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Kalani, M. Yashar S., Maziyar A. Kalani, Ryder Gwinn, Bart Keogh, and Victor C. K. Tse. "Embryological development of the human insula and its implications for the spread and resection of insular gliomas." Neurosurgical Focus 27, no. 2 (2009): E2. http://dx.doi.org/10.3171/2009.5.focus0997.
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The human insular cortex, or the lobus insularis, is considered the developmentally most primitive lobe of the telencephalon. Covered by an overlying cortical lid, the insula has functions that are distinct from yet related to those of the adjacent temporal lobe and deep limbic structures. In the first part of this paper the authors outline the development of the human insula, including the cellular heterogeneity comprising the various parts of the insular lobe. Using the understanding gained from the development of the insula they then address implications of insular development for cortical development and connection as well as for tumorigenesis and tumor spread from the insula to other cortical structures, most notably the temporal lobe. An understanding of cortico-insular development and interconnection allows for both a better understanding of insular pathology and also facilitates planning of resection of cortico-insular gliomas to avoid damage to eloquent structures.
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Salado, Anne Laure, Laurent Koessler, Gabriel De Mijolla, et al. "sEEG is a Safe Procedure for a Comprehensive Anatomic Exploration of the Insula: A Retrospective Study of 108 Procedures Representing 254 Transopercular Insular Electrodes." Operative Neurosurgery 14, no. 1 (2017): 1–8. http://dx.doi.org/10.1093/ons/opx106.
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Abstract BACKGROUND The exploration of the insula in pre-surgical evaluation of epilepsy is considered to be associated with a high vascular risk resulting in an incomplete exploration of the insular cortex. OBJECTIVE To report a retrospective observational study of insular exploration using stereoelectroencephalography (sEEG) with transopercular and parasagittal oblique intracerebral electrodes from January 2008 to January 2016. The first purpose of this study was to evaluate the surgical risks of insular cortex sEEG exploration. The second purpose was to define the ability of placing intracerebral contacts in the whole insular cortex. METHODS Ninety-nine patients underwent 108 magnetic resonance imaging (MRI)-guided stereotactic implantations of intracerebral electrodes in the context of preoperative assessment of drug-resistant epilepsy, including at least 1 electrode placed in the insular cortex. On postoperative computed tomography images co-registered with MRI, followed by MRI segmentation and application of a transformation matrix, intracerebral contact coordinates of the insular electrodes’ contacts were anatomically localized in the Talairach space. Finally, dispersion and clustering analysis was performed. RESULTS There was no morbidity, in particular hemorrhagic complications, or mortality related to insular electrodes. Statistical comparison of intracerebral contact positions demonstrated that whole insula exploration is possible on the left and right sides. In addition, the clustering analysis showed the homogeneous distribution of the electrodes within the insular cortex. CONCLUSION In the presurgical evaluation of drug-resistant epilepsy, the insular cortex can be explored safely and comprehensively using transopercular sEEG electrodes. Parasagittal oblique trajectories may also be associated to achieve an optimal exploration.
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Afif, Afif, Guillaume Becq, and Patrick Mertens. "Definition of a Stereotactic 3-Dimensional Magnetic Resonance Imaging Template of the Human Insula." Operative Neurosurgery 72, no. 1 (2012): ons35—ons46. http://dx.doi.org/10.1227/neu.0b013e31826cdc57.
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Abstract Background: This study proposes a 3-dimensional (3-D) template of the insula in the bicommissural reference system with posterior commissure (PC) as the center of coordinates. Objective: Using the bicommissural anterior commissure (AC)-PC reference system, this study aimed to define a template and design a method for the 3-D reconstruction of the human insula that may be used at an individual level during stereotactic surgery. Methods: Magnetic resonance imaging (MRI)-based morphometric analysis was performed on 100 cerebral cortices with normal insulae based on a 3-step procedure: Step 1: AC-PC reference system-based reconstruction of the insula from the 1-mm thick 3-D T1-weighted MRI slices. Step 2: Digitalization and superposition of the data obtained in the 3 spatial planes. Step 3: Representation of pixels as colors on a scale corresponding to the probability of localization of each insular anatomic component. Results: The morphometric analysis of the insula confirmed our previously reported findings of a more complex shape delimited by 4 peri-insular sulci. A very significant correlation between the coordinates of the main insular structures and the length of AC-PC was demonstrated. This close correlation allowed us to develop a method that allows the 3-D reconstruction of the insula from MRI slices and only requires the localization of AC and PC. This process defines an area deemed to contain insula with 100% probability. Conclusion: This 3-D reconstruction of the insula should be useful to improve its localization and other cortical areas and allow the differentiation of insular cortex from opercular cortex.
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Di Stefano, Vincenzo, Maria Vittoria De Angelis, Chiara Montemitro, et al. "Clinical presentation of strokes confined to the insula: a systematic review of literature." Neurological Sciences 42, no. 5 (2021): 1697–704. http://dx.doi.org/10.1007/s10072-021-05109-1.
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Abstract Background and purpose The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive the appropriate treatment (e.g. thrombolysis). Methods We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords “insular stroke” and “insular infarction”, to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed. Results We identified 25 reports including a total of 49 patients (59.7 ± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache. Conclusions The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations.
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Levitt, Michael R., Jeffrey G. Ojemann, and John Kuratani. "Insular epilepsy masquerading as multifocal cortical epilepsy as proven by depth electrode." Journal of Neurosurgery: Pediatrics 5, no. 4 (2010): 365–67. http://dx.doi.org/10.3171/2009.11.peds09169.
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The insular cortex is an uncommon epileptogenic location from which complex partial seizures may arise. Seizure activity in insular epilepsy may mimic temporal, parietal, or other cortical areas. Semiology, electroencephalography, and even surface electrocorticography recordings may falsely localize other cortical foci, leading to inaccurate diagnosis and treatment. The use of insular depth electrodes allows more precise localization of seizure foci. The authors describe the case of a young girl with seizures falsely localized to the cortex, with foci arising from the insula, as proven by depth electrode recordings. Resection of the insula yielded seizure control.
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Nachtergaele, Pieter, Ahmed Radwan, Stijn Swinnen, et al. "The temporoinsular projection system: an anatomical study." Journal of Neurosurgery 132, no. 2 (2020): 615–23. http://dx.doi.org/10.3171/2018.11.jns18679.
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OBJECTIVEConnections between the insular cortex and the amygdaloid complex have been demonstrated using various techniques. Although functionally well connected, the precise anatomical substrate through which the amygdaloid complex and the insula are wired remains unknown. In 1960, Klingler briefly described the “fasciculus amygdaloinsularis,” a white matter tract connecting the posterior insula with the amygdala. The existence of such a fasciculus seems likely but has not been firmly established, and the reported literature does not include a thorough description and documentation of its anatomy. In this fiber dissection study the authors sought to elucidate the pathway connecting the insular cortex and the mesial temporal lobe.METHODSFourteen brain specimens obtained at routine autopsy were dissected according to Klingler’s fiber dissection technique. After fixation and freezing, anatomical dissections were performed in a stepwise progressive fashion.RESULTSThe insula is connected with the opercula of the frontal, parietal, and temporal lobes through the extreme capsule, which represents a network of short association fibers. At the limen insulae, white matter fibers from the extreme capsule converge and loop around the uncinate fasciculus toward the temporal pole and the mesial temporal lobe, including the amygdaloid complex.CONCLUSIONSThe insula and the mesial temporal lobe are directly connected through white matter fibers in the extreme capsule, resulting in the appearance of a single amygdaloinsular fasciculus. This apparent fasciculus is part of the broader network of short association fibers of the extreme capsule, which connects the entire insular cortex with the temporal pole and the amygdaloid complex. The authors propose the term “temporoinsular projection system” (TIPS) for this complex.
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Afif, Afif, Stephan Chabardes, Lorella Minotti, Philippe Kahane, and Dominique Hoffmann. "Safety and Usefulness of Insular Depth Electrodes Implanted Via an Oblique Approach in Patients with Epilepsy." Operative Neurosurgery 62, suppl_5 (2008): ONS471—ONS480. http://dx.doi.org/10.1227/01.neu.0000326037.62337.80.
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Abstract Objective: This study investigates the feasibility, safety, and usefulness of depth electrodes stereotactically implanted within the insular cortex. Methods: Thirty patients with suspected insular involvement during epileptic seizure underwent presurgical stereotactic electroencephalographic recordings using 10 to 16 depth electrodes per patient. Among these, one or two electrodes were implanted via an oblique approach to widely sample the insular cortex. Results: Thirty-five insular electrodes were implanted in the 30 patients without morbidity. A total of 226 recording contacts (mean, 7.5 contacts/patient) explored the insular cortex. Stereotactic electroencephalographic recordings of seizures allowed the differentiation into groups: Group 1, 10 patients with no insular involvement; Group 2, 15 patients with secondary insular involvement; and Group 3, five patients with an initial insular involvement. In temporal epilepsy (n = 17), the insula was never involved at the seizure onset but was frequently involved during the seizures (11 out of 17). In fron-totemporal or frontal epilepsy, the insula was involved at the onset of seizure in five out of 13 patients. All patients in Groups 1 and 2 underwent surgery, with a seizure-free outcome in 76.2% of patients. In Group 3, only two of the five patients underwent surgery, with a poor outcome. In temporal lobe epilepsy, surgical outcome tended to be better in Group 1 compared with Group 2 in this small series: results were good in 83.3% (Engel I) versus 72.7%. Conclusion: Insula can be safely explored with oblique electrodes. In temporal lobe epilepsy, insular involvement does not significantly modify the short-term postoperative outcome. Future larger studies are necessary to clarify the long-term prognostic value of insular spread.
