Insular dichotomy in the implicit detection of emotions in human faces.

The functional roles of the insula diverge between its posterior portion (PI), mainly connected with somato-sensory and motor areas, and its anterior section (AI) connected with the frontal, limbic, and cingulate regions. We report intracranial recordings of local field evoked potentials from PI, AI, and the visual fusiform gyrus to a full array of emotional faces including pain while the individuals' attention was diverted from emotions. The fusiform gyrus and PI responded equally to all types of faces, including neutrals. Conversely, the AI responded only to emotional faces, maximally to pain and fear, while remaining insensitive to neutrals. The two insular sectors reacted with almost identical latency suggesting their parallel initial activation via distinct functional routes. The consistent responses to all emotions, together with the absence of response to neutral faces, suggest that early responses in the AI reflect the immediate arousal value and behavioral relevance of emotional stimuli, which may be subserved by "fast track" routes conveying coarse-spatial-frequency information via the superior colliculus and dorsal pulvinar. Such responses precede the conscious detection of the stimulus' precise signification and valence, which need network interaction and information exchange with other brain areas, for which the AI is an essentialhub.

Headaches provoked by cortical stimulation: Their localizing value in focal epileptic seizures.

OBJECTIVE: Electrical stimulations performed in awake patients identified dura mater, venous sinuses, and arteries as pain-sensitive intracranial structures. However, cephalic pain has been only occasionally reported in patients with epilepsy undergoing stereo-electroencephalography (SEEG) stimulations. METHODS: The aim of our study was to investigate whether headache can be triggered by SEEG stimulations and might be related to specific cortical areas. Data were gathered from 16 050 stimulations collected in 266 patients who underwent a SEEG as part of a presurgical assessment of their drug-resistant epilepsy. RESULTS: Two-hundred and eight stimulations (1.3%) evoked headaches. Pain was more frequently described as bilateral (42.31%) than ipsilateral (16.83%) or contralateral (14.42%) to the stimulated hemisphere. Headache was more frequently elicited during stimulation of the insulo-limbic regions such as the anterior and medial cingulate gyrus, the mesial part of temporal lobe, and the insula. CONCLUSION: This study shows that cortical stimulation can evoke headache, mostly during stimulation of the temporo-frontal limbic regions. It suggests that brief epileptic headache can be an epileptic symptom caused by a cortical discharge involving somatic or visceral network and does not reflect only trigemino-vascular activation. Although not specific, the occurrence of a brief epileptic headache may point to a seizure origin in the temporo-frontal limbic regions.

How the insula speaks to the heart: Cardiac responses to insular stimulation in humans.

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.

Gustatory and olfactory responses to stimulation of the human insula.

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.

Migraine with brainstem aura: Why not a cortical origin?

Background Migraine with brainstem aura is defined as a migraine with aura including at least two of the following symptoms: dysarthria, vertigo, tinnitus, hypacusis, diplopia, ataxia and/or decreased level of consciousness. Aim The aim of this study is to review data coming from clinical observations and functional mapping that support the role of the cerebral cortex in the initiation of brainstem aura symptoms. Results Vertigo can result from a vestibular cortex dysfunction, while tinnitus and hypacusis can originate within the auditory cortex. Diplopia can reflect a parieto-occipital involvement. Dysarthria can be caused by dysfunctions located in precentral gyri. Ataxia can reflect abnormal processing of vestibular, sensory, or visual inputs by the parietal lobe. Alteration of consciousness can be caused by abnormal neural activation within specific consciousness networks that include prefrontal and posterior parietal cortices. Conclusion Any symptom of so-called brainstem aura can originate within the cortex. Based on these data, we suggest that brainstem aura could have a cortical origin. This hypothesis would explain the co-occurrence of typical and brainstem aura during attacks and would fit with the theory of cortical spreading depression. We propose that migraine with brainstem aura should be classified as a typical migraine aura.

Stereo electroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in drug-resistant focal epilepsy: Results from a 10-year experience.

