Background/Objectives: The human insula is a key structure implicated in integrating internal states and external food cues, yet its precise role remains unclear, in part due to the temporal limitations of neuroimaging techniques like fMRI. To address this gap, we conducted an exploratory study using an intracranial EEG (iEEG) to investigate how the insula encodes both the subjective and objective properties of food-related stimuli, and how this encoding is modulated by hunger and satiety. Methods: Eight patients with drug-resistant epilepsy undergoing a pre-surgical evaluation between 2017 and 2023 participated in this study. Depth electrodes implanted in the insular cortex recorded event-related potentials (ERPs) in response to visual food cues. The sessions were conducted in two prandial states (hungry and satiated). The subjective ratings (appetite and palatability) and objective nutritional values (e.g., calories, carbohydrates) were collected and analyzed using paired t-tests, MANOVAs, and partial correlations. Results: Hunger increased the ERP amplitudes within the 350-450 ms interval, consistent with the EPIC model and positive alliesthesia, while satiety unexpectedly enhanced the early responses (150-250 ms). Importantly, the neural activity related to nutritional values was largely uncorrelated with the subjective ratings, suggestive of distinct processing streams. The mid- and posterior insula showed greater sensitivity to both subjective and nutritional information than the anterior insula. Conclusions: These findings offer novel electrophysiological insights into how the insula differentiates between implicit and explicit food-related signals, depending on the homeostatic state. This work supports a dual-route model of food cue processing, and may inform interventions targeting insular activity in disordered eating.

Background/Objectives: The insula is a deep, functionally heterogeneous region involved in various pathological conditions. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic avenue for neuromodulation, yet very few studies have directly investigated its effects on insular activity. Moreover, empirical evidence of target engagement of this region remains scarce. This study aimed to stimulate the insula with rTMS and assess blood oxygen level-dependent (BOLD) signal modulation using concurrent functional magnetic resonance imaging (fMRI). Methods: Ten participants were recruited, six of whom underwent a single session of 5 Hz high-frequency rTMS over the right insular cortex inside the MRI scanner. Stimulation was delivered using a compatible MRI-B91 TMS coil. Stimulation consisted of 10 trains of 10 s each, with a 50 s interval between trains. Frameless stereotactic neuronavigation ensured precise targeting. Paired t-tests were used to compare the mean BOLD signal obtained between stimulation trains with resting-state fMRI acquired before the rTMS stimulation session. A significant cluster threshold of q < 0.01 (False Discovery Rate; FDR) with a minimum cluster size of 10 voxels was applied. Results: Concurrent rTMS-fMRI revealed the significant modulation of BOLD activity within insular subregions. Increased activity was observed in the anterior, middle, and middle-inferior insula, while decreased activity was identified in the ventral anterior and posterior insula. Additionally, two participants reported transient dysgeusia following stimulation, which provides further evidence of insular modulation. Conclusions: These findings provide preliminary evidence that rTMS can modulate distinct subregions of the insular cortex. The combination of region-specific BOLD responses and stimulation-induced dysgeusia supports the feasibility of using rTMS to modulate insular activity.

ObjectiveThe use of medical cannabis among people with epilepsy (PWE) has been garnering increasing interest. In this scoping review, we aimed to summarize the literature on recreational/non-medical cannabis (NMC) use in PWE, focusing on the experience, habits, and beliefs of PWE regarding NMC.MethodsFour databases (OVID Medline, OVID Embase, Ovid APA PsycInfo, and Web of Science) were searched for studies describing NMC use in PWE. NMC was defined as cannabis products procured from sources other than by prescription. Studies that consisted in original research and that detailed the experience, habits, and/or beliefs of PWE regarding NMC use were included in the analysis. Data pertaining to study identification, demographics, NMC use, and epilepsy characteristics were extracted. Descriptive statistical analyses and reflexive thematic analyses were performed to map these data.ResultsIn total, 3,228 records were screened, and 66 were included for analysis: 45 had mainly adult samples, whereas 21 had mainly pediatric samples. Most studies were published after 2010, originated from the USA, and were cross-sectional. The median number of PWE using cannabis in these studies was 24.5 (1–37,945). No studies showcased elderly PWE, and most had predominantly Caucasian samples. The lifetime prevalence of NMC use in PWE was variable, ranging between 0.69 and 76.8%. Factors frequently associated with NMC use in PWE were male sex, younger adult age, and lower education status. Children with epilepsy took NMC primarily for seizure control, using high CBD/THC ratios, and only orally. Adults with epilepsy took NMC for various reasons including recreationally, using variable CBD/THC ratios, and predominantly through smoking. The majority of PWE across all studies perceived that NMC aided in seizure control. Other aspects pertaining to NMC use in PWE were rarely reported and often conflicting.ConclusionThe literature on NMC use in PWE is sparse and heterogeneous, with many salient knowledge gaps. Further research is necessary to better understanding the experience, habits, and beliefs of PWE pertaining to NMC.