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Alexeeva, N. T., S. V. Klochkova, D. A. Sokolov, and D. B. Nikityuk. "Contemporary data on the structural and functional organization of the insular lobe of cerebral hemispheres." Journal of Anatomy and Histopathology 13, no. 2 (2024): 79–92. http://dx.doi.org/10.18499/2225-7357-2024-13-2-79-92.
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The article presents an analysis of contemporary literature data on the structural and functional organization of the insular lobe of cerebral hemispheres. In adults, the insular lobe is located deep in the lateral sulcus under the frontoparietal and temporal opercula and is divided by the central sulcus of insula into two lobes – anterior and posterior. The relief of the sulci and gyri of the insula has individual variability. The insula receives blood supply from the M2 segment of the middle cerebral artery. The description of the cytoarchitectonics of the insular cortex according to different authors has significant differences. It is believed that the insular cortex is a transitional area from the paleocortex to the neocortex. In the domestic literature, two main cytoarchitectonic fields are described – 13, corresponding to the posterior parts of the insula and 14, occupying the anterior central gyrus of the insula, its short gyri, as well as a number of subregions. In foreign literature, seven cytoarchitectonic zones are distinguished: Ia1, Ig3, Id2, Id3, Id4, Id5, Id6. The insular lobe receives afferent projections from the thalamic nuclei and a number of parts of the cerebral cortex responsible for the perception of sensory stimuli. There are connections with the amygdala and some structures of the limbic system, the associative cortex. Efferent projections of the insular cortex diverge both to the structures of the brainstem and to the subcortical formations: the lateral hypothalamus, amygdala, pontine nuclei, bed nuclei of the stria terminalis, the nucleus of the solitary tract and a number of other formations associated with the control of autonomic functions. In functional terms, four sections are distinguished in the insula: sensorimotor, socioemotional, cognitive, chemosensory. The sensorimotor department ensures a number of visceral reactions, which indicates its participation in the regulation of the autonomic functions of the body. It ensures the perception of somatically sensitive impulses from the face and upper limbs. The role of the insula in thermo- and nociception is described. It is known about the participation of the insular cortex in functioning of the auditory analyzer, processing of taste sensations, vestibular signals, and olfaction. It is believed that the anterior-ventral part of the insula plays a key role in the formation of emotions and subjective sensations, as well as in making decisions associated with risk. The anterior-dorsal department is responsible for the integration of sensory stimuli from the external environment with internal data on the state of the body and the emotional state in order to coordinate the work of brain networks and initiate switching between the network of the passive mode of brain operation and the network of operational problem solving.
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Uddin, Lucina Q., Joshua Kinnison, Luiz Pessoa, and Michael L. Anderson. "Beyond the Tripartite Cognition–Emotion–Interoception Model of the Human Insular Cortex." Journal of Cognitive Neuroscience 26, no. 1 (2014): 16–27. http://dx.doi.org/10.1162/jocn_a_00462.
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Functional MRI studies report insular activations across a wide range of tasks involving affective, sensory, and motor processing, but also during tasks of high-level perception, attention, and control. Although insular cortical activations are often reported in the literature, the diverse functional roles of this region are still not well understood. We used a meta-analytic approach to analyze the coactivation profiles of insular subdivisions—dorsal anterior, ventral anterior, and posterior insula—across fMRI studies in terms of multiple task domains including emotion, memory, attention, and reasoning. We found extensive coactivation of each insular subdivision, with substantial overlap between coactivation partners for each subdivision. Functional fingerprint analyses revealed that all subdivisions cooperated with a functionally diverse set of regions. Graph-theoretical analyses revealed that the dorsal anterior insula was a highly “central” structure in the coactivation network. Furthermore, analysis of the studies that activate the insular cortex itself showed that the right dorsal anterior insula was a particularly “diverse” structure in that it was likely to be active across multiple task domains. These results highlight the nuanced functional profiles of insular subdivisions and are consistent with recent work suggesting that the dorsal anterior insula can be considered a critical functional hub in the human brain.
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Ranjan, M., Y. Starreveld, L. Bello-Espinosa, S. Wiebe, S. Singh, and WJ Hader. "D.06 Insular involvement in intractable epilepsy: results of invasive EEG data." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 43, S2 (2016): S14. http://dx.doi.org/10.1017/cjn.2016.79.
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Background: Exploration of the insular cortex is now commonly considered in patients with refractory epilepsy requiring invasive EEG investigations. The safety and yield of routine insular exploration is uncertain. Methods: All patients (pediatric and adult) who had invasive EEG (iEEG) with insular depth electrode placement, either through SEEG or open implantation, were reviewed. Ictal insular involvement was characterized as primary, secondary or not involved. Results of insular resections were recorded. Results: A total of 173 patients had iEEG of which 26 included insular electrodes (SEEG-18, Open - 8). No complications of placement were identified. Insular involvement was seen in 20 (76%) patients. Primary ictal involvement was identified in 9 (33 %) patients, while secondary spread was noted in 11 (42 %) patients. Six patients went on to have resections including the insular cortex of which 5 patients achieved good seizure control (Engle class I/II). Conclusions: Insular depth electrode placement is a safe and effective adjunct to invasive EEG investigations. Ictal involvement of the insular cortex was commonly identified in our series leading to inclusion of the insula in cortical resections with good seizure control, which may not have been considered without iEEG evidence.
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Labrakakis, Charalampos. "The Role of the Insular Cortex in Pain." International Journal of Molecular Sciences 24, no. 6 (2023): 5736. http://dx.doi.org/10.3390/ijms24065736.
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The transition from normal to chronic pain is believed to involve alterations in several brain areas that participate in the perception of pain. These plastic changes are then responsible for aberrant pain perception and comorbidities. The insular cortex is consistently found activated in pain studies of normal and chronic pain patients. Functional changes in the insula contribute to chronic pain; however, the complex mechanisms by which the insula is involved in pain perception under normal and pathological conditions are still not clear. In this review, an overview of the insular function is provided and findings on its role in pain from human studies are summarized. Recent progress on the role of the insula in pain from preclinical experimental models is reviewed, and the connectivity of the insula with other brain regions is examined to shed new light on the neuronal mechanisms of the insular cortex’s contribution to normal and pathological pain sensation. This review underlines the need for further studies on the mechanisms underlying the involvement of the insula in the chronicity of pain and the expression of comorbid disorders.
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Gujing, Li, He Hui, Li Xin, et al. "Increased Insular Connectivity and Enhanced Empathic Ability Associated with Dance/Music Training." Neural Plasticity 2019 (May 6, 2019): 1–13. http://dx.doi.org/10.1155/2019/9693109.
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Dance and music are expressive art forms. Previous behavioural studies have reported that dancers/musicians show a better sensorimotor ability and emotional representation of others. However, the neural mechanism behind this phenomenon is not completely understood. Recently, intensive researches have identified that the insula is highly enrolled in the empathic process. Thus, to expand the knowledge of insular function associated with empathy under the dance/music training background, we mapped the insular network and its associated brain regions in 21 dancers, 20 musicians, and 24 healthy controls using resting-state functional connectivity (FC) analysis. Whole brain voxel-based analysis was performed using seeds from the posterior insula (PI), the ventral anterior insula (vAI), and the dorsal anterior insula (dAI). The training effects of dance and music on insular subnetworks were then evaluated using one-way analysis of variance ANOVA. Increased insular FC with those seeds was found in dancers/musicians, including PI and anterior cingulated cortex (ACC), vAI and middle temporal gyrus (MTG) and middle cingulated cortex (MCC), and dAI and ACC and MTG. In addition, significant associations were found between discrepant insular FC patterns and empathy scores in dancers and musicians. These results indicated that dance/music training might enhance insular subnetwork function, which would facilitate integration of intero/exteroceptive information and result in better affective sensitivity. Those changes might finally facilitate the subjects’ empathic ability.
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Türe, Uğur, M. Gazi Yaşargil, Ossama Al-Mefty, and Dianne C. H. Yaşargil. "Arteries of the insula." Journal of Neurosurgery 92, no. 4 (2000): 676–87. http://dx.doi.org/10.3171/jns.2000.92.4.0676.
