Insular Volume Research Articles

Brain Morphological and Functional Changes in Adenomyosis with Pain: A Resting State Functional Magnetic Resonance Imaging Study.

The absence of clinically objective methods to evaluate adenomyosis-associated pain and the poor understanding of its pathophysiology lead to treatment limitations. We conducted a resting-state functional magnetic resonance imaging study with 49 patients with pain-related adenomyosis and 30 pain-free controls to investigate brain morphological alterations and regional dysfunctions in patients with pain-related adenomyosis. These patients had significantly higher scores for anxiety and depression than the control group (p < 0.05). They also had a lower gray matter volume (GMV) in the bilateral insula, left angular gyrus, precuneus, left inferior temporal gyrus, and left postcentral gyrus (p < 0.05, AlphaSim corrected). Similarly, decreased voxel-mirrored homotopic connectivity was observed in the bilateral insula, posterior cingulate cortex, middle frontal gyrus, and postcentral gyrus in the adenomyosis patient group (p < 0.05, AlphaSim corrected). Regional homogeneity showed significant differences mainly in the bilateral cerebellum, left inferior frontal gyrus, medial prefrontal cortex, and posterior cingulate gyrus. Correlation analysis showed that the degree of depression in patients with adenomyosis was negatively correlated with the GMV of the left angular gyrus. The results show that these patients exhibited changes in multiple brain regions associated with pain as well as emotion perception and processing.

Autism Is Associated With Interindividual Variations of Gray and White Matter Morphology

BackgroundAlthough many studies have explored atypicalities in gray matter (GM) and white matter (WM) morphology of autism, most of them relied on unimodal analyses that did not benefit from the likelihood that different imaging modalities may reflect common neurobiology. We aimed to establish brain patterns of modalities that differentiate between individuals with and without autism and explore associations between these brain patterns and clinical measures in the autism group. MethodsWe studied 183 individuals with autism and 157 nonautistic individuals (age range, 6–30 years) in a large, deeply phenotyped autism dataset (EU-AIMS LEAP [European Autism Interventions—A Multicentre Study for Developing New Medications Longitudinal European Autism Project]). Linked independent component analysis was used to link all participants’ GM volume and WM diffusion tensor images, and group comparisons of modality shared variances were examined. Subsequently, we performed univariate and multivariate brain-behavior correlation analyses to separately explore the relationships between brain patterns and clinical profiles. ResultsOne multimodal pattern was significantly related to autism. This pattern was primarily associated with GM volume in bilateral insula and frontal, precentral and postcentral, cingulate, and caudate areas and co-occurred with altered WM features in the superior longitudinal fasciculus. The brain-behavior correlation analyses showed a significant multivariate association primarily between brain patterns that involved variation of WM and symptoms of restricted and repetitive behavior in the autism group. ConclusionsOur findings demonstrate the assets of integrated analyses of GM and WM alterations to study the brain mechanisms that underpin autism and show that the complex clinical autism phenotype can be interpreted by brain covariation patterns that are spread across the brain involving both cortical and subcortical areas.

Clinical vitamin D levels are associated with insular volume and inferior temporal gyrus white matter surface area in community-dwelling individuals with knee pain.