Background: Auditory seizures (AS) are a rare type of focal seizures. AS are classically thought to involve a seizure onset zone (SOZ) in the temporal lobe, but there remain uncertainties about their localizing and lateralizing value. We conducted a narrative literature review with the aim of providing an up-to-date description of the lateralizing and localizing value of AS. Methods: The databases PubMed, Scopus, and Google Scholar were searched for literature on AS in December 2022. All cortical stimulation studies, case reports, and case series were analyzed to assess for auditory phenomena that were suggestive of AS and to evaluate if the lateralization and/or localization of the SOZ could be determined. We classified AS according to their semiology (e.g., simple hallucination versus complex hallucination) and the level of evidence with which the SOZ could be predicted. Results: A total of 174 cases comprising 200 AS were analyzed from 70 articles. Across all studies, the SOZ of AS were more often in the left (62%) than in the right (38%) hemisphere. AS heard bilaterally followed this trend. Unilaterally heard AS were more often due to a SOZ in the contralateral hemisphere (74%), although they could also be ipsilateral (26%). The SOZ for AS was not limited to the auditory cortex, nor to the temporal lobe. The areas more frequently involved in the temporal lobe were the superior temporal gyrus (STG) and mesiotemporal structures. Extratemporal locations included parietal, frontal, insular, and rarely occipital structures. Conclusion: Our review highlighted the complexity of AS and their importance in the identification of the SOZ. Due to the limited data and heterogeneous presentation of AS in the literature, the patterns associated with different AS semiologies warrant further research.& COPY; 2023 Elsevier Inc. All rights reserved.

Insular epilepsy is increasingly recognized in epilepsy surgery centers. Recent studies suggest that resection of an epileptogenic zone that involves the insula as a treatment for drug-resistant seizures is associated with good outcomes in terms of seizure control. However, despite the existing evidence of a role of the insula in emotions and affective information processing, the long-term psychological outcome of patients undergoing these surgeries remain poorly documented. A group of 27 adults (18 women) who underwent an insulo-opercular resection (in combination with a part of the temporal lobe in 10, and of the frontal lobe in 5) as part of epilepsy surgery at our center between 2004 and 2019 completed psychometric questionnaires to assess depression (Beck Depression Inventory - 2nd edition; BDI-II), anxiety (State-Trait Anxiety Inventory, Trait Version; STAI-T), and quality of life (Patient Weighted Quality of Life In Epilepsy; QOLIE-10-P). Scores were compared to those of patients who had standard temporal lobe epilepsy (TLE) surgery with similar socio-demographic and disease characteristics. Seizure control after insular epilepsy surgery was comparable to that observed after TLE surgery, with a majority of patients reporting being seizure free (insular: 63.0%; temporal: 63.2%) or having rare disabling seizures (insular: 7.4%; temporal: 18.4%) at the time of questionnaire completion. Statistical comparisons revealed no significant group difference on scores of depression, anxiety, or quality of life. Hemisphere or extent of insular resection had no significant effect on the studied variables. In the total sample, employment status and seizure control, but not location of surgery, significantly predicted quality of life. Self-reported long-term psychological status after insulo-opercular resection as part of epilepsy surgery thus appears to be similar to that observed after TLE surgery, which is commonly performed in epilepsy surgery centers. (C) 2021 Elsevier Inc. All rights reserved.

