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1
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 (April 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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Tanriover, Necmettin, Albert L. Rhoton, Masatou Kawashima, Arthur J. Ulm, and Alexandre Yasuda. "Microsurgical anatomy of the insula and the sylvian fissure." Journal of Neurosurgery 100, no. 5 (May 2004): 891–922. http://dx.doi.org/10.3171/jns.2004.100.5.0891.
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Object. The purpose of this study was to define the topographic anatomy, arterial supply, and venous drainage of the insula and sylvian fissure. Methods. The neural, arterial, and venous anatomy of the insula and sylvian fissure were examined in 43 cerebral hemispheres. Conclusions. The majority of gyri and sulci of the frontoparietal and temporal opercula had a constant relationship to the insular gyri and sulci and provided landmarks for approaching different parts of the insula. The most lateral lenticulostriate artery, an important landmark in insular surgery, arose 14.6 mm from the apex of the insula and penetrated the anterior perforated substance 15.3 mm medial to the limen insulae. The superior trunk of the middle cerebral artery (MCA) and its branches supplied the anterior, middle, and posterior short gyri; the anterior limiting sulcus; the short sulci; and the insular apex. The inferior trunk supplied the posterior long gyrus, inferior limiting sulcus, and limen area in most hemispheres. Both of these trunks frequently contributed to the supply of the central insular sulcus and the anterior long gyrus. The areas of insular supply of the superior and inferior trunks did not overlap. The most constant insular area of supply by the cortical MCA branches was from the prefrontal and precentral arteries that supplied the anterior and middle short gyri, respectively. The largest insular perforating arteries usually arose from the central and angular arteries and most commonly entered the posterior half of the central insular sulcus and posterior long gyrus. Insular veins drained predominantly to the deep middle cerebral vein, although frequent connections to the superficial venous system were found. Of all the insular veins, the precentral insular vein was the one that most commonly connected to the superficial sylvian vein.
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Rachidi, Inès, Lorella Minotti, Guillaume Martin, Dominique Hoffmann, Julien Bastin, Olivier David, and Philippe Kahane. "The Insula: A Stimulating Island of the Brain." Brain Sciences 11, no. 11 (November 19, 2021): 1533. http://dx.doi.org/10.3390/brainsci11111533.
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Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and trigger seizures. Clinical responses to insular DCS are frequent and diverse, showing a partial segregation with spatial overlap, including a posterior somatosensory, auditory, and vestibular part, a central olfactory-gustatory region, and an anterior visceral and cognitive-emotional portion. The study of cortico-cortical evoked potentials (CCEPs) has shown that the anterior (resp. posterior) insula has a higher connectivity rate with itself than with the posterior (resp. anterior) insula, and that both the anterior and posterior insula are closely connected, notably between the homologous insular subdivisions. All insular gyri show extensive and complex ipsilateral and contralateral extra-insular connections, more anteriorly for the anterior insula and more posteriorly for the posterior insula. As a rule, CCEPs propagate first and with a higher probability around the insular DCS site, then to the homologous region, and later to more distal regions with fast cortico-cortical axonal conduction delays. Seizures elicited by insular DCS have rarely been specifically studied, but their rate does not seem to differ from those of other DCS studies. They are mainly provoked from the insular seizure onset zone but can also be triggered by stimulating intra- and extra-insular early propagation zones. Overall, in line with the neuroimaging studies, insular DCS studies converge on the view that the insula is a multimodal functional hub with a fast propagation of information, whose organization helps understand where insular seizures start and how they propagate.
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Kaneko, Nobuyuki, Warren W. Boling, Takaharu Shonai, Kazumi Ohmori, Yoshiaki Shiokawa, Hiroki Kurita, and Takanori Fukushima. "Delineation of the Safe Zone in Surgery of Sylvian Insular Triangle: Morphometric Analysis and Magnetic Resonance Imaging Study." Operative Neurosurgery 70, suppl_2 (August 9, 2011): ons290—ons299. http://dx.doi.org/10.1227/neu.0b013e3182315112.
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ABSTRACT BACKGROUND: Surgery within the insula carries significant risk of morbidity, particularly hemiparesis, because of the difficulty in detecting the internal capsule boundaries. OBJECTIVE: We analyzed the anatomy of the insula and identified landmarks anticipated to facilitate surgery for intrinsic insular lesions. METHODS: Insular region anatomy was studied in 11 cadaveric brains harvested within 72 hours postmortem. MRI of the specimens was acquired using 3.0 T with T2-weighting and 25 directions of diffusion tensor imaging. Landmarks easily recognizable during surgery were identified on the surface of the insula. The interrelationships between surface landmarks and critical structures were analyzed. RESULTS: The posterior inferior insular point (PIIP) and the upper central insular point (UCIP) were newly established as landmarks on the insula. The PIIP corresponded to the obvious bend in the posterior long insular gyrus. The UCIP is the meeting point between the central insular sulcus and superior peri-insular sulcus. The corticospinal tract was identified as a high-intensity area in the posterior limb of the internal capsule on T2-weighted imaging and its course confirmed with diffusion tensor imaging tractography. The corticospinal tract took a course deep to the posterosuperior insula on T2-weighted imaging, 4.8 mm from the UCIP and 6.2 mm from the PIIP. CONCLUSION: The posterosuperior part of the insula forms the region at greatest risk to corticospinal tract injury. The PIIP and UCIP are crucial to understanding the relationship of the insula with the posterior limb of the internal capsule including the corticospinal tract.
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Martino, Juan, Francesco Vergani, Santiago Gil Robles, and Hugues Duffau. "New Insights Into the Anatomic Dissection of the Temporal Stem With Special Emphasis on the Inferior Fronto-occipital Fasciculus: Implications in Surgical Approach to Left Mesiotemporal and Temporoinsular Structures." Operative Neurosurgery 66, suppl_1 (March 1, 2010): ons—4—ons—12. http://dx.doi.org/10.1227/01.neu.0000348564.28415.fa.
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Abstract Objective: To analyze the 3-dimensional relationships of the inferior fronto-occipital fasciculus (IFOF) within the temporal stem using anatomic dissection and to study the surgical application. Methods: Ten postmortem human hemispheres (5 right, 5 left) were dissected using the Klingler fiber dissection technique. The 3-dimensional relationships of the IFOF with different landmarks of the temporal stem, insula, and temporal lobe were analyzed and measured. Results: An average distance of 10.9 mm (range, 8–15 mm) was observed between the limen insulae and the anterior edge of the IFOF under the inferior limiting sulcus of the insula. This anterior one-third of the temporal stem is crossed by the uncinate fasciculus. The IFOF crosses the posterior two-thirds of the temporal stem, in the space between the posterior limit of the uncinate fasciculus and the lateral geniculate body. The average superoinferior distance between the IFOF and the inferior limiting sulcus was 3.8 mm. The auditory radiations and the claustro-opercular and insulo-opercular fibers of the external and extreme capsules pass through the temporal stem above the IFOF, whereas the optic radiations pass below. Conclusion: In the transsylvian approach to the mesiotemporal structures in the left dominant hemisphere, an incision within the posterior 8 mm from the limen insulae is less likely to damage the IFOF than more posterior incisions along the inferior limiting sulcus. In the temporal transopercular approach to left temporo-insular gliomas, the IFOF constitutes the deep functional limit of the resection within the temporal stem.
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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 (September 14, 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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Parellada, M., L. Pina-Camacho, C. Moreno, Y. Aleman, M. O. Krebs, M. Desco, J. Merchán-Naranjo, et al. "Insular pathology in young people with high-functioning autism and first-episode psychosis." Psychological Medicine 47, no. 14 (April 24, 2017): 2472–82. http://dx.doi.org/10.1017/s0033291717000988.