ContextVitamin D is an essential, fat soluble micronutrient long-known for its effects on calcium homeostasis and bone health. With advances in technology, it is being discovered that Vitamin D exerts its effects beyond the musculoskeletal system. Vitamin D has since been noted in nervous system health and functioning, and is becoming a target of interest in brain health, aging, and chronic pain outcomes.ObjectivesWe and others have previously shown that deficient Vitamin D status is associated with greater pain severity across a variety of conditions, however the reason as to why this relationship exists is still being understood. Here, we sought to examine associations between Vitamin D status and brain structure in those with chronic knee pain.MethodsStructural MRI imaging techniques and whole brain analyses were employed and serum Vitamin D were collected on 140 participants with chronic pain. Covariates included age, sex, race and site, as these data were collected at two separate institutions. ANOVAs using the clinical cut points for Vitamin D status (deficient, insufficient, and optimal) as well as continuous regression-based Vitamin D effects were employed to observe differences in brain volume. P-value was set to 0.017 after correction for multiple comparisons.ResultsWe discovered that individuals in our sample (age = 50+; 63.6% female; 52.1% Non-Hispanic Black) who were either clinically deficient (<20 ng/mL) or insufficient (20–30 ng/mL) in serum Vitamin D had significant differences in the gray matter of the left circular insular cortex, left inferior temporal gyrus, right middle temporal gyrus, as well as decreased white matter surface area in the right inferior temporal gyrus compared to those considered to have optimal levels (>30 ng/mL) of serum Vitamin D.ConclusionEvidence from these data suggests that Vitamin D, or lack thereof, may be associated with pain outcomes by mediating changes in regions of the brain known to process and interpret pain. More research understanding this phenomenon as well as the effects of Vitamin D supplementation is warranted.

The Neuroanatomic Correlates of Olfactory Identification Impairment in Healthy Older Adults and in Persons with Mild Cognitive Impairment.

Olfactory identification (OI) impairment appears early in the course of Alzheimer's disease dementia (AD), prior to detectable cognitive impairment. However, the neuroanatomical correlates of impaired OI in cognitively normal older adults (CN) and persons with mild cognitive impairment (MCI) are not fully understood. We examined the neuroanatomic correlates of OI impairment in older adults from the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Our sample included 1,600 older adults without dementia who completed clinical assessment and structural brain imaging from 2011 to 2013. We characterized OI impairment using the 12-item Sniffin' Sticks odor identification test (score ≤6). We used voxel-based morphometry (VBM) and region of interest (ROI) analyses to examine the neuroanatomic correlates of impaired OI in CN and MCI, after adjusting for potential confounders. Analyses were also separately stratified by race and sex. In CN, OI impairment was associated with smaller amygdala gray matter (GM) volume (p &lt; 0.05). In MCI, OI impairment was associated with smaller GM volumes of the olfactory cortex, amygdala, entorhinal cortex, hippocampus, and insula (ps &lt; 0.05). Differential associations were observed by sex in MCI; OI impairment was associated with lower insular GM volumes among men but not among women (p-interaction = 0.04). There were no meaningful interactions by race. The brain regions associated with OI impairment in individuals without dementia are specifically those regions known to be the primary targets of AD pathogenic processes. These findings highlight the potential utility of olfactory assessment in the identification and stratification of older adults at risk for AD.

Exploring Links Between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning

The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far. To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD), and schizophrenia; estimate predictability in patients with bvFTD and schizophrenia based on sociodemographic, clinical, and biological data; and examine prognostic value, genetic underpinnings, and progression in patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD). This study included 1870 individuals from 5 cohorts, including (1) patients with bvFTD (n = 108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157), or major depression (n = 102) to derive and compare diagnostic patterns and (2) patients with CHR (n = 160) or ROD (n = 161) to test patterns' prognostic relevance and progression. Healthy individuals (n = 1042) were used for age-related and cohort-related data calibration. Data were collected from January 1996 to July 2019 and analyzed between April 2020 and April 2022. Case assignments based on diagnostic patterns; sociodemographic, clinical, and biological data; 2-year functional outcomes and genetic separability of patients with CHR and ROD with high vs low pattern expression; and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery vs preserved recovery. Of 1870 included patients, 902 (48.2%) were female, and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern comprising prefrontal, insular, and limbic volume reductions was more expressed in patients with schizophrenia (65 of 157 [41.2%]) and major depression (22 of 102 [21.6%]) than the temporo-limbic AD patterns (28 of 157 [17.8%] and 3 of 102 [2.9%], respectively). bvFTD expression was predicted by high body mass index, psychomotor slowing, affective disinhibition, and paranoid ideation (R2 = 0.11). The schizophrenia pattern was expressed in 92 of 108 patients (85.5%) with bvFTD and was linked to the C9orf72 variant, oligoclonal banding in the cerebrospinal fluid, cognitive impairment, and younger age (R2 = 0.29). bvFTD and schizophrenia pattern expressions forecasted 2-year psychosocial impairments in patients with CHR and were predicted by polygenic risk scores for frontotemporal dementia, AD, and schizophrenia. Findings were not associated with AD or accelerated brain aging. Finally, 1-year bvFTD/schizophrenia pattern progression distinguished patients with nonrecovery from those with preserved recovery. Neurobiological links may exist between bvFTD and psychosis focusing on prefrontal and salience system alterations. Further transdiagnostic investigations are needed to identify shared pathophysiological processes underlying the neuroanatomical interface between the 2 disease spectra.

Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer's Disease Pathology, and Cognitive Decline.

IntroductionElevated cortisol levels have been reported in Alzheimer’s disease (AD) and may accelerate the development of brain pathology and cognitive decline. Dehydroepiandrosterone sulfate (DHEAS) has anti-glucocorticoid effects and it may be involved in the AD pathophysiology.ObjectivesTo investigate associations of cerebrospinal fluid (CSF) cortisol and DHEAS levels with (1) cognitive performance at baseline; (2) CSF biomarkers of amyloid pathology (as assessed by CSF Aβ levels), neuronal injury (as assessed by CSF tau), and tau hyperphosphorylation (as assessed by CSF p-tau); (3) regional brain volumes; and (4) clinical disease progression.Materials and MethodsIndividuals between 49 and 88 years (n = 145) with mild cognitive impairment or dementia or with normal cognition were included. Clinical scores, AD biomarkers, brain MRI volumetry along with CSF cortisol and DHEAS were obtained at baseline. Cognitive and functional performance was re-assessed at 18 and 36 months from baseline. We also assessed the following covariates: apolipoprotein E (APOE) genotype, BMI, and education. We used linear regression and mixed models to address associations of interest.ResultsHigher CSF cortisol was associated with poorer global cognitive performance and higher disease severity at baseline. Cortisol and cortisol/DHEAS ratio were positively associated with tau and p-tau CSF levels, and negatively associated with the amygdala and insula volumes at baseline. Higher CSF cortisol predicted more pronounced cognitive decline and clinical disease progression over 36 months. Higher CSF DHEAS predicted more pronounced disease progression over 36 months.ConclusionIncreased cortisol in the CNS is associated with tau pathology and neurodegeneration, and with decreased insula and amygdala volume. Both CSF cortisol and DHEAS levels predict faster clinical disease progression. These results have implications for the identification of patients at risk of rapid decline as well as for the development of interventions targeting both neurodegeneration and clinical manifestations of AD.

Gray Matter Brain Alterations in Type 1 Diabetes - Findings Based on Detailed Phenotyping of Neuropathy Status.

This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and cognitive measurements. Sixty individuals with type 1 diabetes and 20 healthy controls were included in the study. Nineteen individuals with type 1 diabetes and neuropathic pain, 19 with type 1 diabetes and DPN, 18 with type 1 diabetes without DPN, and 20 healthy controls were included in the brain analyses. We utilized structural brain magnetic resonance imaging to investigate total and regional gray matter volume. Significant lower gray matter volume was found in type 1 diabetes with neuropathic pain and in type 1 diabetes without DPN compared to healthy controls (p=0.024 and p=0.019, respectively). Lower insula volume was observed in all three diabetes groups (all p≤0.050). Thalamus and hippocampus volume was lower in type 1 diabetes with neuropathic pain, cerebellum volume was lower in type 1 diabetes with DPN, and somatosensory cortex volume was lower in type 1 diabetes without DPN (all p≤0.018). Attenuated memory was associated with lower gray matter volume in type 1 diabetes with DPN. No associations were found between gray matter volume and clinical/peripheral measurements. We demonstrated lower gray matter volume in individuals with type 1 diabetes regardless of the presence of DPN and neuropathic pain. Hence, central gray matter alteration was not associated with peripheral alterations.

Association between startle reactivity to uncertain threats and structural brain volume.

