2022

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10 pages, 1917 KiB

Open AccessArticle

Acute Effects of High-Frequency Insular Stimulation on Interictal Epileptiform Discharge Rates in Patients with Refractory Epilepsy

by Thi Phuoc Yen Tran, Antoine Dionne, Denahin Toffa, David Bergeron, Sami Obaid, Manon Robert, Alain Bouthillier, Elie Bou Assi and Dang Khoa Nguyen

Brain Sci. 2022, 12(12), 1616; https://doi.org/10.3390/brainsci12121616 - 25 Nov 2022

Viewed by 1076

Abstract

Rationale: Deep brain stimulation (DBS) of several sites, such as the thalamus, has been shown to reduce seizure frequency and interictal epileptiform activity in patients with refractory epilepsy. Recent findings have demonstrated that the insula is part of the ‘rich club’ of [...] Read more.

Rationale: Deep brain stimulation (DBS) of several sites, such as the thalamus, has been shown to reduce seizure frequency and interictal epileptiform activity in patients with refractory epilepsy. Recent findings have demonstrated that the insula is part of the ‘rich club’ of highly connected brain regions. This pilot study investigated short-term effects of high-frequency (HF) insular DBS on interictal epileptiform discharge (IED) rate in patients with refractory epilepsy. Methods: Six patients with drug-resistant epilepsy undergoing an intracranial electroencephalographic study received two sets of 10 min continuous 150 Hz HF-DBS of the insula. For each patient, epileptiform activity was analyzed for a total of 80 min, starting 20 min prior to stimulation set 1 (S1), and ending 20 min after stimulation set 2 (S2). All IEDs were identified and classified according to their anatomic localization by a board-certified epileptologist. The IED rate during the 20 min preceding S1 served as a baseline for comparison with IED rate during S1, S2 and post-stimulation periods. Results: HF-DBS of the anterior insula (aINS) was performed in a patient with an aINS epileptic focus (patient 1). HF-DBS of the posterior insula (pINS) was performed in two patients with a pINS epileptic focus (patients 2 and 4), in one patient with an aINS focus (patient 3), and in two non-insular patients (patients 5 and 6). The total IED (irrespective of their location) rate significantly decreased (p < 0.01) in two patients (patients 1 and 2) during the stimulation period, whereas it significantly increased (p < 0.01) in one patient (patient 6); there was no change in the other three patients. Looking at subsets of spike localization, HF-DBS of the aINS significantly reduced aINS and orbitofrontal IEDs in patient 1 (p < 0.01), while HF-DBS of the pINS had an effect on pINS IEDs (p < 0.01) in both patients with a pINS focus; there was no significant effect of HF-DBS of the insula on IEDs in temporal or other frontal regions. Conclusion: Short-term HF-DBS of the insula had heterogeneous effects on the IED rate. Further work is required to examine factors underlying these heterogeneous effects, such as stimulation frequency, location of IEDs and subregions of the insula stimulated. Full article

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16 pages, 283 KiB

Open AccessEditor’s ChoiceArticle

Insular Involvement in Cases of Epilepsy Surgery Failure

by Jimmy Li, Sandra Reiter-Campeau, Dina Namiranian, Dènahin Hinnoutondji Toffa, Alain Bouthillier, François Dubeau and Dang Khoa Nguyen

Brain Sci. 2022, 12(2), 125; https://doi.org/10.3390/brainsci12020125 - 18 Jan 2022

Cited by 7 | Viewed by 2304

Abstract

Background: Epilepsy surgery failure is not uncommon, with several explanations having been proposed. In this series, we detail cases of epilepsy surgery failure subsequently attributed to insular involvement. Methods: We retrospectively identified patients investigated at the epilepsy monitoring units of two Canadian tertiary [...] Read more.

