Brain’s dorsal anterior insular play a major role in ecstatic experiences

The epileptic “aura” is a subjective phenomenon that sometimes precedes the visible clinical features of a seizure.

Investigators tested three epileptic patients prior to potential surgery to try to determine where their seizures originate.

They observed that these patients reported an ecstatic aura only when the dorsal anterior insula of the brain was stimulated.

Their findings in the journal Brain Stimulation provide additional support of a major role played by the dorsal anterior insula in ecstatic experiences.

Throughout history some people have experienced states of ecstasy.

In these moments they describe a blissful altered consciousness with a sense of hyper-reality, a hyper awareness of the present moment, and a feeling of union with the Universe.

Attaining or producing these states is a key component of many religious traditions.

“An important modern question is whether these states arise from activity in specific brain regions and if so, where,” explained lead investigator Fabrice Bartolomei, MD, PhD, Aix-Marseille University, INSERM, INS, Institute of Neuroscience Systems, and APHM, Timone Hospital, Clinical Neurophysiology and Epileptology Department, Marseille, France.

“A better understanding of the network mechanisms underlying this fascinating subjective experience may help to unravel some mysteries of human consciousness.

The insula, a lobe in the brain behind the ears that is insulated because it is hidden deep in the brain, has recently been proposed to be a key region to elicit these symptoms.”

Some patients with epilepsy experience a type of aura referred to as “ecstatic.” Patients use terms like “hyper-reality,” “clarity,” “evidence,” “certainty,” “understanding,” “insight,” “enlightenment,” or “epiphany” to describe this state.

The Russian writer Fyodor Dostoevsky, who experienced such seizures himself, gave a famous description in his novel The Idiot, in which one of his characters reports feeling “overflowing with unbounded joy and rapture, ecstatic devotion, and completest life.”

Investigators describe three patients with refractory focal epilepsy, who had probes inserted into their brains to try to determine where their seizures originated, potentially to remove those regions surgically and cure their disease.

They studied functional connectivity changes in several brain areas during the induction of ecstatic auras by direct electrical stimulation of the dorsal anterior insular cortex in patients implanted with intracerebral electrodes (stereotactic-EEG, SEEG) during their pre-surgical evaluation.

These patients were selected on the basis of the occurrence of ecstatic symptoms triggered by direct intracerebral electrical stimulation of the antero-dorsal part of the insula.

Electrical stimulation was performed in a bipolar fashion to each contact in the gray matter during a three-second period to map functional cortices and trigger habitual seizures. One stimulation inducing ecstatic changes in each patient was analyzed.

Functional connectivity analysis was performed by measuring interdependencies between SEEG signals before and after stimulations.

Each patient reported an ecstatic aura only when the dorsal anterior insula was stimulated. Investigators measured brain wave activity (EEG) during periods of ecstasy and found that the anterior insula was serving as a critical node or hub in the network activity, suggesting that in some way this region can produce or release this feeling.

“The field of brain stimulation is still in its infancy.

While these patients had to have wires inserted into their brains in order to produce ecstasy, in the future it may be possible to stimulate this spot non-invasively,” commented Dr. Bartolomei.

A: Localization of the contacts inducing an ecstatic aura in the operculo-insular region in the three patients (P1, P2, and P3), in blue.

The red dots correspond to other implanted electrodes.

Localization was performed using in-house Gardel software. B: Stereotactic EEG (SEEG) traces and an example of insular stimulation in P3. The image is credited to the researchers/Brain Stimulation.

“Science routinely progresses through hypothesis-driven research conducted by large teams of researchers,” added Mark George, MD, Editor-in-Chief of Brain Stimulation. “However, accidental ‘discoveries’ are also important.

These serendipitous observations can help us understand the world around us, particularly the world within our skulls, the human brain.

Perhaps in the near future we can use noninvasive brain stimulation methods to stimulate this region and determine if it truly is the seat of ecstasy.

Dr. George cautions that, while this is an important clue for the field, it is important to remember that these results were observed in patients with epilepsy, so we do not yet know if this effect is generalizable to people without epilepsy.

Understanding the brain networks involved in consciousness and altered states is important for many reasons, some therapeutic and others philosophical and cultural.