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Object. The insula is located at the base of the sylvian fissure and is a potential site for pathological processes such as tumors and vascular malformations. Knowledge of insular anatomy and vascularization is essential to perform accurate microsurgical procedures in this region.Methods. Arterial vascularization of the insula was studied in 20 human cadaver brains (40 hemispheres). The cerebral arteries were perfused with red latex to enhance their visibility, and they were dissected with the aid of an operating microscope.Arteries supplying the insula numbered an average of 96 (range 77–112). Their mean diameter measured 0.23 mm (range 0.1–0.8 mm), and the origin of each artery could be traced to the middle cerebral artery (MCA), predominantly the M2 segment. In 22 hemispheres (55%), one to six insular arteries arose from the M1 segment of the MCA and supplied the region of the limen insulae. In an additional 10 hemispheres (25%), one or two insular arteries arose from the M3 segment of the MCA and supplied the region of either the superior or inferior periinsular sulcus. The insular arteries primarily supply the insular cortex, extreme capsule, and, occasionally, the claustrum and external capsule, but not the putamen, globus pallidus, or internal capsule, which are vascularized by the lateral lenticulostriate arteries (LLAs). However, an average of 9.9 (range four–14) insular arteries in each hemisphere, mostly in the posterior insular region, were similar to perforating arteries and some of these supplied the corona radiata. Larger, more prominent insular arteries (insuloopercular arteries) were also observed (an average of 3.5 per hemisphere, range one–seven). These coursed across the surface of the insula and then looped laterally, extending branches to the medial surfaces of the opercula.Conclusions. Complete comprehension of the intricate vascularization patterns associated with the insula, as well as proficiency in insular anatomy, are prerequisites to accomplishing appropriate surgical planning and, ultimately, to completing successful exploration and removal of pathological lesions in this region.
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Khachatryan, R. G., G. S. Ibatova, T. M. Alekseeva, and W. A. Khachatryan. "Diagnostic evaluation of drug-resistant insular epilepsy." Epilepsia and paroxyzmal conditions 10, no. 4 (2019): 83–93. http://dx.doi.org/10.17749/2077-8333.2018.10.4.083-092.
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About 30% of patients with temporal epilepsy are resistant to antiepileptic drugs; in such cases, surgical treatment is considered to be the best option. Existence of an extra-temporal epileptogenic focus in the insula is a possible cause of seizures after temporal lobe surgery in about 20% of patients. Because of its localization, the anatomical features of the insular lobe, as well as the entire concept of insular epilepsy have not been well documented. Yet, it has been established that the seizures developing from the insular cortex can mimic the paroxysms arising from the temporal lobe. When the insula is involved in the epileptic process, resection of the insular cortex improves the outcome of surgical treatment. Rational and well-based selection of candidates for surgical treatment is of paramount importance for patients with drug-resistant epilepsy. The article presents a review of the up-to-date literature on this matter.
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Schwartz, Theodore H. "Insular Seizures: Have We Been Missing the Boat?" Epilepsy Currents 5, no. 4 (2005): 147–48. http://dx.doi.org/10.1111/j.1535-7511.2005.00040.x.
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Clinical Manifestations of Insular Lobe Seizures: A Stereo-electroencephalographic Study Isnard J, Guenot M, Sindou M, Mauguiere F Epilepsia 2004;45:1079–1090 Purpose In this study, we report the clinical features of insular lobe seizures based on data from video and stereoelectroencephalographic ictal recordings and direct electric insular stimulation of the insular cortex performed in patients referred for presurgical evaluation of temporal lobe epilepsy (TLE). Methods Since our first recordings of insular seizures, the insular cortex has been included as one of the targets of stereoelectroencephalographic electrode implantation in 50 consecutive patients with TLE whose seizures were suspected to originate from, or rapidly to propagate to, the perisylvian cortex. In six, a stereotyped sequence of ictal symptoms associated with intrainsular discharges could be identified. Results This ictal sequence occurred in full consciousness, beginning with a sensation of laryngeal constriction and paresthesiae, often unpleasant, affecting large cutaneous territories, most often at the onset of a complex partial seizure (five of the six patients). It was eventually followed by dysarthric speech and focal motor convulsive symptoms. The insular origin of these symptoms was supported by the data from functional cortical mapping of the insula by using direct cortical stimulations. Conclusions This sequence of ictal symptoms looks reliable enough to characterize insular lobe epileptic seizures. Observation of this clinical sequence at the onset of seizures on video-EEG recordings in TLE patients strongly suggests that the seizure-onset zone is located not in the temporal but in the insular lobe; recording directly from the insular cortex should occur before making any decision regarding epilepsy surgery.
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Erbay, Mehmet Fatih, and Esra Porgalı Zayman. "The Role of Insular Cortex in Response to Group Therapy in Vaginismus Patients: Magnetic Resonance Spectroscopy Study." Psychiatry Investigation 17, no. 6 (2020): 608–12. http://dx.doi.org/10.30773/pi.2019.0331.
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Objective Disgust has been propounded as a potential etiological factor in certain sexual dysfunctions such as vaginismus. Studies reports that insular cortex is activated as a response to disgust. The present study aimed to investigate the predictive role of metabolites in insular cortex in response to group therapy among vaginismus patients.Methods Study sample consisted of 51 vaginismus patients attended an ambulatory group therapy, of whom 26 benefited from 8-week group therapy and 25 were unresponsive to group therapy. All of the patients underwent H magnetic resonance spectroscopy (H-MRS), and insular cortex N-acetyl aspartate (NAA), Creatinine (Cr), Glutamine (Gln), Glutathione (GSH), Choline (Cho), Myo-inositol (mIns), Glutamate (Glu) and Lactate (Lac) concentrations were compared between the groups.Results Comparing insular cortex metabolite concentrations between the groups, Cho was statistically significantly higher (p=0.005) but mIns was significantly lower (p=0.001) in the unresponsive to group therapy group.Conclusion MR spectroscopy findings of the present study indicated significant metabolic changes such as increased Cho/Cr ratio and decreased mIns/Cr ratio in the insular cortex of vaginismus patients who were unresponsive to group therapy. Our results support the studies suggesting that disgust is an important emotion in vaginismus patients and also that insula plays a role in the neurobiology of disgust.
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Rieger, Nathaniel S., Juan A. Varela, Alexandra J. Ng, et al. "Insular cortex corticotropin-releasing factor integrates stress signaling with social affective behavior." Neuropsychopharmacology 47, no. 6 (2022): 1156–68. http://dx.doi.org/10.1038/s41386-022-01292-7.
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AbstractImpairments in identifying and responding to the emotions of others manifest in a variety of psychopathologies. Therefore, elaborating the neurobiological mechanisms that underpin social responses to social emotions, or social affective behavior, is a translationally important goal. The insular cortex is consistently implicated in stress-related social and anxiety disorders, which are associated with diminished ability to make and use inferences about the emotions of others to guide behavior. We investigated how corticotropin-releasing factor (CRF), a neuromodulator evoked upon exposure to stressed conspecifics, influenced the insula. We hypothesized that social affective behavior requires CRF signaling in the insular cortex in order to detect stress in social interactions. In acute slices from male and female rats, CRF depolarized insular pyramidal neurons. In males, but not females, CRF suppressed presynaptic GABAergic inhibition leading to greater excitatory synaptic efficacy in a CRF receptor 1 (CRF1)- and cannabinoid receptor 1 (CB1)-dependent fashion. In males only, insular CRF increased social investigation, and CRF1 and CB1 antagonists interfered with social interactions with stressed conspecifics. To investigate the molecular and cellular basis for the effect of CRF we examined insular CRF1 and CB1 mRNAs and found greater total insula CRF1 mRNA in females but greater CRF1 and CB1 mRNA colocalization in male insular cortex glutamatergic neurons that suggest complex, sex-specific organization of CRF and endocannabinoid systems. Together these results reveal a new mechanism by which stress and affect contribute to social affective behavior.
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Leavitt, Lydia, Amy Baohan, Howard Heller, Liana Kozanno, Matthew P. Frosch, and Gavin Dunn. "Surgical management of an abscess of the insula." Surgical Neurology International 13 (December 23, 2022): 591. http://dx.doi.org/10.25259/sni_871_2022.
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Background: Mass lesions within the insular are diagnostically and surgically challenging due to the numerous critical cortical, subcortical, and vascular structures surrounding the region. Two main surgical techniques – the transsylvian approach and the transcortical approach – provide access to the insular cortex. Of the range of pathologies encountered, abscesses in the insula are surprisingly rare. Case Description: A 34-year-old patient was admitted for surgical resection of a suspected high-grade glioma in the insula of the dominant hemisphere. A rapid clinical decline prompted emergent neurosurgical intervention using a transsylvian approach. Surprisingly, abundant purulent material was encountered on entering the insular fossa. Pathological analysis confirmed an insular abscess, although a source of infection could not be identified. The patient required a second evacuation for reaccumulation of the abscess and adjuvant corticosteroids for extensive cerebral edema. Conclusion: An abscess located in the insular cortex is an incredibly rare occurrence. Surgical management using the transsylvian approach is one option to approach this region. Familiarity with this approach is thus extremely beneficial in situations requiring emergent access to the dominant insula when awake mapping is not feasible. In addition, treatment of abscesses with adjuvant corticosteroids is indicated when extensive, life-threatening cerebral edema is present.
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Klein, Alexandra S., Nate Dolensek, Caroline Weiand, and Nadine Gogolla. "Fear balance is maintained by bodily feedback to the insular cortex in mice." Science 374, no. 6570 (2021): 1010–15. http://dx.doi.org/10.1126/science.abj8817.
