Insula Functional Connectivity Research Articles

Bilateral insular functional connectivity in epilepsy patients: A cortico-cortical evoked potential study

Objective To explore bilateral insular functional connectivity in refractory epilepsy patients using electrical cortical stimulation by stereoelectroencephalography (SEEG) electrodes. Methods We retrospectively analyzed the clinical data of 4 patients with insular or insular-related drug resistant epilepsy at Epilepsy Center of Yuquan Hospital of Tsinghua University from January 2014 to August 2016. Four patients were implanted with SEEG electrodes in bilateral insular lobes for cortical electrical stimulation. The evoked potential response of each contact was determined by visual analysis and nonparametric test. The evoked potential response was recorded at the contralateral insular lobe electrode on the stimulating side, and the response rate and anatomical distribution were determined. Results A total of 28 SEEG electrodes (98 contacts) were implanted into the insular lobe in 4 patients, of which 12 electrodes (47 contacts) were implanted into the left insular lobe. Cortical-cortical evoked potential (CCEP) responses were found between bilateral insular lobes in 4 patients, and homotopic bidirectional CCEP connections were found between bilateral insular lobes. The response rate of contralateral insular CCEP was 39.8%, and the peak latency was 15.5-196.0 ms. There were bi-directional CCEP connections between corresponding bilateral insular gyri. Conclusions There are bi-directional functional connections between bilateral insular lobes in patients with insular or insular-related epilepsy, particularly in patients with post-viral encephalitis epilepsy. However, more studies are needed to confirm this result. Key words: Epilepsy; Insular; Stereoelectroencephalography; Electrical cortical stimulation; Cortico-cortical evoked potential

Insula Functional Connectivity in Schizophrenia: Subregions, Gradients, and Symptoms

BackgroundThe insular cortex is connected to a diverse network of cortical and subcortical areas. This study aimed to investigate whether the diversity in functional connectivity across the insula’s topography is altered in individuals with schizophrenia and relates to the clinical symptoms of the disorder. MethodsInsula-to-whole-brain functional connectivity was mapped using resting-state functional magnetic resonance imaging at the resolution of voxels in individuals with schizophrenia (n = 49) and healthy comparison individuals (n = 52). Diversity in functional connectivity across the insula’s topography was represented as discrete subregions and gradients of continuous variation. Canonical correlation analysis was used to relate interindividual variation in insula connectivity to clinical symptoms. ResultsInsula connectional diversity was parcellated into two subregions: dorsoanterior and ventroposterior. Compared with the healthy comparison group, subjects with schizophrenia were associated with an overall reduction in insula functional connectivity as well as reduced differentiation in connectivity profiles between these subregions. A significant interaction effect between diagnosis and insula subregion indicated that the anterior subregion in schizophrenia was connected with increased strength to the somatosensory, motor, occipital, and parietal cortices, whereas the posterior subregion showed increased connectivity with the thalamus and prefrontal cortex. Insula connectivity with the anterior cingulate and auditory cortices was significantly associated with cognitive impairment, negative symptoms, poor psychosocial functioning, and longer duration of illness (r = .64, p = .03). ConclusionsDiversity in functional connectivity across the insula’s rostrocaudal axis is reduced in schizophrenia, resulting in reduced differentiation between anterior and posterior insula. Interindividual variation in insula connectivity explains variability in some of the clinical symptoms of schizophrenia.

Altered Sensory Insular Connectivity in Chronic Postsurgical Pain Patients.

Chronic postsurgical pain (CPSP) occurs in up to 50% of individuals after surgeries and 32% after hysterectomy, leading to major adverse effects on quality of life and socioeconomic burden. Little is known about whether and how large-scale neural networks being affected in CPSP, particularly with regard to the functional connectivity (FC) of insula which is known to be the hub of the intrinsic neural network playing a critical role in pain processing. Here, we sought to examine the dynamics of insular FC in the context of noxious stimuli in CPSP patients. To this aim, resting state fMRI data were acquired, before and after acute heat pain stimulation, from 11 individuals with chronic post-hysterectomy pain (CPHP) and 22 age-matched healthy controls (HCs) who had a hysterectomy but without chronic post-surgical pain. We examined whole-brain FC were mapped by seeding at the sensorimotor and chemosensory subfields of the insula and found significant group × stimulation interaction effects. Specifically, the HC group had increased FC between the left sensorimotor insula and right angular and middle occipital gyrus (MOG) and increased FC between the left chemosensory insula and bilateral angular and MOG following pain stimulation. In contrast, such pain stimulation related FC changes were absent in the CPHP group. Furthermore, higher insular FC at baseline and smaller increased insular FC after pain stimulation correlated with clinical pain scores in CPHP patients. Our findings suggest that CPSP is associated with altered dynamics of large-scale functional networks anchored in the insula.

