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We report the case of a patient with nonlesional, pharmacoresistant epilepsy. Bilateral synchronous discharges as well as focal discharges were identified on electroencephalogram (EEG). After non-invasive and invasive presurgical evaluation, a probable epileptogenic zone was identified with concordant results of focal origin involvement of the left temporal pole. Resective epilepsy surgery provided seizure freedom (last follow-up at 12 months). The case nicely illustrates that bilateral synchronous discharges or/and a lack of lesions on neuroimaging are not contraindications to presurgical evaluation of epilepsy, which on the contrary should be offered to all patients with pharmacoresistant epilepsy. The case also illustrates the importance of combining electrophysiological, imaging, and neuropsychological information to guide intracranial EEG placement and improve postsurgical outcome.

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

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.

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.

The scientific literature suggests that emotional memories benefit from a privileged consolidation over neutral memories. This effect extends to consolidation processes that occur during sleep. Indeed, during sleep, a complex set of oscillations (namely slow-oscillations, theta rhythm and spindles) mediates the communication between brain regions involved in the long-term integration of memories. However, whether sleep oscillations may contribute to the reactivation and consolidation of emotional memories in humans is still unclear. Because non-invasive electroencephalography (EEG) has limited access to deep brain regions implicated in memory and emotion (e.g., hippocampus, amygdala, orbitofrontal cortex), here we recorded EEG signal from these brain regions using intracranial electrodes placed in medically-resistant epileptic patients in the context of presurgical investigation. During wakefulness, we presented the patients with emotional (i.e., humorous) vs emotionally neutral pictures paired with a sound. Then, we tested for the reinstatement of emotional-associations by delivering the sound during a subsequent period of sleep. We found that the reactivation of emotional (compared to neutral) memories during sleep enhanced slow-oscillation and spindle activity in the orbitofrontal cortex, paralleled with an increase in theta connectivity between the hippocampus and the orbitofrontal cortex.In addition, we observed that the theta response to emotional memories reactivated at subsequent wake was different than for neutral memories, suggesting a change in memory traces with targeted memory reactivation. These data suggest that consolidation of emotional events during sleep is due to a larger expression of sleep features (in the slow-oscillation, theta and sigma frequency bands) and that the mechanisms of brain plasticity also take place in emotional brain regions during NREM sleep.

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.

Objective: In patients with epilepsy, interictal epileptic discharges are a diag-nostic 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 epi-leptic 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 under-went intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the ex-istence 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 oscil-lations 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 neu-ronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodu-lation strategies aiming at disrupting proepileptic mechanisms.

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.

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.

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.

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.

In patients with medically refractory focal epilepsy who are candidates for epilepsy surgery, concordant non-invasive neuroimaging data are useful to guide invasive electroencephalographic recordings or surgical resection. Simultaneous electroencephalography and functional magnetic resonance imaging recordings can reveal regions of haemodynamic fluctuations related to epileptic activity and help localize its generators. However, many of these studies (40-70%) remain inconclusive, principally due to the absence of interictal epileptiform discharges during simultaneous recordings, or lack of haemodynamic changes correlated to interictal epileptiform discharges. We investigated whether the presence of epilepsy-specific voltage maps on scalp electroencephalography correlated with haemodynamic changes and could help localize the epileptic focus. In 23 patients with focal epilepsy, we built epilepsy-specific electroencephalographic voltage maps using averaged interictal epileptiform discharges recorded during long-term clinical monitoring outside the scanner and computed the correlation of this map with the electroencephalographic recordings in the scanner for each time frame. The time course of this correlation coefficient was used as a regressor for functional magnetic resonance imaging analysis to map haemodynamic changes related to these epilepsy-specific maps (topography-related haemodynamic changes). The method was first validated in five patients with significant haemodynamic changes correlated to interictal epileptiform discharges on conventional analysis. We then applied the method to 18 patients who had inconclusive simultaneous electroencephalography and functional magnetic resonance imaging studies due to the absence of interictal epileptiform discharges or absence of significant correlated haemodynamic changes. The concordance of the results with subsequent intracranial electroencephalography and/or resection area in patients who were seizure free after surgery was assessed. In the validation group, haemodynamic changes correlated to voltage maps were similar to those obtained with conventional analysis in 5/5 patients. In 14/18 patients (78%) with previously inconclusive studies, scalp maps related to epileptic activity had haemodynamic correlates even when no interictal epileptiform discharges were detected during simultaneous recordings. Haemodynamic changes correlated to voltage maps were spatially concordant with intracranial electroencephalography or with the resection area. We found better concordance in patients with lateral temporal and extratemporal neocortical epilepsy compared to medial/polar temporal lobe epilepsy, probably due to the fact that electroencephalographic voltage maps specific to lateral temporal and extratemporal epileptic activity are more dissimilar to maps of physiological activity. Our approach significantly increases the yield of simultaneous electroencephalography and functional magnetic resonance imaging to localize the epileptic focus non-invasively, allowing better targeting for surgical resection or implantation of intracranial electrode arrays.