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How the body regulates fear Although fear is important for survival, it is maladaptive if it is either too strong, as in anxiety disorders, or too weak, as in exaggerated risk taking. Working in mice, Klein et al . observed that the insular cortex has an unparalleled dual role in either enhancing or weakening the extinction of fear, depending on the internal fear state of the animal (see the Perspective by Christianson). This insula function helps to maintain fear within a homeostatic range and depends on bodily feedback signals: Fear-induced freezing behavior is associated with a slowed heart rate, which in turn dampens fear-evoked activity of the insular cortex. Two opposite signals, prediction of threat by fear-associated cues and negative feedback signals from the body, are thus integrated within the insular cortex. —PRS
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Stoeckel, M. Cornelia, Roland W. Esser, Matthias Gamer, Christian Büchel, and Andreas von Leupoldt. "Brain Responses during the Anticipation of Dyspnea." Neural Plasticity 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/6434987.
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Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.
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Vuddagiri, S., L. Bello-Espinosa, S. Singh, et al. "B.03 Safety and effectiveness of insular resections for drug-resistant epilepsy." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 44, S2 (2017): S11. http://dx.doi.org/10.1017/cjn.2017.74.
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Background: Insular cortex involvement as a part of epileptogenic zone is often suspected in the context of operculo-insular semiology and can be confirmed by routine interrogation of the insula with stereo-electroencephalography (SEEG). However the safety and efficacy of insular resections remains unclear. Methods: We reviewed all the patients who underwent insular resection for drug-resistant epilepsy, from 2002 – 2016, in the Calgary Epilepsy Program. Details of the comprehensive pre-surgical evaluation, surgery performed, complications and seizure outcome at the latest follow-up were collected. Results: Fifteen patients (8 males, 7 females) with age range 3 – 41 years were identified. MRI was normal in 9 patients. The decision to resect the Insula was made based on clinical semiology and structural and functional imaging in 6 patients and on SEEG findings in 9 patients. Insular resection was total in 11 and partial in 4 patients. Four (26%) patients had transient hemiparesis and 1 patient had permanent mild upper extremity weakness following total resection. After a mean follow-up period of 45.6 months (range 2 – 150 months), 40% of the patients are seizure free. Conclusions: Insular cortex resections for drug resistant epilepsy can be performed safely and may contribute to additional effectiveness in seizure outcomes in patients with challenging extra-temporal epilepsy.
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Kulesh, A. A., S. P. Kulikova, V. E. Drobakha, et al. "Role of insular cortex lesions in determining the pathogenetic subtype of ischemic stroke." Neurology, Neuropsychiatry, Psychosomatics 14, no. 2 (2022): 11–17. http://dx.doi.org/10.14412/2074-2711-2022-2-11-17.
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Timely evaluation of cardioembolic stroke (CES) caused by atrial fibrillation is critical from the point of view of the possibility of prescribing effective secondary prevention with oral anticoagulants. Insular lesion is considered as a promising neuroimaging marker of CES.Objective: to analyze the role of insular cortex lesions using magnetic resonance imaging (MRI) of the brain as a potential neuroimaging marker of the pathogenetic subtype of ischemic stroke (IS).Patients and methods. 225 patients in the acute period of IS were examined. Depending on the stroke etiology, patients were divided into three groups: cryptogenic stroke (CS; n=99), CES (n=45), and non-CES (n=81). All patients underwent an MRI of the brain to analyze the insular cortex lesions. In 57 patients, foci of cerebral infarction were additionally marked manually on axial slices of diffusion-weighted MRI using the Anatomist software. The calculated MRI characteristics of foci for CES and non-CES groups were used to construct a decision tree in the WEKA 3.6 package. Echocardiographic markers of atrial cardiopathy were assessed in all patients – the left atrium (LA) emptying fraction and LA function index; in 68 patients, the concentration of serum NT-proBNP was also assessed.Results and discussion. The insula was affected in 12% of patients: most often in CES (33%), significantly less often in CS and non-CES (6 and 7.4%, respectively), without significant differences between the latter groups. The presence of insula lesion in relation to CES has a sensitivity of 33% and a specificity of 93% (p=0.002); odds ratio 6.25; 95% confidence interval 2.22–17.63. In most patients, the posterior insular cortex was involved in the pathological process. Isolated insular infarction occurred in only one patient with CES, while the involvement of the insula and adjacent zone, and the combination of insular infarction with territorial infarction, were observed more often. The group of patients with insular lesions was distinguished by the predominance of women, greater severity of stroke at admission, less deficit at discharge, larger LA diameter, lower LA emptying fraction, and functional index. CES was four times more common in the insular lesion group, while CS was two times more common in those without insular lesions. Insula involvement identifies three out of five CES patients according to the decision tree. Further analysis of the total lesion volume can locate almost all remaining patients with CES: they are characterized by the indicator >12 sm3.Conclusion. Insular lesions allow reliable differentiation of patients with CES and non-CES and can be considered a potential marker of the cardioembolic subtype of IS, which requires further investigation.
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Nagai, M., K. Kishi, and S. Kato. "Insular cortex and neuropsychiatric disorders: A review of recent literature." European Psychiatry 22, no. 6 (2007): 387–94. http://dx.doi.org/10.1016/j.eurpsy.2007.02.006.
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AbstractThe insular cortex is located in the centre of the cerebral hemisphere, having connections with the primary and secondary somatosensory areas, anterior cingulate cortex, amygdaloid body, prefrontal cortex, superior temporal gyrus, temporal pole, orbitofrontal cortex, frontal and parietal opercula, primary and association auditory cortices, visual association cortex, olfactory bulb, hippocampus, entorhinal cortex, and motor cortex. Accordingly, dense connections exist among insular cortex neurons. The insular cortex is involved in the processing of visceral sensory, visceral motor, vestibular, attention, pain, emotion, verbal, motor information, inputs related to music and eating, in addition to gustatory, olfactory, visual, auditory, and tactile data. In this article, the literature on the relationship between the insular cortex and neuropsychiatric disorders was summarized following a computer search of the Pub-Med database. Recent neuroimaging data, including voxel based morphometry, PET and fMRI, revealed that the insular cortex was involved in various neuropsychiatric diseases such as mood disorders, panic disorders, PTSD, obsessive-compulsive disorders, eating disorders, and schizophrenia. Investigations of functions and connections of the insular cortex suggest that sensory information including gustatory, olfactory, visual, auditory, and tactile inputs converge on the insular cortex, and that these multimodal sensory information may be integrated there.
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Cohen, Jeremy, Taylor Smith, Khalil Thompson, Armond Collins, Tracey Knaus, and Helen Tager-Flusberg. "Altered Anterior Insular Asymmetry in Pre-teen and Adolescent Youth with Autism Spectrum Disorder." Annals of Behavioral Neuroscience 1, no. 1 (2018): 24–35. http://dx.doi.org/10.18314/abne.v1i1.1120.
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Autism Spectrum Disorder (ASD) is hallmarked by social-emotional reciprocity deficits. Social-emotional responding requires the clear recognition of social cues as well as the internal monitoring of emotional salience. Insular cortex is central to the salience network, and plays a key role in approach-avoidance emotional valuation. Consistent right anterior insular hypoactivity and variable volumetric differences of insular cortical volumes were shown previously. The current study analyzed anterior and posterior insular volume/asymmetry changes in ASD across age. Age was used as an additional grouping variable as previous studies indicated differential regional volume in ASD individuals before and after puberty onset. In the current sample, pre-teen ASD expressed left lateralized anterior insula, while adolescent ASD had right lateralization. Typically developing (TD) individuals expressed the opposite lateralization of anterior insula in both age-groups (right greater than left anterior insular volume among pre-teen TD and left greater than right anterior insular volume among adolescent TD). Social-emotional calibrated severity scores from the ADOS were positively correlated with leftward anterior insular asymmetry and negatively correlated with proportional right anterior insular volumes in ASD. Insular cortex has a lateralized role in autonomic nervous system regulation (parasympathetic control in the left, sympathetic control in the right). Atypical insular asymmetry in ASD may contribute to the development of networks with a diminished salience signal to human faces and voices, and may lead to more learned passive avoidant responses to such stimuli at younger ages, leading to more distressed responses in adolescence. Data here supports the use of early behavioral intervention to increase awareness of and reward for social-emotional cues.
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Türe, Uğur, Dianne C. H. Yaşargil, Ossama Al-Mefty, and M. Gazi Yaşargil. "Topographic anatomy of the insular region." Journal of Neurosurgery 90, no. 4 (1999): 720–33. http://dx.doi.org/10.3171/jns.1999.90.4.0720.