Sensitivity to uncertain threat (U-threat) is a clinically important individual difference factor in multiple psychopathologies. Recent studies have implicated a specific frontolimbic circuit as a key network involved in the anticipation of aversive stimuli. In particular, the insula, thalamus, and dorsal anterior cingulate cortex (dACC) have recently been found to be robustly activated by anticipation of U-threat. However, no study to date has examined the association between U-threat reactivity and structural brain volume. In the present study, we utilized a pooled sample of 186 young adult volunteers who completed a structural MRI scan and the well-validated No-Predictable-Unpredictable (NPU) threat of electric shock task. Startle eyeblink potentiation was collected during the NPU task as an objective index of aversive reactivity. ROI-based analyses revealed that increased startle reactivity to U-threat was associated with reduced gray matter volume in the right insula and bilateral thalamus, but not the dACC. These results add to a growing literature implicating the insula and thalamus as core nodes involved in individual differences in U-threat reactivity.

Vitamin D Is Associated with Insular Volume and Inferior Temporal Gyrus White Matter Surface Area

Vitamin D is an essential, fat soluble micronutrient long-known for its effects on calcium homeostasis and bone health. With advances in technology, it is being discovered that Vitamin D exerts its effects beyond the musculoskeletal system. Vitamin D has since been noted in nervous system health and functioning, and is becoming a target of interest in brain health, aging, and chronic pain outcomes. We and others have previously shown that deficient Vitamin D status is associated with greater pain severity across a variety of conditions, however the reason as to why this relationship exists is still being understood. Here, we sought to examine associations between Vitamin D status and brain structure in those with chronic knee pain. Using whole brain MRI analyses techniques with Freesurfer, we discovered that individuals (n=140) who were either clinically deficient (<20 ng/mL) or insufficient (20-30 ng/mL) in serum Vitamin D had significant differences in the grey matter of the insular cortex, inferior temporal gyrus, middle temporal gyrus, as well as decreased white matter surface area in the inferior temporal sulcus compared to those considered to have optimal levels (>30 ng/mL) of serum Vitamin D. These data suggest that Vitamin D, or lack thereof, may be influencing pain outcomes by mediating changes in regions of the brain known to process and interpret pain. More research understanding this phenomenon as well as the effects of Vitamin D supplementation is warranted. Grant support from NIH/NIA Grants R01AG059809, R01AG067757 (PI: Yenisel Cruiz-Almeida), and R37AG033906 (PI: Roger Fillingim).

Association of disease course and brain structural alterations in major depressive disorder.

The investigation of disease course-associated brain structural alterations in Major Depressive Disorder (MDD) have resulted in heterogeneous findings, possibly due to low reliability of single clinical variables used for defining disease course. The present study employed a principal component analysis (PCA) on multiple clinical variables to investigate effects of cumulative lifetime illness burden on brain structure in a large and heterogeneous sample of MDD patients. Gray matter volumes (GMV) was estimated in n = 681 MDD patients (mean age: 35.87 years; SD = 12.89; 66.6% female) using voxel-based-morphometry. Five clinical variables were included in a PCA to obtain components reflecting disease course to associate resulting components with GMVs. The PCA yielded two main components: Hospitalization reflected by patients' frequency and duration of inpatient treatment and Duration of Illness reflected by the frequency and duration of depressive episodes. Hospitalization revealed negative associations with bilateral dorsolateral prefrontal cortex (DLPFC) and left insula volumes. Duration of Illness showed significant negative associations with left hippocampus and right DLPFC volumes. Results in the DLPFC and hippocampus remained significant after additional control for depressive symptom severity, psychopharmacotherapy, psychiatric comorbidities, and remission status. This study shows that a more severe and chronic lifetime disease course in MDD is associated with reduced volume in brain regions relevant for executive and cognitive functions and emotion regulation in a large sample of patients representing the broad heterogeneity of MDD disease course. These findings were only partly influenced by other clinical characteristics (e.g., remission status, psychopharmacological treatment).

