Jacques Jonas

Intracranial evaluation of the epileptogenic zone in regional infrasylvian polymicrogyria

Purpose:  To define the relationship between the epileptogenic zone and the polymicrogyric area using intracranial electroencephalography (EEG) recordings in patients with structural epilepsy associated with regional infrasylvian polymicrogyria (PMG).

A face-selective ventral occipito-temporal map of the human brain with intracerebral potentials

Significance Understanding the neural basis of face perception, arguably the most important visual function for human social ecology, is of the utmost importance. With an original fast periodic visual stimulation approach, we provide a comprehensive quantification of selective brain responses to faces throughout the ventral visual stream with direct recordings in the gray matter. Selective responses to faces are distributed in the whole ventral occipito-temporal cortex, with a right hemispheric and regional specialization supporting two decades of indirect recordings of human brain activity in neuroimaging. We also disclose three distinct face-selective regions in the anterior temporal lobe, an undersampled region in neuroimaging, and reveal exclusive responses to faces at the neural population level in these regions. Human neuroimaging studies have identified a network of distinct face-selective regions in the ventral occipito-temporal cortex (VOTC), with a right hemispheric dominance. To date, there is no evidence for this hemispheric and regional specialization with direct measures of brain activity. To address this gap in knowledge, we recorded local neurophysiological activity from 1,678 contact electrodes implanted in the VOTC of a large group of epileptic patients (n = 28). They were presented with natural images of objects at a rapid fixed rate (six images per second: 6 Hz), with faces interleaved as every fifth stimulus (i.e., 1.2 Hz). High signal-to-noise ratio face-selective responses were objectively (i.e., exactly at the face stimulation frequency) identified and quantified throughout the whole VOTC. Face-selective responses were widely distributed across the whole VOTC, but also spatially clustered in specific regions. Among these regions, the lateral section of the right middle fusiform gyrus showed the largest face-selective response by far, offering, to our knowledge, the first supporting evidence of two decades of neuroimaging observations with direct neural measures. In addition, three distinct regions with a high proportion of face-selective responses were disclosed in the right ventral anterior temporal lobe, a region that is undersampled in neuroimaging because of magnetic susceptibility artifacts. A high proportion of contacts responding only to faces (i.e., “face-exclusive” responses) were found in these regions, suggesting that they contain populations of neurons involved in dedicated face-processing functions. Overall, these observations provide a comprehensive mapping of visual category selectivity in the whole human VOTC with direct neural measures.

Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex.

Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low‐intensity with depth electrodes implanted in the occipito‐parieto‐temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito‐parieto‐temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Hum Brain Mapp 35:3360–3371, 2014.

Risk factors of postictal generalized EEG suppression in generalized convulsive seizures

Objective: To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). Methods: We reviewed the video-EEG recordings of 417 patients included in the REPO2MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. Results: A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p < 0.001) and lack of early administration of oxygen (p < 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4–801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2–20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2–55.9). Conclusion: The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen.

Direct evidence of nonadherence to antiepileptic medication in refractory focal epilepsy

The adherence to medication in drug‐resistant focal epilepsy (RFE) remains largely unknown. The present work aimed to assess the frequency of recent adherence to antiepileptic drugs (AEDs) in patients with RFE. This prospective observational study screened all patients with RFE, admitted to the Nancy University Hospital between April 2006 and September 2008, for a 5‐day hospitalization without AED tapering. The adherence to AEDs was assessed by measuring serum drug levels on day 1 (reflecting the recent “at home” adherence) and day 5 (reflecting the individual reference concentration when drug ingestion was supervised). A patient was considered nonadherent if at least one of their serum drug levels was different between days 1 and 5. The day‐1 value was considered different from day 5 when it was at least 30% lower (underdosed) or 30% higher (overdosed). Nonadherent patients were classified as under‐consumers in the case of one or more underdosed day‐1 values, over‐consumers in the case of one or more overdosed day‐1 values, or undefined if they exhibited both underdosed and overdosed day‐1 values. Forty‐four of the 48 screened patients were included. Eighteen (40.9%) of 44 patients were nonadherent. Among them, 12 (66.7%) were over‐consumers, 4 (22.2%) were under‐consumers, and 2 (11.1%) were undefined nonadherents. The study indicates that recent adherence to antiepileptic medication in this group of patients with RFE is poor. Overconsumption is the most frequent form of nonadherence in this population and should be specifically assessed to prevent its possible consequences in terms of AEDs dose‐dependent adverse events.