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Object. The insula is one of the paralimbic structures and constitutes the invaginated portion of the cerebral cortex, forming the base of the sylvian fissure. The authors provide a detailed anatomical study of the insular region to assist in the process of conceptualizing a reliable surgical approach to allow for a successful course of surgery.Methods. The topographic anatomy of the insular region was studied in 25 formalin-fixed brain specimens (50 hemispheres). The periinsular sulci (anterior, superior, and inferior) define the limits of the frontoorbital, frontoparietal, and temporal opercula, respectively. The opercula cover and enclose the insula. The limen insula is located in the depths of the sylvian fissure and constitutes the anterobasal portion of the insula. A central insular sulcus divides the insula into two portions, the anterior insula (larger) and the posterior insula (smaller). The anterior insula is composed of three principal short insular gyri (anterior, middle, and posterior) as well as the accessory and transverse insular gyri. All five gyri converge at the insular apex, which represents the most superficial aspect of the insula. The posterior insula is composed of the anterior and posterior long insular gyri and the postcentral insular sulcus, which separates them. The anterior insula was found to be connected exclusively to the frontal lobe, whereas the posterior insula was connected to both the parietal and temporal lobes. Opercular gyri and sulci were observed to interdigitate within the opercula and to interdigitate the gyri and sulci of the insula. Using the fiber dissection technique, various unique anatomical features and relationships of the insula were determined.Conclusions. The topographic anatomy of the insular region is described in this article, and a practical terminology for gyral and sulcal patterns of surgical significance is presented. This study clarifies and supplements the information presently available to help develop a more coherent surgical concept.
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Bouthillier, Alain, Werner Surbeck, Alexander G. Weil, Tania Tayah, and Dang K. Nguyen. "The Hybrid Operculo-Insular Electrode." Neurosurgery 70, no. 6 (2011): 1574–80. http://dx.doi.org/10.1227/neu.0b013e318246a3b7.
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Abstract BACKGROUND: Precise localization of an epileptic focus in the perisylvian/insular area is a major challenge. The difficult access and the high density of blood vessels within the sylvian fissure have lead to poor coverage of intrasylvian (opercular and insular) cortex by available electrodes. OBJECTIVE: To report the creation of a novel electrode designed to record epileptic activity from both the insular cortex and the hidden surfaces of the opercula. METHODS: The hybrid operculo-insular electrode was fabricated by Ad-Tech Medical Instrument Corporation (Racine, Wisconsin). It was used in combination with regular subdural and depth electrodes for long-term intracranial recordings. The hybrid electrode, which contains both a depth and a strip (opercular) component, is inserted after microsurgical opening of the sylvian fissure. The depth component is implanted directly into the insular cortex. The opercular component has 1 or 2 double-sided recording contacts that face the hidden surfaces of the opercula. RESULTS: The hybrid operculo-insular electrode was used in 5 patients. This method of invasive investigation allowed including (2 patients) or excluding (3 patients) the insula as part of the epileptic focus and the surgical resection. It also allowed extending the epileptogenic zone to include the hidden surface of the frontal operculum in 1 patient. There were no complications related to the insertion of this new electrode. CONCLUSION: The new hybrid operculo-insular electrode can be used for intracranial investigation of perisylvian/insular refractory epilepsy. It can contribute to increasing cortical coverage of this complex region and may allow better definition of the epileptic focus.
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Hale, Andrew T., Luke Tomycz, Ali S. Haider, Dave Clarke, and Mark R. Lee. "209 Surgical Outcomes with Insular and Insular-Plus Pediatric Epilepsy: A Single-Institution Experience." Neurosurgery 64, CN_suppl_1 (2017): 256. http://dx.doi.org/10.1093/neuros/nyx417.209.
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Abstract INTRODUCTION It has been increasingly recognized that the insular cortex plays an important role in frontotemporal-parietal epilepsy (FTPE) in children. The insula, however, cannot be properly interrogated with conventional subdural grids, and its anatomy makes it difficult to implicate the insula with semiology or non-invasive modalities. At last year's meeting, we reported on the safety and utility of insular-depth electrode placement for interrogation of the insula. Here, we report post-surgical outcomes on 31 patients with insular-depth electrode confirmed refractory epilepsy. METHODS We used Current Procedural Terminology (CPT) billing records to identify cases of depth electrode insertion performed at our institution. Clinical information, operative reports, and pathology data from patients undergoing operative intervention was then retrospectively collected. RESULTS >Thirty-one patients underwent direct invasive sampling implicating the insula in seizure onset and prompted either thermoablation or surgical resection of some portion of the insula. Fourteen patients had biopsy-proven cortical dysplasia, Fourteen patients had suspected cortical dysplasia, two patients had tuberous sclerosis and one patient had a primary brain tumor. Fourteen patients had prior intracranial operations. Fourteen patients underwent thermoablation of the insula and seventeen underwent resection of some portion of the insula. 31% of patients who underwent thermoablation of the insular had an Engel Class outcome of I compared to 63% of patients who underwent open insular resection. Thus, in our cohort, insular resection was superior to thermoablation in achieving superior functional outcomes as measured by Engel Class. CONCLUSION Surgical resection and thermoablation of the insula are both acceptable treatments for insular and insular-plus epilepsy. In our cohort, outcomes with surgical resection were improved, although the reasons for this are unclear. Further study is required to delineate optimal operative care in patients with insular and insular-plus epilepsy.
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Duan, Xujun, Maolin Hu, Xinyue Huang, et al. "Effect of Risperidone Monotherapy on Dynamic Functional Connectivity of Insular Subdivisions in Treatment-Naive, First-Episode Schizophrenia." Schizophrenia Bulletin 46, no. 3 (2019): 650–60. http://dx.doi.org/10.1093/schbul/sbz087.
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Abstract Objective The insula consists of functionally diverse subdivisions, and each division plays different roles in schizophrenia neuropathology. The current study aimed to investigate the abnormal patterns of dynamic functional connectivity (dFC) of insular subdivisions in schizophrenia and the effect of antipsychotics on these connections. Methods Longitudinal study of the dFC of insular subdivisions was conducted in 42 treatment-naive first-episode patients with schizophrenia at baseline and after 8 weeks of risperidone treatment based on resting-state functional magnetic resonance image (fMRI). Results At baseline, patients showed decreased dFC variance (less variable) between the insular subdivisions and the precuneus, supplementary motor area and temporal cortex, as well as increased dFC variance (more variable) between the insular subdivisions and parietal cortex, compared with healthy controls. After treatment, the dFC variance of the abnormal connections were normalized, which was accompanied by a significant improvement in positive symptoms. Conclusions Our findings highlighted the abnormal patterns of fluctuating connectivity of insular subdivision circuits in schizophrenia and suggested that these abnormalities may be modified after antipsychotic treatment.
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Tomycz, Luke D., Andrew T. Hale, Ali S. Haider, Dave F. Clarke, and Mark R. Lee. "Invasive Insular Sampling in Pediatric Epilepsy: A Single-Institution Experience." Operative Neurosurgery 15, no. 3 (2017): 310–17. http://dx.doi.org/10.1093/ons/opx253.
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Abstract BACKGROUND It has been increasingly recognized that the insular cortex plays an important role in frontotemporal-parietal epilepsy in children. The insula, however, cannot be properly interrogated with conventional subdural grids, and its anatomy makes it difficult to implicate the insula with semiology or noninvasive modalities. Frame-based, stereotactic placement of insular depth electrodes for direct extraoperative monitoring is a relatively low-risk maneuver that allows for conclusive interrogation of this region, and, in select cases, can easily be replaced with a laser applicator for minimally invasive treatment via thermoablation. OBJECTIVE To describe the largest reported series of pediatric patients with refractory epilepsy undergoing insular depth electrode placement. METHODS We used current procedural terminology billing records to identify cases of depth electrode insertion performed at our institution. Clinical information from patients undergoing invasive insular sampling was then retrospectively collected. RESULTS Seventy-four insular depth electrodes were placed in 49 patients for extraoperative, inpatient monitoring. The decision to place insular depth electrodes was determined by a multidisciplinary epilepsy team. In 65.3% of cases, direct invasive sampling implicated the insula in seizure onset and prompted either thermoablation or surgical resection of some portion of the insula. There were no serious adverse effects or complications associated with the placement of insular depth electrodes. CONCLUSION Given the low morbidity of insular depth electrode insertion and the high proportion of patients who exhibited insular involvement, it is worth considering whether insular depth electrodes should be part of the standard presurgical evaluation in children with treatment-refractory frontotemporal-parietal epilepsy.
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Gras-Combe, Guillaume, Lorella Minotti, Dominique Hoffmann, Alexandre Krainik, Philippe Kahane, and Stephan Chabardes. "Surgery for Nontumoral Insular Epilepsy Explored by Stereoelectroencephalography." Neurosurgery 79, no. 4 (2016): 578–88. http://dx.doi.org/10.1227/neu.0000000000001257.