Altruistic Social Activity, Depressive Symptoms, and Brain Regional Gray Matter Volume: Voxel-Based Morphometry Analysis From 8,695 Old Adults.

Altruistic social activity, such as giving support to others, has shown protective benefits on dementia risk and cognitive decline. However, the pathological mechanism is unclear. In the present study, we investigated the association between altruistic social activity and brain regional gray matter. Furthermore, to explore the psychological interplay in altruistic social activity, we tested mediating effect of depressive symptoms on brain regional gray matter. We performed a cross-sectional voxel-based morphology (VBM) analysis including 8 695 old adults (72.9 ± 6.1 years) from Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) Cohort. We measured altruistic social activities by self-report questionnaires, depressive symptoms by Geriatric Depression Scale (GDS)-short version. We employed the whole-brain VBM method to detect relevant structural properties related to altruistic social activity. We then performed multiple regression models to detect the mediating effect of depressive symptoms on particular brain regional gray matter volume while adjusting possible physical and social lifestyle covariables. We found that altruistic social activity is associated with larger gray matter volume in posterior insula, middle cingulate gyrus, hippocampus, thalamus, superior temporal gyrus, anterior orbital gyrus, and middle occipital gyrus. Depressive symptoms mediated over 10% on altruistic social activity and hippocampus volume, over 20% on altruistic social activity and cingulate gyrus volume. Our results indicated that altruistic social activity might preserve brain regional gray matter which are sensitive to aging and cognitive decline. Meanwhile, this association may be explained by indirect effect on depressive symptoms, suggesting that altruistic social activity may mitigate the neuropathology of dementia.

227 Measurement of the Cortical Structures of the Insula Among Young Adult Sudanese Using Automatic Segmentation

Abstract Aim The insula is important in gustatory (taste) and visceral sensations, pain, emotion, and tactile senes. This study aimed to measure the cortical structure of the insula in young adults and the effect of gender, age, Body mass index (BMI) and education on it. This will provide base line data about cortical volume and thickness of the insula in normal subjects. Method A cross-sectional descriptive was done in 60 individuals, their age was ranged from 20–40 years. MRI imaging using 1.5 Tesla Philips scanners was done, version: 3.2.1. T1-weighted images was obtained using three-dimensional acquisition by Magnetization Prepared Rapid Acquisition (MP-RAGE). Images was analysed using the BrainSuite software, and the data was analysed using SPSS version 26. Results The mean cortical volume of the right and left insula were 8.60±1.31 and 8.01±1.26 cm3, respectively. There was significant asymmetry between the right and left sides. Additionally, there was a statistically significant difference between the cortical structures of the insula and the gender; also, there was statistically significant correlation between the insular cortical volume and the education. However, there was no statistically significant correlation between the cortical volume and age or body mass index. Conclusions Measurements of the right and left insula cortical structures among Sudanese adults were similar to the previous studies with males having larger volume than females. The right insula cortical volume was significantly larger than the left. I. There was a significant correlation between the cortical volume and education. Further studies with larger samples are needed to support these data.

The relationship between craving and insular morphometry in regular cocaine users: Does sex matter?

While it has been suggested that cocaine use and relapse in women is more strongly related to stress‐relief craving, whereas cocaine use in men is more strongly related to reward craving, the neural mechanisms that underlie these differences are poorly understood. The aim of this study was to investigate sex‐dependent differences in insular morphometry and associations with craving, in a sample of regular cocaine users (CUs) and non‐drug using controls (non‐CUs). It was hypothesized that insular volume, thickness and surface area would be lower in CU women, compared with CU men and non‐CUs. It was furthermore hypothesized that insular morphometry, particularly insular thickness, would be negatively associated to reward craving in CU men, while being negatively associated with stress‐relief craving in CU women. In contrast to the hypothesis, we did not find evidence of sex‐specific differences in insular morphometry in CUs. However, sex‐specific association between stress‐relief craving and insular morphometry were found: Right insular volume was negatively associated with stress‐relief craving in CU women, whereas this association was positive in CU men. Additionally, right insular surface area was negatively associated with stress‐relief craving in cocaine‐using men, whereas this association was positive in cocaine‐using women. In conclusion, the current study provides first evidence of sex‐specific differences in the association between craving and insular morphometry in a sample of regular cocaine users. Although speculative, these sex‐specific alterations in insular morphometry may underlie higher stress‐induced craving and relapse in CU women compared with CU men.