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Insula structure and connectivity

Location

The insular cortex is located deep within the lateral sulcus of the brain. Also known as the “Island of Reil” based on its initial discovery by Johann Chrstian Reil in 1809, the insula is a region of cortex not visible from the surface view. Traditionally, the insular cortex has been described as paralimbic or limbic integration cortex¹.

Gyral subdivision and anatomic definitions

The insula is mostly surrounded by the peri-insular sulcus, and is divided in two by the central insular sulcus.

Though there is some variability in insular gyri number, the more anterior portion of the insula is typically comprised of the anterior, middle, and posterior short insular gyri, which are separated by the anterior and precentral insular sulcus. The posterior portion of the insula is comprised of the anterior and posterior long insular gyri, separated by the postcentral insular sulcus² (Figure 1).

Vascularization

Here we provide a brief description of the vascularization of the insula. The insular cortex is hidden under dense arterial and venous blood vessels, making it somewhat difficult to operate on. Arterial supply of the insula is provided by the M2 segment of the middle cerebral artery (MCA) through perforating vessels.

These vessels arise at the inferior part of the insula and follow the insular sulci.

The superior trunk of the MCA supplies the anterior, middle, and posterior short gyri and the inferior trunck supplies the posterior long gyrus. Venous blood of the insula drains mainly to the deep middle cerebral vein².

Cytoarchitecture, structural and functional connectivity

Some of the earliest work on the human insula provided evidence for a posterior granular area and an anterior dysgranular area separated by the central insular sulcus^3, 4.

The only study to comprehensively analyze the cytoarchitecture of the human posterior insula using an observer-independent approach points to the existence of three distinct areas therein; two granular areas referred to as Ig1 and Ig2 (“insular lobe granular areas)” found in the dorsal posterior insula, and a dysgranular area labeled Id1 (“d” for dysgranular area) found in the ventral posterior insula⁵. Similarly detailed cytoarchitectonic mapping has not yet been undertaken in the human anterior insula.

Most of the information regarding structural connectivity of the insula is derived from what is known regarding its anatomy in the macaque monkey. Early studies investigating structural connections of the insula in the macaque utilized invasive direct cortical stimulation and ablation techniques.

Direct cortical stimulation of the insula produced motor movements in the face, body, and tail of the macaque monkey and also resulted in changes to respiration, heart beat, blood pressure, and saliva/mucus production⁶.

This suggested direct structural connections between the insula and motor cortices and well as with the autonomic nervous system.

Ablation techniques identified connections of the insula through neural degeneration related to surgically induced insular lesions. Structural white matter degeneration in response to insula ablations were found in the external and extreme capsules, corona radiata, corpus collosum, anterior commissure, and superior/inferior longitudinal fasciculi; these white matter tracts connect the insula with frontal, parietal, temporal, cingular, olfactory, and subcortical brain areas such as the hippocampus and amygdala⁶.

Later macaque studies utilized tracer techniques to identify structural connections from the insula to the frontal cortex, olfactory cortex, parietal lobe, cingulate cortex, somatosensory cortices, and the temporal lobe⁷.

Such tracer studies also identified an anterior-posterior difference for insular structural connections, where more anterior portions of the insula had a greater number of connections to the frontal cortex while posterior portions had a greater number of connections to cingulate and parietal cortices. Additionally, only the anterior insula had connections to the olfactory cortex.

In humans, in-vivo diffusion weighted imaging studies have demonstrated anterior-posterior differences in insular structural connections similar to those found in the macaque.

The anterior portion of the insula primarily has connections with the anterior cingulate, frontal, orbitofrontal, and anterior temporal areas while the posterior insula primarily has connections with posterior temporal, parietal, and sensorimotor areas^8–11. Diffusion studies have also identified a mid-insula “transitional area” that demonstrates structural connections similar to both anterior and posterior insula cortices^8, 9.

Functional connectivity (e.g. temporal correlation in blood-oxygen-level-dependent signal)¹² of the human insular cortex has been examined using resting state fMRI, which measures intrinsic, spontaneous correlations among brain areas¹⁵.

These functional connectivity studies provide evidence for at least three distinct subdivisions within the human insula.

A dorsal anterior insula (dAI) region with connections to frontal, anterior cingulate, and parietal areas is involved in cognitive control processes, a ventral anterior insula (vAI) subdivision has connections with limbic areas and is involved in affective processes, and a mid-posterior insula (PI) subdivision has connections with brain regions for sensorimotor processing^17–19.