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BackgroundAutism Spectrum Disorders (ASD) and psychosis share deficits in social cognition. The insular region has been associated with awareness of self and reality, which may be basic for proper social interactions.MethodsTotal and regional insular volume and thickness measurements were obtained from a sample of 30 children and adolescents with ASD, 29 with early onset first-episode psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level volume and thickness measurements were compared between groups (with correction for multiple comparisons), and the relationship between these measurements and symptom severity was explored.ResultsCompared with HC, a shared volume deficit was observed for the right (but not the left) anterior insula (ASD: p = 0.007, FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011, FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter volume and thickness deficit in the left posterior insula. Within patients, right anterior (r = −0.28, p = 0.041) and left posterior (r = −0.29, p = 0.030) insular volumes negatively correlated with the severity of insight deficits, and left posterior insular volume negatively correlated with the severity of ‘autistic-like’ symptoms (r = −0.30, p = 0.028).ConclusionsThe shared reduced volume and thickness in the anterior and posterior regions of the insula in ASD and FEP provides the first tentative evidence that these conditions share structural pathology that may be linked to shared symptomatology.
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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 (April 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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Liang, Despoina, and Charalampos Labrakakis. "Multiple Posterior Insula Projections to the Brainstem Descending Pain Modulatory System." International Journal of Molecular Sciences 25, no. 17 (August 24, 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.
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Desai, Atman, Kimon Bekelis, Terrance M. Darcey, and David W. Roberts. "Surgical techniques for investigating the role of the insula in epilepsy: a review." Neurosurgical Focus 32, no. 3 (March 2012): E6. http://dx.doi.org/10.3171/2012.1.focus11325.
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Intracranial electroencephalography monitoring of the insula is an important tool in the investigation of the insula in medically intractable epilepsy and has been shown to be safe and reliable. Several methods of placing electrodes for insular coverage have been reported and include open craniotomy as well as stereotactic orthogonal and stereotactic anterior and posterior oblique trajectories. The authors review each of these techniques with respect to current concepts in insular epilepsy.
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Bhattacharyya, S., X. Cai, and J. P. Klein. "Dyscalculia, Dysgraphia, and Left-Right Confusion from a Left Posterior Peri-Insular Infarct." Behavioural Neurology 2014 (2014): 1–4. http://dx.doi.org/10.1155/2014/823591.
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The Gerstmann syndrome of dyscalculia, dysgraphia, left-right confusion, and finger agnosia is generally attributed to lesions near the angular gyrus of the dominant hemisphere. A 68-year-old right-handed woman presented with sudden difficulty completing a Sudoku grid and was found to have dyscalculia, dysgraphia, and left-right confusion. Magnetic resonance imaging (MRI) showed a focus of abnormal reduced diffusivity in the left posterior insula and temporoparietal operculum consistent with acute infarct. Gerstmann syndrome from an insular or peri-insular lesion has not been described in the literature previously. Pathological and functional imaging studies show connections between left posterior insular region and inferior parietal lobe. We postulate that the insula and operculum lesion disrupted key functional networks resulting in a pseudoparietal presentation.
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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 (March 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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Nachtergaele, Pieter, Ahmed Radwan, Stijn Swinnen, Thomas Decramer, Mats Uytterhoeven, Stefan Sunaert, Johannes van Loon, and Tom Theys. "The temporoinsular projection system: an anatomical study." Journal of Neurosurgery 132, no. 2 (February 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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Long, Ting, Haijun Li, Yongqiang Shu, Kunyao Li, Wei Xie, Yaping Zeng, Ling Huang, Li Zeng, Xiang Liu, and Dechang Peng. "Functional Connectivity Changes in the Insular Subregions of Patients with Obstructive Sleep Apnea after 6 Months of Continuous Positive Airway Pressure Treatment." Neural Plasticity 2023 (February 21, 2023): 1–10. http://dx.doi.org/10.1155/2023/5598047.
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This study was aimed at investigating the functional connectivity (FC) changes between the insular subregions and whole brain in patients with obstructive sleep apnea (OSA) after 6 months of continuous positive airway pressure (CPAP) treatment and at exploring the relationship between resting-state FC changes and cognitive impairment in OSA patients. Data from 15 patients with OSA before and after 6 months of CPAP treatment were included in this study. The FC between the insular subregions and whole brain was compared between baseline and after 6 months of CPAP treatment in OSA. After 6 months of treatment, OSA patients had increased FC from the right ventral anterior insula to the bilateral superior frontal gyrus and bilateral middle frontal gyrus and increased FC from the left posterior insula to the left middle temporal gyrus and left inferior temporal gyrus. Hyperconnectivity was found from the right posterior insula to the right middle temporal gyrus, bilateral precuneus, and bilateral posterior cingulate cortex, which mainly involved the default mode network. There are changes in functional connectivity patterns between the insular subregions and whole brain in OSA patients after 6 months of CPAP treatment. These changes provide a better understanding of the neuroimaging mechanisms underlying the improvement in cognitive function and emotional impairment in OSA patients and can be used as potential biomarkers for clinical CPAP treatment.
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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 (September 28, 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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Wynford-Thomas, Ray, and Rob Powell. "THE INSULA: ISLAND OF REIL." Journal of Neurology, Neurosurgery & Psychiatry 86, no. 11 (October 14, 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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Bergeron, David, Sami Obaid, Marie-Pierre Fournier-Gosselin, Alain Bouthillier, and Dang Khoa Nguyen. "Deep Brain Stimulation of the Posterior Insula in Chronic Pain: A Theoretical Framework." Brain Sciences 11, no. 5 (May 15, 2021): 639. http://dx.doi.org/10.3390/brainsci11050639.
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Introduction: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. Methods: We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain. Results: Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds. Conclusion: In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain.
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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 (July 4, 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 (January 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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Benet, Arnau, Shawn L. Hervey-Jumper, Jose Juan González Sánchez, Michael T. Lawton, and Mitchel S. Berger. "Surgical assessment of the insula. Part 1: surgical anatomy and morphometric analysis of the transsylvian and transcortical approaches to the insula." Journal of Neurosurgery 124, no. 2 (February 2016): 469–81. http://dx.doi.org/10.3171/2014.12.jns142182.
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OBJECT Transcortical and transsylvian corridors have been previously described as the main surgical approaches to the insula, but there is insufficient evidence to support one approach versus the other. The authors performed a cadaveric comparative study regarding insular exposure, surgical window and freedom, between the transcortical and transsylvian approaches (with and without cutting superficial sylvian bridging veins). Surgical anatomy and skull surface reference points to the different insular regions are also described. METHODS Sixteen cadaveric specimens were embalmed with a customized formula to enhance neurosurgical simulation. Two different blocks were defined in the study: first, transsylvian without (TS) and with the superficial sylvian bridging veins cut (TSVC) and transcortical (TC) approaches to the insula were simulated in all (16) specimens. Insular surface exposure, surgical window and surgical freedom were calculated for each procedure and related to the Berger-Sanai insular glioma classification (Zones I–IV) in 10 specimens. Second, the venous drainage pattern and anatomical landmarks considered critical for surgical planning were studied in all specimens. RESULTS In the insular Zone I (anterior-superior), the TC approach provided the best insular exposure compared with both TS and TSVC. The surgical window obtained with the TC approach was also larger than that obtained with the TS. The TC approach provided 137% more surgical freedom than the TS approach. Only the TC corridor provided complete insular exposure. In Zone II (posterior-superior), results depended on the degree of opercular resection. Without resection of the precentral gyrus in the operculum, insula exposure, surgical windows and surgical freedom were equivalent. If the opercular cortex was resected, the insula exposure and surgical freedom obtained through the TC approach was greater to that of the other groups. In Zone III (posterior-inferior), the TC approach provided better surgical exposure than the TS, yet similar to the TSVC. The TC approach provided the best insular exposure, surgical window, and surgical freedom if components of Heschl’s gyrus were resected. In Zone IV (anterior-inferior), the TC corridor provided better exposure than both the TS and the TSVC. The surgical window was equivalent. Surgical freedom provided by the TC was greater than the TS approach. This zone was completely exposed only with the TC approach. A dominant anterior venous drainage was found in 87% of the specimens. In this group, 50% of the specimens had good alternative venous drainage. The sylvian fissure corresponded to the superior segment of the squamosal suture in 14 of 16 specimens. The foramen of Monro was 1.9 cm anterior and 4.42 cm superior to the external acoustic meatus. The M2 branch over the central sulcus of the insula became the precentral M4 (rolandic) artery in all specimens. CONCLUSIONS Overall, the TC approach to the insula provided better insula exposure and surgical freedom compared with the TS and the TSVC. Cortical and subcortical mapping is critical during the TC approach to the posterior zones (II and III), as the facial motor and somatosensory functions (Zone II) and language areas (Zone III) may be involved. The evidence provided in this study may help the neurosurgeon when approaching insular gliomas to achieve a greater extent of tumor resection via an optimal exposure.