Altered functional connectivity in the fear network of firefighters with repeated traumatic stress.

Firefighters are routinely exposed to various traumatic events and often experience a range of trauma-related symptoms. Although these repeated traumatic exposures rarely progress to the development of post-traumatic stress disorder, firefighters are still considered to be a vulnerable population with regard to trauma.AimsTo investigate how the human brain responds to or compensates for the repeated experience of traumatic stress. We included 98 healthy firefighters with repeated traumatic experiences but without any diagnosis of mental illness and 98 non-firefighter healthy individuals without any history of trauma. Functional connectivity within the fear circuitry, which consists of the dorsal anterior cingulate cortex, insula, amygdala, hippocampus and ventromedial prefrontal cortex (vmPFC), was examined using resting-state functional magnetic resonance imaging. Trauma-related symptoms were evaluated using the Impact of Event Scale - Revised. The firefighter group had greater functional connectivity between the insula and several regions of the fear circuitry including the bilateral amygdalae, bilateral hippocampi and vmPFC as compared with healthy individuals. In the firefighter group, stronger insula-amygdala connectivity was associated with greater severity of trauma-related symptoms (β = 0.36, P = 0.005), whereas higher insula-vmPFC connectivity was related to milder symptoms in response to repeated trauma (β = -0.28, P = 0.01). The current findings suggest an active involvement of insular functional connectivity in response to repeated traumatic stress. Functional connectivity of the insula in relation to the amygdala and vmPFC may be potential pathways that underlie the risk for and resilience to repeated traumatic stress, respectively.Declaration of interestNone.

Deficits in frontoparietal activation and anterior insula functional connectivity during regulation of cognitive-affective interference in bipolar disorder.

Bipolar disorders (BD) are characterized by emotion and cognitive dysregulation. Mapping deficits in the neurocircuitry of cognitive-affective regulation allows for potential identification of intervention targets. This study used functional MRI data in BD patients and healthy controls during performance on a task requiring cognitive and inhibitory control superimposed on affective images, assessing cognitive and affective interference. Functional MRI data were collected from 39 BD patients and 36 healthy controls during performance on the Multi-Source Interference Task overlaid on images from the International Affective Picture System (MSIT-IAPS). Analyses examined patterns of activation in a priori regions implicated in cognitive and emotional processing. Functional connectivity to the anterior insula during task performance was also examined, given this region's role in emotion-cognition integration. BD patients showed significantly less activation during cognitive interference trials in inferior parietal lobule, dorsomedial prefrontal cortex, anterior insula, mid-cingulate, and ventrolateral prefrontal cortex regardless of affective valence. BD patients showed deviations in functional connectivity with anterior insula in regions of the default mode and frontoparietal control networks during negatively valenced cognitive interference trials. Our findings show disruptions in cognitive regulation and inhibitory control in BD patients in the presence of irrelevant affective distractors. Results of this study suggest one pathway to dysregulation in BD is through inefficient integration of affective and cognitive information, and highlight the importance of developing interventions that target emotion-cognition integration in BD.

Face perception enhances insula and motor network reactivity in Tourette syndrome.

Tourette syndrome is a neurodevelopmental disorder, characterized by motor and phonic tics. Tics are typically experienced as avolitional, compulsive, and associated with premonitory urges. They are exacerbated by stress and can be triggered by external stimuli, including social cues like the actions and facial expressions of others. Importantly, emotional social stimuli, with angry facial stimuli potentially the most potent social threat cue, also trigger behavioural reactions in healthy individuals, suggesting that such mechanisms may be particularly sensitive in people with Tourette syndrome. Twenty-one participants with Tourette syndrome and 21 healthy controls underwent functional MRI while viewing faces wearing either neutral or angry expressions to quantify group differences in neural activity associated with processing social information. Simultaneous video recordings of participants during neuroimaging enabled us to model confounding effects of tics on task-related responses to the processing of faces. In both Tourette syndrome and control participants, face stimuli evoked enhanced activation within canonical face perception regions, including the occipital face area and fusiform face area. However, the Tourette syndrome group showed additional responses within the anterior insula to both neutral and angry faces. Functional connectivity during face viewing was then examined in a series of psychophysiological interactions. In participants with Tourette syndrome, the insula showed functional connectivity with a set of cortical regions previously implicated in tic generation: the presupplementary motor area, premotor cortex, primary motor cortex, and the putamen. Furthermore, insula functional connectivity with the globus pallidus and thalamus varied in proportion to tic severity, while supplementary motor area connectivity varied in proportion to premonitory sensations, with insula connectivity to these regions increasing to a greater extent in patients with worse symptom severity. In addition, the occipital face area showed increased functional connectivity in Tourette syndrome participants with posterior cortical regions, including primary somatosensory cortex, and occipital face area connectivity with primary somatosensory and primary motor cortices varied in proportion to tic severity. There were no significant psychophysiological interactions in controls. These findings highlight a potential mechanism in Tourette syndrome through which heightened representation within insular cortex of embodied affective social information may impact the reactivity of subcortical motor pathways, supporting programmed motor actions that are causally implicated in tic generation. Medicinal and psychological therapies that focus on reducing insular hyper-reactivity to social stimuli may have potential benefit for tic reduction in people with Tourette syndrome.