Using dynamic functional network connectivity (dFNC) analyses to examine time-varying properties of interactions between insular subdivisions and other brain regions, it has been demonstrated that the dAI exhibits more variable connections than the other insular subdivisions²⁰.

This is in line with earlier work demonstrating functional “diversity” of the dAI, which is active across multiple task domains¹⁹.

Time-varying dFNC analyses and static analyses have also demonstrated that the three functionally distinct insula subdivisions can also act in concert to integrate information within and across cognitive, affective, visual, and sensorimotor networks during an fMRI scan^19, 20.

Thus, the three aforementioned insula subdivisions can operate both independently and cooperatively, demonstrating how the insula can be both specialized and integrative. This may help to explain how the insula serves as a network hub that coordinates information across multiple cognitive domains and processes.

In the most comprehensive multi-modal whole-brain parcellation study to date, Glasser and colleagues²¹ delineated 13 insular/frontal operculum subdivisions on the basis of a combination of features derived from resting state fMRI, task fMRI, myelin maps, and cortical thickness.

In their parcellation scheme these areas are labeled 52, PI (ParaInsular cortex), Ig (Insula granular), Posterior Insular areas PoI1 and PoI2, Frontal Opercular areas FOP2 and FOP3, a Middle Insular area MI, an Anterior Ventral Insular area AVI, an Anterior Agranular Insular Complex AAIC, the Piriform cortex Pir, and Frontal Opercular areas FOP4 and FOP5 (Figure 2).

Insula function

The insula is one of the least understood brain regions. This is mainly due to its location, in the depths of the Sylvian fissure, which makes it difficult to access, and to the very low prevalence of isolated insular lesions²².

Among the first insights about the role of the human insula came from the seminal works by Wilder Penfield using electro-cortical stimulation, in the mid-20^thcentury²³.

After removal of the temporal lobe for the treatment of drug-refractory seizures in patients suffering from epilepsy, stimulation of the exposed inferior portion of the insular cortex elicited a variety of visceral sensory and motor responses, as well as somatic sensory responses, especially in the face, tongue, and upper limbs.

This contributed to the conception of the insula as a primarily visceral-somatic region. While recent investigations have replicated these findings, other types of sensory and motor responses were also documented, thanks to a more complete coverage of the insular cortex by intracranial electrodes^24–26, suggesting a role beyond visceral-somatic processing.

Interest in the function of the insular cortex has increased drastically since the advent of functional neuroimaging techniques, which revealed insular activation in response to a wide variety of stimuli and paradigms, often unexpectedly.

A meta-analysis of nearly 1,800 functional neuroimaging experiments by Kurth and colleagues⁵ suggested the existence of four functionally distinct regions in the human insula:

1) a sensorimotor region located in the mid-posterior insula;

2) a central-olfactogustatory region;

3) a socio-emotional region in the anterior-ventral insula; and

4) a cognitive anterior-dorsal region.

Although these functional subdivisions probably represent an oversimplification of the actual functional neuroanatomy of the insula¹⁹, this broad categorization helps understand the main functions attributed to the insula in relation to its connectivity with other brain areas.

Sensorimotor processing

Visceral sensations, autonomic control, and interoception

Early reports of a large proportion of visceral responses elicited by direct electro-cortical stimulation of the insula prompted researchers to dub the insula the ‘visceral brain’²³.

In recent years, tract-tracing studies have supported the view of a central viscero-somatosensory role for the insula, which is now known to receive visceral afferent projections conveying interoceptive information from all over the body²⁷.

Later studies of direct electro-cortical stimulation confirmed Penfield’s findings^25, 26, 28.

Visceral sensations were described as unpleasant feelings of constriction ranging from a simple breathing discomfort to painful paresthesia, and motor responses included borborygmi and vomiting. This role in visceral processing has led researchers to posit that the insula could also play an important role in the regulation of autonomic function.

This conjecture is supported by reports of heart rate and blood pressure changes following electrical stimulation and focal lesions of the insula^29, 30.

Beyond visceral information processing, it has been proposed that the insula plays a broader role in interoception, i.e., the sense of the physiological condition of the body²⁷.

Indeed, functional neuroimaging studies have reported heightened insular activation when participants are made aware of their thirst, heartbeat, and distention of the esophagus, stomach, bladder, or rectum^27,31.