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Casanova, José Patricio, Marcelo Aguilar-Rivera, María de los Ángeles Rodríguez, Todd P. Coleman, and Fernando Torrealba. "The activity of discrete sets of neurons in the posterior insula correlates with the behavioral expression and extinction of conditioned fear." Journal of Neurophysiology 120, no. 4 (October 1, 2018): 1906–13. http://dx.doi.org/10.1152/jn.00318.2018.
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The interoceptive insular cortex is known to be involved in the perception of bodily states and emotions. Increasing evidence points to an additional role for the insula in the storage of fear memories. However, the activity of the insula during fear expression has not been studied. We addressed this issue by recording single units from the posterior insular cortex (pIC) of awake behaving rats expressing conditioned fear during its extinction. We found a set of pIC units showing either significant increase or decrease in activity during high fear expression to the auditory cue (“freezing units”). Firing rate of freezing units showed high correlation with freezing and outlasted the duration of the auditory cue. In turn, a different set of units showed either significant increase or decrease in activity during low fear state (“extinction units”). These findings show that expression of conditioned freezing is accompanied with changes in pIC neural activity and suggest that the pIC is important to regulate the behavioral expression of fear memory. NEW & NOTEWORTHY Here, we show novel single-unit data from the interoceptive insula underlying the behavioral expression of fear. We show that different populations of neurons in the insula codify expression and extinction of conditioned fear. Our data add further support for the insula as an important player in the regulation of emotions.
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Gujing, Li, He Hui, Li Xin, Zhang Lirong, Yao Yutong, Ye Guofeng, Lu Jing, 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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Li, Xuejing, Ling Wang, Qian Chen, Yongsheng Hu, Jubao Du, Xin Chen, Weimin Zheng, Jie Lu, and Nan Chen. "The Reorganization of Insular Subregions in Individuals with Below-Level Neuropathic Pain following Incomplete Spinal Cord Injury." Neural Plasticity 2020 (March 10, 2020): 1–9. http://dx.doi.org/10.1155/2020/2796571.
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Objective. To investigate the reorganization of insular subregions in individuals suffering from neuropathic pain (NP) after incomplete spinal cord injury (ISCI) and further to disclose the underlying mechanism of NP. Method. The 3D high-resolution T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all individuals were obtained using a 3.0 Tesla MRI system. A comparative analysis of structure and function connectivity (FC) with insular subareas as seeds in 10 ISCI individuals with below-level NP (ISCI-P), 11 ISCI individuals without NP (ISCI-N), and 25 healthy controls (HCs) was conducted. Associations between the structural and functional alteration of insula subregions and visual analog scale (VAS) scores were analyzed using the Pearson correlation in SPSS 20. Results. Compared with ISCI-N patients, when the left posterior insula as the seed, ISCI-P showed increased FC in right cerebellum VIIb and cerebellum VIII, Brodmann 37 (BA 37). When the left ventral anterior insula as the seed, ISCI-P indicated enhanced FC in right BA18 compared with ISCI-N patients. These increased FCs positively correlated with VAS scores. Relative to HCs, ISCI-P presented increased FC in the left hippocampus when the left dorsal anterior insula was determined as the seed. There was no statistical difference in the volume of insula subregions among the three groups. Conclusion. Our study indicated that distinctive patterns of FC in each subregion of insula suggest that the insular subareas participate in the NP processing through different FC following ISCI. Further, insula subregions could serve as a therapeutic target for NP following ISCI.
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Baumgärtner, Ulf, Gian Domenico Iannetti, Laura Zambreanu, Peter Stoeter, Rolf-Detlef Treede, and Irene Tracey. "Multiple Somatotopic Representations of Heat and Mechanical Pain in the Operculo-Insular Cortex: A High-Resolution fMRI Study." Journal of Neurophysiology 104, no. 5 (November 2010): 2863–72. http://dx.doi.org/10.1152/jn.00253.2010.
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Whereas studies of somatotopic representation of touch have been useful to distinguish multiple somatosensory areas within primary (SI) and secondary (SII) somatosensory cortex regions, no such analysis exists for the representation of pain across nociceptive modalities. Here we investigated somatotopy in the operculo-insular cortex with noxious heat and pinprick stimuli in 11 healthy subjects using high-resolution (2 × 2 × 4 mm) 3T functional magnetic resonance imaging (fMRI). Heat stimuli (delivered using a laser) and pinprick stimuli (delivered using a punctate probe) were directed to the dorsum of the right hand and foot in a balanced design. Locations of the peak fMRI responses were compared between stimulation sites (hand vs. foot) and modalities (heat vs. pinprick) within four bilateral regions of interest: anterior and posterior insula and frontal and parietal operculum. Importantly, all analyses were performed on individual, non-normalized fMRI images. For heat stimuli, we found hand-foot somatotopy in the contralateral anterior and posterior insula [hand, 9 ± 10 (SD) mm anterior to foot, P < 0.05] and in the contralateral parietal operculum (SII; hand, 7 ±10 mm lateral to foot, P < 0.05). For pinprick stimuli, we also found somatotopy in the contralateral posterior insula (hand, 9 ±10 mm anterior to foot, P < 0.05). Furthermore, the response to heat stimulation of the hand was 11 ± 12 mm anterior to the response to pinprick stimulation of the hand in the contralateral (left) anterior insula ( P < 0.05). These results indicate the existence of multiple somatotopic representations for pain within the operculo-insular region in humans, possibly reflecting its importance as a sensory-integration site that directs emotional responses and behavior appropriately depending on the body site being injured.
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Berret, Emmanuelle, Michael Kintscher, Shriya Palchaudhuri, Wei Tang, Denys Osypenko, Olexiy Kochubey, and Ralf Schneggenburger. "Insular cortex processes aversive somatosensory information and is crucial for threat learning." Science 364, no. 6443 (May 16, 2019): eaaw0474. http://dx.doi.org/10.1126/science.aaw0474.
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Learning about threats is essential for survival. During threat learning, an innocuous sensory percept such as a tone acquires an emotional meaning when paired with an aversive stimulus such as a mild footshock. The amygdala is critical for threat memory formation, but little is known about upstream brain areas that process aversive somatosensory information. Using optogenetic techniques in mice, we found that silencing of the posterior insula during footshock reduced acute fear behavior and impaired 1-day threat memory. Insular cortex neurons respond to footshocks, acquire responses to tones during threat learning, and project to distinct amygdala divisions to drive acute fear versus threat memory formation. Thus, the posterior insula conveys aversive footshock information to the amygdala and is crucial for learning about potential dangers in the environment.