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Abstract BACKGROUND Hidden by the perisylvian operculi, insular cortex has long been underexplored in the context of epilepsy surgery. Recent studies advocated stereoelectroencephalography (SEEG) as a reliable tool to explore insular cortex and its involvement in intractable epilepsy and suggested that insular seizures could be an underestimated entity. However, the results of insular resection to treat pharmacoresistant epilepsy are rarely reported. OBJECTIVE We report 6 consecutive cases of right insular resection performed based on anatomoelectroclinical correlations provided by SEEG. METHODS Six right-handed patients (3 male, 3 female) with drug-resistant epilepsy underwent comprehensive presurgical evaluation. Based on video electroencephalographic recordings, they all underwent SEEG evaluation with bilateral (n = 4) or unilateral right (n = 2) insular depth electrode placement. All patients had both orthogonal and oblique (1 anterior, 1 posterior) insular electrodes (n = 4-6 electrodes). Preoperative magnetic resonance imaging findings were normal in 4 patients, 1 patient had right insular focal cortical dysplasia, and 1 patient had a right opercular postoperative scar (cavernous angioma). All patients underwent right partial insular corticectomy via the subpial transopercular approach. RESULTS Intracerebral recordings demonstrated an epileptogenic zone confined to the right insula in all patients. After selective insular resection, 5 of 6 patients were seizure free (Engel class I) with a mean follow-up of 36.2 months (range, 18-68 months). Histological findings revealed focal cortical dysplasia in 5 patients and a gliosis scar in 1 patient. All patients had minor transient neurological deficit (eg, facial paresis, dysarthria). CONCLUSION Insular resection based on SEEG findings can be performed safely with a significant chance of seizure freedom.
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Roy-Côté, Frédérique, Rayane Zahal, Johannes Frasnelli, Dang Khoa Nguyen, and Olivier Boucher. "Insula and Olfaction: A Literature Review and Case Report." Brain Sciences 11, no. 2 (2021): 198. http://dx.doi.org/10.3390/brainsci11020198.
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(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.
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Wynford-Thomas, Ray, and Rob Powell. "THE INSULA: ISLAND OF REIL." Journal of Neurology, Neurosurgery & Psychiatry 86, no. 11 (2015): e4.155-e4. http://dx.doi.org/10.1136/jnnp-2015-312379.63.
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Just as ‘no man is an island’, despite its misleading name, the insula is not an island. Sitting deeply within the cerebrum, the insular cortex and its connections play an important role in both normal brain function and seizure generation. Stimulating specific areas of the insula can produce somatosensory, viscerosensory, somatomotor and visceroautonomic symptoms, as well as effects on speech processing and pain. Insular onset seizures are rare, but may mimic both temporal and extra-temporal epilepsy and if not recognised, may lead to failure of epilepsy surgery. We therefore highlight the semiology of insular epilepsy by discussing three cases with different auras. Insular onset seizures can broadly be divided into three main types both anatomically and according to seizure semiology:1. Seizures originating in the antero-inferior insula present with laryngeal constriction, along with visceral and gustatory auras (similar to those originating in medial temporal structures).2. Antero-superior onset seizures can have a silent onset, but tend to propagate rapidly to motor areas causing focal motor or hypermotor seizures.3. Seizures originating in the posterior insula present with contralateral sensory symptoms.
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Fathy, Yasmine Y., Susanne E. Hoogers, Henk W. Berendse, et al. "Differential insular cortex sub-regional atrophy in neurodegenerative diseases: a systematic review and meta-analysis." Brain Imaging and Behavior 14, no. 6 (2019): 2799–816. http://dx.doi.org/10.1007/s11682-019-00099-3.
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Abstract The insular cortex is proposed to function as a central brain hub characterized by wide-spread connections and diverse functional roles. As a result, its centrality in the brain confers high metabolic demands predisposing it to dysfunction in disease. However, the functional profile and vulnerability to degeneration varies across the insular sub-regions. The aim of this systematic review and meta-analysis is to summarize and quantitatively analyze the relationship between insular cortex sub-regional atrophy, studied by voxel based morphometry, with cognitive and neuropsychiatric deficits in frontotemporal dementia (FTD), Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). We systematically searched through Pubmed and Embase and identified 519 studies that fit our criteria. A total of 41 studies (n = 2261 subjects) fulfilled the inclusion criteria for the meta-analysis. The peak insular coordinates were pooled and analyzed using Anatomic Likelihood Estimation. Our results showed greater left anterior insular cortex atrophy in FTD whereas the right anterior dorsal insular cortex showed larger clusters of atrophy in AD and PD/DLB. Yet contrast analyses did not reveal significant differences between disease groups. Functional analysis showed that left anterior insular cortex atrophy is associated with speech, emotion, and affective-cognitive deficits, and right dorsal atrophy with perception and cognitive deficits. In conclusion, insular sub-regional atrophy, particularly the anterior dorsal region, may contribute to cognitive and neuropsychiatric deficits in neurodegeneration. Our results support anterior insular cortex vulnerability and convey the differential involvement of the insular sub-regions in functional deficits in neurodegenerative diseases.
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Williamson, J. W., R. McColl, D. Mathews, M. Ginsburg, and J. H. Mitchell. "Activation of the insular cortex is affected by the intensity of exercise." Journal of Applied Physiology 87, no. 3 (1999): 1213–19. http://dx.doi.org/10.1152/jappl.1999.87.3.1213.
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The purpose of this investigation was to determine whether there were differences in the magnitude of insular cortex activation across varying intensities of static and dynamic exercise. Eighteen healthy volunteers were studied: eight during two intensities of leg cycling and ten at different time periods during sustained static handgrip at 25% maximal voluntary contraction or postexercise cuff occlusion. Heart rate, blood pressure (BP), perceived exertion, and regional cerebral blood flow (rCBF) distribution data were collected. There were significantly greater increases in insular rCBF during lower (6.3 ± 1.7%; P < 0.05) and higher (13.3 ± 3.8%; P < 0.05) intensity cycling and across time during static handgrip (change from rest for right insula at 2–3 min, 3.8 ± 1.1%, P < 0.05; and at 4–5 min, 8.6 ± 2.8%, P < 0.05). Insular rCBF was decreased during postexercise cuff occlusion (−5.5 ± 1.2%; P < 0.05) with BP sustained at exercise levels. Right insular rCBF data, but not left, were significantly related, with individual BP changes ( r 2 = 0.80; P < 0.001) and with ratings of perceived exertion ( r 2 = 0.79; P < 0.01) during exercise. These results suggest that the magnitude of insular activation varies with the intensity of exercise, which may be further related to the level of perceived effort or central command.
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Williamson, J. W., R. McColl, and D. Mathews. "Evidence for central command activation of the human insular cortex during exercise." Journal of Applied Physiology 94, no. 5 (2003): 1726–34. http://dx.doi.org/10.1152/japplphysiol.01152.2002.
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The purpose of this investigation was to determine whether central command activated regions of the insular cortex, independent of muscle metaboreflex activation and blood pressure elevations. Subjects ( n = 8) were studied during 1) rest with cuff occlusion, 2) static handgrip exercise (SHG) sufficient to increase mean blood pressure (MBP) by 15 mmHg, and 3) post-SHG exercise cuff occlusion (PECO) to sustain the 15-mmHg blood pressure increase. Data were collected for heart rate, MBP, ratings of perceived exertion and discomfort, and regional cerebral blood flow (rCBF) by using single-photon-emission computed tomography. When time periods were compared when MBP was matched during SHG and PECO, heart rate (7 ± 3 beats/min; P < 0.05) and ratings of perceived exertion (15 ± 2 units; P < 0.05) were higher for SHG. During SHG, there were significant increases in rCBF for hand sensorimotor (9 ± 3%), right inferior posterior insula (7 ± 3%), left inferior anterior insula (8 ± 2%), and anterior cingluate regions (6 ± 2%), not found during PECO. There was significant activation of the inferior (ventral) thalamus and right inferior anterior insular for both SHG and PECO. Although prior studies have shown that regions of the insular cortex can be activated independent of mechanoreflex input, it was not presently assessed. These findings provide evidence that there are rCBF changes within regions of the insular and anterior cingulate cortexes related to central command per se during handgrip exercise, independent of metaboreflex activation and blood pressure elevation.
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Aleksandrov, Vjacheslav G., Nina P. Aleksandrova, and Vitaly A. Bagaev. "Identification of a respiratory related area in the rat insular cortex." Canadian Journal of Physiology and Pharmacology 78, no. 7 (2000): 582–86. http://dx.doi.org/10.1139/y00-031.
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The aim of this study was to map areas within the rat insular cortex from which respiratory responses originate and compare those sites with gastrointestinal control regions. The insular cortex was systematically microstimulated and histological location of responsive sites determined. Increased inspiratory airflow and decreased respiratory cycle duration were considered to be respiratory excitatory responses. The responses were localized in dysgranular and agranular insular cortex at levels caudal to the joining of the anterior commissure. More rostrally, respiratory inhibitory responses were elicited: these were manifested as a decrease in inspiratory airflow without a significant alteration in respiratory cycle duration. Respiratory inhibitory responses were usually accompanied by changes in gastric motility. These results suggest that the respiratory area in the rat insular cortex consist of two distinct zones which overlap a region modulating the gastrointestinal activity.Key words: rats, insular cortex, respiration, gastrointestinal motility.
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Staszko, Stephanie M., John D. Boughter, and Max L. Fletcher. "Taste coding strategies in insular cortex." Experimental Biology and Medicine 245, no. 5 (2020): 448–55. http://dx.doi.org/10.1177/1535370220909096.