Congruently, insular lesions have been associated with delayed moment-to-moment awareness of cardiovascular sensations and with anoognosia for hemiplegia/hemiparesis^32, 33.

Craig³¹ proposed a posterior-to-anterior progression of integration of visceral information in the insula, whereby the primary interceptive signals are first represented in its posterior portion, then abstracted in the mid and anterior parts, where integrated perceptual maps of the organism state are more refined.

Somatic processing and pain

Somatosensory manifestations represent a large proportion of responses elicited by electrical stimulation of the insular cortex in humans³⁴.

These include paresthesia such as tingling, electric, warm, cold, shiver, and constriction sensations, predominantly in the contralateral face and arm regions, although ipsilateral, bilateral, and midline regions may be involved. Painful somatic sensations (e.g., pinprick, burning) are also regularly obtained^24, 26, 35.

In neuroimaging studies, both non-painful tactile and painful stimulation lead to insular activation³⁶.

The role of the posterior insula in thermosensory function and pain have received considerable attention. In a seminal PET study, Craig and colleagues³⁷ showed that the intensity of graded cooling of the right hand correlated with activity in the dorsal margin of the contralateral middle/posterior insula, but not in the parietal somatosensory regions, suggesting that the thermosensory cortex is located in the insula.

This has been supported by isolated deficits in temperature perception following lesions of the posterior insula³⁸. The posterior insula is also thought to play a fundamental role in pain perception, showing consistent activation in response to noxious stimuli in neuroimaging studies, irrelevant of modality or body part^39, 40.

Interestingly, strokes and cortical resections involving the posterior insula and the innermost parietal operculum have been associated with a central pain syndrome with dissociated contralateral thermoalgesic sensory loss⁴¹, suggesting an intimate relation between the thermal and nociceptive functions of the insula.

Auditory processing

Involvement of the insular cortex in central auditory processing is not surprising given the efferent projections it receives from the primary auditory, auditory association, and post-auditory cortices¹. As such, auditory responses – mostly illusions and distortions – have been reported following electrical stimulation of the lower posterior part of the insula^24, 25, 28.

Insular activation is also typically observed in functional neuroimaging paradigms involving sound detection, auditory temporal processing, and non-verbal stimuli and phonological processing⁴².

Congruently, central auditory deficits following isolated insular lesions are relatively frequent. In a study of eight patients with strokes affecting the insula, all patients were found to have central auditory deficits including temporal resolution and sequencing deficits⁴³.

Hyperacusis (i.e., increased sensitivity to sounds), as revealed by decreased loudness discomfort levels, was also documented after isolated insular stroke and following insular resection as part of epilepsy surgery⁴⁴, suggesting a role in auditory intensity processing. More anecdotic auditory impairments that have been reported include unilateral deficits in processing speech sounds⁴⁵ and non-verbal auditory agnosia⁴⁶.

Chemosensory functions

The primary gustatory area in nonhuman primates is located in the anterior insula and adjoining frontal operculum, and functional neuroimaging studies suggest that it is located somewhat more caudally in humans, probably in the mid-insula⁴⁷.

The insula is thought to be involved in processing the intensity, quality, and affective value of taste stimuli^47,48.

However, precise localization of the primary gustatory cortex in the insula is complicated by the fact that the same region is also involved in oral somatosensory processing and in higher order processes related to attention to taste and expectations⁴⁹.

The role of the insula in primary processing of taste is further supported by the fact that electrocortical stimulation of the short insular gyri or mid-insular cortex may elicit gustatory hallucinations, such as metallic or bitter taste^26, 28, 34.

A few case studies have also reported taste deficits following insular damage, including ipsi- and bilateral taste recognition and intensity deficits^50, 51.

The insula is also involved in olfaction, although its specific role is less clearly established. In functional neuroimaging studies, the insula is consistently activated by olfactory stimuli, along with other regions including the piriform and orbitofrontal cortex, the amygdala, and the ventral putamen⁵².

Increased contralateral sensitivity to odors and taste has previously been reported following left posterior insular stroke⁵³.

Interestingly, odor intensity changes were more pronounced for unpleasant odors. Increased sensitivity to odors has also been reported by an epileptic patient following right insular resection⁴⁴, which may suggest a role in modulating the intensity of olfactory stimuli.

Vestibular function

The involvement of the parietal operculum-insular region in vestibular processing is supported by various findings. Vestibular responses have been elicited by posterior insular stimulation³⁵.