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Corrivetti, Francesco, Sébastien Froelich, and Emmanuel Mandonnet. "Endoscopic Approach of the Insula Through the Anterior Middle Temporal Gyrus: A Feasibility Study in the Laboratory." Operative Neurosurgery 14, no. 4 (July 25, 2017): 441–48. http://dx.doi.org/10.1093/ons/opx128.
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Abstract BACKGROUND Insular glioma surgery still represents a challenge. Nonetheless, advances in microsurgical anatomy and brain mapping techniques have allowed an increase in the extent of resection with acceptable morbidity rates. Transsylvian and transcortical approaches constitute the main surgical corridors, the latter providing considerable advantages and a high degree of reliability. Nevertheless, both surgical corridors yield remarkable difficulties in reaching the most posterior insular region. OBJECTIVE To study the feasibility of an endoscopic transtemporal approach in brain specimens, with the aim to provide a suitable access for posterior insular region. METHODS Four postmortem human hemispheres, embalmed using Klingler's technique, were dissected by means of a 30° rigid endoscope. The specimens underwent magnetic resonance imaging scans and, using the neuronavigation system, we were able to design a safe cortical window and an optimized endoscopic trajectory for the posterior insular dissection. RESULTS Insular dissection was led subpially through a small 2-cm cortical access, located in the anterior part of the middle temporal gyrus. During the posterior insula dissection, the endoscope allowed for optimized surgical view all along the long gyri, up to the posterior insular point. Anterior insular dissection was accomplished with more difficulties, as the endoscopic trajectory was not aligned to the axis of the short gyri. CONCLUSION This new surgical approach provides a favorable transcortical access to reach the most posterior insular portion. It seems to be a promising tool, in combination with intraoperative functional brain mapping, to further improve extent of resection rates in insular glioma surgery.
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Lee, Jeungchan, Richard L. Lin, Ronald G. Garcia, Jieun Kim, Hyungjun Kim, Marco L. Loggia, Ishtiaq Mawla, et al. "Reduced insula habituation associated with amplification of trigeminal brainstem input in migraine." Cephalalgia 37, no. 11 (August 13, 2016): 1026–38. http://dx.doi.org/10.1177/0333102416665223.
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Background Impaired sensory processing in migraine can reflect diminished habituation, increased activation, or even increased gain or amplification of activity from the primary synapse in the brainstem to higher cortical/subcortical brain regions. Methods We scanned 16 episodic migraine (interictal) and 16 healthy controls (cross-sectional study), and evaluated brain response to innocuous air-puff stimulation over the right forehead in the ophthalmic nerve (V1) trigeminal territory. We further evaluated habituation, and cortical/subcortical amplification relative to spinal trigeminal nucleus (Sp5) activation. Results Migraine subjects showed greater amplification from Sp5 to the posterior insula and hypothalamus. In addition, while controls showed habituation to repetitive sensory stimulation in all activated cortical regions (e.g. the bilateral posterior insula and secondary somatosensory cortices), for migraine subjects, habituation was not found in the posterior insula. Moreover, in migraine, the habituation slope was correlated with the amplification ratio in the posterior insula and secondary somatosensory cortex, i.e. greater amplification was associated with reduced habituation in these regions. Conclusions These findings suggest that in episodic migraine, amplified information processing from spinal trigeminal relay nuclei is linked to an impaired habituation response. This phenomenon was localized in the posterior insula, highlighting the important role of this structure in mechanisms supporting altered sensory processing in episodic migraine.
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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 (November 5, 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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Young, G., and WT Blume. "P.005 Painful epileptic seizures involving the insula." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 44, S2 (June 2017): S15. http://dx.doi.org/10.1017/cjn.2017.90.
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Background: We have previously described painful epileptic seizures involving the primary and second somatosensory cortices. A recently encountered 24 year old man described left hemicorporial, painful seizures in association with a tumor involving the right insula. Methods: Case description with imaging and EEG. Results: The patient described frequent, sharp pains simultaneously involving the left face, upper and lower limbs and trunk that lasted from several seconds to a minute and were 10/10 in intensity. These markedly lessened in frequency but the severity of the pain persisted with a maintenance dose of 600 mg/day of carbamazepine. Neurological examination, including cortical sensation, was normal. MRI revealed a 3 cm rounded lesion deep to but immediately against the entire right insula but not extending cortically beyond the confines of the insula. EEGs have been unremarkable. The lesion has been stable for over 1 year. Conclusions: Insular seizures can produce brief, sharp, intense pain that involves the whole of the contralateral body simultaneously. This is in keeping with the insula as part of the pain matrix with connections with the thalamus. Stimulation of the posterior insula can produce hemicorporial pain without a march similar to that experienced by our patient.
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Noll, Kyle, Evan D. Bander, Romulo A. Andrade de Almeida, Scott Seaman, Matei Banu, Victoria E. Clark, Dima Suki, et al. "NCOG-31. NEUROCOGNITIVE OUTCOME FOLLOWING AWAKE CRANIOTOMY FOR INSULAR GLIOMA RESECTION: IMPACT OF SURGICAL APPROACH AND TUMOR CLASSIFICATION." Neuro-Oncology 26, Supplement_8 (November 1, 2024): viii231. http://dx.doi.org/10.1093/neuonc/noae165.0913.
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Abstract BACKGROUND Insular glioma resection harbors similar risk of neurocognitive function (NCF) decline as other tumor locations. However, differences in outcomes according to transsylvian versus transcortical surgical approach and tumor classification remain unknown. METHODS 53 patients with newly diagnosed insular glioma (47% high-grade; 23% GBM; 75% left hemisphere) underwent awake craniotomy for resection (transsylvian, 64%; transcortical, 36%). Patients completed neuropsychological testing preoperatively and <2 months postoperatively (M interval=23.7 days). Tumor location was described with Berger-Sinai zones collapsed into anterior (I and/or IV), posterior (II and/or III), superior (I and/or II), and inferior (III and/or IV) groups. Tumor extension was characterized with the Pitskhelauri system into insula only, insula with extension (lobar or medial), and predominantly (>50%) extra-insular groups. Result: Decline (z-score change<-1.0) on at least 1 test occurred in 85% of patients with largest effect (partial η2) in memory (.29–.44) and verbal fluency (.39). There was no interaction with approach on any NCF change score, though transcortical was associated with more frequent fluency decline (61% vs. 26%, p=.014). Left hemisphere tumor was associated with poorer outcome on 6/12 tests (all p<.01). Predominantly extra-insular tumors showed greater reductions in fluency (M=-1.21, SD=0.90) than insula only tumors (M=-0.10, SD=0.76; p=0.024). Number of Berger-Sanai quadrants involved was inversely associated with change in executive functioning (r=-0.34, p=.018). Poorer executive function outcome was also found in anterior (M=-0.61, SD=1.41) versus posterior tumors (M=0.86, SD=1.51; p=.014), and recognition memory outcome worse for inferior (M=-2.44, SD=1.81) than superior lesions (M=-0.31, SD=1.47; p=.021). CONCLUSIONS NCF decline is common in the early term following resection of insular glioma. While risk of verbal fluency decline may be greater for transcortical surgeries, outcomes were largely similar across approaches. In addition to hemisphere, tumor extension and insular zone localization may inform domain-specific risk of NCF decline following resection.