Recent research has shown that heartbeat-evoked potentials (HEPs), brain activity in response to heartbeats, are a useful neural measure for investigating the functional role of brain-body interactions in cognitive processes including self-consciousness. In 2 experiments, using intracranial electroencephalography (EEG), we investigated (1) the neural sources of HEPs, (2) the underlying mechanisms for HEP generation, and (3) the functional role of HEPs in bodily self-consciousness. In Experiment-1, we found that shortly after the heartbeat onset, phase distributions across single trials were significantly concentrated in 10% of the recording sites, mainly in the insula and the operculum, but also in other regions including the amygdala and fronto-temporal cortex. Such phase concentration was not accompanied by increased spectral power, and did not correlate with spectral power changes, suggesting that a phase resetting, rather than an additive "evoked potential" mechanism, underlies HEP generation. In Experiment-2, we further aimed to anatomically refine previous scalp EEG data that linked HEPs with bodily self-consciousness. We found that HEP modulations in the insula reflected an experimentally induced altered sense of self-identification. Collectively, these results provide novel and solid electrophysiological evidence on the neural sources and underlying mechanisms of HEPs, and their functional role in self-consciousness.

Resection of abnormal brain tissue lying near the sensorimotor cortex entails precise localization of the central sulcus. Mapping of this area is achieved by applying invasive direct cortical electrical stimulation. However, noninvasive methods, particularly functional magnetic resonance imaging (fMRI), are also used. As a supplement to fMRI, localization of somatosensory-evoked potentials (SEPs) recorded with an electroencephalogram (EEG) has been proposed, but has not found its place in clinical practice.To assess localization accuracy of the hand somatosensory cortex with SEP source imaging.We applied electrical source imaging in 49 subjects, recorded with high-density EEG (256 channels). We compared it with fMRI in 18 participants and with direct cortical electrical stimulation in 6 epileptic patients.Comparison of SEP source imaging with fMRI indicated differences of 3 to 8 mm, with the exception of the mesial-distal orientation, where variances of up to 20 mm were found. This discrepancy is explained by the fact that the source maximum of the first SEP peak is localized deep in the central sulcus (area 3b), where information initially arrives. Conversely, fMRI showed maximal signal change on the lateral surface of the postcentral gyrus (area 1), where sensory information is integrated later in time. Electrical source imaging and fMRI showed mean Euclidean distances of 13 and 14 mm, respectively, from the contacts where electrocorticography elicited sensory phenomena of the contralateral upper limb.SEP source imaging, based on high-density EEG, reliably identifies the depth of the central sulcus. Moreover, it is a simple, flexible, and relatively inexpensive alternative to fMRI.

