or if ESI was located within the resection as determined by the postoperative MRI. RESULTS: Twelve patients were postoperatively seizure-free (Engel Class IA), while the remaining eight were in class IB to IV. Visual analysis and ESI showed sensitivity of 58% and 75%, specificity of 75% and 87%, and accuracy of 65% and 80%, respectively. In 70% of cases, visual analysis and ESI provided concordant results. CONCLUSIONS: Localization of the electrodes with maximal spike amplitude provides very good estimation of the localization of the underlying source. However, ESI has a higher accuracy and adds 3D information; therefore, it should remain the tool of choice for presurgical evaluation. SIGNIFICANCE: The present study proposes the possibility to analyze HD-EEG visually, in tandem with ESI or alone, if ESI is not accessible.

Localizing non-epileptiform abnormal brain function in children using high density EEG: Electric Source Imaging of focal slowing.

BACKGROUND: Electric Source Imaging (ESI) of interictal epileptiform discharges (IED) is increasingly validated for localizing epileptic activity. In children, IED can be absent or multifocal even in cases of a focal epileptogenic zone and additional electrophysiological markers are needed. Here, we investigated ESI of pathological focal slowing (FS) recorded on EEG as a new localizing marker in children with drug-resistant epilepsy. METHODS: We selected 15 children (median: 12; range: 4-18yrs), with high-density EEG (hdEEG), presurgical evaluation and surgical resection. One patient had a non-lesional MRI. ESI of patient-specific focal slow activity was performed (distributed linear inverse solution and individual head model). The maximal average power in the band of interest was considered as the source of focal slowing (ESI-FS). The Euclidian distance between ESI-FS and the resection (5 mm margin) was compared to the localization of maximal ESI of interictal epileptiform discharges (ESI-IED), interictal FDG-PET and ictal SPECT/SISCOM. RESULTS: In 9/15 patients (60%), ESI of focal slowing (ESI-FS) was inside or ≤5 mm from resection margins. The remaining 6/15 cases had distances ≤15 mm. In 9/15 patients with interictal spikes, the ESI-IED was concordant with the resection. 6/15 patients with concordant ESI-FS showed also interictal concordant ESI of IED; in 3/15 patients, ESI-FS but not ESI-IED was concordant with the resection. In 10/15 patients, ESI-FS was concordant with MRI lesion and for ESI-IED this concordance was on 8/15 patients. Maximal hypometabolism and SISCOM were concordant with the resection for 7/15 and 7/12, respectively. CONCLUSION: These findings suggest that "non-epileptiform" EEG activity, such as focal slowing, could be a complementary useful marker to localize the epileptogenic zone. ESI-FS may notably be applied in young patients without focal interictal spikes or multifocal spikes. This potential new marker of brain dysfunction has potential applications to other neurological disorders associated with slow EEG activity.

The rough sound of salience enhances aversion through neural synchronisation.

Being able to produce sounds that capture attention and elicit rapid reactions is the prime goal of communication. One strategy, exploited by alarm signals, consists in emitting fast but perceptible amplitude modulations in the roughness range (30-150 Hz). Here, we investigate the perceptual and neural mechanisms underlying aversion to such temporally salient sounds. By measuring subjective aversion to repetitive acoustic transients, we identify a nonlinear pattern of aversion restricted to the roughness range. Using human intracranial recordings, we show that rough sounds do not merely affect local auditory processes but instead synchronise large-scale, supramodal, salience-related networks in a steady-state, sustained manner. Rough sounds synchronise activity throughout superior temporal regions, subcortical and cortical limbic areas, and the frontal cortex, a network classically involved in aversion processing. This pattern correlates with subjective aversion in all these regions, consistent with the hypothesis that roughness enhances auditory aversion through spreading of neural synchronisation.

Human amygdala response to unisensory and multisensory emotion input: No evidence for superadditivity from intracranial recordings.