Background: Epilepsy surgery failure is not uncommon, with several explanations having been proposed. In this series, we detail cases of epilepsy surgery failure subsequently attributed to insular involvement. Methods: We retrospectively identified patients investigated at the epilepsy monitoring units of two Canadian tertiary care centers (2004–2020). Included patients were adults who had undergone epilepsy surgeries with recurrence of seizures post-operatively and who were subsequently determined to have an insular epileptogenic focus. Clinical, electrophysiological, neuroimaging, and surgical data were synthesized. Results: We present 14 patients who demonstrated insular epileptic activity post-surgery-failure as detected by intracranial EEG, MEG, or seizure improvement after insular resection. Seven patients had manifestations evoking possible insular involvement prior to their first surgery. Most patients (8/14) had initial surgeries targeting the temporal lobe. Seizure recurrence ranged from the immediate post-operative period to one year. The main modality used to determine insular involvement was MEG (8/14). Nine patients underwent re-operations that included insular resection; seven achieved a favorable post-operative outcome (Engel I or II). Conclusions: Our series suggests that lowering the threshold for suspecting insular epilepsy may be necessary to improve epilepsy surgery outcomes. Detecting insular epilepsy post-surgery-failure may allow for re-operations which may lead to good outcomes. Full article

2021

Jump to: 2022

17 pages, 1497 KiB

Open AccessArticle

MR Spectroscopy of the Insula: Within- and between-Session Reproducibility of MEGA-PRESS Measurements of GABA+ and Other Metabolites

by Claire Shyu, Sonja Elsaid, Peter Truong, Sofia Chavez and Bernard Le Foll

Brain Sci. 2021, 11(11), 1538; https://doi.org/10.3390/brainsci11111538 - 19 Nov 2021

Cited by 3 | Viewed by 2055

Abstract

The insula plays a critical role in many neuropsychological disorders. Research investigating its neurochemistry with magnetic resonance spectroscopy (MRS) has been limited compared with cortical regions. Here, we investigate the within-session and between-session reproducibility of metabolite measurements in the insula on a 3T [...] Read more.

The insula plays a critical role in many neuropsychological disorders. Research investigating its neurochemistry with magnetic resonance spectroscopy (MRS) has been limited compared with cortical regions. Here, we investigate the within-session and between-session reproducibility of metabolite measurements in the insula on a 3T scanner. We measure N-acetylaspartate + N-acetylaspartylglutamate (tNAA), creatine + phosphocreatine (tCr), glycerophosphocholine + phosphocholine (tCho), myo-inositol (Ins), glutamate + glutamine (Glx), and γ-aminobutyric acid (GABA) in one cohort using a j-edited MEGA-PRESS sequence. We measure tNAA, tCr, tCho, Ins, and Glx in another cohort with a standard short-TE PRESS sequence as a reference for the reproducibility metrics. All participants were scanned 4 times identically: 2 back-to-back scans each day, on 2 days. Preprocessing was done using LCModel and Gannet. Reproducibility was determined using Pearson’s r, intraclass-correlation coefficients (ICC), coefficients of variation (CV%), and Bland–Altman plots. A MEGA-PRESS protocol requiring averaged results over two 6:45-min scans yielded reproducible GABA measurements (CV% = 7.15%). This averaging also yielded reproducibility metrics comparable to those from PRESS for the other metabolites. Voxel placement inconsistencies did not affect reproducibility, and no sex differences were found. The data suggest that MEGA-PRESS can reliably measure standard metabolites and GABA in the insula. Full article

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12 pages, 1916 KiB

Open AccessReview

The Insula: A Stimulating Island of the Brain

by Inès Rachidi, Lorella Minotti, Guillaume Martin, Dominique Hoffmann, Julien Bastin, Olivier David and Philippe Kahane

Brain Sci. 2021, 11(11), 1533; https://doi.org/10.3390/brainsci11111533 - 19 Nov 2021

Cited by 7 | Viewed by 3455

Abstract

Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and [...] Read more.

Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and trigger seizures. Clinical responses to insular DCS are frequent and diverse, showing a partial segregation with spatial overlap, including a posterior somatosensory, auditory, and vestibular part, a central olfactory-gustatory region, and an anterior visceral and cognitive-emotional portion. The study of cortico-cortical evoked potentials (CCEPs) has shown that the anterior (resp. posterior) insula has a higher connectivity rate with itself than with the posterior (resp. anterior) insula, and that both the anterior and posterior insula are closely connected, notably between the homologous insular subdivisions. All insular gyri show extensive and complex ipsilateral and contralateral extra-insular connections, more anteriorly for the anterior insula and more posteriorly for the posterior insula. As a rule, CCEPs propagate first and with a higher probability around the insular DCS site, then to the homologous region, and later to more distal regions with fast cortico-cortical axonal conduction delays. Seizures elicited by insular DCS have rarely been specifically studied, but their rate does not seem to differ from those of other DCS studies. They are mainly provoked from the insular seizure onset zone but can also be triggered by stimulating intra- and extra-insular early propagation zones. Overall, in line with the neuroimaging studies, insular DCS studies converge on the view that the insula is a multimodal functional hub with a fast propagation of information, whose organization helps understand where insular seizures start and how they propagate. Full article