Ambient air pollution exposure and increasing depressive symptoms in older women: The mediating role of the prefrontal cortex and insula

Exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) have been associated with the emergence of depressive symptoms in older adulthood, although most studies used cross-sectional outcome measures. Elucidating the brain structures mediating the adverse effects can strengthen the causal role between air pollution and increasing depressive symptoms. We evaluated whether smaller volumes of brain structures implicated in late-life depression mediate associations between ambient air pollution exposure and changes in depressive symptoms. This prospective study included 764 community-dwelling older women (aged 81.6 ± 3.6 in 2008–2010) from the Women's Health Initiative Memory Study (WHIMS) Magnetic Resonance Imaging study (WHIMS-MRI; 2005–06) and WHIMS-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO; 2008–16). Three-year average annual mean concentrations (scaled by interquartile range [IQR]) of ambient PM2.5 (in μg/m3; IQR = 3.14 μg/m3) and NO2 (in ppb; IQR = 7.80 ppb) before WHIMS-MRI were estimated at participants' addresses via spatiotemporal models. Mediators included structural brain MRI-derived grey matter volumes of the prefrontal cortex and structures of the limbic-cortical-striatal-pallidal-thalamic circuit. Depressive symptoms were assessed annually by the 15-item Geriatric Depression Scale. Structural equation models were constructed to estimate associations between exposure, structural brain volumes, and depressive symptoms. Increased exposures (by each IQR) were associated with greater annual increases in depressive symptoms (βPM2.5 = 0.022; 95% Confidence Interval (CI) = 0.003, 0.042; βNO2 = 0.019; 95% CI = 0.001, 0.037). The smaller volume of prefrontal cortex associated with exposures partially mediated the associations of increased depressive symptoms with NO2 (8%) and PM2.5 (13%), and smaller insula volume associated with NO2 contributed modestly (13%) to the subsequent increase in depressive symptoms. We demonstrate the first evidence that the smaller volumes of the prefrontal cortex and insula may mediate the subsequent increases in depressive symptoms associated with late-life exposures to NO2 and PM2.5.

Common and specific patterns of functional and structural brain alterations in schizophrenia and bipolar disorder: a multimodal voxel-based meta-analysis.

Background:Schizophrenia and bipolar disorder have been linked to alterations in the functional activity and grey matter volume of some brain areas, reflected in impaired regional homogeneity and aberrant voxel-based morphometry. However, because of variable findings and methods used across studies, identifying patterns of brain alteration in schizophrenia and bipolar disorder has been difficult.Methods:We conducted a meta-analysis of differences in regional homogeneity and voxel-based morphometry between patients and healthy controls for schizophrenia and bipolar disorder separately, using seed-based d mapping.Results:We included 45 publications on regional homogeneity (26 in schizophrenia and 19 in bipolar disorder) and 190 publications on voxel-based morphometry (120 in schizophrenia and 70 in bipolar disorder). Patients with schizophrenia showed increased regional homogeneity in the frontal cortex and striatum and the supplementary motor area; they showed decreased regional homogeneity in the insula, primary sensory cortex (visual and auditory cortices) and sensorimotor cortex. Patients with bipolar disorder showed increased regional homogeneity in the frontal cortex and striatum; they showed decreased regional homogeneity in the insula. Patients with schizophrenia showed decreased grey matter volume in the superior temporal gyrus, inferior frontal gyrus, cingulate cortex and cerebellum. Patients with bipolar disorder showed decreased grey matter volume in the insula, cingulate cortex, frontal cortex and thalamus. Overlap analysis showed that patients with schizophrenia displayed decreased regional homogeneity and grey matter volume in the left insula and left superior temporal gyrus; patients with bipolar disorder displayed decreased regional homogeneity and grey matter volume in the left insula.Limitations:The small sample size for our subgroup analysis (unmedicated versus medicated patients and substantial heterogeneity in the results for some regions could limit the interpretability and generalizability of the results.Conclusion:Patients with schizophrenia and bipolar disorder shared a common pattern of regional functional and structural alterations in the insula and frontal cortex. Patients with schizophrenia showed more widespread functional and structural impairment, most prominently in the primary sensory motor areas.