Entrenched deep within the Sylvian fissure, the insula has long been considered one of the least understood regions of the human brain, in part due to its restricted accessibility. However, recent evidence suggests that the insula plays a key role in gustation, interoception, cognitive and emotional processes, and likely integrates these different functions to contribute to the homeostatic control of food intake. In the past decade, our team has identified the insula as a potential site of epileptogenicity, which can be successfully treated by microsurgical resection. While most surgeries are successful in controlling insular epileptic seizures and lead to few postoperative deficits, the subtle changes that may occur in food-related experiences are still unknown. Using a selfreport questionnaire, the present study sought to fill this gap by assessing changes in appetite in patients who underwent unilateral partial or complete insular resections (n = 17) as part of their epilepsy surgery. We compared them to a group of patients who underwent temporal lobe epilepsy surgery (n = 22) as a lesion-control group. A majority (59%) of the insular patients reported an alteration in appetite, with most of these changes being characterized by a persistent reduction. Such changes were rarely reported following temporal lobectomy (14%). While they significantly differed in terms of appetite changes, both groups were similar when examining post-surgical changes in weight, diet, exercise and eating habits. Insular patients with altered appetite also showed behavioral signs of dysfunctional interoceptive and gustatory functions, corroborating the idea that these systems play a role in the regulation of feeding behaviours. This research pushes our understanding of the mechanisms underlying food intake and could lead to avenues for the treatment of eating disorders.

Functional neuroimaging studies using auditory stimuli consistently show activation of the insular cortex. However, due to the limited temporal resolution of non-invasive neuroimaging techniques, the role(s) of the insula in auditory processing remains unclear. As the anterior insula (aI) and the posterior insula (pI) have different connections and are thought to be functionally distinct, it is likely that these two areas contribute differently to auditory processing. Our study examines the spatiotemporal dynamics of auditory processing in the insula using intracranial electroencephalography (EEG). Eight epileptic patients completed two passive listening tasks and one three-stimulus auditory oddball detection task during the intracranial EEG monitoring of their drug-resistant seizures. Recordings were obtained from depth electrodes implanted in 11 insulae. Event-related potentials (ERPs) were analyzed using permutation analyses during the N100 and the P300 intervals, and modulations of alpha, theta, and gamma band responses were compared using Wilcoxon/Mann–Whitney analyses. N100 responses to auditory stimuli were mostly observed in the pI and were little affected by task conditions. Auditory target detection was associated with P300 ERPs, and alpha, theta, high- and low-gamma responses, preferentially at aI contacts. Results suggest that the aI is involved in voluntary attentional processing of task-relevant information, whereas the pI is involved in automatic auditory processing.

Depressive symptoms and anxiety are common complaints in patients who have had epilepsy surgery. Recent studies have reported disturbances in emotional memory, facial and vocal emotion recognition, and affective learning after temporal lobe and/or insular resection for drug-resistant seizures, suggesting that these regions may be involved in emotional processes underlying psychological symptoms. The insula is a core component of the salience network and is thought to be involved in processing emotions such as disgust, and the role of mesial temporal lobe structures in affective processing is well established. However, to our knowledge, no study has yet investigated whether attentional processing of affective information is altered when these structures are resected as part of an epilepsy surgery. The present study examined the interference control capacity and attentional biases for emotional information in adult patients with epilepsy who underwent temporal lobe resections including the amygdala and hippocampus (n = 15) and/or partial or complete insular resections (n = 16). Patients were tested on an Emotional Stroop test and on a Dot-Probe task using fearful and disgusting pictures and were compared with a healthy control group (n = 30) matched for age, gender, and education. Repeated-measures analyses of variances revealed a significant effect of emotional words on color naming speed in the Emotional Stroop task among insular patients, which was not observed in the other groups. By contrast, the groups did not differ on Dot-Probe task performance. These preliminary findings suggest that insular damage may alter emotional interference control.