Summary Purpose Patients with tuberous sclerosis complex (TSC) often suffer from medically refractory epilepsy. Despite the multifocality of the disease, resection of the most epileptogenic tuber can lead to major improvement of seizure control. Therefore, non-invasive imaging methods are needed for detecting epileptogenic sources. We assessed the utility of electric source imaging (ESI) in the presurgical work-up of TSC patients and its combination with Positron Emission Tomography (PET) and ictal/interictal Single Photon Emission Computed Tomography (SISCOM). Methods Thirteen patients underwent high density ESI (8/13) and/or low density ESI (13/13). We investigated the concordance between ESI, PET, SISCOM and the resection area in the 11 operated patients (nine seizure-free). Results High resolution ESI was partially or completely concordant with the resected area in 5/5 seizure free patients. Low resolution ESI was partially or completely concordant in 7/9 seizure free patients. PET and SPECT were concordant (partially or completely) in 8/9 and 6/9 cases, respectively. We found multifocal ESI sources in 2/9 seizure free patients, marked multifocal PET hypometabolism in 3/9 and multifocal SISCOM in 4/9. The region of concordant ESI and PET accurately predicted the dominant epileptogenic source in 6/9 patients. The same was true for concordant ESI and SISCOM in 4/9 patients, whereas the coregistration of only PET and SISCOM was insufficient in 3/9 successfully operated cases. The combination of all three imaging modalities could successfully identify the resection area in all but one patient with a favorable post-operation outcome. Conclusion ESI is an important tool for the pre-surgical evaluation of TSC patients. It complements PET and SPECT results and can improve the management of candidates for surgery when integrated with electro-clinical information.

Complex auditory hallucinations are often characterized by hearing voices and are then called auditory verbal hallucinations (AVHs). While AVHs have been extensively investigated in psychiatric patients suffering from schizophrenia, reports from neurological patients are rare and, in most cases, incomplete. Here, we characterize AVHs in 9 patients suffering from pharmacoresistant epilepsy by analyzing the phenomenology of AVHs and patients' neuropsychological and lesion profiles. From a cohort of 352 consecutively examined patients with epilepsy, 9 patients suffering AVHs were identified and studied by means of a semistructured interview, neuropsychological tests, and multimodal imaging, relying on a combination of functional and structural neuroimaging data and surface and intracranial EEG. We found that AVHs in patients with epilepsy were associated with prevalent language deficits and damage to posterior language areas and basal language areas in the left temporal cortex. Auditory verbal hallucinations, most of the times, consisted in hearing a single voice of the same gender and language as the patient and had specific spatial features, being, most of the times, perceived in the external space, contralateral to the lesion. We argue that the consistent location of AVHs in the contralesional external space, the prominence of associated language deficits, and the prevalence of lesions to the posterior temporal language areas characterize AVHs of neurological origin, distinguishing them from those of psychiatric origin.

Objective It remains controversial whether interictal spikes are a surrogate of the seizure onset zone (SOZ). Electric source imaging (ESI) is an increasingly validated non-invasive approach for localising the epileptogenic focus in patients with drug-resistant epilepsy undergoing evaluation for surgery, using high-density scalp EEG and advanced source localisation algorithms that include the patient9s own MRI. Here we investigate whether localisation of interictal spikes by ESI provides valuable information on the SOZ. Methods In 38 patients with focal epilepsy who later underwent intracranial EEG monitoring, we performed ESI of interictal spikes recorded with 128–256-channel EEG. We measured the distance between the ESI maximum and the nearest intracranial electrodes in the SOZ and irritative zone (IZ, the source of interictal spikes). The resection of the region harbouring the ESI maximum was correlated to surgical outcome. Results The median distance from the ESI maximum to the nearest electrode involved in the SOZ was 17 mm (IQR 8–27). The IZ and SOZ colocalised in most patients (median distance 0 mm, IQR 0–14), supporting the notion that localising interictal spikes is a valid surrogate for the SOZ. There was no difference in accuracy among patients with temporal or extratemporal epilepsy. In the 32 patients who underwent resective surgery, including the ESI maximum in the resection correlated with favourable outcome (p=0.03). Conclusions Localisation of interictal spikes provides an excellent estimate of the SOZ in the majority of patients. ESI should be taken into account for the management of patients undergoing intracranial recordings.