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31 pages, 861 KiB

Open AccessArticle

Heart Rate Variability in Insulo-Opercular Epilepsy

by Thi Phuoc Yen Tran, Philippe Pouliot, Elie Bou Assi, Pierre Rainville, Kenneth A. Myers, Manon Robert, Alain Bouthillier, Mark R. Keezer and Dang Khoa Nguyen

Brain Sci. 2021, 11(11), 1505; https://doi.org/10.3390/brainsci11111505 - 13 Nov 2021

Viewed by 1782

Abstract

Background: We aimed to evaluate heart rate variability (HRV) changes in insulo-opercular epilepsy (IOE) and after insulo-opercular surgery. Methods: We analyzed 5-min resting HRV of IOE patients before and after surgery. Patients’ SUDEP-7 risk inventory scores were also calculated. Results were compared with [...] Read more.

Background: We aimed to evaluate heart rate variability (HRV) changes in insulo-opercular epilepsy (IOE) and after insulo-opercular surgery. Methods: We analyzed 5-min resting HRV of IOE patients before and after surgery. Patients’ SUDEP-7 risk inventory scores were also calculated. Results were compared with age- and sex-matched patients with temporal lobe epilepsy (TLE) and healthy individuals. Results: There were no differences in HRV measurements between IOE, TLE, and healthy control groups (and within each IOE group and TLE group) in preoperative and postoperative periods. In IOE patients, the SUDEP-7 score was positively correlated with pNN50 (percentage of successive RR intervals that differ by more than 50 ms) (p = 0.008) and RMSSD (root mean square of successive RR interval differences) (p = 0.019). We stratified IOE patients into those whose preoperative RMSSD values were below (Group 1a = 7) versus above (Group 1b = 9) a cut-off threshold of 31 ms (median value of a healthy population from a previous study). In group 1a, all HRV values significantly increased after surgery. In group 1b, time-domain parameters significantly decreased postoperatively. Conclusions: Our results suggest that in IOE, HRV may be either decreased in parasympathetic tone or increased globally in both sympathetic and parasympathetic tones. We found no evidence that insulo-opercular surgeries lead to major autonomic dysfunction when a good seizure outcome is reached. The increase in parasympathetic tone observed preoperatively may be of clinical concern, as it was positively correlated with the SUDEP-7 score. Full article

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8 pages, 1538 KiB

Open AccessReview

Epilepsy and Ecstatic Experiences: The Role of the Insula

by Fabienne Picard, Peter Bossaerts and Fabrice Bartolomei

Brain Sci. 2021, 11(11), 1384; https://doi.org/10.3390/brainsci11111384 - 22 Oct 2021

Cited by 11 | Viewed by 2601

Abstract

Ecstatic epilepsy is a rare form of focal epilepsy in which the aura (beginning of the seizures) consists of a blissful state of mental clarity/feeling of certainty. Such a state has also been described as a “religious” or mystical experience. While this form [...] Read more.

Ecstatic epilepsy is a rare form of focal epilepsy in which the aura (beginning of the seizures) consists of a blissful state of mental clarity/feeling of certainty. Such a state has also been described as a “religious” or mystical experience. While this form of epilepsy has long been recognized as a temporal lobe epilepsy, we have accumulated evidence converging toward the location of the symptomatogenic zone in the dorsal anterior insula during the 10 last years. The neurocognitive hypothesis for the genesis of a mental clarity is the suppression of the interoceptive prediction errors and of the unexpected surprise associated with any incoming internal or external signal, usually processed by the dorsal anterior insula. This mimics a perfect prediction of the world and induces a feeling of certainty. The ecstatic epilepsy is thus an amazing model for the role of anterior insula in uncertainty and surprise. Full article