Altered structural and functional connectivity of the insula in functional dyspepsia.

Functional dyspepsia (FD) is a common functional gastrointestinal disease. Neuroimaging studies have identified that insula is involved in the pathogenesis of FD. However, less is known about structural and functional connectivity of insula in FD. In this study, 67 FD patients and 46 healthy controls (HCs) underwent structural MRI, resting-state functional MRI, diffusion tensor imaging (DTI) scans, and clinical assessment. We used the 3 neuroimaging modalities to investigate structural and functional connectivity of insula between FD patients and HCs, and we examined relationships between the neuroimaging findings and clinical symptoms. Compared with HCs, (i) FD patients had decreased gray matter density in right insula according to voxel-based morphometry method, which region was targeted as region of interest for further analysis of structural and functional connectivity; (ii) FD patients had lower connection probability in right anterior insula with right thalamus, right internal capsule (IC), and right external capsule (EC); (iii) FD patients had decreased functional connectivity of the right anterior insula with right thalamus and right pregenual anterior cingulate cortex (pACC); and (iv) FD patients had negative correlation between disease duration and the functional connectivity of right anterior insula with thalamus. The present findings reveal that alterations of structural and/or functional connectivity of right anterior insula with regions, including thalamus, IC, EC, and pACC, may be mainly implicated in abnormalities of visceral sensory processing and related affective responses in FD patients. Finally, this study could enhance understanding of the pathophysiology of FD.

F158. FUNCTIONAL CONNECTIVITY DIVERSITY OF THE INSULA CORTEX IN SCHIZOPHRENIA: SUBREGIONS OR CONTINUA?

BackgroundThe function, cytoarchitecture and connectivity of the insula cortex are diverse. Cluster analyses have been applied to functional magnetic resonance imaging (MRI) connectivity data to parse this diversity and subdivide the insula into discrete subregions. However, the number of subregions comprising the insula remains vexed and whether these putative subregions are disturbed in neuropsychiatric illness are unknown. The present study aimed to (i) rigorously evaluate the number of subregions (if any) into which the insula can be subdivided based on topographic variation in whole-brain patterns of insula functional connectivity; and, (ii) establish whether the connectional topography of the insula is altered in schizophrenia.MethodsTwo alternative models explaining the heterogeneity of insula connectivity were tested: (Model i) insula comprising discrete subregions, each associated with a distinct connectivity fingerprint; and, (Model ii) connectivity varying as a continuum across insula, without marked boundaries. Cluster analysis was used to delineate discrete subregions, and a novel gradient-based method was developed to evaluate whether connectivity varied continuously across the insula. These models were tested in a sample of individuals with schizophrenia (N=49), healthy comparison individuals (N=52) and an independent validation cohort from the Human Connectome Project (N=50).ResultsCluster analyses indicated that the insula comprised anterior and posterior subregions, with significantly less differentiation in connectivity patterns between these two clusters in the schizophrenia group (right: P=.0038; left: P=.002). The anterior insula was more strongly connected to the sensory-motor, occipital/parietal cortex and posterior lobe of cerebellum in the schizophrenia group, whereas the connectivity between the posterior insula and prefrontal cortex and thalamus was stronger in the patients (PFWE<.05). The dysconnectivity between anterior insula and anterior cingulate cortex was correlated with the severity of emotion withdrawal (Jonckeere-Terpstra test; JT=-3.74, P<.001). Most importantly however, for the majority of individuals in both datasets, the degree of cluster separation between insula subregions identified with cluster analyses was not significantly improved compared to clusters delineated in null data that was generated from white matter, where no clusters were expected. Modeling patterns of insula connectivity as continua of variation across a rostrocaudal axis was found to provide a more parsimonious model than using distinct subregions segregated by sharp boundaries. The variation in connectivity across this rostrocaudal axis was significantly reduced in schizophrenia patients (P=0.02).DiscussionThis is the first study that comprehensively investigate the potential differences in connectional pathology of insula between its anterior and posterior aspects. We conclude that the connectional diversity of the insula inferred from resting-state functional connectivity should be conceptualized as continua of variation, rather than discrete subregions. We posit that the reduced differentiation between the anterior and posterior insula in schizophrenia may impact on the ability in discriminating self-generated from externally-generated sensory information, possibly contributing to hallucinations in the disorder.