Electrical source imaging (ESI) aims at reconstructing the electrical brain activity from scalp EEG. When applied to interictal epileptiform discharges (IEDs), this technique is of great use for identifying the irritative zone in focal epilepsies. Inaccuracies in the modeling of electro-magnetic field propagation in the head (forward model) may strongly influence ESI and lead to mislocalization of IED generators. However, a systematic study on the influence of the selected head model on the localization precision of IED in a large number of patients with known focus localization has not yet been performed. We here present such a performance evaluation of different head models in a dataset of 38 epileptic patients who have undergone high-density scalp EEG, intracranial EEG and, for the majority, subsequent surgery. We compared ESI accuracy resulting from three head models: a Locally Spherical Model with Anatomical Constraints (LSMAC), a Boundary Element Model (BEM) and a Finite Element Model (FEM). All of them were computed from the individual MRI of the patient and ESI was performed on averaged IED. We found that all head models provided very similar source locations. In patients having a positive post-operative outcome, at least 74% of the source maxima were within the resection. The median distance from the source maximum to the nearest intracranial electrode showing IED was 13.2, 15.6 and 15.6 mm for LSMAC, BEM and FEM, respectively. The study demonstrates that in clinical applications, the use of highly sophisticated and difficult to implement head models is not a crucial factor for an accurate ESI., Highlights • Electrical source imaging was performed on 38 patients with refractory epilepsy. • Three different realistic head models were used: LSMAC, BEM and FEM. • We found accurate and generally similar source localization for all head models. • FEM is less robust to MRI segmentation inaccuracies. • There is no need for highly sophisticated head models in clinical applications.

Pre-operative assessment and surgical management of patients with non-lesional extratemporal epilepsy remain challenging due to a lack of precise localisation of the epileptic zone. In most cases, invasive recording with depth or subdural electrodes is required. Here, we describe the case of 6.5-year-old girl who underwent comprehensive non-invasive phase I video-EEG investigation for drug-resistant epilepsy, including electric source and nuclear imaging. Left operculo-insular epilepsy was diagnosed. Post-operatively, she developed aphasia which resolved within one year, corroborating the notion of enhanced language plasticity in children. The patient remained seizure-free for more than three years.

PurposeTo study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location.MethodsEight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction.ResultsThe distances between active electrode location and estimated ictal onset zone were 11±4.3 or 9.1±2.3mm for patients with a >50% or 50% seizure frequency reduction, 100% had the active contacts located 3mm to the subiculum.ConclusionDecrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.

Functional magnetic resonance imaging (fMRI) has become part of routine brain mapping in patients with epilepsy or tumor undergoing resective surgery. However, robust localization of crucial functional areas is required.To establish a simple, short fMRI task that reliably localizes crucial language areas in individual patients who undergo respective surgery.fMRI was measured during an 8-minute auditory semantic decision task in 28 healthy controls and 35 consecutive patients who had focal epilepsy or a brain tumor. Nineteen underwent resective surgery. Group and individual analyses were performed. Results in patients were compared with postsurgical language outcome and electrocortical stimulation when available.fMRI activations concordant with the anterior and posterior language areas were found in 96% and 89% of the controls, respectively. The anterior and posterior language areas were both activated in 93% of the patients. These results were concordant with electrocortical stimulation results in 5 patients. Transient postsurgical language deficits were found in 2 patients in whom surgery was performed in the vicinity of the fMRI activations or who had postsurgical complications implicating areas of fMRI activations.The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects. It appears to be a valuable complementary tool for surgical planning of epileptogenic foci and of brain tumors.

The main model of visual processing in primates proposes an anatomo-functional distinction between the dorsal stream, specialized in spatio-temporal information, and the ventral stream, processing essentially form information. However, these two pathways also communicate to share much visual information. These dorso-ventral interactions have been studied using form-from-motion (FfM) stimuli, revealing that FfM perception first activates dorsal regions (e.g., MT+/V5), followed by successive activations of ventral regions (e.g., LOC). However, relatively little is known about the implications of focal brain damage of visual areas on these dorso-ventral interactions. In the present case report, we investigated the dynamics of dorsal and ventral activations related to FfM perception (using topographical ERP analysis and electrical source imaging) in a patient suffering from a deficit in FfM perception due to right extrastriate brain damage in the ventral stream. Despite the patient's FfM impairment, both successful (observed for the highest level of FfM signal) and absent/failed FfM perception evoked the same temporal sequence of three processing states observed previously in healthy subjects. During the first period, brain source localization revealed cortical activations along the dorsal stream, currently associated with preserved elementary motion processing. During the latter two periods, the patterns of activity differed from normal subjects: activations were observed in the ventral stream (as reported for normal subjects), but also in the dorsal pathway, with the strongest and most sustained activity localized in the parieto-occipital regions. On the other hand, absent/failed FfM perception was characterized by weaker brain activity, restricted to the more lateral regions. This study shows that in the present case report, successful FfM perception, while following the same temporal sequence of processing steps as in normal subjects, evoked different patterns of brain activity. By revealing a brain circuit involving the most rostral part of the dorsal pathway, this study provides further support for neuro-imaging studies and brain lesion investigations that have suggested the existence of different brain circuits associated with different profiles of interaction between the dorsal and the ventral streams.