Altered structural covariance and functional connectivity of the insula in patients with Crohn's disease.

Crohn's disease (CD) is a clinically chronic inflammatory bowel disease, which has been shown to be closely related to the brain-gut axis dysfunction. Although traditionally considered to be a limbic region, the insula has also been commonly identified as an abnormal brain region in previous CD-related studies. Structural magnetic resonance imaging (MRI) and resting-state functional MRI images were acquired from 45 CD patients in remission and 40 healthy controls (HCs). Three neuroimaging analysis methods including voxel-based morphometry (VBM), structural covariance, and functional connectivity (FC) were applied to investigate structural and functional alterations of the insulae between the CD patients and HCs. Pearson correlation was then used to examine the relationships between neuroimaging findings and clinical symptoms. Compared with the HCs, CD patients exhibited decreased gray matter volume (GMV) in the left dorsal anterior insula (dAI) and bilateral posterior insula (PI). Taking these three areas including the left dAI, right PI, and left PI as regions of interest (ROIs), differences were observed in the structural covariance and FC of the ROI with several regions between the two groups. After controlling for psychological factors, the differences of several regions involved in emotional processing in GMV in the left dAI, the FC of the dAI, and the right PI were not significant. The FC of the parahippocampus/hippocampus with dAI and PI were negatively correlated with the CD activity index (CDAI). We suggest that the insula-centered structural and/or functional changes may be associated with abnormal visceral sensory processing and related emotional responses in CD patients.

The association between local brain structure and disgust propensity

Research has discovered structural differences in the brains of people with different personality types. In the present voxel-based morphometry study we focused on the association between disgust propensity (DP: the temporally stable tendency to experience disgust across different situations) and grey matter volume (GMV) in regions of interest [insula, orbitofrontal cortex (OFC), basal ganglia]. We collected structural brain scans from 498 healthy individuals (352 females, 146 males; mean age = 27 years). Regression analyses were performed to test the association between three domains of DP (core, animal-reminder, contamination) and GMV. We observed negative correlations between animal-reminder DP and the volume of the insula, and contamination DP and OFC volume. Animal-reminder DP correlated positively with GMV in the basal ganglia (putamen). This study identified weak correlations between local brain volume and disgust propensity. The association between DP and insula volume concerned the posterior insula and was in the opposite of the expected direction. The findings of this study are inconsistent with the concept of the anterior insula as a region that specifically mediates DP.

Insula volumes in first-episode and chronic psychosis: A longitudinal MRI study

BackgroundAlterations in insular grey matter (GM) volume has been consistently reported for affective and non-affective psychoses both in chronic and first-episode patients, ultimately suggesting that the insula might represent a good region to study in order to assess the longitudinal course of psychotic disorders. Therefore, in this longitudinal Magnetic Resonance Imaging (MRI) study, we aimed at further investigating the key role of insular volumes in psychosis. Material and Methods68 First-Episode Psychosis (FEP) patients, 68 patients with Schizophrenia (SCZ), 47 Bipolar Disorder (BD) patients, and 94 Healthy Controls (HC) were enrolled and underwent a 1.5 T MRI evaluation. A subsample of 99 subjects (10 HC, 23 BD, 29 SCZ, 37 FEP) was rescanned after 2,53 ± 1,68 years. The insular cortex was manually traced and then divided into an anterior and posterior portion. Group and correlation analyses were then performed both at baseline and at follow-up. ResultsAt baseline, greater anterior and lower posterior insular GM volumes were observed in chronic patients. At follow-up, we found that FEP patients had a significant GM volume increase from baseline to follow-up, especially in the posterior insula whereas chronic patients showed a relative stability. Finally, significant negative correlations between illness severity and pharmacological treatment and insular GM volumes were observed in the whole group of psychotic patients. ConclusionsThe longitudinal assessment of both chronic and first-episode patients allowed us to detect a complex pattern of GM abnormalities in selective sub-portions of insular volumes, ultimately suggesting that this structure could represent a key biological marker of psychotic disorders.