The insular cortex is now well-established as a potential site of epileptogenesis in patients with drug-resistant epilepsy, and its resection has been associated with good outcomes in terms of seizure control. However, given the role of the insula in sensory processing and in visceral information integration, it remains unclear whether insular cortex epilepsy and its surgery are associated with disturbances in sensory information processing and visceral sensation processes as experienced in daily life. In the present study, we examined such sensory disturbances in a group of patients (n = 17) who underwent epilepsy surgery involving a resection of the insula and compared them to a lesion-control group of patients with temporal epilepsy surgery (n = 22) and a healthy control group (n = 29) matched for age, gender, and education. Participants were assessed on the self-report "Adolescent/Adult Sensory Profile" questionnaire at least four months after surgery. Our series of one-way analyses of variance (ANOVAs) revealed that insular and temporal resections in patients with drug-refractory epilepsy were associated with a low "sensation seeking" behavior reflecting a lack of engagement with sensory inputs from the environment. Furthermore, insular resections were associated with impairments in the "active behavioral responses" for the gustatory/olfactory modalities. These preliminary findings suggest that insular resections may be associated with mild to moderate alterations in sensory processing.

Functional neuroimaging studies suggest that the insular cortex—and more especially the anterior insula (aI)—is involved in attentional processes and plays a crucial role in the “salience network”. However, its specific role in attentional processing remains unclear, which is partly attributable to the low temporal resolution of non-invasive neuroimaging techniques. This study aims to examine the spatio-temporal dynamics of visual target processing using intracranial EEG recorded directly from the insula. Eight epileptic patients (four women, age 18–44 years) completed a three-stimulus visual oddball task during the extraoperative invasive intracranial EEG (iEEG) monitoring of their drug-resistant seizures. Depth electrodes were implanted in ten insular lobes (5 left and 5 right) and provided a total of 59 recording contacts in the insula. Event-related potentials (ERPs) and high-gamma-band responses (GBRs) were processed offline. Permutation analyses were performed to compare ERP signals across conditions during the P300 (225–400) interval, and modulations of GBRs (70−150 Hz) were computed for separate 100 ms time windows (from 0 to 1000 ms post-stimulus) and compared across conditions using non-parametric Wilcoxon test. Target stimuli were associated with a P300 (250–338 ms) component for 39% of contacts implanted in the aI, most probably reflecting voluntary attentional processing. Amplitude was significantly greater for target than for standard stimuli for all of these contacts, and was greater than for novel stimuli for 72%. In the posterior insula (pI), 16% of contacts showed preferential responses to target stimulus in the P300 interval. Increased GBRs in response to targets were observed in 53% of aI contacts (from ≈ 200 to 300 ms) and in 43% of pI contacts (from ≈ 400 to 500 ms). This study is the first to characterize the spatio-temporal dynamics of visual target processing in the insula using iEEG. Results suggest that visual targets elicit a P300 in the aI which corresponds in latency to the P3b component, suggesting that this region is involved in top–down processing of task-relevant information. GBRs to visual targets occur earlier in the aI than in the pI, further characterizing their respective roles in voluntary attentional processing.

The insula, considered as the fifth lobe of the human brain, is one of the least understood areas of the brain, and its role in neuropsychological functioning remains enigmatic for many. In recent years, electrocortical stimulation, lesion, and neuroimaging studies in humans have shed light on several functions of this brain region. However, these functions are often looked at separately. This review article aims to summarize the current knowledge about the functions of the insula in humans. After a brief description of the anatomy and connectivity of the insula, we review its role in three main domains of neuropsychological function: (1) sensorimotor processing (viscerosensory and visceromotor function, interoception, somatosensory processing, and chemosensation); (2) emotion processing (emotional experience, empathy, and risky decision-making); and (3) cognitive functions (salience processing and speech). Broad anatomo-functional subdivisions within the insular lobe itself are presented. Finally, the insula’s potential involvement in psychopathology, especially anxiety, schizophrenia, autism, and addiction, are discussed. The insula's contribution to these many functions and pathologies may largely be attributable to its role in the subjective representation of body states. This article provides clinical neuropsychologists and researchers with a global and exhaustive portrait of the insula's role in neuropsychological functioning.