Insular Cortex Area Research Articles

A Group Level Analysis of Self-evaluations Associated with Cognitive Load

Self-evaluation, or self-rating, is the process by which people evaluate themselves with the purpose of improving several aspects of their personalities or skills and it is closely related to the cognitive function of metacognition. The purpose of the study was to investigate the degree of implication of various brain areas to meta-cognition as it relates to subjective ratings of cognitive effort when performing mathematical problems of different complexity. To achieve this, participants were recruited to solve mathematical problems (addition, subtraction, multiplication, and division) in three levels of difficulty, while inside an fMRI scanner. After solving a given task, they were asked to evaluate the amount of effort they spent to solve it. Brain signal was collected during their answers, which was then analyzed with the aid of computer software. Results of the analysis show that increases in task difficulty activate the frontal lobe, cingulate and insular cortex areas. The parietal lobule, the precuneus and the cingulate gyrus were found to be active as well as during all four mathematical operations.

A Study of Differentiation Analysis of Metabolites in the Bilateral Insular Area of Smoker/Non-smokers and Identification of Differences in Brain Connectivity Between Male University Students in Their 20s

The aim of this study was to investigate difference in brain metabolites between smokers and non-smokers in the brain insular region related to addiction for men in their twenties. Differences in brain connectivity between the two groups were also determined. A total of 20 males volunteers (10 smokers and 10 nonsmokers) were enrolled for this study. Magnetic resonance spectroscopy (MRS) was performed using a 3.0 Tesla MRI scanner. MRS data of left/right insular brain areas were acquired via point-resolved spectroscopy. A total of 3,096 functional magnetic resonance imaging (fMRI) images were obtained under axial conditions in 2D mode. Non-smokers showed significant differences in glycerophosphorylcholine, total choline, free creatine, and total creatine between left and right insular cortical regions. Differences in concentrations of metabolites in the islet cortex between smokers and non-smokers were higher in the left islet region than in the right insular region of non-smokers. Concentrations of tCr metabolites in the left insular area of non-smokers were higher than those of smokers. In addition, smokers showed higher connectivity in the right gyrus and occipital fusiform regions than non-smokers, whereas non-smokers had stronger connectivity between the left insular cortex area and the frontal role right than smokers. This study is meaningful in that it provides a new strategy using fMRI as well as MRS to identify differences in metabolism between smokers and non-smokers in a specific age group.

Association of blood pressure with brain structure in youth with and without bipolar disorder

BackgroundWe previously found that blood pressure (BP) is elevated, and associated with poorer neurocognition, in youth with bipolar disorder (BD). While higher BP is associated with smaller brain structure in adults, studies have not examined this topic in BD or youth. MethodsParticipants were 154 youth, ages 13–20 (n = 81 BD, n = 73 HC). Structural magnetic resonance imaging and diastolic (DBP), and systolic (SBP) pressure were obtained. Region of interest (ROI; anterior cingulate cortex [ACC], insular cortex, hippocampus) and vertex-wise analyses controlling for age, sex, body-mass-index, and intracranial volume investigated BP-neurostructural associations; a group-by-BP interaction was also assessed. ResultsIn ROI analyses, higher DBP in the overall sample was associated with smaller insular cortex area (β=-0.18 p = 0.007) and was associated with smaller ACC area to a significantly greater extent in HC vs. BD (β=-0.14 p = 0.015). In vertex-wise analyses, higher DBP and SBP were associated with smaller area and volume in the insular cortex, frontal, parietal, and temporal regions in the overall sample. Additionally, higher SBP was associated with greater thickness in temporal and parietal regions. Finally, higher SBP was associated with smaller area and volume in frontal, parietal, and temporal regions to a significantly greater extent in BD vs. HC. LimitationsCross-sectional design, single assessment of BP. ConclusionBP is associated with brain structure in youth, with variability related to structural phenotype (volume vs. thickness) and psychiatric diagnosis (BD vs. HC). Future studies evaluating temporality of these findings, and the association of BP changes on brain structure in youth, are warranted.