OBJECTIVE: Stereo electroencephalography (SEEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) has been proposed since 2004 as a possible treatment of some focal drug-resistant epilepsy. The aim of this study is to provide extensive data about efficacy and safety of SEEG-guided RF-TC. METHODS: Over a 10-year period, 162 patients with drug-resistant focal epilepsy were eligible for SEEG-guided RF-TG during phase II invasive investigation by SEEG. All follow-up and safety data were collected prospectively. The primary outcome was seizure freedom at 2 months and at 1 year after SEEG-guided RF-TC. Secondary outcomes were the responders' rate (patient with at least 50% decrease in seizure frequency) and their long-term follow-up. RESULTS: Twenty-five percent of patients were seizure-free at 2 months and 7% at 1 year. We reported 67% of responders at 2 months and 48% at 1 year; 58% of responders maintained their status during the long-term follow-up. The seizure outcome was significantly better when the SEEG-guided RF-TC involved the occipital region (p = 0.007). When surgery followed an SEEG-guided RF-TC, the positive predictive value of being a responder 2 months after an SEEG-guided RF-TC and to be Engel's class I or II after surgery was 93%. We reported 1.1% of permanent deficit and 2.4% of transient side effects. SIGNIFICANCE: Our results, gathered in a large population over a 10-year period, confirm that SEEG-guided RF-TC is a safe technique, being efficient in many cases. More than two thirds of patients showed a short-term improvement, and almost half of them were responders at 1-year follow-up. The technique appears to be especially interesting for limited epileptic zone inaccessible to surgery and when epilepsy is related to a large unilateral network (network disruption by multiple RF-TC). Furthermore, SEEG-guided RF-TC effect is a predictor of outcome after conventional cortectomy in patients eligible for surgery.

The neural dynamics of reward value and risk coding in the human orbitofrontal cortex.

The orbitofrontal cortex is known to carry information regarding expected reward, risk and experienced outcome. Yet, due to inherent limitations in lesion and neuroimaging methods, the neural dynamics of these computations has remained elusive in humans. Here, taking advantage of the high temporal definition of intracranial recordings, we characterize the neurophysiological signatures of the intact orbitofrontal cortex in processing information relevant for risky decisions. Local field potentials were recorded from the intact orbitofrontal cortex of patients suffering from drug-refractory partial epilepsy with implanted depth electrodes as they performed a probabilistic reward learning task that required them to associate visual cues with distinct reward probabilities. We observed three successive signals: (i) around 400 ms after cue presentation, the amplitudes of the local field potentials increased with reward probability; (ii) a risk signal emerged during the late phase of reward anticipation and during the outcome phase; and (iii) an experienced value signal appeared at the time of reward delivery. Both the medial and lateral orbitofrontal cortex encoded risk and reward probability while the lateral orbitofrontal cortex played a dominant role in coding experienced value. The present study provides the first evidence from intracranial recordings that the human orbitofrontal cortex codes reward risk both during late reward anticipation and during the outcome phase at a time scale of milliseconds. Our findings offer insights into the rapid mechanisms underlying the ability to learn structural relationships from the environment.

Thalamic pain: anatomical and physiological indices of prediction.

Thalamic pain is a severe and treatment-resistant type of central pain that may develop after thalamic stroke. Lesions within the ventrocaudal regions of the thalamus carry the highest risk to develop pain, but its emergence in individual patients remains impossible to predict. Because damage to the spino-thalamo-cortical system is a crucial factor in the development of central pain, in this study we combined detailed anatomical atlas-based mapping of thalamic lesions and assessment of spinothalamic integrity using quantitative sensory analysis and laser-evoked potentials in 42 thalamic stroke patients, of whom 31 had developed thalamic pain. More than 97% of lesions involved an area between 2 and 7 mm above the anterior-posterior commissural plane. Although most thalamic lesions affected several nuclei, patients with central pain showed maximal lesion convergence on the anterior pulvinar nucleus (a major spinothalamic target) while the convergence area lay within the ventral posterior lateral nucleus in pain-free patients. Both involvement of the anterior pulvinar nucleus and spinothalamic dysfunction (nociceptive thresholds, laser-evoked potentials) were significantly associated with the development of thalamic pain, whereas involvement of ventral posterior lateral nucleus and lemniscal dysfunction (position sense, graphaesthesia, pallaesthesia, stereognosis, standard somatosensory potentials) were similarly distributed in patients with or without pain. A logistic regression model combining spinothalamic dysfunction and anterior pulvinar nucleus involvement as regressors had 93% sensitivity and 87% positive predictive value for thalamic pain. Lesion of spinothalamic afferents to the posterior thalamus appears therefore determinant to the development of central pain after thalamic stroke. Sorting out of patients at different risks of developing thalamic pain may be achievable at the individual level by combining lesion localization and functional investigation of the spinothalamic system. As the methods proposed here do not need complex manipulations, they can be added to routine patients' work up, and the results replicated by other investigators in the field.