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Hassanpour, Mahlega S., Lirong Yan, Danny J. J. Wang, Rachel C. Lapidus, Armen C. Arevian, W. Kyle Simmons, Jamie D. Feusner, and Sahib S. Khalsa. "How the heart speaks to the brain: neural activity during cardiorespiratory interoceptive stimulation." Philosophical Transactions of the Royal Society B: Biological Sciences 371, no. 1708 (November 19, 2016): 20160017. http://dx.doi.org/10.1098/rstb.2016.0017.
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Prominent theories emphasize key roles for the insular cortex in the central representation of interoceptive sensations, but how this brain region responds dynamically to changes in interoceptive state remains incompletely understood. Here, we systematically modulated cardiorespiratory sensations in humans using bolus infusions of isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline. To identify central neural processes underlying these parametrically modulated interoceptive states, we used pharmacological functional magnetic resonance imaging (phMRI) to simultaneously measure blood-oxygenation-level dependent (BOLD) and arterial spin labelling (ASL) signals in healthy participants. Isoproterenol infusions induced dose-dependent increases in heart rate and cardiorespiratory interoception, with all participants endorsing increased sensations at the highest dose. These reports were accompanied by increased BOLD and ASL activation of the right insular cortex at the highest dose. Different responses across insula subregions were also observed. During anticipation, insula activation increased in more anterior regions. During stimulation, activation increased in the mid-dorsal and posterior insula on the right, but decreased in the same regions on the left. This study demonstrates the feasibility of phMRI for assessing brain activation during adrenergic interoceptive stimulation, and provides further evidence supporting a dynamic role for the insula in representing changes in cardiorespiratory states. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
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Yang, Xiu, DianXuan Guo, Wei Huang, and Bing Chen. "Intrinsic Brain Functional Activity Abnormalities in Episodic Tension-Type Headache." Neural Plasticity 2023 (May 24, 2023): 1–6. http://dx.doi.org/10.1155/2023/6560298.
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Objective. The neurobiological basis of episodic tension-type headache (ETTH) remains largely unclear. The aim of the present study was to explore intrinsic brain functional activity alterations in ETTH. Methods. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 32 patients with ETTH and 32 age- and gender-matched healthy controls (HCs). Differences in intrinsic brain functional activity between patients with ETTH and HCs were analyzed utilizing the fractional amplitude of low-frequency fluctuation (fALFF) approach. Correlation analyses were performed to examine the relationship between fALFF alterations and clinical characteristics. Results. Compared to HCs, patients with ETTH exhibited increased fALFF in the right posterior insula and anterior insula and decreased fALFF in the posterior cingulate cortex. Moreover, the fALFF in the right anterior insula was negatively correlated with attack frequency in ETTH. Conclusions. This study highlights alterations in the intrinsic brain functional activity in the insula and posterior cingulate cortex in ETTH that can help us understand its neurobiological underpinnings.
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Wei, Pengxu, and Ruixue Bao. "The Role of Insula-Associated Brain Network in Touch." BioMed Research International 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/734326.
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The insula is believed to be associated with touch-evoked effects. In this work, functional MRI was applied to investigate the network model of insula function when 20 normal subjects received tactile stimulation over segregated areas. Data analysis was performed with SPM8 and Conn toolbox. Activations in the contralateral posterior insula were consistently revealed for all stimulation areas, with the overlap located in area Ig2. The area Ig2 was then used as the seed to estimate the insula-associated network. The right insula, left superior parietal lobule, left superior temporal gyrus, and left inferior parietal cortex showed significant functional connectivity with the seed region for all stimulation conditions. Connectivity maps of most stimulation conditions were mainly distributed in the bilateral insula, inferior parietal cortex, and secondary somatosensory cortex. Post hoc ROI-to-ROI analysis and graph theoretical analysis showed that there were higher correlations between the left insula and the right insula, left inferior parietal cortex and right OP1 for all networks and that the global efficiency was more sensitive than the local efficiency to detect differences between notes in a network. These results suggest that the posterior insula serves as a hub to functionally connect other regions in the detected network and may integrate information from these regions.
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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 (September 1, 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, Akio Takahashi, Takanobu Kaido, Yuu Kaneko, Masaki Iwasaki, Nobutaka Kawahara, and Taisuke Otsuki. "Surgical strategy to avoid ischemic complications of the pyramidal tract in resective epilepsy surgery of the insula: technical case report." Journal of Neurosurgery 128, no. 4 (April 2018): 1173–77. http://dx.doi.org/10.3171/2017.1.jns161278.
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Surgical treatment of the insula is notorious for its high probability of motor complications, particularly when resecting the superoposterior part. Ischemic damage to the pyramidal tract in the corona radiata has been regarded as the cause of these complications, resulting from occlusion of the perforating arteries to the pyramidal tract through the insular cortex. The authors describe a strategy in which a small piece of gray matter is spared at the bottom of the periinsular sulcus, where the perforating arteries pass en route to the pyramidal tract, in order to avoid these complications. This method was successfully applied in 3 patients harboring focal cortical dysplasia in the posterior insula and frontoparietal operculum surrounding the periinsular sulcus. None of the patients developed permanent postoperative motor deficits, and seizure control was achieved in all 3 cases. The method described in this paper can be adopted for functional preservation of the pyramidal tract in the corona radiata when resecting epileptogenic pathologies involving insular and opercular regions.
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Shin, Jung H., Yu K. Kim, Hyo-Jung Kim, and Ji-Soo Kim. "Altered brain metabolism in vestibular migraine: Comparison of interictal and ictal findings." Cephalalgia 34, no. 1 (August 5, 2013): 58–67. http://dx.doi.org/10.1177/0333102413498940.
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Background Vestibular symptoms/signs frequently coexist with migraine, but the mechanisms of migraine-related vestibular dysfunction remain to be elucidated. This study aimed to determine altered brain metabolism in vestibular migraine. Methods Two patients with vestibular migraine underwent 18F-fluorodeoxy glucose (FDG) positron-emission tomography (PET) during and between attacks of vestibular migraine in addition to detailed neurotological evaluation. We analyzed the regional brain metabolism of the patients in comparison with that of age-matched healthy controls in each patient. We also compared ictal with interictal FDG PET using a subtraction method. Results During the attacks, both patients showed an activation of the bilateral cerebellum and frontal cortices, and deactivation of the bilateral posterior parietal and occipitotemporal areas. One patient also showed hypermetabolism in the dorsal pons and midbrain, right posterior insula, and right temporal cortex while the other patient had an additional activation of the left temporal cortex. Compared with interictal images, ictal PET showed increased metabolism in the bilateral cerebellum, frontal cortices, temporal cortex, posterior insula, and thalami. Conclusion During the attacks of vestibular migraine, the increased metabolism in the temporo-parieto-insular areas and bilateral thalami indicates activation of the vestibulo-thalamo-cortical pathway, and decreased metabolism in the occipital cortex may represent reciprocal inhibition between the visual and vestibular systems.
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Horing, Björn, and Christian Büchel. "The human insula processes both modality-independent and pain-selective learning signals." PLOS Biology 20, no. 5 (May 6, 2022): e3001540. http://dx.doi.org/10.1371/journal.pbio.3001540.