Peripheral and central smell regions in children with epilepsy: An MRI evaluation

ObjectivesWe investigated the peripheral and central olfactory regions in children with epilepsy using cranial MRI. MethodsIn this retrospective study, cranial MRI images were obtained from 23 children with epilepsy and 23 healthy controls. Olfactory bulb (OB) volume and olfactory sulcus (OS) depth in the peripheral olfactory region and insular cortex and corpus amygdala areas in the central olfactory region were measured. ResultsThere was no significant difference in the OB volume and OS depth in the peripheral olfactory regions in the two groups (p > 0.05). In the central olfactory region, the insular cortex and corpus amygdala areas in the epilepsy group were significantly smaller than those in the control group (p < 0.05). In both groups, the OS depth on the right side was significantly higher than that on the left side (p < 0.05). In the epilepsy group, there were positive correlations between each of the OB volumes, OS depths, insular cortex areas, and corpus amygdala areas bilaterally (p < 0.05). In both groups, there were positive correlations between the OB volume and OS depth, OS depth and insular cortex area and insular cortex area and corpus amygdala areas (p < 0.05). ConclusionA change in the central olfactory region in epileptic patients may be related to central tissue damage due to epilepsy. This finding has important implications for epilepsy patients, with early diagnosis and treatment potentially preventing a reduction in the volumes/depths of components of the central olfactory region in the pediatric population.

Dexamethasone attenuates the modulatory effect of the insular cortex on the baroreflex in anesthetized rat.

The arterial baroreflex (BR) is an important neural mechanism for the stabilization of arterial pressure (AP). It is known that the insular cortex (IC) and other parts of the central autonomic network (CAN) are able to modulate the BR arc, altering baroreflex sensitivity (BRS). In addition, the sensitivity of the BR changes under the influence of hormones, in particular glucocorticoids (GCs). It has been suggested that GCs may influence BRS by altering the ability of the IC to modulate the BR. This hypothesis has been tested in experiments on rats anesthetized with urethane. It was found that microelectrostimulation of the visceral area in the left IC causes a short-term drop in AP, which is accompanied by bradycardia and impairs BRS. The synthetic GC dexamethasone (DEX) did not significantly affect the magnitude of depressor responses but increased BRS and impaired the effect of IC stimulation on the BR. The results obtained confirm the hypothesis put forward and suggest that GC can attenuate the inhibitory effects of the IC on the BR arc, thereby enhancing the sensitivity of the BR.

Attention Networks in the Parietooccipital Cortex Modulate Activity of the Human Vestibular Cortex during Attentive Visual Processing.

Previous studies in human subjects reported that the parieto-insular vestibular cortex (PIVC), a core area of the vestibular cortex, is inhibited when visual processing is prioritized. However, it has remained unclear which networks in the brain modulate this inhibition of PIVC. Based on previous results showing that the inhibition of PIVC is strongly influenced by visual attention, we here examined whether attention networks in the parietooccipital cortex modulate the inhibition of PIVC. Using diffusion-weighted and resting-state fMRI in a group of female and male subjects, we found structural and functional connections between PIVC and the posterior parietal cortex (PPC), a major brain region of the cortical attention network. We then temporarily inhibited PPC by repetitive transcranial magnetic stimulation (rTMS) and hypothesized that the modulatory influence of PPC over PIVC would be reduced; and, as a result, PIVC would be less inhibited. Subjects performed a visual attentional tracking task immediately after rTMS, and the inhibition of PIVC during attentive tracking was measured with fMRI. The results showed that the inhibition of PIVC during attentive tracking was less pronounced compared with sham rTMS. We also examined the effects of inhibitory rTMS over the occipital cortex and found that the visual-vestibular posterior insular cortex area was less activated during attentive tracking compared with sham rTMS or rTMS over PPC. Together, these results suggest that attention networks in the parietooccipital cortex modulate activity in core areas of the vestibular cortex during attentive visual processing.SIGNIFICANCE STATEMENT Although multisensory integration is generally considered beneficial, it can become detrimental when cues from different senses are in conflict. The occurrence of such multisensory conflicts can be minimized by inhibiting core cortical areas of the subordinate sensory system (e.g., vestibular), thus reducing potential conflict with ongoing processing of the prevailing sensory (e.g., visual) cues. However, it has remained unclear which networks in the brain modulate the magnitude of inhibition of the subordinate sensory system. Here, by investigating the inhibition of the vestibular sensory system when visual processing is prioritized, we show that attention networks in the parietooccipital cortex modulate the magnitude of inhibition of the vestibular cortex.