Neurophysiological assessment of brain dysfunction in critically ill patients: an update.

The aim of this review was to provide up-to-date information about the usefulness of clinical neurophysiology testing in the management of critically ill patients. Evoked potentials (EPs) and electroencephalogram (EEG) are non-invasive clinical neurophysiology tools that allow an objective assessment of the central nervous system's function at the bedside in intensive care unit (ICU). These tests are quite useful in diagnosing cerebral complications, and establishing the vital and functional prognosis in ICU. EEG keeps a particularly privileged importance in detecting seizures phenomena such as subclinical seizures and non-convulsive status epilepticus. Quantitative EEG (QEEG) analysis techniques commonly called EEG Brain mapping can provide obvious topographic displays of digital EEG signals characteristics, showing the potential distribution over the entire scalp including filtering, frequency, and amplitude analysis and color mapping. Evidences of usefulness of QEEG for seizures detection in ICU are provided by several recent studies. Furthermore, beyond detection of epileptic phenomena, changes of some QEEG panels are early warning indicators of sedation level as well as brain damage or dysfunction in ICU. EPs offer the opportunity for assessing brainstem's functional integrity, as well as subcortical and cortical brain areas. A multimodal use, combining EEG and various modalities of EPs is recommended since this allows a more accurate functional exploration of the brain and helps caregivers to tailor therapeutic measures according to neurological worsening trends and to anticipate the prognosis in ICU.

Diagnostic utility of somatosensory evoked potentials in chronic polyradiculopathy without electrodiagnostic signs of peripheral demyelination.

INTRODUCTION: Diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) remains uncertain when nerve conduction studies (NCS) fail to show demyelination. METHODS: We conducted a retrospective study of patients who presented with clinical criteria of CIDP in whom electrodiagnostic (EDx) criteria of definite or probable CIDP were missing [axonal sensorimotor neuropathy (n = 23), normal EDx with pure sensory presentation (n = 3)]. All patients received immunomodulatory treatment. Twenty-six patients were evaluated with somatosensory evoked potentials (SSEPs), MRI of spinal roots, cerebrospinal fluid analysis, and/or nerve biopsy. Diagnosis of CIDP was considered to be confirmed in patients who responded to immunotherapy. RESULTS: Twenty-two of 26 patients (85%) had SSEPs reflecting abnormal proximal conduction in sensory fibers, including 14 who had only clinical and SSEP data in favor of CIDP. SSEPs were abnormal in 16 of 20 responders (80%) to immunotherapy. CONCLUSION: SSEP recording contributes to the diagnosis of CIDP when nerve conduction studies fail to detect peripheral demyelination.

Central Nervous System Underpinnings of Sensory Hypersensitivity in Migraine: Insights from Neuroimaging and Electrophysiological Studies.

Whereas considerable data have been generated about the pathophysiology of pain processing during migraine attacks, relatively little is known about the neural basis of sensory hypersensitivity. In migraine, the term "hypersensitivity" encompasses different and probably distinct pathophysiological aspects of sensory sensitivity. During attacks, many patients have enhanced sensitivity to visual, auditory and/or olfactory stimuli, which can enhance headache while interictally, migraineurs often report abnormal sensitivity to environmental stimuli that can cause nonpainful discomfort. In addition, sensorial stimuli can influence and trigger the onset of migraine attacks. The pathophysiological mechanisms and the origin of such sensitivity (individual predisposition to develop migraine disease or consequence of repeated migraine attacks) are ill understood. Functional neuroimaging and electrophysiological studies allow for noninvasive measures of neuronal responses to external stimuli and have contributed to our understanding of mechanisms underlying sensory hypersensitivity in migraine. The purpose of this review is to present pivotal neuroimaging and neurophysiological studies that explored the basal state of brain responsiveness to sensory stimuli in migraineurs, the alterations in habituation and attention to sensory inputs, the fluctuations of responsiveness to sensory stimuli before and during migraine attacks, and the relations between sensory hypersensitivity and clinical sensory complaints.

Vestibular responses to direct stimulation of the human insular cortex.