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16 pages, 301 KiB

Open AccessArticle

Emotional Autobiographical Memory Associated with Insular Resection in Epileptic Patients: A Comparison with Temporal Lobe Resection

by Mélanie Descamps, Olivier Boucher, Dang Khoa Nguyen and Isabelle Rouleau

Brain Sci. 2021, 11(10), 1316; https://doi.org/10.3390/brainsci11101316 - 03 Oct 2021

Cited by 3 | Viewed by 1673

Abstract

The insula is involved in a wide variety of functions, including social and emotional processing. Despite the numerous connections it shares with brain structures known to play a role in autobiographical memory (AM), little is known on the contribution of the insula to [...] Read more.

The insula is involved in a wide variety of functions, including social and emotional processing. Despite the numerous connections it shares with brain structures known to play a role in autobiographical memory (AM), little is known on the contribution of the insula to AM processing. The aim of the study was to examine emotional AM retrieval in patients with insular resection for drug-resistant epilepsy. Ten patients who underwent partial or complete insular resection (IR) were matched on age, sex, and education, to fifteen patients who underwent temporal lobectomy (TL), and to fifteen healthy controls. Participants were asked to recall four positive, four negative, and four neutral memories from their past using the autobiographical interview procedure. The results suggest that AM for emotional and neutral events after IR was comparable to that of healthy controls, whereas deficits were observed after TL. However, an independent examiner judged IR patients’ memories as poorer than those of healthy controls on the episodic richness scale, suggesting a lack of some aspects of rich and vivid remembering. Furthermore, analysis on subjective self-rated scales revealed that, contrary to healthy controls, patients with IR judged their neutral memories as more emotional. This study suggests that AM is generally preserved after IR. However, given the small sample size and varied lesion location, one cannot totally exclude a potential role of specific insular sub-regions on some aspects of autobiographical memory. In addition, IR patients showed poor emotional judgment for neutral memories, which is congruent with previous findings of altered emotional processing in this population. Full article

17 pages, 8377 KiB

Open AccessArticle

The Self and Its Right Insula—Differential Topography and Dynamic of Right vs. Left Insula

by Andrea Scalabrini, Angelika Wolman and Georg Northoff

Brain Sci. 2021, 11(10), 1312; https://doi.org/10.3390/brainsci11101312 - 02 Oct 2021

Cited by 21 | Viewed by 2965

Abstract

Various studies demonstrate a special role of the right compared to the left anterior insula in mediating our self. However, the neural features of the right insula that allow for its special role remain unclear. Presupposing a spatiotemporal model of self—“Basis model of [...] Read more.

Various studies demonstrate a special role of the right compared to the left anterior insula in mediating our self. However, the neural features of the right insula that allow for its special role remain unclear. Presupposing a spatiotemporal model of self—“Basis model of self-specificity” (BMSS)—we here address the following question: what spatial-topographic and temporal-dynamic features render neural activity in the right insula to be more suitable in mediating self-specificity than the left insula? First, applying fMRI, we demonstrate that the right insula (i) exhibits higher degrees of centrality in rest, and (ii) higher context-dependent functional connectivity in a self-specific task among regions of distinct layers of self (intero-, extero-proprioceptive, and mental). Second, using EEG in rest and task, we show that the right insula shows longer autocorrelation window (ACW) in its neural activity than both left insula and other regions of the different layers of self. Together, we demonstrate special topographic, i.e., high functional connectivity, and dynamic, i.e., long ACW, neural features of the right insula compared to both left insula and other regions of the distinct layers of self. This suits neural activity in the right insula ideally for high functional integration and temporal continuity as key features of the self including its intero-, extero-proprioceptive, and mental layers. Full article

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16 pages, 4773 KiB

Open AccessArticle

Structural Connectivity Alterations in Operculo-Insular Epilepsy

by Sami Obaid, François Rheault, Manon Edde, Guido I. Guberman, Etienne St-Onge, Jasmeen Sidhu, Alain Bouthillier, Alessandro Daducci, Jimmy Ghaziri, Michel W. Bojanowski, Dang K. Nguyen and Maxime Descoteaux

Brain Sci. 2021, 11(8), 1041; https://doi.org/10.3390/brainsci11081041 - 05 Aug 2021

Cited by 6 | Viewed by 3086

Abstract

Operculo-insular epilepsy (OIE) is an under-recognized condition that can mimic temporal and extratemporal epilepsies. Previous studies have revealed structural connectivity changes in the epileptic network of focal epilepsy. However, most reports use the debated streamline-count to quantify ‘connectivity strength’ and rely on standard [...] Read more.