The parieto-insular vestibular cortex in humans: more than a single area?

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.

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin-labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone.

Metabotropic Glutamate Receptor Dependent Cortical Plasticity in Chronic Pain.

Many cortical areas play crucial roles in higher order brain functions such as pain and emotion-processing, decision-making, and cognition. Among them, anterior cingulate cortex (ACC) and insular cortex (IC) are two key areas. Glutamate mediates major excitatory transmission during long-term plasticity in both physiological and pathological conditions. Specifically related to nociceptive or pain behaviors, metabotropic glutamate subtype receptors (mGluRs) have been involved in different types of synaptic modulation and plasticity from periphery to the spinal cord. However, less is known about their functional roles in plasticity related to pain and its related behaviors within cortical regions. In this review, we first summarized previous studies of synaptic plasticity in both the ACC and IC, and discussed how mGluRs may be involved in both cortical long-term potentiation (LTP) and long-term depression (LTD)-especially in LTD. The activation of mGluRs contributes to the induction of LTD in both ACC and IC areas. The loss of LTD caused by peripheral amputation or nerve injury can be rescued by priming ACC or IC with activations of mGluR1 receptors. We also discussed the potential functional roles of mGluRs for pain-related behaviors. We propose that targeting mGluRs in the cortical areas including the ACC and IC may provide a new therapeutic strategy for the treatment of chronic pain, phantom pain or anxiety.

Mentalizing and the Role of the Posterior Superior Temporal Sulcus in Sharing Others' Embarrassment

The experience of embarrassment provides a highly salient cue for the human moral apparatus. Interestingly, people also experience embarrassment on behalf of others' inappropriate conditions. The perceiver's embarrassment often lacks an equivalent expression of embarrassment in the social counterpart. The present study examines this phenomenon and distinguishes neural circuits involved in embarrassment with and embarrassment for another person's mishaps. Using functional magnetic resonance imaging, we show that the embarrassment on behalf of others engages the temporal pole and the medial prefrontal cortex, central structures of the mentalizing network, together with the anterior insula and anterior cingulate cortex. In contrast, sharing others' embarrassment additionally stimulated the posterior superior temporal sulcus (STS), which exhibited increased functional integration with inferior parietal and insular cortex areas. These findings characterize common neural circuits involved in the embodied representation of embarrassment and further unravel the unique role of the posterior STS in sharing others' affective state.

A volumetric comparison of the insular cortex and its subregions in primates

The neuronal composition of the insula in primates displays a gradient, transitioning from granular neocortex in the posterior-dorsal insula to agranular neocortex in the anterior-ventral insula with an intermediate zone of dysgranularity. Additionally, apes and humans exhibit a distinctive subdomain in the agranular insula, the frontoinsular cortex (FI), defined by the presence of clusters of von Economo neurons (VENs). Studies in humans indicate that the ventral anterior insula, including agranular insular cortex and FI, is involved in social awareness, and that the posterodorsal insula, including granular and dysgranular cortices, produces an internal representation of the body's homeostatic state. We examined the volumes of these cytoarchitectural areas of insular cortex in 30 primate species, including the volume of FI in apes and humans. Results indicate that the whole insula scales hyperallometrically (exponent = 1.13) relative to total brain mass, and the agranular insula (including FI) scales against total brain mass with even greater positive allometry (exponent = 1.23), providing a potential neural basis for enhancement of social cognition in association with increased brain size. The relative volumes of the subdivisions of the insular cortex, after controlling for total brain volume, are not correlated with species typical social group size. Although its size is predicted by primate-wide allometric scaling patterns, we found that the absolute volume of the left and right agranular insula and left FI are among the most differentially expanded of the human cerebral cortex compared to our closest living relative, the chimpanzee.