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.

Processing of nociceptive input from posterior to anterior insula in humans.

Previous brain imaging studies have shown robust activations in the insula during nociceptive stimulation. Most activations involve the posterior insular cortex but they can cover all insular gyri in some fMRI studies. However, little is known about the timing of activations across the different insular sub-regions. We report on the distribution of intracerebrally recorded nociceptive laser evoked potentials (LEPs) acquired from the full extent of the insula in 44 epileptic patients. Our study shows that both posterior and anterior subdivisions of the insular cortex respond to a nociceptive heat stimulus within a 200-400 ms latency range. This nociceptive cortical potential occurs firstly, and is larger, in the posterior granular insular cortex. The presence of phase reversals in LEP components in both posterior and anterior insular regions suggests activation of distinct, presumably functionally separate, sources in the posterior and anterior parts of the insula. Our results suggest that nociceptive input is first processed in the posterior insula, where it is known to be coded in terms of intensity and anatomical location, and then conveyed to the anterior insula, where the emotional reaction to pain is elaborated.

The value of magnetoencephalography for seizure-onset zone localization in magnetic resonance imaging-negative partial epilepsy.

Surgical treatment of epilepsy is a challenge for patients with non-contributive brain magnetic resonance imaging. However, surgery is feasible if the seizure-onset zone is precisely delineated through intracranial electroencephalography recording. We recently described a method, volumetric imaging of epileptic spikes, to delineate the spiking volume of patients with focal epilepsy using magnetoencephalography. We postulated that the extent of the spiking volume delineated with volumetric imaging of epileptic spikes could predict the localizability of the seizure-onset zone by intracranial electroencephalography investigation and outcome of surgical treatment. Twenty-one patients with non-contributive magnetic resonance imaging findings were included. All patients underwent intracerebral electroencephalography investigation through stereotactically implanted depth electrodes (stereo-electroencephalography) and magnetoencephalography with delineation of the spiking volume using volumetric imaging of epileptic spikes. We evaluated the spatial congruence between the spiking volume determined by magnetoencephalography and the localization of the seizure-onset zone determined by stereo-electroencephalography. We also evaluated the outcome of stereo-electroencephalography and surgical treatment according to the extent of the spiking volume (focal, lateralized but non-focal or non-lateralized). For all patients, we found a spatial overlap between the seizure-onset zone and the spiking volume. For patients with a focal spiking volume, the seizure-onset zone defined by stereo-electroencephalography was clearly localized in all cases and most patients (6/7, 86%) had a good surgical outcome. Conversely, stereo-electroencephalography failed to delineate a seizure-onset zone in 57% of patients with a lateralized spiking volume, and in the two patients with bilateral spiking volume. Four of the 12 patients with non-focal spiking volumes were operated upon, none became seizure-free. As a whole, patients having focal magnetoencephalography results with volumetric imaging of epileptic spikes are good surgical candidates and the implantation strategy should incorporate volumetric imaging of epileptic spikes results. On the contrary, patients with non-focal magnetoencephalography results are less likely to have a localized seizure-onset zone and stereo electroencephalography is not advised unless clear localizing information is provided by other presurgical investigation methods.

Theta signal as the neural signature of social exclusion.

The feeling of being excluded from a social interaction triggers social pain, a sensation as intense as actual physical pain. Little is known about the neurophysiological underpinnings of social pain. We addressed this issue using intracranial electroencephalography in 15 patients performing a ball game where inclusion and exclusion blocks were alternated. Time-frequency analyses showed an increase in power of theta-band oscillations during exclusion in the anterior insula (AI) and posterior insula, the subgenual anterior cingulate cortex (sACC), and the fusiform "face area" (FFA). Interestingly, the AI showed an initial fast response to exclusion but the signal rapidly faded out. Activity in the sACC gradually increased and remained significant thereafter. This suggests that the AI may signal social pain by detecting emotional distress caused by the exclusion, whereas the sACC may be linked to the learning aspects of social pain. Theta activity in the FFA was time-locked to the observation of a player poised to exclude the participant, suggesting that the FFA encodes the social value of faces. Taken together, our findings suggest that theta activity represents the neural signature of social pain. The time course of this signal varies across regions important for processing emotional features linked to social information.

Cortical representation of pain in primary sensory-motor areas (S1/M1)--a study using intracortical recordings in humans.