Changes in brain activity characterizing impaired speech production after brain damage have usually been investigated by comparing aphasic speakers with healthy subjects because prestroke data are normally not available. However, when interpreting the results of studies of stroke patients versus healthy controls, there is an inherent difficulty in disentangling the contribution of neuropathology from other sources of between-subject variability. In the present work, we had an unusual opportunity to study an aphasic patient with severe anomia who had incidentally performed a picture naming task in an ERP study as a control subject one year before suffering a left hemisphere stroke. The fortuitous recording of this patient's brain activity before his stroke allows direct comparison of his pre- and poststroke brain activity in the same language production task. The subject did not differ from other healthy subjects before his stroke, but presented major electrophysiological differences after stroke, both in comparison to himself before stroke and to the control group. ERP changes consistently appeared after stroke in a specific time window starting about 250 msec after picture onset, characterized by a single divergent but stable topographic configuration of the scalp electric field associated with a cortical generator abnormally limited to left temporal posterior perilesional areas. The patient's pattern of anomia revealed a severe lexical–phonological impairment and his ERP responses diverged from those of healthy controls in the time window that has previously been associated with lexical–phonological processes during picture naming. Given that his prestroke ERPs were indistinguishable from those of healthy controls, it seems highly likely that the change in his poststroke ERPs is due to changes in language production processes as a consequence of stroke. The patient's neurolinguistic deficits, combined with the ERPs results, provide unique evidence for the role of left temporal cortex in lexical–phonological processing from about 250 to 450 msec during word production.

Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission-computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (

We recorded intracranial local field potentials from structurally intact human visual cortex during several face processing tasks in a patient before brain surgery. Intracranial local field potentials were measured from subdural electrodes implanted in a right fusiform region with face-sensitive activity and a more medial location in posterior parahippocampal gyrus with house-selective activity. This electrode implantation allowed us to compare neural responses with different facial properties within two adjacent but functionally distinct cortical regions. Five experiments were conducted to determine the temporal dynamics of perceptual (Experiments 1 and 5), emotional (Experiments 2 and 3), and social (Experiment 4) effects on face-specific responses in the right fusiform. Our findings showed an early negative deflection (N200) that primarily reflected category-selective perceptual encoding of facial information, whereas higher order effects of face individuation, emotional expression, and gaze direction produced selective modulations in the same face-specific region during a later time period (from 200 to 1000 msec after onset). These results shed new lights on the time course of face recognition mechanisms in human visual cortex and reveal for the first time anatomically overlapping but temporally distinct influences of identity or emotional/social factors on face processing in right fusiform gyrus, which presumably reflect top–down feedback effects from distant brain areas.

PURPOSE: Patients with magnetic resonance (MR)-negative focal epilepsy (MRN-E) have less favorable surgical outcomes (between 40% and 70%) compared to those in whom an MRI lesion guides the site of surgical intervention (60-90%). Patients with extratemporal MRN-E have the worst outcome (around 50% chance of seizure freedom). We studied whether electroencephalography (EEG) source imaging (ESI) of interictal epileptic activity can contribute to the identification of the epileptic focus in patients with normal MRI. METHODS: We carried out ESI in 10 operated patients with nonlesional MRI and a postsurgical follow-up of at least 1 year. Five of the 10 patients had extratemporal lobe epilepsy. Evaluation comprised surface and intracranial EEG monitoring of ictal and interictal events, structural MRI, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), ictal and interictal perfusion single photon emission computed tomography (SPECT) scans. Eight of the 10 patients also underwent intracranial monitoring. RESULTS: ESI correctly localized the epileptic focus within the resection margins in 8 of 10 patients, 9 of whom experienced favorable postsurgical outcomes. DISCUSSION: The results highlight the diagnostic value of ESI and encourage broadening its application to patients with MRN-E. If the surface EEG contains fairly localized spikes, ESI contributes to the presurgical decision process.