Differences in cerebral response to esophageal acid stimuli and psychological anticipation in GERD subtypes - An fMRI study

BackgroundTo evaluate whether there are differences in the cerebral response to intraesophageal acid and psychological anticipation stimuli among subtypes of gastroesophageal reflux disease (GERD).MethodsThirty nine patients with GERD and 11 healthy controls were enrolled in this study after gastroscopy and 24 hr pH monitoring. GERD subjects were divided into four subgroups: RE (reflux esophagitis), NERD+ (non-erosive reflux disease with excessive acid reflux), NERD-SI+ (normal acid exposure and positive symptom index) and NERD-SI+ (normal acid exposure and negative symptom index, but responded to proton pump inhibitor trial). Cerebral responses to intraesophageal acid and psychological anticipation were evaluated with fMRI.ResultsDuring intraesophageal acid stimulation, the prefrontal cortex (PFC) region was significantly activated in all subgroups of GERD; the insular cortex (IC) region was also activated in RE, NERD+ and NERD-SI- groups; the anterior cingulated cortex (ACC) region was activated only in RE and NERD-SI- groups. The RE subgroup had the shortest peak time in the PFC region after acid was infused, and presented the greatest change in fMRI signals in the PFC and ACC region (P = 0.008 and P = 0.001, respectively). During psychological anticipation, the PFC was significantly activated in both the control and GERD groups. Activation of the IC region was found in the RE, NERD-SI+ and NERD-SI- subgroups. The ACC was activated only in the NERD-SI+ and NERD-SI- subgroups. In the PFC region, the NERD-SI- subgroup had the shortest onset time (P = 0.008) and peak time (P < 0.001). Compared with actual acid infusion, ACC in RE and IC in NERD+ were deactivated while additional areas including the IC and ACC were activated in the NERD-SI+ group; and in NERD-SI- group, onset-time and peak time in the PFC and IC areas were obviously shorter in induced anticipation than in actual acid infusion.ConclusionsThe four subgroups of GERD patients and controls showed distinctly different activation patterns and we therefore conclude GERD patients have different patterns of visceral perception and psychological anticipation. Psychological factors play a more important role in NERD-SI+ and NERD-SI- groups than in RE and NERD+ groups.

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Increased cellular activity in rat insular cortex after water and salt ingestion induced by fluid depletion.

Insular cortex (IC) receives inputs from multiple sensory systems, including taste, and from receptors that monitor body electrolyte and fluid balance and blood pressure. This work analyzed metabolic activity of IC cells after water and sodium ingestion induced by sodium depletion. Rats were injected with the diuretic furosemide (10 mg/kg body wt), followed 5 min later by injections of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg body wt). After 90 min, some rats received water and 0.3 M NaCl to drink for 2 h while others did not. A third group had access to water and saline but was not depleted of fluids. All rats were killed for processing of brain tissue for Fos-immunoreactivity (Fos-ir). Nondepleted animals had weak-to-moderate levels of Fos-ir within subregions of IC. Fluid-depleted rats without fluid access had significantly increased Fos-ir in all areas of IC. Levels of Fos-ir were highest in fluid-depleted rats that drank water and sodium. Fos-ir levels were highest in anterior regions of IC and lowest in posterior regions of IC. These results implicate visceral, taste, and/or postingestional factors in the increased metabolic activity of cells in IC.

Two loci of the insular cortex project to the taste zone of the nucleus of the solitary tract in rats

Distribution of insular cortical neurons projecting to the taste zone of the solitary tract nucleus (NTS) was examined histologically in rats. Injection of wheat germ agglutinin–conjugated horseradish peroxidase (WGA–HRP) into the taste responsive regions in the NTS resulted in labeling of cells in layer V within almost entire extent of the rostrocaudal axis of the granular and dysgranular areas of the insular cortex (IC) bilaterally with a clear contralateral dominance. The density of the cells was highest in the taste area of the IC [11] and second highest in the IC area around the bregma level, showing a bimodal distribution. After WGA–HRP injection into the IC taste area or the caudal IC, dense or sparse anterograde labeling was seen in the rostral NTS, respectively. The results indicate that not only the IC taste area but also the caudal IC exerts control influences directly upon the NTS taste zone.

Identification of gastric related neurones in the rat insular cortex

Location peculiarities of insular neurones implicated in the regulation of gastrointestinal motility have been studied in acute experiments on rats. After microinjection of a horseradish peroxidase solution in a part of the dorsal vagal complex that receive gastric afferent inputs, retrogradely labelled cell bodies are observed in a certain area of the agranular and disgranular insular cortex. Electrical stimulation of the insular cortex area had no significant effect on heart and respiration rate but had evoked gastric tone changes. These results suggest that the insular cortex contains a specific cell group that provides direct output to the bulbar ‘gastric’ centre and takes part in regulation of gastrointestinal functions.