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Prediction errors (PEs) are generated when there are differences between an expected and an actual event or sensory input. The insula is a key brain region involved in pain processing, and studies have shown that the insula encodes the magnitude of an unexpected outcome (unsigned PEs). In addition to signaling this general magnitude information, PEs can give specific information on the direction of this deviation—i.e., whether an event is better or worse than expected. It is unclear whether the unsigned PE responses in the insula are selective for pain or reflective of a more general processing of aversive events irrespective of modality. It is also unknown whether the insula can process signed PEs at all. Understanding these specific mechanisms has implications for understanding how pain is processed in the brain in both health and in chronic pain conditions. In this study, 47 participants learned associations between 2 conditioned stimuli (CS) with 4 unconditioned stimuli (US; painful heat or loud sound, of one low and one high intensity each) while undergoing functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) measurements. We demonstrate that activation in the anterior insula correlated with unsigned intensity PEs, irrespective of modality, indicating an unspecific aversive surprise signal. Conversely, signed intensity PE signals were modality specific, with signed PEs following pain but not sound located in the dorsal posterior insula, an area implicated in pain intensity processing. Previous studies have identified abnormal insula function and abnormal learning as potential causes of pain chronification. Our findings link these results and suggest that a misrepresentation of learning relevant PEs in the insular cortex may serve as an underlying factor in chronic pain.
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Liu, Yiyong, Lin Shi, Xiubao Song, Changzheng Shi, Wutao Lou, Dong Zhang, Alan D. Wang, and Liangping Luo. "Altered Brain Regional Homogeneity in First-Degree Relatives of Type 2 Diabetics: A functional MRI Study." Experimental and Clinical Endocrinology & Diabetes 128, no. 11 (May 28, 2019): 737–44. http://dx.doi.org/10.1055/a-0883-4955.
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Abstract Objective This study aimed to investigate regional homogeneity in the first-degree relatives of type 2 diabetes patients. Methods Seventy-eight subjects, including 26 type 2 diabetes patients, 26 first-degree relatives, and 26 healthy controls, were assessed. All participants underwent resting-state functional magnetic resonance imaging scanning. The estimated regional homogeneity value was used to evaluate differences in brain activities. Results In first-degree relatives, we observed significantly decreased regional homogeneity in the left anterior cingulate cortex, left insula, and bilateral temporal lobes, and increased regional homogeneity in the left superior frontal gyrus, right anterior cingulate cortex, and bilateral posterior cingulate cortex compared to healthy controls. In type 2 diabetes patients, we detected altered regional homogeneity in the left anterior cingulate cortex, left insula, bilateral posterior cingulate cortex, and several other brain regions compared to healthy controls. Both first-degree relatives and type 2 diabetes patients showed decreased regional homogeneity in the left superior temporal gyrus, right middle temporal gyrus, left anterior cingulate cortex, left insula, and increased regional homogeneity in the left superior frontal gyrus and bilateral posterior cingulate cortex. Conclusion These findings suggest that altered regional homogeneity in the left anterior cingulate cortex, left insula, left superior frontal gyrus, bilateral posterior cingulate cortex, and bilateral temporal lobes might be a neuroimaging biomarker of type 2 diabetes -related brain dysfunction.
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Kishima, Haruhiko, Youichi Saitoh, Yasuhiro Osaki, Hiroshi Nishimura, Amami Kato, Jun Hatazawa, and Toshiki Yoshimine. "Motor cortex stimulation in patients with deafferentation pain: activation of the posterior insula and thalamus." Journal of Neurosurgery 107, no. 1 (July 2007): 43–48. http://dx.doi.org/10.3171/jns-07/07/0043.
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Object The mechanisms underlying deafferentation pain are not well understood. Motor cortex stimulation (MCS) is useful in the treatment of this kind of chronic pain, but the detailed mechanisms underlying its effects are unknown. Methods Six patients with intractable deafferentation pain in the left hand were included in this study. All were right-handed and had a subdural electrode placed over the right precentral gyrus. The pain was associated with brainstem injury in one patient, cervical spine injury in one patient, thalamic hemorrhage in one patient, and brachial plexus avulsion in three patients. Treatment with MCS reduced pain; visual analog scale (VAS) values for pain were 82 ± 20 before MCS and 39 ± 20 after MCS (mean ± standard error). Regional cerebral blood flow (rCBF) was measured by positron emission tomography with H215O before and after MCS. The obtained images were analyzed with statistical parametric mapping software (SPM99). Results Significant rCBF increases were identified after MCS in the left posterior thalamus and left insula. In the early post-MCS phase, the left posterior insula and right orbitofrontal cortex showed significant rCBF increases, and the right precentral gyrus showed an rCBF decrease. In the late post-MCS phase, a significant rCBF increase was detected in the left caudal part of the anterior cingulate cortex (ACC). Conclusions These results suggest that MCS modulates the pathways from the posterior insula and orbitofrontal cortex to the posterior thalamus to upregulate the pain threshold and pathways from the posterior insula to the caudal ACC to control emotional perception. This modulation results in decreased VAS scores for deafferentation pain.
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Pallud, Johan, Alexandre Roux, Bénédicte Trancart, Sophie Peeters, Alessandro Moiraghi, Myriam Edjlali, Catherine Oppenheim, et al. "Surgery of Insular Diffuse Gliomas—Part 2: Probabilistic Cortico-Subcortical Atlas of Critical Eloquent Brain Structures and Probabilistic Resection Map During Transcortical Awake Resection." Neurosurgery 89, no. 4 (August 12, 2021): 579–90. http://dx.doi.org/10.1093/neuros/nyab255.
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Abstract BACKGROUND Insular diffuse glioma surgery is challenging, and tools to help surgical planning could improve the benefit-to-risk ratio. OBJECTIVE To provide a probabilistic resection map and frequency atlases of critical eloquent regions of insular diffuse gliomas based on our surgical experience. METHODS We computed cortico-subcortical “eloquent” anatomic sites identified intraoperatively by direct electrical stimulations during transcortical awake resection of insular diffuse gliomas in adults. RESULTS From 61 insular diffuse gliomas (39 left, 22 right; all left hemispheric dominance for language), we provided a frequency atlas of eloquence of the opercula (left/right; pars orbitalis: 0%/5.0%; pars triangularis: l5.6%/4.5%; pars opercularis: 37.8%/27.3%; precentral gyrus: 97.3%/95.4%; postcentral and supramarginal gyri: 75.0%/57.1%; temporal pole and superior temporal gyrus: 13.3%/0%), which tailored the transcortical approach (frontal operculum to reach the antero-superior insula, temporal operculum to reach the inferior insula, parietal operculum to reach the posterior insula). We provided a frequency atlas of eloquence identifying the subcortical functional boundaries (36.1% pyramidal pathways, 50.8% inferior fronto-occipital fasciculus, 13.1% arcuate and superior longitudinal fasciculi complex, 3.3% somatosensory pathways, 8.2% caudate and lentiform nuclei). Vascular boundaries and increasing errors during testing limited the resection in 8.2% and 11.5% of cases, respectively. We provided a probabilistic 3-dimensional atlas of resectability. CONCLUSION Functional mapping under awake conditions has to be performed intraoperatively in each patient to guide surgical approach and resection of insular diffuse gliomas in right and left hemispheres. Frequency atlases of opercula eloquence and of subcortical eloquent anatomic boundaries, and probabilistic 3-dimensional atlas of resectability could guide neurosurgeons.
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Di Stefano, Vincenzo, Maria Vittoria De Angelis, Chiara Montemitro, Mirella Russo, Claudia Carrarini, Massimo di Giannantonio, Filippo Brighina, Marco Onofrj, David J. Werring, and Robert Simister. "Clinical presentation of strokes confined to the insula: a systematic review of literature." Neurological Sciences 42, no. 5 (February 11, 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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Harfeldt, Kristin, Louise Alexander, Julia Lam, Sven Månsson, Hans Westergren, Peter Svensson, Pia C. Sundgren, and Per Alstergren. "Spectroscopic differences in posterior insula in patients with chronic temporomandibular pain." Scandinavian Journal of Pain 18, no. 3 (July 26, 2018): 351–61. http://dx.doi.org/10.1515/sjpain-2017-0159.