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While the cortical representation of sensory stimuli is well described for some sensory systems, a clear understanding of the cortical representation of taste stimuli remains elusive. Recent investigations have focused on both spatial and temporal organization of taste responses in the putative taste region of insular cortex. This review highlights recent literature focused on spatiotemporal coding strategies in insular cortex. These studies are examined in the context of the organization and function of the entire insular cortex, rather than a specific gustatory region of insular cortex. In regard to a taste quality-specific map, imaging studies have reported conflicting results, whereas electrophysiology studies have described a broad distribution of taste-responsive neurons found throughout insular cortex with no spatial organization. The current collection of evidence suggests that insular cortex may be organized into a hedonic or “viscerotopic” map, rather than one ordered according to taste quality. Further, it has been proposed that cortical taste responses can be separated into temporal “epochs” representing stimulus identity and palatability. This coding strategy presents a potential framework, whereby the coordinated activity of a population of neurons allows for the same neurons to respond to multiple taste stimuli or even other sensory modalities, a well-documented phenomenon in insular cortex neurons. However, these representations may not be static, as several studies have demonstrated that both spatial representation and temporal dynamics of taste coding change with experience. Collectively, these studies suggest that cortical taste representation is not organized in a spatially discrete map, but rather is plastic and spatially dispersed, using temporal information to encode multiple types of information about ingested stimuli. Impact statement The organization of taste coding in insular cortex is widely debated. While early work has focused on whether taste quality is encoded via labeled line or ensemble mechanisms, recent work has attempted to delineate the spatial organization and temporal components of taste processing in insular cortex. Recent imaging and electrophysiology studies have reported conflicting results in regard to the spatial organization of cortical taste responses, and many studies ignore potentially important temporal dynamics when investigating taste processing. This review highlights the latest research in these areas and examines them in the context of the anatomy and physiology of the insular cortex in general to provide a more comprehensive description of taste coding in insular cortex.
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van Ettinger-Veenstra, Helene, Rebecca Boehme, Bijar Ghafouri, Håkan Olausson, Rikard K. Wicksell, and Björn Gerdle. "Exploration of Functional Connectivity Changes Previously Reported in Fibromyalgia and Their Relation to Psychological Distress and Pain Measures." Journal of Clinical Medicine 9, no. 11 (2020): 3560. http://dx.doi.org/10.3390/jcm9113560.
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Neural functional connectivity changes in the default mode network (DMN), Central executive network (CEN), and insula have been implicated in fibromyalgia (FM) but stem from a sparse set of small-scale studies with limited power for the investigation of confounding effects. We investigated whether anxiety, depression, pain sensitivity, and pain intensity modulated functional connectivity related to DMN nodes, CEN nodes, and insula. Resting-state functional magnetic resonance imaging data were collected from 31 females with FM and 28 age-matched healthy controls. Connectivity was analysed with a region-based connectivity analysis between DMN nodes in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex, CEN nodes in the intraparietal sulcus (IPS), and bilateral insula. FM patients displayed significantly higher levels of anxiety and depressive symptoms than controls. The right IPS node of the CEN showed a higher level of connectivity strength with right insula in FM with higher pain intensity compared to controls. More anxiety symptoms in FM correlated with higher levels of connectivity strength between the vmPFC DMN node and right sensorimotor cortex. These findings support the theory of altered insular connectivity in FM and also suggest altered IPS connectivity in FM. Interestingly, no change in insular connectivity with DMN was observed.
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Potts, Matthew B., Edward F. Chang, William L. Young, and Michael T. Lawton. "Transsylvian-Transinsular Approaches to the Insula and Basal Ganglia." Neurosurgery 70, no. 4 (2011): 824–34. http://dx.doi.org/10.1227/neu.0b013e318236760d.
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Abstract BACKGROUND: Lesions in the insula and basal ganglia can be risky to resect because of their depth and proximity to critical structures, particularly in the dominant hemisphere. Transsylvian approaches shorten the surgical distance to these lesions, preserve perisylvian temporal and frontal cortex, and minimize brain transgression. OBJECTIVE: To report our experience with transsylvian-transinsular approaches to vascular lesions. METHODS: The anterior approach opened the sphenoidal and insular portions of the sylvian fissure and exposed the limen insulae and short gyri, whereas the posterior approach opened the insular and opercular portions of the sylvian fissure and exposed the circular sulcus and long gyri. RESULTS: Forty-one patients with vascular lesions (24 arteriovenous malformations [AVMs] and 17 cavernous malformations) were treated surgically with a transsylvian-transinsular approach. Complete resection was obtained in 87.5% of AVMs and 95% of cavernous malformations. Permanent neurological morbidity related to surgery was observed in 2 AVM patients (5%), with the remaining 39 patients (95%) improved or unchanged postoperatively (modified Rankin Scale scores 0-2 in 83%). There were no new language deficits in patients with dominant hemisphere lesions. CONCLUSION: Transsylvian-transinsular approaches safely expose vascular pathology in or deep to the insula while preserving overlying eloquent cortex in the frontal and temporal lobes. The anterior transsylvian-transinsular approach can be differentiated from the posterior approach based on technical differences in splitting the sylvian fissure and anatomic differences in final exposure. Discriminating patient selection and careful microsurgical technique are essential.
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Benarroch, Eduardo E. "Insular cortex." Neurology 93, no. 21 (2019): 932–38. http://dx.doi.org/10.1212/wnl.0000000000008525.
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Mutschler, I., J. Wankerl, E. Seifritz, and T. Ball. "The role of the human insular cortex in pain processing." European Psychiatry 26, S2 (2011): 1001. http://dx.doi.org/10.1016/s0924-9338(11)72706-7.
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The human insular cortex is involved in a wide range of functions. A recent study done by conducting an activation likelihood estimate (ALE) meta-analysis suggests that there are anatomical subregions with functional specializations for motor processing, auditory perception and homeostatic control, which plays an important role in emotional processing (Mutschler et al., 2009). An increasing number of studies propose the involvement of the anterior insula in experiencing pain and empathy for pain, e.g. when someone perceives a loved one feeling pain (Craig, 2009, Singer et al., 2004). In this present work, the activation likelihood estimate (ALE) method (Turkeltaub et al., 2002) was applied and 59 studies reporting pain processing and 19 investigating empathy for pain entered the meta-analysis to investigate the questions whether there are functional specializations within the insular cortex for pain processing and empathy for pain. Pain studies revealed activation in the posterior and mid-anterior part of the insula. In contrast, the ALE-maximum of studies investigating empathy for pain was located more anterior than studies investigating physically induced pain. The present findings provide insights into the organization of the human anterior insula and support the posterior-to-anterior gradient for interoceptive representations in the Insula proposed by Craig (2009). According to this view, an increasingly elaborate and complex representation of bodily states may progress from the posterior to the anterior insula region. Meta-analyses represent an important methodological approach for ruling out false positive results and contribute to the generation of hypotheses which can be experimentally proven.
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Liu, Ming-Gang, SukJae Joshua Kang, Tian-Yao Shi, et al. "Long-term potentiation of synaptic transmission in the adult mouse insular cortex: multielectrode array recordings." Journal of Neurophysiology 110, no. 2 (2013): 505–21. http://dx.doi.org/10.1152/jn.01104.2012.
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The insular cortex (IC) is widely believed to be an important forebrain structure involved in cognitive and sensory processes such as memory and pain. However, little work has been performed at the cellular level to investigate the synaptic basis of IC-related brain functions. To bridge the gap, the present study was designed to characterize the basic synaptic mechanisms for insular long-term potentiation (LTP). Using a 64-channel recording system, we found that an enduring form of late-phase LTP (L-LTP) could be reliably recorded for at least 3 h in different layers of IC slices after theta burst stimulation. The induction of insular LTP is protein synthesis dependent and requires activation of both GluN2A and GluN2B subunits of the NMDA receptor, L-type voltage-gated calcium channels, and metabotropic glutamate receptor 1. The paired-pulse facilitation ratio was unaffected by insular L-LTP induction, and expression of insular L-LTP required the recruitment of postsynaptic calcium-permeable AMPA receptors. Our results provide the first in vitro report of long-term multichannel recordings of L-LTP in the IC in adult mice and suggest its potential important roles in insula-related memory and chronic pain.
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Cechetto, D. F., and S. J. Chen. "Subcortical sites mediating sympathetic responses from insular cortex in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 258, no. 1 (1990): R245—R255. http://dx.doi.org/10.1152/ajpregu.1990.258.1.r245.
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Stimulation of the insular cortex elicits a number of autonomic responses. The insular cortex projects directly to the lateral hypothalamic area, the parabrachial nucleus, and the nucleus of the solitary tract, which in turn project directly to sympathetic preganglionic areas. To determine which of these subcortical sites mediates sympathetic responses evoked from the insular cortex, changes in renal nerve activity were recorded before and after injection of the synaptic blocking agent cobalt into each of these regions. Blood pressure, heart rate, and renal nerve activity were continuously monitored in chloralose or urethan-anesthetized rats. Single-pulse electrical stimulation (200 microA, 1 ms) elicited either an early increase or decrease in renal nerve activity from pressor and depressor sites, respectively, in the insular cortex. Cobalt injections (500 nl) into the lateral hypothalamic area attenuated the nerve response 10-100%. Cobalt injections into the nucleus of the solitary tract significantly enhanced the initial increase in the nerve response obtained from pressor sites in the insular cortex. Injections into the parabrachial nucleus did not affect the nerve responses. These results suggest that there is a mandatory synapse in the lateral hypothalamic area in the pathway from the insular cortex to the sympathetic nervous system.