To screen for patients at risk for memory decline after temporal lobe epilepsy (TLE) surgery, selective amobarbital procedures, such as injection into the anterior choroidal artery (ACA-IAT), are sometimes used. We investigated the extent of the territory affected during ACA-IAT and its predictive value with respect to postoperative memory. Seventeen patients with TLE underwent ACA-IAT. In 9 of 17 patients, intraarterial SPECT co-registrated to MRI allowed delineation of amobarbital-perfused structures. Another subgroup of 9 of 17 patients underwent anterior temporal lobectomy. Verbal memory was tested pre- and postoperatively and during ACA-IAT. Major variations in the ACA-IAT perfusion pattern occurred and were not correlated with the verbal memory scores during ACA-IAT. Postoperatively, no patient experienced a severe verbal memory decline, but individual postoperative performance was not correlated with results during ACA-IAT. Our study suggests that ACA-IAT can be used to screen for severe postoperative amnesia in inconclusive cases, but cannot predict individual outcome, even when the perfusion pattern is taken into account.

SummaryIn patients with pharmacologically intractable epilepsy who are not eligible for surgery, deep brain stimulation is currently under evaluation as an alternative treatment. Optimal stimulation parameters, including high (HFS) versus low frequency (LFS) stimulation, are not well defined. Here, we report the effects of HFS (130 pulses per second, pps) and LFS (5pps) of the principal epileptogenic focus, in three patients with non-lesional temporal lobe epilepsy. HFS, but not LFS, was associated with a reduction of the interictal discharges and absence of seizures. HFS may be beneficial in patients with non-lesional temporal lobe epilepsy who are not surgical candidates.

The exquisite sensitivity of the human visual system to form-from-motion (FfM) cues is well documented. However, identifying the neural correlates of this sensitivity has proven difficult, particularly determining the respective contributions of different motion areas in extrastriate visual cortex. Here we measured visual FfM perception and more elementary visual motion (VM) perception in a group of 32 patients suffering from acute posterior brain damage, and performed MRI-based lesion analysis. Our results suggest that severe FfM perception deficits without an associated deficit of VM perception are due to damage to ventral occipito-temporal cortex (VOT), whereas associated deficits of FfM and VM perception are due to damage either in proximity to area MT+/V5 or an area including lateral occipital complex (LOC) and VOT. These data suggest the existence of at least three functionally and anatomically distinct regions in human visual cortex that process FfM signals.

Purpose: In patients with pharmacoresistant focal epilepsy, resection of the epileptic focus can lead to freedom from seizures or significant improvement in well-selected candidates. Localization of the epileptic focus with multimodal concordance is crucial for a good postoperative outcome. Beyond the detection of epileptogenic lesions on structural MRI and focal hypometabolism on FDG PET, EEG-based Electric Source Imaging (ESI) and simultaneous EEG and functional MRI (EEG-fMRI) are increasingly applied for mapping epileptic activity. We here report presurgical multimodal interictal imaging using a hybrid PET/MR scanner for single-session FDG PET, MRI, EEG-fMRI and ESI. Methods: This quadrimodal imaging procedure was performed in a single session in 12 patients using a high-density (256 electrodes) MR-compatible EEG system and a hybrid PET/MR scanner. EEG was used to exclude subclinical seizures during uptake of the PET tracer, to compute ESI on interictal epileptiform discharges and to guide fMRI analysis for mapping haemodynamic changes correlated with interictal epileptiform activity. Results: The whole multimodal recording was performed in less than 2hours with good patient comfort and data quality. Clinically contributory examinations with at least two modalities were obtained in nine patients and with all modalities in five patients. Conclusion: This single-session quadrimodal imaging procedure provided reliable and contributory interictal clinical data. This procedure avoids multiple scanning sessions and is associated with less radiation exposure than PET-CT. Moreover, it guarantees the same medication level and medical condition for all modalities. The procedure improves workflow and could reduce the duration and cost of presurgical epilepsy evaluations.