The amygdala is crucially implicated in processing emotional information from various sensory modalities. However, there is dearth of knowledge concerning the integration and relative time-course of its responses across different channels, i.e., for auditory, visual, and audiovisual input. Functional neuroimaging data in humans point to a possible role of this region in the multimodal integration of emotional signals, but direct evidence for anatomical and temporal overlap of unisensory and multisensory-evoked responses in amygdala is still lacking. We recorded event-related potentials (ERPs) and oscillatory activity from 9 amygdalae using intracranial electroencephalography (iEEG) in patients prior to epilepsy surgery, and compared electrophysiological responses to fearful, happy, or neutral stimuli presented either in voices alone, faces alone, or voices and faces simultaneously delivered. Results showed differential amygdala responses to fearful stimuli, in comparison to neutral, reaching significance 100-200 ms post-onset for auditory, visual and audiovisual stimuli. At later latencies, ∼400 ms post-onset, amygdala response to audiovisual information was also amplified in comparison to auditory or visual stimuli alone. Importantly, however, we found no evidence for either super- or subadditivity effects in any of the bimodal responses. These results suggest, first, that emotion processing in amygdala occurs at globally similar early stages of perceptual processing for auditory, visual, and audiovisual inputs; second, that overall larger responses to multisensory information occur at later stages only; and third, that the underlying mechanisms of this multisensory gain may reflect a purely additive response to concomitant visual and auditory inputs. Our findings provide novel insights on emotion processing across the sensory pathways, and their convergence within the limbic system.

Neurophysiological evidence for early modulation of amygdala activity by emotional reappraisal.

How emotions unfold through time in the brain, and how fast they can be regulated by voluntary control, remain unresolved. Psychological accounts of emotion regulation posit cognitive reappraisal mechanisms may alter early emotion generative processes directly, whereas suppression impacts only later processing stages, after emotion has arisen. However, to date, there is no neurophysiological data concerning the precise latency of emotion regulation effects on the amygdala, a major emotion processing relay in the brain. Here we record amygdala activity from six patients undergoing surgery for pharmaco-resistant epilepsy during both reappraisal and suppression. We find that emotion reappraisal strategy, but not suppression, modulates early neural responses to emotional scenes during an extended period of time, starting 130 ms post-stimulus onset. Further, reappraisal produced earlier impact on amygdala responses to positive compared to negative scenes. Our results provide the first neurophysiological support for theoretical accounts of emotion regulation that postulate an early modulation of emotion generative processes by reappraisal.

Audio-Tactile and Peripersonal Space Processing Around the Trunk in Human Parietal and Temporal Cortex: An Intracranial EEG Study.

Interactions with the environment happen within one's peripersonal space (PPS)-the space surrounding the body. Studies in monkeys and humans have highlighted a multisensory distributed cortical network representing the PPS. However, knowledge about the temporal dynamics of PPS processing around the trunk is lacking. Here, we recorded intracranial electroencephalography (iEEG) in humans while administering tactile stimulation (T), approaching auditory stimuli (A), and the 2 combined (AT). To map PPS, tactile stimulation was delivered when the sound was far, intermediate, or close to the body. The 19% of the electrodes showed AT multisensory integration. Among those, 30% showed a PPS effect, a modulation of the response as a function of the distance between the sound and body. AT multisensory integration and PPS effects had similar spatiotemporal characteristics, with an early response (~50 ms) in the insular cortex, and later responses (~200 ms) in precentral and postcentral gyri. Superior temporal cortex showed a different response pattern with AT multisensory integration at ~100 ms without a PPS effect. These results, represent the first iEEG delineation of PPS processing in humans and show that PPS and multisensory integration happen at similar neural sites and time periods, suggesting that PPS representation is based on a spatial modulation of multisensory integration.

Temporal Dissociation of Neocortical and Hippocampal Contributions to Mental Time Travel Using Intracranial Recordings in Humans.

In mental time travel (MTT) one is "traveling" back-and-forth in time, remembering, and imagining events. Despite intensive research regarding memory processes in the hippocampus, it was only recently shown that the hippocampus plays an essential role in encoding the temporal order of events remembered, and therefore plays an important role in MTT. Does it also encode the temporal relations of these events to the remembering self? We asked patients undergoing pre-surgical evaluation with depth electrodes penetrating the temporal lobes bilaterally toward the hippocampus to project themselves in time to a past, future, or present time-point, and then make judgments regarding various events. Classification analysis of intracranial evoked potentials revealed clear temporal dissociation in the left hemisphere between lateral-temporal electrodes, activated at ~100-300 ms, and hippocampal electrodes, activated at ~400-600 ms. This dissociation may suggest a division of labor in the temporal lobe during self-projection in time, hinting toward the different roles of the lateral-temporal cortex and the hippocampus in MTT and the temporal organization of the related events with respect to the experiencing self.