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Objective: Visceral sensations are bodily symptoms which are component manifestations of emotions frequently reported during epileptic seizures. Nowadays, the underlying mechanism and location of brain areas involved in the processing of these sensations remain unclear. Our objectives were to characterize the type and frequency of visceral and emotional responses evoked by electrical stimulations, to produce a mapping of brain structures involved in their processing, and to assess the link between visceral sensations and emotional feelings., Methods: We reviewed 12,088 bipolar stimulations performed in 203 patients during the presurgical evaluation of drug refractory epilepsy. Responses to stimulation were divided into viscero-sensitive, viscero-vegetative, and emotional sensations. Univariate analysis and conditional logistic regression were used to assess the association between visceral and emotional sensations and localization of the stimulated contacts., Results: In total, 543 stimulations evoked visceral and emotional sensations. Stimulations of operculo-insulolimbic structures (amygdala, anterior and posterior insula, anterior and mid-cingulate cortex, hippocampus, parahippocampus, temporal pole, frontal and parietal operculum) were significantly more associated with visceral and emotional sensations than all other cortical regions. Preferential implication of certain brain structures, depending on the type of visceral responses was evidenced: temporo-mesial structures, insula, and frontoparietal operculum for viscero-sensitive sensations; amygdala, insula, anterior and mid-cingulate cortex, and temporal pole for viscero-vegetative sensations; temporo-mesial structures, anterior cingulate cortex, and frontal operculum for emotional sensations., Interpretation: Our data can help to guide SEEG explorations when visceral or emotional symptoms are part of the ictal semiology. They also bring some insights into the mechanisms of visceroception and the functional significance of the co-localization of visceral and emotional representations in the human brain., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To identify which cortical regions are associated with direct electrical stimulation (DES)-induced alteration of breathing significant enough to impair pulse oximetry (SpO 2 )., Methods: Evolution of SpO 2 after 1,352 DES was analyzed in 75 patients with refractory focal epilepsy who underwent stereo-EEG recordings. For each DES, we assessed the change in SpO 2 from 30 seconds prior to DES onset to 120 seconds following the end of the DES. The primary outcome was occurrence of stimulation-induced transient hypoxemia as defined by decrease of SpO 2 ≥5% within 60 seconds after stimulation onset as compared to pre-DES SpO 2 or SpO 2 nadir <90% during at least 5 seconds. Localization of the stimulated contacts was defined according to MarsAtlas brain parcellation and Freesurfer segmentation., Results: A stimulation-induced transient hypoxemia was observed after 16 DES (1.2%) in 10 patients (13%), including 6 in whom SpO 2 nadir was <90%. Among these 16 DES, 7 (44%) were localized within the perisylvian cortex. After correction for individual effects and the varying number of DES contributed by each person, significant decrease of SpO 2 was significantly associated with the localization of DES ( p = 0.019)., Conclusion: Though rare, a significant decrease of SpO 2 could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex., (© 2020 American Academy of Neurology.)

Despite numerous studies suggesting the role of insular cortex in the control of autonomic activity, the exact location of cardiac motor regions remains controversial. We provide here a functional mapping of autonomic cardiac responses to intracortical stimulations of the human insula. The cardiac effects of 100 insular electrical stimulations into 47 epileptic patients were divided into tachycardia, bradycardia, and no cardiac response according to the magnitude of RR interval (RRI) reactivity. Sympathetic (low frequency, LF, and low to high frequency powers ratio, LF/HF ratio) and parasympathetic (high frequency power, HF) reactivity were studied using RRI analysis. Bradycardia was induced by 26 stimulations (26%) and tachycardia by 21 stimulations (21%). Right and left insular stimulations induced as often a bradycardia as a tachycardia. Tachycardia was accompanied by an increase in LF/HF ratio, suggesting an increase in sympathetic tone; while bradycardia seemed accompanied by an increase of parasympathetic tone reflected by an increase in HF. There was some left/right asymmetry in insular subregions where increased or decreased heart rates were produced after stimulation. However, spatial distribution of tachycardia responses predominated in the posterior insula, whereas bradycardia sites were more anterior in the median part of the insula. These findings seemed to indicate a posterior predominance of sympathetic control in the insula, whichever the side; whereas the parasympathetic control seemed more anterior. Dysfunction of these regions should be considered when modifications of cardiac activity occur during epileptic seizures and in cardiovascular diseases., (© 2019 Wiley Periodicals, Inc.)