Recent activation likelihood estimation meta-analyses identified the posterior parietal operculum and retroinsular region as crucial regions for central vestibular processing^54, 55.

Whether the posterior insula per se plays an essential role in vestibular processing remains, however, equivocal.

To our knowledge, only one case study reported vestibular symptoms (i.e., vertigo and imbalance) following isolated insular damage, and the damage was unexpectedly localized in the anterior portion of the insula⁵⁶.

In a study of 10 consecutive cases of acute unilateral stroke restricted to the insula, none of the patients displayed vestibular otolith dysfunction nor vertigo⁵⁷.

Socio-emotional processing

Emotional experience

The James-Lange theory of emotion posits that emotional feelings are activated by bodily changes evoked by emotional stimuli, emphasizing the importance of internal body sensations on the subjective experience of emotions^58, 59.

As a cortical center of visceral information processing and interoception, the anterior insula is thought to play a crucial role in emotional experience and subjective feelings²⁷.

Indeed, inter-individual differences in interoceptive sensitivity correlate with reports of negative emotional experience, both of which are predicted by right anterior insular activation while paying attention to internal bodily processes⁶⁰.

Furthermore, functional neuroimaging employing emotionally arousing stimuli such as disgusting, scaring, happy, sad, or sexual pictures, have also consistently reported activation in the insula³¹.

Cerebral damage involving the insula has been associated with a variety of alterations of subjective emotional experience.

Calder et al.⁶¹ first described the case of a young adult patient who manifested a specific impairment in the experience and recognition of the emotion of disgust following a left hemisphere infarction involving insula and basal ganglia.

Other studies, however, did not find such a specific impairment in disgust experience following insular lesions.

Borg and colleagues⁶² reported the fascinating case of a rare patient who reported her emotions as less intense and who developed a new compulsive need to paint following stroke in the left posterior insula-SII territory. Studies using voxel-based lesion-symptom mapping in patients with traumatic brain injury have associated insular lesions with apathy⁶³, and anxiety⁶⁴.

Empathy and social cognition

Empathy is the ability to perceive, understand and experience others’ feelings in relation to oneself, implying an emotional and cognitive response⁶⁵.

To be processed and felt, this emotion entails interoception and self-awareness to relate to another’s feeling, as well as social cognition and the sensorimotor system for subjective feeling and social interaction, all are functions relating to the insula^31, 65–67.

The role of the anterior insula in empathy has been supported by numerous neuroimaging studies reporting activation in response to others in pain (e.g. painful physical or thermal heat stimuli) and to expressions of disgust, fear, anxiety, and happiness.

In a meta-analysis of fMRI studies on empathy, Fan et al.⁶⁸ found that the right anterior insula was associated with the affective-perceptual form of empathy, while the left insula was associated with both the affective-perceptual and cognitive-evaluative forms of empathy.

The role of the insula in empathy and social cognition has been confirmed in lesion studies. In a voxel-based lesion-symptom mapping study conducted in a large group of patients with focal penetrating traumatic brain injury, lesions localized were associated in the left insula difficulties recognizing both unpleasant and pleasant emotions⁶⁹.

Contrasting with earlier reports of a specific impairment in disgust recognition⁶¹, a consecutive study of 15 patients who underwent insular resection as part of epilepsy surgery reported significant impairments in recognizing facial expressions of fear, happiness, and surprise, but not disgust⁷⁰.

A recent study using intraoperative stimulation in awake patients undergoing neurosurgery for removal of a glioma showed that stimulation of the left insula altered the ability to recognize emotions in facial expressions, which turned out to be statistically significant only for the emotion of disgust⁷¹. Taken together, these studies enlighten the important role of the left anterior insula in social affect, such as empathy, to distinguish primordial emotions like disgust, fear and happiness.

Risky decision making

Decisions under uncertainty are the result of both rational and emotional drives, which is illustrated by the influence of affective states and of judgement biases on decision making^72, 73.

The ‘somatic marker’ hypothesis posits that emotions influence the decision process through internal sensations, visceral, and musculoskeletal physiologic changes which are associated with reinforcing stimuli⁷⁴.

Given its role in viscerosensory processing and its connexions with the orbitofrontal cortex – a key structure in the decision-making circuitry – the insula is likely to play a critical role in risky decisions.