Objective: Electroencephalography (EEG) is an important tool for studying the temporal dynamics of the human brain's large-scale neuronal circuits. However, most EEG applications fail to capitalize on all of the data's available information, particularly that concerning the location of active sources in the brain. Localizing the sources of a given scalp measurement is only achieved by solving the so-called inverse problem. By introducing reasonable a priori constraints, the inverse problem can be solved and the most probable sources in the brain at every moment in time can be accurately localized. Methods and Results: Here, we review the different EEG source localization procedures applied during the last two decades. Additionally, we detail the importance of those procedures preceding and following source estimation that are intimately linked to a successful, reliable result. We discuss (1) the number and positioning of electrodes, (2) the varieties of inverse solution models and algorithms, (3) the integration of EEG source estimations with MRI data, (4) the integration of time and frequency in source imaging, and (5) the statistical analysis of inverse solution results. Conclusions and Significance: We show that modern EEG source imaging simultaneously details the temporal and spatial dimensions of brain activity, making it an important and affordable tool to study the properties of cerebral, neural networks in cognitive and clinical neurosciences.

The relationship between interictal epileptiform activity and the epileptogenic zone is complex. Despite the fact that intraspike propagation may occur, the peak of the spike is often used as indicator of the site of ictal onset. In this investigation, spatio-temporal segmentation was used to demonstrate this intraspike propagation and to determine at which time point the voltage pattern corresponded best to the epileptogenic zone. Sixteen patients with focal epilepsy were recorded with 125-channel EEG. Between one and five different map topographies were identified during the rising phase of the spike. A distributed source model (EPIFOCUS) was used to localize the source of each map, and the distance from the EPIFOCUS maximum to the anatomic lesion was calculated. In only 3 of 16 cases was the entire rising phase of the spike accounted for by one single map. In another five patients, several maps were obtained, although all were located within the epileptogenic lesion. In the remaining eight patients, however, parts of the rising phase had locations outside the epileptogenic lesion. On the average, 80% of the rising time had within lesion locations the most reliable time period being halfway between onset and peak. The results illustrate that intraspike propagation has to be considered in source localizations, and they also illustrate the usefulness of spatio-temporal segmentation for visualizing this propagation.

Motion blindness (MB) is defined as the selective disturbance of visual motion perception despite intact perception of other features of the visual scene. MB is characterized by a pandirectional deficit of motion direction discrimination and is assumed to result from damage to the visual motion pathway, especially area MT/V5. However, the most characteristic feature of primate MT/V5 neurons is not their motion selectivity but their preference for one direction of motion (direction selectivity), which changes incrementally at neighbouring columns. In addition to this microscopic directional organization, studies in nonhuman and human primates suggest that single directions of motion are also coded at a more macroscopic level. We thus hypothesized that if MB in humans results from damage to direction-selective neurons in the visual motion pathway, posterior brain damage might cause MB which is direction selective, not pandirectional. The present study investigated motion direction discrimination in patients with posterior unilateral brain damage and determined separate psychophysical thresholds for the four cardinal directions. In addition, we analysed whether the direction of erroneous motion perception (i.e. the perception of right motion for upward motion) was random or showed a directional bias. We report three principal findings. First, motion direction discrimination was severely impaired in one or two directions while it was normal in the other directions. This constituted direction-selective MB. Second, MB was characterized not only by a quantitative direction-selective increase in psychophysical thresholds but also by a qualitative impairment of perceiving motion direction systematically in wrong directions. Both findings suggest that the cortical modules specialized for the perception of a single direction of motion might be larger than previously thought. Third, lesion analysis showed that unilateral damage, not only the human homologue of MT/V5 but also to parieto-occipital cortex, leads to MB.