Electrical stimulations of the insula performed during stereo-electro-encephalography (SEEG) reproduce the ictal symptoms observed during the development of insular seizures and are also a unique opportunity to provide a functional mapping of the insular cortex. We provide here a functional mapping of the insular cortex obtained by electrical stimulation, based on our previous work and a review of literature. The most frequent responses to insula stimulation were somatosensory sensations followed by visceral responses. Then, in decreasing order of frequency, auditory sensations, vestibular illusions, speech impairment, gustato-olfactory sensations and motor reactions were evoked. A bipolar organization could be evidenced with a posterior part assigned to somatosensory functions and notably to pain perception; and an anterior part assigned to visceral functions. Although some degree of spatial segregation could be evidenced, there was a clear spatial overlap between the representations of the different types of responses. These data provide a better understanding of physiological insular functions, insula seizures semiology and a prediction of post-surgical deficits. Insula is the only cortical region where stimulations demonstrate such a multi-modal representation, perhaps supporting its integrative functions of polymodal inputs., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: Despite numerous studies suggesting the role of insular cortex in the processing of gustatory and olfactory inputs, the exact location of olfactogustatory representation in the insula remains controversial. Here we provide a functional mapping of olfactory-gustatory responses to stimulation of the human insular cortex., Methods: We reviewed 651 electrical stimulations of the insula that were performed in 221 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory epilepsy., Results: Gustatory sensations were evoked in 15 (2.7%) of the 550 stimulations that elicited a clinical response. They were exclusively obtained after stimulation of a relatively delimited zone of insula, located in its mid-dorsal part (posterior short gyrus). Six olfactory sensations (1.1%) could be obtained during stimulations of an insular region that partially overlapped with the gustatory representation., Interpretation: Our study provides a functional mapping of gustatory representation in the insular posterior short gyrus and the first detailed description of olfactory sensations obtained by direct stimulation of mid-dorsal insula. Our data also show a spatial overlap between gustatory, olfactory, and oral somatosensory representation in the mid-dorsal insula, and suggest that this part of the insula may be an integrated oral sensory region that plays a key role in flavor perception. It also indicates that dysfunction in this region should be considered during the evaluation of gustatory and olfactory epileptic seizures. Ann Neurol 2017;82:360-370., (© 2017 American Neurological Association.)

Introduction: Stereotactic stimulations of the insular cortex through intracranial electrodes aim at characterizing the semiology of insular seizures. These stimulations, carried out in the context of Stereo-Electro-Encephalography (SEEG) during presurgical monitoring of epilepsy, reproduce the ictal symptoms observed during the development of insular seizures., Methods: The authors reviewed the results of insular stimulations performed in 222 patients admitted between 1997 and 2015 for presurgical SEEG exploration of atypical temporal or perisylvian epilepsy. Stimulations (50 Hz, trains of 5 seconds, pulses of 0.5 ms, intensity 0.2-3.5 mA) were carried out using transopercular electrodes implanted orthogonal to midsagittal plane., Results: Out of a total of 669 stimulations, 550 were clinically eloquent in the absence of any postdischarge (237 and 313, respectively, in the right and left insulae). Somatosensory responses (61% of evoked sensations) including pain and visceral sensations (14.9%) were the most frequent, followed by auditory sensations (8%), vestibular illusions (7.5%), speech impairment (5%), gustatory, (2.7%), and olfactory (1%) sensations. Although these responses showed some functional segregation (in particular a privileged pain representation in the postero-superior quadrant), there was a clear spatial overlap between representations of the different modalities., Conclusions: Symptoms evoked by insular stimulations are multiple. None of them can be considered as absolutely specific to the insular cortex, but the occurrence in given seizure of a somatosensory symptom such as pain or of a laryngeal spasm associated with vestibular, auditory, aphasic, or olfacto-gustatory symptoms points to a discharge development in the insular cortex, which is the only cortical region where stimulations demonstrate such a multimodal representation.

Long-term EEG in adults includes three modalities: sleep deprived-EEG lasting 1 to 3 hours, 24 hours ambulatory-EEG and continuous prolonged video-EEG lasting from several hours to several days. The main indications of long-term EEG are: syndromic classification of epilepsy; search for interictal discharges when epilepsy is suspected or for the purpose of therapeutic evaluation; positive diagnosis of paroxysmal clinical events; and pre-surgical evaluation of drug-resistant epilepsy. Sleep deprived-EEG and ambulatory-EEG are indicated to detect interictal discharges in order to validate a syndromic classification of epilepsy when standard EEG is negative. These exams can help in evaluating treatment efficacy, especially when clinical evaluation is difficult. Long-term video EEG is indicated for drug-resistant epilepsy, to analyze electro-clinical correlations in a pre-surgical evaluation context, and to refine a positive diagnosis when paroxysmal clinical events are frequent., (Copyright © 2015. Published by Elsevier SAS.)