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Saleh, Tarek M., and Barry J. Connell. "Role of the insular cortex in the modulation of baroreflex sensitivity." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274, no. 5 (1998): R1417—R1424. http://dx.doi.org/10.1152/ajpregu.1998.274.5.r1417.
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Cervical vagal stimulation for 2 h results in a depressed baroreflex sensitivity produced by an enhanced sympathetic output, as indicated by increased plasma norepinephrine levels. The current study examined the role of the insular cortex in modulating the vagal stimulation-induced changes in baroreflex sensitivity. Male Sprague-Dawley rats were anesthetized with thiobutabarbitol sodium and instrumented for recording blood pressure, heart rate, intravenous drug administration, and vagal afferent nerve stimulation. Stereotaxic microinjections (300 nl) of either 5% lidocaine or 0.9% saline were made bilaterally into the insula. Thirty minutes after 2 h of vagal stimulation, the baroreflex was significantly depressed and plasma norepinephrine levels were significantly elevated in both groups. The baroreflex was also significantly depressed after bilateral lidocaine injections into the insula, independent of vagal stimulation. However, no significant change in plasma norepinephrine was observed, suggesting that an attenuated parasympathetic output contributed to the altered baroreflex. Taken together, the results suggest that the insular cortex modulates the cardiac baroreflex through a modulation of parasympathetic output.
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Roper, Steven N., Michel F. Levesque, William W. Sutherling, and Jerome Engel. "Surgical treatment of partial epilepsy arising from the insular cortex." Journal of Neurosurgery 79, no. 2 (1993): 266–69. http://dx.doi.org/10.3171/jns.1993.79.2.0266.
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✓ Despite its documented connections with many limbic structures, the role of the insula in the etiology of partial seizures is poorly understood. Two patients are described in whom lesions of the insula were associated with intractable partial seizures. In the first patient, the seizures involved visceral sensory hallucinations followed by motor automatism. Seizures in the second patient began with somatic sensory hallucinations and then produced visceral motor effects. Both patients were found to have low-grade astrocytomas of the insula. In both instances, resection of the lesion and adjacent insular cortex resulted in a cure of the seizures. These cases are placed within the context of the existing literature on the subject.
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Davis, K. D., G. E. Pope, A. P. Crawley, and D. J. Mikulis. "Perceptual Illusion of “Paradoxical Heat” Engages the Insular Cortex." Journal of Neurophysiology 92, no. 2 (2004): 1248–51. http://dx.doi.org/10.1152/jn.00084.2004.
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Paradoxical heat (PH), the illusion of skin heat, accompanies many neurological disorders. Using the technique of percept-related functional MRI, we found a region of the right insular cortex specifically activated when subjects perceive a heat sensation in their right hand even though their skin temperature is cool or at neutral. This region was suppressed during mild skin cooling. We propose that this differential response is a manifestation of the role of the insula in signaling temperature perceptions regardless of the actual temperature of the skin. These findings suggest that a region within the insula has a complex role in heat perception, perhaps contributing to a specific, rather than general, thermosensory perception. These data provide insight to our basic understanding of normal and pathological thermosensory perceptions.
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Frank, Sebastian M., and Mark W. Greenlee. "The parieto-insular vestibular cortex in humans: more than a single area?" Journal of Neurophysiology 120, no. 3 (2018): 1438–50. http://dx.doi.org/10.1152/jn.00907.2017.
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Here, we review the structure and function of a core region in the vestibular cortex of humans that is located in the midposterior Sylvian fissure and referred to as the parieto-insular vestibular cortex (PIVC). Previous studies have investigated PIVC by using vestibular or visual motion stimuli and have observed activations that were distributed across multiple anatomical structures, including the temporo-parietal junction, retroinsula, parietal operculum, and posterior insula. However, it has remained unclear whether all of these anatomical areas correspond to PIVC and whether PIVC responds to both vestibular and visual stimuli. Recent results suggest that the region that has been referred to as PIVC in previous studies consists of multiple areas with different anatomical correlates and different functional specializations. Specifically, a vestibular but not visual area is located in the parietal operculum, close to the posterior insula, and likely corresponds to the nonhuman primate PIVC, while a visual-vestibular area is located in the retroinsular cortex and is referred to, for historical reasons, as the posterior insular cortex area (PIC). In this article, we review the anatomy, connectivity, and function of PIVC and PIC and propose that the core of the human vestibular cortex consists of at least two separate areas, which we refer to together as PIVC+. We also review the organization in the nonhuman primate brain and show that there are parallels to the proposed organization in humans.
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Ikegaya, Naoki, Masaki Iwasaki, Yuu Kaneko, et al. "Cognitive and developmental outcomes after pediatric insular epilepsy surgery for focal cortical dysplasia." Journal of Neurosurgery: Pediatrics 26, no. 5 (2020): 543–51. http://dx.doi.org/10.3171/2020.5.peds2058.
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OBJECTIVECognitive risk associated with insular cortex resection is not well understood. The authors reviewed cognitive and developmental outcomes in pediatric patients who underwent resection of the epileptogenic zone involving the insula.METHODSA review was conducted of 15 patients who underwent resective epilepsy surgery involving the insular cortex for focal cortical dysplasia, with a minimum follow-up of 12 months. The median age at surgery was 5.6 years (range 0.3–13.6 years). Developmental/intelligence quotient (DQ/IQ) scores were evaluated before surgery, within 4 months after surgery, and at 12 months or more after surgery. Repeated measures multivariate ANOVA was used to evaluate the effects on outcomes of the within-subject factor (time) and between-subject factors (resection side, anterior insular resection, seizure control, and antiepileptic drug [AED] reduction).RESULTSThe mean preoperative DQ/IQ score was 60.7 ± 22.8. Left-side resection and anterior insular resection were performed in 9 patients each. Favorable seizure control (International League Against Epilepsy class 1–3) was achieved in 8 patients. Postoperative motor deficits were observed in 9 patients (permanent in 6, transient in 3). Within-subject changes in DQ/IQ were not significantly affected by insular resection (p = 0.13). Postoperative changes in DQ/IQ were not significantly affected by surgical side, anterior insular resection, AED reduction, or seizure outcome. Only verbal function showed no significant changes before and after surgery and no significant effects of within-subject factors.CONCLUSIONSResection involving the insula in children with impaired development or intelligence can be performed without significant reduction in DQ/IQ, but carries the risk of postoperative motor deficits.
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Oppenheimer, Stephen, and David Cechetto. "The Insular Cortex and the Regulation of Cardiac Function." Comprehensive Physiology 6, no. 2 (2016): 1081–133. https://doi.org/10.1002/j.2040-4603.2016.tb00691.x.
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ABSTRACTCortical representation of the heart challenges the orthodox view that cardiac regulation is confined to stereotyped, preprogrammed and rigid responses to exteroceptive or interoceptive environmental stimuli. The insula has been the region most studied in this regard; the results of clinical, experimental, and functional radiological studies show a complex interweave of activity with patterns dynamically varying regarding lateralization and antero‐posterior distribution of responsive insular regions. Either acting alone or together with other cortical areas including the anterior cingulate, medial prefrontal, and orbito‐frontal cortices as part of a concerted network, the insula can imbue perceptions with autonomic color providing emotional salience, and aiding in learning and behavioral decision choice. In these functions, cardiovascular input and the right anterior insula appear to play an important, if not pivotal role. At a more basic level, the insula gauges cardiovascular responses to exteroceptive and interoceptive stimuli, taking into account memory, cognitive, and reflexive constructs thereby ensuring appropriate survival responses and maintaining emotional and physiological homeostasis. When acquired derangements to the insula occur after stroke, during a seizure or from abnormal central processing of interoceptive or exteroceptive environmental cues as in psychiatric disorders, serious consequences can arise including cardiac electrophysiological, structural and contractile dysfunction and sudden cardiac death. © 2016 American Physiological Society. Compr Physiol 6:1081‐1133, 2016.
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Liang, Despoina, and Charalampos Labrakakis. "Multiple Posterior Insula Projections to the Brainstem Descending Pain Modulatory System." International Journal of Molecular Sciences 25, no. 17 (2024): 9185. http://dx.doi.org/10.3390/ijms25179185.
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The insular cortex is an important hub for sensory and emotional integration. It is one of the areas consistently found activated during pain. While the insular’s connections to the limbic system might play a role in the aversive and emotional component of pain, its connections to the descending pain system might be involved in pain intensity coding. Here, we used anterograde tracing with viral expression of mCherry fluorescent protein, to examine the connectivity of insular axons to different brainstem nuclei involved in the descending modulation of pain in detail. We found extensive connections to the main areas of descending pain control, namely, the periaqueductal gray (PAG) and the raphe magnus (RMg). In addition, we also identified an extensive insular connection to the parabrachial nucleus (PBN). Although not as extensive, we found a consistent axonal input from the insula to different noradrenergic nuclei, the locus coeruleus (LC), the subcoereuleus (SubCD) and the A5 nucleus. These connections emphasize a prominent relation of the insula with the descending pain modulatory system, which reveals an important role of the insula in pain processing through descending pathways.