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Abstract Background and aims Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (MI), glutamate (Glu), and the combination of Glu and glutamine in the posterior insula in patients with chronic generalized or regional chronic TMD pain (gTMD and rTMD, respectively) compared to healthy individuals (HI) in relation to clinical findings of TMD pain. Methods Thirty-six female patients with chronic rTMD or gTMD with at least 3 months duration were included in the study. Ten healthy women were included as controls. All participants completed a questionnaire that comprised assessment of degrees of depression, anxiety, stress, catastrophizing, pain intensity, disability and locations. A clinical Diagnostic Criteria for Temporomandibular Disorders examination that comprised assessment of pain locations, headache, mouth opening capacity, pain on mandibular movement, pain on palpation and temporomandibular joint noises was performed. Pressure-pain threshold (PPT) over the masseter muscle and temporal summation to pressure stimuli were assessed with an algometer. Within a week all participants underwent non-contrast enhanced MRI on a 3T MR scanner assessing T1-w and T2-w fluid attenuation inversion recovery. A single-voxel 1H-MRS examination using point-resolved spectroscopy was performed. The metabolite concentrations of NAA, tCr, Cho, MI, Glu and Glx were analyzed with the LC model. Metabolite levels were calculated as absolute concentrations, normalized to the water signal. Metabolite concentrations were used for statistical analysis from the LC model if the Cramér–Rao bounds were less than 20%. In addition, the ratios NAA/tCr, Cho/tCr, Glu/tCr and MI/tCr were calculated. Results The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (p=0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (rs=−0.42, n=28, p=0.031 and rs=−0.48, n=28, p=0.034, respectively) as well as pressure-pain threshold on the hand (rs=−0.41, n=28, p=0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (rs=0.42, n=26, p=0.034). Conclusions The present study found that increased concentrations of Cho and Glu in the posterior insular cortex is related to clinical characteristics of chronic TMD pain, including generalized pain. These findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. Implications The findings in this study have indirect implications for the diagnosis and management of TMD patients. That said, the findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. It is also a further step towards understanding and accepting chronic pain as a disorder in itself.
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Kleckner, Ian, Richard Aslin, Charles E. Heckler, Michelle Christine Janelsins, Nimish Mohile, Matthew Asare, Calvin Cole, et al. "A longitudinal brain fMRI study of chemotherapy-induced peripheral neuropathy in 50 breast cancer patients." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 10095. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.10095.
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10095 Background: Over half of patients receiving taxane, platinum, and vinca alkaloid chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which involves numbness and neuropathic pain in the hands and feet. CIPN has no effective treatments partly because its etiology is poorly understood. We theorize that CIPN symptoms are partly caused by impairment of interoceptive brain circuitry, which processes bodily sensations via the posterior insula and anterior cingulate cortex (ACC). We investigated whether CIPN is associated with altered connectivity in interoceptive brain circuitry. Methods: Fifty women with breast cancer (50±9 years) reported CIPN symptoms (CIPN-20) and underwent resting fMRI one or more times: before surgery, one month after completion of chemotherapy, and one year after chemotherapy. We used an a priori seed-based investigation of connectivity between the posterior insula and ACC. We compared connectivity between 31 patients without CIPN symptoms (≤10 CIPN-20-Sensory), 19 patients with CIPN symptoms ( > 10 CIPN-20-Sensory), and 280 healthy adults (174 women, 19.3 years) from another study. Results: Patients with CIPN symptoms had significantly reduced connectivity between the posterior insula and the ACC compared to patients without CIPN symptoms (p = 0.01, d = 0.73). Connectivity between the posterior insula and the ACC was negative in patients with CIPN symptoms but positive in both healthy adults and patients without CIPN symptoms. Conclusions: CIPN is characterized by reduced connectivity in interoceptive brain circuitry. Interoceptive networks may be a target for the development of therapies directed to prevent or treat CIPN. Future work will assess causal relationships between CIPN symptoms and reduced connectivity.
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Pal, Amrita, Jennifer A. Ogren, Ravi S. Aysola, Rajesh Kumar, Luke A. Henderson, Ronald M. Harper, and Paul M. Macey. "Insular functional organization during handgrip in females and males with obstructive sleep apnea." PLOS ONE 16, no. 2 (February 18, 2021): e0246368. http://dx.doi.org/10.1371/journal.pone.0246368.
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Study objectives Brain regulation of autonomic function in obstructive sleep apnea (OSA) is disrupted in a sex-specific manner, including in the insula, which may contribute to several comorbidities. The insular gyri have anatomically distinct functions with respect to autonomic nervous system regulation; yet, OSA exerts little effect on the organization of insular gyral responses to sympathetic components of an autonomic challenge, the Valsalva. We further assessed neural responses of insular gyri in people with OSA to a static handgrip task, which principally involves parasympathetic withdrawal. Methods We measured insular function with blood oxygen level dependent functional MRI. We studied 48 newly-diagnosed OSA (age mean±std:46.5±9 years; AHI±std:32.6±21.1 events/hour; 36 male) and 63 healthy (47.2±8.8 years;40 male) participants. Subjects performed four 16s handgrips (1 min intervals, 80% subjective maximum strength) during scanning. fMRI time trends from five insular gyri—anterior short (ASG); mid short (MSG); posterior short (PSG); anterior long (ALG); and posterior long (PLG)—were assessed for within-group responses and between-group differences with repeated measures ANOVA (p<0.05) in combined and separate female-male models; age and resting heart-rate (HR) influences were also assessed. Results Females showed greater right anterior dominance at the ASG, but no differences emerged between OSA and controls in relation to functional organization of the insula in response to handgrip. Males showed greater left anterior dominance at the ASG, but there were also no differences between OSA and controls. The males showed a group difference between OSA and controls only in the ALG. OSA males had lower left activation at the ALG compared to control males. Responses were mostly influenced by HR and age; however, age did not impact the response for right anterior dominance in females. Conclusions Insular gyri functional responses to handgrip differ in OSA vs controls in a sex-based manner, but only in laterality of one gyrus, suggesting anterior and right-side insular dominance during sympathetic activation but parasympathetic withdrawal is largely intact, despite morphologic injury to the overall structure.
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Li, Han, Zheng Gan, Lirong Wang, Manfred Josef Oswald, and Rohini Kuner. "Prolonged Suppression of Neuropathic Hypersensitivity upon Neurostimulation of the Posterior Insula in Mice." Cells 11, no. 20 (October 20, 2022): 3303. http://dx.doi.org/10.3390/cells11203303.
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Neurostimulation-based therapeutic approaches are emerging as alternatives to pharmacological drugs, but need further development to optimize efficacy and reduce variability. Despite its key relevance to pain, the insular cortex has not been explored in cortical neurostimulation approaches. Here, we developed an approach to perform repetitive transcranial direct current stimulation of the posterior insula (PI tDCS) and studied its impact on sensory and aversive components of neuropathic pain and pain-related anxiety and the underlying neural circuitry in mice using behavioral methods, pharmacological interventions and the expression of the activity-induced gene product, Fos. We observed that repetitive PI tDCS strongly attenuates the development of neuropathic mechanical allodynia and also reverses chronically established mechanical and cold allodynia for several weeks post-treatment by employing descending opioidergic antinociceptive pathways. Pain-related anxiety, but not pain-related aversion, were inhibited by PI tDCS. These effects were associated with a long-term suppression in the activity of key areas involved in pain modulation, such as the cingulate, prefrontal and motor cortices. These data uncover the significant potential of targeting the insular cortex with the objective of pain relief and open the way for more detailed mechanistic analyses that will contribute to improving cortical neurostimulation therapies for use in the clinical management of pain.