Objective: To explore whether painful somatosensory seizures (PSS) are generated in the primary somatosensory cortex (SI area) or in the operculo-insular cortex., Methods: We analyzed ictal recordings and data from stimulation using intracerebral electrodes exploring the operculo-insular cortex (including secondary somatosensory [SII] region), SI area,and other areas of the pain matrix (cingulate gyrus and supplementary motor area) in a case series study of 5 patients with PSS., Results: Clinical features of PSS were different from those of seizures arising from the SI area: (1)pain intensity was higher; (2) pain spreading was not from one somatotopic territory to adjacentones; and (3) the spatial extent of pain was large, fitting better with the size of somatosensory receptive fields of the insula and SII region than of the SI area. The insula and SII region were systematically involved at the onset of seizures, rapidly followed by the opercular portion of SI area.The upper part of SI cortex was involved at a lesser degree, with some delay, and pain duration did not correlate in time with that of the discharge in SI. Ictal pain was consistently reproduced by stimulation of the insula or SII region but never by stimulating the SI area., Conclusions: These data strongly suggest that PSS originate in the operculo-insular cortex and not in the SI area and corroborate the concept that this region is involved in the sensory discriminative processing of pain inputs. Pain at the onset of PSS has a high value for localizing the epileptogenic area.

Objective: The present study provides a functional mapping of vestibular responses in the human insular cortex., Methods: A total of 642 electrical stimulations of the insula were performed in 219 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory partial epilepsy. We retrospectively identified 41 contacts where stimulation elicited vestibular sensations (VSs) and analyzed their location with respect to (1) their stereotactic coordinates (for all contacts), (2) the anatomy of insula gyri (for 20 vestibular sites), and (3) the probabilistic cytoarchitectonic maps of the insula (for 9 vestibular sites)., Results: VSs occurred in 7.6% of the 541 evoked sensations after electrical stimulations of the insula. VSs were mostly obtained after stimulation of the posterior insula, that is, in the granular insular cortex and the postcentral insular gyrus. The data also suggest a spatial segregation of the responses in the insula, with the rotatory and translational VSs being evoked at more posterior stimulation sites than other less definable VSs. No left-right differences were observed., Interpretation: These results demonstrate vestibular sensory processing in the insula that is centered on its posterior part. The present data add to the understanding of the multiple sensory functions of the insular cortex and of the cortical processing of vestibular signals. The data also indicate that lesion or dysfunction in the posterior insula should be considered during the evaluation of vestibular epileptic seizures., (© 2014 American Neurological Association.)

The question whether pain encoding in the human insula shows some somatotopic organization is still pending. We studied 142 patients undergoing depth stereotactic EEG (SEEG) exploration of the insular cortex for pre-surgical evaluation of epilepsy. 472 insular electrical stimulations were delivered, of which only 49 (10.5%) elicited a painful sensation in 38 patients (27%). Most sites where low intensity electric stimulation produced pain, without after-discharge or concomitant visually detectable change in EEG activity outside the insula, were located in the posterior two thirds of the insula. Pain was located in a body area restricted to face, upper limb or lower limb for 27 stimulations (55%) and affected more than one of these regions for all others. The insular cortex being oriented parallel to the medial sagittal plane we found no significant difference between body segment representations in the medio-lateral axis. Conversely a somatotopic organization of sites where stimulation produced pain was observed along the rostro-caudal and vertical axis of the insula, showing a face representation rostral to those of upper and lower limbs, with an upper limb representation located above that of the lower limb. These data suggest that, in spite of large and often bilateral receptive fields, pain representation shows some degree of somatotopic organization in the human insula.

Somatosensory and pain responses to direct intracerebral stimulations of the SII area were obtained in 14 patients referred for epilepsy surgery. Stimulations were delivered using transopercular electrodes exploring the parietal opercular cortex (SII area), the suprasylvian parietal cortex (SI area) and the insular cortex. SII responses were compared to those from adjacent SI and insular cortex. In the three areas we elicited mostly somatosensory responses, including paresthesiae, temperature and pain sensations. The rate of painful sensations (10%) was similar in SII and in the insula, while no painful sensation was evoked in SI. A few non-somatosensory responses were evoked by SII stimulation. Conversely various types of non-somatosensory responses (auditory, vegetative, vestibular, olfacto-gustatory, etc.) were evoked only by insular stimulation, confirming that SII, like SI, are mostly devoted to the processing of somatosensory inputs whereas the insular cortex is a polymodal area. We also found differences in size and lateralization of skin projection fields of evoked sensations between the three studied areas, showing a spatial resolution of the somatotopic map in SII intermediate between those found in SI and insula. This study shows the existence of three distinct somatosensory maps in the suprasylvian, opercular and insular regions, and separate pain representations in SII and insular cortex.