This is supported by robust insular activation revealed by neuroimaging during gambling tasks, in which decisions must be made between options associated with uncertain outcomes (e.g.,^75, 76).

In an fMRI experiment, anterior insular activation has been found to mediate the relationship between mood state and decision bias⁷⁷.

Despite limited by small sample size and heterogeneity in the extent of cerebral damage, a growing number of studies using gambling tasks in patients with insular lesions have reported decision making deficits.

The gambler’s fallacy and near-miss effects, two types of cognitive biases affecting decision making in healthy individuals, were found to be absent in stroke patients with insular damage⁷⁸.

In a group of patients who underwent selective operculo-insular resection for drug-resistant epileptic seizures, sensitivity to expected value when making risky vs. safe decisions was found to be selectively impaired when facing a potential loss⁷⁹, consistent with a role in loss aversion⁸⁰.

Taken together, these findings suggest that the insula is actively involved in the emotional aspects of risky decision making.

Cognitive functions

Attention and salience processing

The insula is one of the most popular brain regions in cognitive neuroscience, with a high likelihood of activation across various states⁸¹.

One of the most consistent findings with respect to insula function is its involvement in detection of novel stimuli across sensory modalities. Insula activation, along with dorsal anterior cingulate (dACC), is observed in response to “oddball” stimuli interspersed among a series of the same item^82, 83.

Together, the insula and dACC, amygdala, and other subcortical structures are often referred to as the “salience network”, the function of which is to identify the most homeostatically relevant among multiple competing internal and external stimuli⁸⁴.

Analysis of effective or causal connectivity across auditory, visual, and task-free conditions demonstrate that the dorsal anterior insula causally influences other large-scale brain networks including the default mode network (DMN, underlying self-related and social cognitive processes) and central executive network (CEN, which implements the maintenance and manipulation of information and decision-making)⁸⁵.

In tasks requiring greater cognitive control, the dAI exerts stronger causal influence⁸⁶.

Taken together, the body of available empirical work suggests that the dAI is in a position to integrate external sensory information with internal emotional and bodily state signals to coordinate brain network dynamics and to initiate switches between the DMN and CEN⁸⁷.

Speech

Although the contribution of Broca’s area to language production is undisputed, there is considerable evidence suggesting that the insular cortex is also involved in speech, although controversy remains concerning the nature of its contribution(s).

Dronkers⁸⁸ found that the left precentral insular gyrus was damaged in all of her stroke patients suffering from apraxia of speech, suggesting a role in the motor planning of speech.

This was supported later by a voxel-based lesion symptom mapping study which showed that performance on an articulation task was dependent on the left precentral insular gyrus⁸⁹.

However, although speech deficits have been reported following isolated left insular strokes and resections, patients most often fully recover in days or weeks following lesion^{22, 90}, which questions the critical role of the left insula in speech production.

Furthermore, the contribution of the insula to speech may not be confined to the dominant hemisphere, as right posterior insula damage has also been related to dysarthria⁹¹.

Congruently, electric stimulation of the insular cortex from both hemispheres has also been associated with speech arrest, dysarthria, and reduced voice intensity^24, 25, 34. In their study of 10 patients with isolated insular stroke, Baier et al.⁵⁷ reported that only those with left hemisphere damage showed aphasia during the acute period, while damage to either of the hemispheres displayed dysarthria.

In a group of 18 epileptic patients who underwent insulectomy, although expressive aphasia was observed in the post-surgery period in patients with left hemisphere resections, the only statistically significant long-lasting (> 6 months) deterioration on a standard neuropsychological assessment battery was a slight delay in oro-motor speed, and this effect was also present when analyses were restricted to right-hemisphere surgeries⁷⁰.

In conclusion, the insula appears to be involved in speech production, but whether this role is critical or secondary (e.g., through higher-order articulatory processes), remains unclear⁹².

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Source:
Elsevier
Media Contacts: 
Damon Mastandrea – Elsevier
Image Source:
The image is credited to the researchers/Brain Stimulation.

Original Research: Open access
“The role of the dorsal anterior insula in ecstatic sensation revealed by direct electrical brain stimulation”. F. Bartolomei, S. Lagardea,b, D. Scavarda, R. Carron, C.G. Bénar, F. Picard.
Brain Stimulation. doi:10.1016/j.brs.2019.06.005