Intracortical evoked potentials to nonnoxious Aß (electrical) and noxious Aδ (laser) stimuli within the human primary somatosensory (S1) and motor (M1) areas were recorded from 71 electrode sites in 9 epileptic patients. All cortical sites responding to specific noxious inputs also responded to nonnoxious stimuli, while the reverse was not always true. Evoked responses in S1 area 3b were systematic for nonnoxious inputs, but seen in only half of cases after nociceptive stimulation. Nociceptive responses were systematically recorded when electrode tracks reached the crown of the postcentral gyrus, consistent with an origin in somatosensory areas 1-2. Sites in the precentral cortex also exhibited noxious and nonnoxious responses with phase reversals indicating a local origin in area 4 (M1). We conclude that a representation of thermal nociceptive information does exist in human S1, although to a much lesser extent than the nonnociceptive one. Notably, area 3b, which responds massively to nonnoxious Aß activation was less involved in the processing of noxious heat. S1 and M1 responses to noxious heat occurred at latencies comparable to those observed in the supra-sylvian opercular region of the same patients, suggesting a parallel, rather than hierarchical, processing of noxious inputs in S1, M1 and opercular cortex. This study provides the first direct evidence for a spinothalamic related input to the motor cortex in humans.

Stimulation of the human cortex and the experience of pain: Wilder Penfield's observations revisited.

Thanks to the seminal work of Wilder Graves Penfield (1891-1976) at the Montreal Neurological Institute, electrical stimulation is used worldwide to localize the epileptogenic cortex and to map the functionally eloquent areas in the context of epilepsy surgery or lesion resections. In the functional map of elementary and experiential responses he described through >20 years of careful exploration of the human cortex via stimulation of the cortical surface, Penfield did not identify any 'pain cortical area'. We reinvestigated this issue by analysing subjective and videotaped behavioural responses to 4160 cortical stimulations using intracerebral electrodes implanted in all cortical lobes that were carried out over 12 years during the presurgical evaluation of epilepsy in 164 consecutive patients. Pain responses were scarce (1.4%) and concentrated in the medial part of the parietal operculum and neighbouring posterior insula where pain thresholds showed a rostrocaudal decrement. This deep cortical region remained largely inaccessible to the intraoperative stimulation of the cortical surface carried out by Penfield after resection of the parietal operculum. It differs also from primary sensory areas described by Penfield et al. in the sense that, with our stimulation paradigm, pain represented only 10% of responses. Like Penfield et al., we obtained no pain response anywhere else in the cortex, including in regions consistently activated by pain in most functional imaging studies, i.e. the first somatosensory area, the lateral part of the secondary somatosensory area, anterior and mid-cingulate gyri (mid-cingulate cortex), anterior frontal, posterior parietal and supplementary motor areas. The medial parietal operculum and posterior insula are thus the only areas where electrical stimulation is able to trigger activation of the pain cortical network and thus the experience of somatic pain.

Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans.

Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep.

Central control of cardiac activity as assessed by intra-cerebral recordings and stimulations.

Some of the most important integrative control centers for the autonomic nervous system are located in the brainstem and the hypothalamus. However, growing recent neuroimaging evidence support that a set of cortical regions, named the central autonomic network (CAN), is involved in autonomic control and seems to play a major role in continuous autonomic cardiac adjustments to high-level emotional, cognitive or sensorimotor cortical activities. Intracranial explorations during stereo-electroencephalography (SEEG) offer a unique opportunity to address the question of the brain regions involved in heart-brain interaction, by studying: (i) direct cardiac effects produced by the electrical stimulation of specific brain areas; (ii) epileptic seizures inducing cardiac modifications; (iii) cortical regions involved in cardiac interoception and source of cardiac evoked potentials. In this review, we detail the available data assessing cardiac central autonomic regulation using SEEG, address the strengths and also the limitations of this technique in this context, and discuss perspectives. The main cortical regions that emerge from SEEG studies as being involved in cardiac autonomic control are the insula and regions belonging to the limbic system: the amygdala, the hippocampus, and the anterior and mid-cingulate. Although many questions remain, SEEG studies have already demonstrated afferent and efferent interactions between the CAN and the heart. Future studies in SEEG should integrate these afferent and efferent dimensions as well as their interaction with other cortical networks to better understand the functional heart-brain interaction.