Identification of gastric related neurones in the rat insular cortex

Location peculiarities of insular neurones implicated in the regulation of gastrointestinal motility have been studied in acute experiments on rats. After microinjection of a horseradish peroxidase solution in a part of the dorsal vagal complex that receive gastric afferent inputs, retrogradely labelled cell bodies are observed in a certain area of the agranular and disgranular insular cortex. Electrical stimulation of the insular cortex area had no significant effect on heart and respiration rate but had evoked gastric tone changes. These results suggest that the insular cortex contains a specific cell group that provides direct output to the bulbar ‘gastric’ centre and takes part in regulation of gastrointestinal functions.

Visuotopic organization of the lateral suprasylvian area and of an adjacent area of the ectosylvian gyrus of cat cortex: A physioligical and connectional study

We have explored the visuotopic organization of the territory surrounding the middle suprasylvian sulcus (MSS) of cat cerebral cortex by electrophysiological mapping, and by tracing the topography of its cortical and subcortical connections using wheatgerm-agglutinin horseradish peroxidase (WGA-HRP). Observations from the two approaches were concordant, and confirmed the presence of two separate visual areas in the MSS that approximate, but do not exactly correspond, to the location and internal organization of the posterior medial and posterior lateral lateral suprasylvian (PMLS, PLLS) areas of Palmer et al. (1978). We define as part of the lateral suprasylvian (LS) area the territory on the medial bank and caudal end of the lateral bank of the MSS that receives a topographically organized projection from the region of area 17 representing the lower visual quadrant. This territory is connected with other structures that are themselves striate-recipient (cortical areas 18 and 19, and the lateral division of the lateral posterior (LPl) nucleus), and with a variety of nuclei that receive direct retinal input, such as the C-laminae of the LGd, the medial interlaminar nucleus (MIN), and the superficial layers of the superior colliculus (SC). Its connections with the LPl, LGd, MIN, and SC correspond topographically with the input from area 17. Revised maps of area LS were produced from the physiological and connectional data: its rostral border is formed by a representation of lower visual elevations with the horizontal meridian represented caudally, and its lateral border is formed by the vertical meridian; area LS shares a representation of the center of gaze with the visual area of the lateral bank at its caudal end. The adjacent lateral bank area has larger receptive fields than area LS, and very different connectivity. It receives no input from area 17 and little input from striate-recipient structures, including area LS, but instead is connected to more remote extrastriate visual areas, such as the anterior ectosylvian visual (AEV) area in insular cortex, and to zones of the thalamus in receipt of tectal input (LPm and the lateromedial-suprageniculate nuclear complex). According to both mapping approaches, the lateral bank area contains representations of both the upper and lower visual quadrants but a rather limited degree of visuotopic order. We refer to it as the posterior ectosylvian visual (PEV) area, because it appears to be functionally and connectionally dissociated from area LS, but is possibly a functional antecedent of area AEV.

On the morphological evaluation of the neurovirulence safety of attenuated mumps virus strains in monkeys

In tests with intracerebral inoculation of Macacus rhesus, the neurovirulent properties of two variants of attenuated mumps virus, obtained at different passage levels (19th and 22nd) in the primary cultures of guinea-pig kidney and Japanese quail embryo fibroblast cells, were studied. Neither variants damaged the neurons, but caused ventriculitis phenomena, often most pronounced in the posterior portions of central parts of lateral ventricles, i.e. far from the site of virus inoculation. By the immunofluorescent method the specificity of the pathological process was confirmed: the antigen mostly detected in the ependyma, the subependymal zone, in the cells of inflammatory infiltrates located in this zone and in the stroma of choroid plexus, as well as in a number of neurons in the insular cortex area. Tests revealed that the neurovirulent properties are enhanced in the higher passage level variant, after the inoculation in which some monkeys developed a picture of adhesive ventriculitis, sometimes up to an almost complete obliteration of the ventricle lumen. Attention is drawn to the necessity of investigating the brain ventricular system when attenuated strains—candidates for live mumps vaccines—are studied in the neurovirulence safety test in monkeys.