Operculo-insular epilepsy (OIE) is an under-recognized condition that can mimic temporal and extratemporal epilepsies. Previous studies have revealed structural connectivity changes in the epileptic network of focal epilepsy. However, most reports use the debated streamline-count to quantify ‘connectivity strength’ and rely on standard tracking algorithms. We propose a sophisticated cutting-edge method that is robust to crossing fibers, optimizes cortical coverage, and assigns an accurate microstructure-reflecting quantitative conectivity marker, namely the COMMIT (Convex Optimization Modeling for Microstructure Informed Tractography)-weight. Using our pipeline, we report the connectivity alterations in OIE. COMMIT-weighted matrices were created in all participants (nine patients with OIE, eight patients with temporal lobe epilepsy (TLE), and 22 healthy controls (HC)). In the OIE group, widespread increases in ‘connectivity strength’ were observed bilaterally. In OIE patients, ‘hyperconnections’ were observed between the insula and the pregenual cingulate gyrus (OIE group vs. HC group) and between insular subregions (OIE vs. TLE). Graph theoretic analyses revealed higher connectivity within insular subregions of OIE patients (OIE vs. TLE). We reveal, for the first time, the structural connectivity distribution in OIE. The observed pattern of connectivity in OIE likely reflects a diffuse epileptic network incorporating insular-connected regions and may represent a structural signature and diagnostic biomarker. Full article

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15 pages, 263 KiB

Open AccessReview

Deep Brain Stimulation of the Posterior Insula in Chronic Pain: A Theoretical Framework

by David Bergeron, Sami Obaid, Marie-Pierre Fournier-Gosselin, Alain Bouthillier and Dang Khoa Nguyen

Brain Sci. 2021, 11(5), 639; https://doi.org/10.3390/brainsci11050639 - 15 May 2021

Cited by 21 | Viewed by 4142

Abstract

Introduction: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. Methods: We present a narrative review highlighting the theoretical [...] Read more.

Introduction: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. Methods: We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain. Results: Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds. Conclusion: In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain. Full article

10 pages, 492 KiB

Open AccessCase Report

Insula and Olfaction: A Literature Review and Case Report

by Frédérique Roy-Côté, Rayane Zahal, Johannes Frasnelli, Dang Khoa Nguyen and Olivier Boucher

Brain Sci. 2021, 11(2), 198; https://doi.org/10.3390/brainsci11020198 - 05 Feb 2021

Cited by 6 | Viewed by 3371

Abstract

(1) Background: It is well established that the insula is involved in olfaction, though its specific role in olfactory processing remains uncertain. In this paper, we first review the current literature on the insula and olfaction. Then, we describe the case of a [...] Read more.

(1) Background: It is well established that the insula is involved in olfaction, though its specific role in olfactory processing remains uncertain. In this paper, we first review the current literature on the insula and olfaction. Then, we describe the case of a 56-year-old man with a left insular cavernoma that caused olfactory disturbances. (2) Results: Structural neuroimaging studies suggest that insular gray matter volume is related to olfactory function, and functional neuroimaging shows that various types of stimuli lead to either lateralized or bilateral insular activations. Studies using electro-cortical stimulation reveal a specific region of the insular cortex, around the central insular sulcus, that could be related to unpleasant odor processing. Previous cases of insular lesions leading to olfactory disturbances suggest that left-sided insular lesions may more frequently lead to olfactory changes. In our patient with a left insular cavernoma, odors that were previously perceived as pleasant started smelling unpleasant and were hard to distinguish. Despite these subjective complaints, olfactory function assessed with the Sniffin’ Sticks test was normal. (3) Conclusions: Current tests may not be sensitive to all types of olfactory impairments associated with insular damage, and further studies should be conducted to develop olfactory tests assessing the hedonic appreciation of odors. Full article

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Insula: Rediscovering the Hidden Lobe of the Brain

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