Heart rate and heart rate variability in patients with chronic inflammatory joint disease: the role of pain duration and the insular cortex

BackgroundChronic inflammatory joint diseases (CIJD) have been linked to increased cardiovascular morbidity and mortality. A decisive reason could be a dysregulation of the autonomic nervous system, which is responsible for the control of cardiovascular function. So far, the cause of changes in autonomic nervous system functions remains elusive. In this study, we investigate the role of chronic pain and the insular cortex in autonomic control of cardiac functioning in patients with CIJD.MethodsWe studied the autonomic nervous system through the assessment of heart rate and heart rate variability (HRV) at rest and under cognitive stimulation. Furthermore, we investigated insular cortex volume by performing surface-based brain morphometry with FreeSurfer. For this study, 47 participants were recruited, 22 individual age- and sex-matched pairs for the magnetic resonance imaging analyses and 14 for the HRV analyses. All available patients’ data were used for analysis.ResultsPain duration was negatively correlated with the resting heart rate in patients with chronic inflammatory joint diseases (n = 20). In a multiple linear regression model including only CIJD patients with heart rate at rest as a dependent variable, we found a significant positive relationship between heart rate at rest and the volume of the left insular cortex and a significant negative relationship between heart rate at rest and the volume of the right insular cortex. However, we found no significant differences in HRV parameters or insular cortex volumes between both groups.ConclusionsIn this study we provide evidence to suggest insular cortex involvement in the process of ANS changes due to chronic pain in CIJD patients.The study was preregistered with the German Clinical Trials Register (https://www.drks.de; DRKS00012791; date of registration: 28 July 2017).

Irritable bowel syndrome in women: Association between decreased insular subregion volumes and gastrointestinal symptoms

ObjectiveIrritable bowel syndrome (IBS) is a chronic pain disorder characterized by disturbed interactions between the gut and the brain with depression as a common comorbidity. In both IBS and depression, structural brain alterations of the insular cortices, key structures for pain processing and interoception, have been demonstrated but the specificity of these findings remains unclear. We compared the gray matter volume (GMV) of insular cortex (IC) subregions in IBS women and healthy controls (HC) and examined relations to gastrointestinal (GI) symptoms and glutamate + glutamine (Glx) concentrations. We further analyzed GMV of IC subregions in women with major depression (MDD) compared to HC and addressed possible differences between depression, IBS, IBS with depression and HC. DesignWomen with IBS (n = 75), MDD (n = 41) and their respective HC (n = 39 and n = 43) underwent structural brain MRI. IC subregion volumes were estimated using statistical parametric mapping software. General linear model approaches were applied to IC volumetric data and FDR-corrected partial correlation analyses assessed relations between GMV, GI symptoms and Glx concentrations. ResultsIBS patients had significantly smaller IC subregions than HC in both hemispheres but there was no significant difference between MDD compared with IBS and HC for any insular subregion. In IBS, the dorsal anterior insular volumes were negatively correlated with symptoms of nausea and pain, and the left ventral subregion showed a positive correlation with straining to defecate, while the posterior subregion volumes showed no relation to symptoms. In the anterior insula, concentration of Glx showed positive correlations with GMV bilaterally in HC and with GMV of the right anterior insula in IBS. ConclusionAs the interoceptive cortex, the insula shows substantial and disease-specific structural differences in patients with chronic interoceptive visceral pain. Particularly changes in the anterior proportions might be related to chronic exposure to or enhanced salience towards adverse interoceptive visceral signals and could be linked to biochemical changes, calling for further multimodal and longitudinal work.