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Tran, Thi Phuoc Yen, Antoine Dionne, Denahin Toffa, David Bergeron, Sami Obaid, Manon Robert, Alain Bouthillier, Elie Bou Assi, and Dang Khoa Nguyen. "Acute Effects of High-Frequency Insular Stimulation on Interictal Epileptiform Discharge Rates in Patients with Refractory Epilepsy." Brain Sciences 12, no. 12 (November 25, 2022): 1616. http://dx.doi.org/10.3390/brainsci12121616.
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Rationale: Deep brain stimulation (DBS) of several sites, such as the thalamus, has been shown to reduce seizure frequency and interictal epileptiform activity in patients with refractory epilepsy. Recent findings have demonstrated that the insula is part of the ‘rich club’ of highly connected brain regions. This pilot study investigated short-term effects of high-frequency (HF) insular DBS on interictal epileptiform discharge (IED) rate in patients with refractory epilepsy. Methods: Six patients with drug-resistant epilepsy undergoing an intracranial electroencephalographic study received two sets of 10 min continuous 150 Hz HF-DBS of the insula. For each patient, epileptiform activity was analyzed for a total of 80 min, starting 20 min prior to stimulation set 1 (S1), and ending 20 min after stimulation set 2 (S2). All IEDs were identified and classified according to their anatomic localization by a board-certified epileptologist. The IED rate during the 20 min preceding S1 served as a baseline for comparison with IED rate during S1, S2 and post-stimulation periods. Results: HF-DBS of the anterior insula (aINS) was performed in a patient with an aINS epileptic focus (patient 1). HF-DBS of the posterior insula (pINS) was performed in two patients with a pINS epileptic focus (patients 2 and 4), in one patient with an aINS focus (patient 3), and in two non-insular patients (patients 5 and 6). The total IED (irrespective of their location) rate significantly decreased (p < 0.01) in two patients (patients 1 and 2) during the stimulation period, whereas it significantly increased (p < 0.01) in one patient (patient 6); there was no change in the other three patients. Looking at subsets of spike localization, HF-DBS of the aINS significantly reduced aINS and orbitofrontal IEDs in patient 1 (p < 0.01), while HF-DBS of the pINS had an effect on pINS IEDs (p < 0.01) in both patients with a pINS focus; there was no significant effect of HF-DBS of the insula on IEDs in temporal or other frontal regions. Conclusion: Short-term HF-DBS of the insula had heterogeneous effects on the IED rate. Further work is required to examine factors underlying these heterogeneous effects, such as stimulation frequency, location of IEDs and subregions of the insula stimulated.
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Fayed, Nicolas, Barbara Oliván, Yolanda Lopez del Hoyo, Eva Andrés, Mari Cruz Perez-Yus, Alicia Fayed, Luisa F. Angel, Antoni Serrano-Blanco, Miquel Roca, and Javier Garcia Campayo. "Changes in metabolites in the brain of patients with fibromyalgia after treatment with an NMDA receptor antagonist." Neuroradiology Journal 32, no. 6 (June 19, 2019): 408–19. http://dx.doi.org/10.1177/1971400919857544.
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The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p = 0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p = 0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p = 0.01) and the anterior insula (7.56 vs. 7.70; p = 0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p = 0.022) and the posterior insula (1.77 vs. 2.00; p = 0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p = 0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p = 0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD = 2.95 vs. 34.40, SD = 0.6; p = 0.005), depression measured by the Hamilton Depression Scale (7.70, SD = 0.81 vs. 7.56, SD = 0.68; p = 0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD = 0.96 vs. 5.31, SD = 1.12; p = 0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia.
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Kulesh, A. A., S. P. Kulikova, V. E. Drobakha, S. A. Mekhryakov, E. V. Bartuli, A. V. Buzmakov, L. I. Syromyatnikova, K. V. Sobyanin, and Yu V. Karakulova. "Role of insular cortex lesions in determining the pathogenetic subtype of ischemic stroke." Neurology, Neuropsychiatry, Psychosomatics 14, no. 2 (April 17, 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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Godina, Sara L., Caterina Rosano, Peter J. Gianaros, Howard J. Aizenstein, Michelle C. Carlson, Philippa Clarke, and Andrea L. Rosso. "NEIGHBORHOOD SOCIOECONOMIC STATUS AND GRAY MATTER VOLUME IN OLDER ADULTS." Innovation in Aging 3, Supplement_1 (November 2019): S414. http://dx.doi.org/10.1093/geroni/igz038.1542.
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Abstract Lower neighborhood socioeconomic status (nSES) is associated with poorer cognitive function; underlying neural correlates are unknown. Cross-sectional associations of nSES (six census-derived measures of income, education, and occupation) and gray matter volume (GMV) of eight memory-related regions (hippocampus, middle frontal gyrus, amygdala, insula, parahippocampal gyrus, anterior, middle, and posterior cingulum) were examined in 264 community-dwelling older adults (mean age=83, 56.82% female, 39.02% black). In linear mixed effects models adjusted for total brain atrophy and accounting for geographic clustering, higher nSES was associated with greater GMV of the left hippocampus, left posterior cingulum, and bilateral insula, middle frontal, and parahippocampal gyri. nSES remained associated with GMV of the right insula (β= -32.26, p=0.026, 95%CI: -60.66, -3.86) after adjusting for individual level age, gender, race, income, and education. The nSES and cognitive function association may not be due to gray matter volume differences; other behavioral and biological mediators should be explored.
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Przybylowski, Colin J., Jacob F. Baranoski, Veronica M. So, Jeffrey Wilson, and Nader Sanai. "Surgical morbidity of transsylvian versus transcortical approaches to insular gliomas." Journal of Neurosurgery 132, no. 6 (June 2020): 1731–38. http://dx.doi.org/10.3171/2018.12.jns183075.
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OBJECTIVEThe choice of transsylvian versus transcortical corridors for resection of insular gliomas remains controversial. Functional pathway compromise from transcortical transgression and vascular injury during transsylvian dissection are the primary concerns. In this study, data from a single-center experience with both approaches were compared to determine whether one approach was associated with a higher rate of morbidity than the other.METHODSThe authors identified 100 consecutive patients who underwent resection of pure insular gliomas at the Barrow Neurological Institute. Volumetric analysis was performed using FLAIR and contrast-enhanced T1-weighted MRI for low- and high-grade gliomas, respectively, for extent of resection (EOR) and diffusion-weighted sequences were used to detect for postoperative ischemia. Step-wise logistic regression analysis was performed to identify predictors of neurological morbidity.RESULTSData from 100 patients with low-grade or high-grade insular gliomas were analyzed. Fifty-two patients (52%) underwent a transsylvian approach, and 48 patients (48%) underwent a transcortical approach. The mean (± SD) EOR was 91.6% ± 12.4% in the transsylvian group and 88.6% ± 14.2% in the transcortical group (p = 0.26). Clinical outcome metrics for the 2 groups were similar. Overall, 13 patients (25%) in the transsylvian group and 10 patients (21%) in the transcortical group had evidence of ischemia on postoperative MR images. For both approaches, high-grade histology was associated with permanent morbidity (p = 0.01). For patients with gliomas located within the superior-posterior quadrant of the insula, development of postoperative ischemia was associated with only the transsylvian approach (46% vs 0%, p = 0.02).CONCLUSIONSAreas of restricted diffusion are common on postoperative MRI following resection of insular gliomas, but only a minority of these patients develop permanent neurological deficits. Insular glioma patients with high-grade histology may be at particular risk for developing symptomatic postoperative ischemia. Both the transcortical and transsylvian corridors are associated with reasonable morbidity profiles, although gliomas situated within the superior-posterior quadrant of the insula are more safely accessed with a transcortical approach.