Effect of hyperventilation on seizure activation: potentiation by antiepileptic drug tapering

Objective To determine prospectively the efficacy of hyperventilation (HV) to activate epileptic seizures and the contribution of antiepileptic drug tapering. Methods Eighty patients with proven epilepsy and referred for long-term video-EEG monitoring were consecutively enrolled from November 2007 to December 2008. A seizure was considered as ‘activated’ if it occurred during HV or within 5 min after completion. The rate of activated seizures (number of seizures/h) was compared with the rate of spontaneous seizure. The authors finally compared the effect of HV before and during antiepileptic drug (AED) tapering. Results The authors analysed 247 days of monitoring. Among 52 recorded seizures, 18 were activated by HV. The rate of activated seizure was nine times higher than the rate of control seizures (p=0.001). In the subgroup of patients with no AED tapering, there was no significant activating effect of HV on seizures. In the subgroup undergoing AED tapering, the effect of HV was not significant before (p=0.257) but very significant during AED tapering (p<0.004). Discussion The findings confirm that hyperventilation is efficient to activate epileptic seizures in epileptic patients referred for long-term video-EEG monitoring and that this activating effect is mainly related to the potentiating effect of AED tapering. Repeated HVs combined with AED tapering increase the rate of recorded seizures and the diagnostic yield of daytime video-EEG monitoring.

The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex.

Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage. SIGNIFICANCE STATEMENT Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks.

Self-face hallucination evoked by electrical stimulation of the human brain.

Objectives: Self-face hallucination (autoscopic hallucination or AH) has been reported in patients with widespread brain damage or retrospectively after epileptic seizures. The neural basis and the self-processing operations underlying AH remain unknown. Methods: We report the results of intracerebral electrical stimulations of the right medial occipitoparietal cortex (right precuneus and occipitoparietal sulcus) in 2 patients with epilepsy who underwent a stereo-EEG. Results: Immediately after the onset of the stimulation, the 2 patients reported seeing their current own face, facing themselves, in their left visual field. Conclusions: Our study shows that the medial occipitoparietal junction has a key role in generating AH. This region has been shown to have a central role in various self-processing operations and especially in self-face recognition. Our observations further reveal that this region is involved in a visual representation of our own face, which is generated during the pathologic phenomenon of AH. This visual representation of our own face may be useful for self-face recognition and social cognition processes involving judgment of self-facial resemblance to others.

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.

Distortion of time interval reproduction in an epileptic patient with a focal lesion in the right anterior insular/inferior frontal cortices.

This case report on an epileptic patient suffering from a focal lesion at the junction of the right anterior insular cortex (AIC) and the adjacent inferior frontal cortex (IFC) provides the first evidence that damage to this brain region impairs temporal performance in a visual time reproduction task in which participants had to reproduce the presentation duration (3, 5 and 7s) of emotionally-neutral and -negative pictures. Strikingly, as compared to a group of healthy subjects, the AIC/IFC case considerably overestimated reproduction times despite normal variability. The effect was obtained in all duration and emotion conditions. Such a distortion in time reproduction was not observed in four other epileptic patients without insular or inferior frontal damage. Importantly, the absolute extent of temporal over-reproduction increased in proportion to the magnitude of the target durations, which concurs with the scalar property of interval timing, and points to an impairment of time-specific rather than of non temporal (such as motor) mechanisms. Our data suggest that the disability in temporal reproduction of the AIC/IFC case would result from a distorted memory representation of the encoded duration, occurring during the process of storage and/or of recovery from memory and leading to a deviation of the temporal judgment during the reproduction task. These findings support the recent proposal that the anterior insular/inferior frontal cortices would be involved in time interval representation.