Functional Connectivity Between Anterior Insula and Key Nodes of Frontoparietal Executive Control and Salience Networks Distinguish Bipolar Depression From Unipolar Depression and Healthy Control Subjects

BackgroundPatients with bipolar depression are characterized by dysregulation across the full spectrum of mood, differentiating them from patients with unipolar depression. The ability to switch neural resources among the default mode network, salience network, and executive control network (ECN) has been proposed as a key mechanism for adaptive mood regulation. The anterior insula is implicated in the modulation of functional network switching. Differential connectivity between anterior insula and functional networks may provide insights into pathophysiological differences between bipolar and unipolar mood disorders, with implications for diagnosis and treatment. MethodsResting-state functional magnetic resonance imaging data were collected from 98 subjects (35 unipolar, 24 bipolar, and 39 healthy control subjects). Pearson correlations were computed between bilateral insula seed regions and a priori defined target regions from the default mode network, salience network, and ECN. After r-to-z transformation, a one-way multivariate analysis of covariance was conducted to identify significant differences in connectivity between groups. Post hoc pairwise comparisons were conducted and Bonferroni corrections were applied. Receiver-operating characteristics were computed to assess diagnostic sensitivity. ResultsPatients with bipolar depression evidenced significantly altered right anterior insula functional connectivity with the inferior parietal lobule of the ECN relative to patients with unipolar depression and control subjects. Right anterior insula–inferior parietal lobule connectivity significantly discriminated patients with bipolar depression. ConclusionsImpaired functional connectivity between the anterior insula and the inferior parietal lobule of the ECN distinguishes patients with bipolar depression from those with unipolar depression and healthy control subjects. This finding highlights a pathophysiological mechanism with potential as a therapeutic target and a clinical biomarker for bipolar disorder, exhibiting reasonable sensitivity and specificity.

Music Intervention Leads to Increased Insular Connectivity and Improved Clinical Symptoms in Schizophrenia.

Schizophrenia is a syndrome that is typically accompanied by delusions and hallucinations that might be associated with insular pathology. Music intervention, as a complementary therapy, is commonly used to improve psychiatric symptoms in the maintenance stage of schizophrenia. In this study, we employed a longitudinal design to assess the effects of listening to Mozart music on the insular functional connectivity (FC) in patients with schizophrenia. Thirty-six schizophrenia patients were randomly divided into two equal groups as follows: the music intervention (MTSZ) group, which received a 1-month music intervention series combined with antipsychotic drugs, and the no-music intervention (UMTSZ) group, which was treated solely with antipsychotic drugs. Resting-state functional magnetic resonance imaging (fMRI) scans were performed at the following three timepoints: baseline, 1 month after baseline and 6 months after baseline. Nineteen healthy participants were recruited as controls. An FC analysis seeded in the insular subregions and machine learning techniques were used to examine intervention-related changes. After 1 month of listening to Mozart music, the MTSZ showed increased FC in the dorsal anterior insula (dAI) and posterior insular (PI) networks, including the dAI-ACC, PI-pre/postcentral cortices, and PI-ACC connectivity. However, these enhanced FCs had vanished in follow-up visits after 6 months. Additionally, a support vector regression on the FC of the dAI-ACC at baseline yielded a significant prediction of relative symptom remission in response to music intervention. Furthermore, the validation analyses revealed that 1 month of music intervention could facilitate improvement of the insular FC in schizophrenia. Together, these findings revealed that the insular cortex could potentially be an important region in music intervention for patients with schizophrenia, thus improving the patients' psychiatric symptoms through normalizing the salience and sensorimotor networks.

Structural and functional abnormalities of the insular cortex in trigeminal neuralgia: a multimodal magnetic resonance imaging analysis.

Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by intense, lancinating attacks of facial pain. Increasing evidence suggests that TN is accompanied by abnormalities in brain morphology, white matter microstructure, and function. However, whether these abnormalities are linked or reflect independent etiologies remains unknown. Using multimodal magnetic resonance imaging data of 20 patients with TN and 21 healthy controls, we investigated cortical gyrification abnormalities, their relationships with abnormalities of the underlying white matter microstructure and gray matter morphology, as well as their functional significance in TN. Compared with controls, patients with TN showed significant local gyrification index (LGI) reductions predominantly in the left insular cortex, which were negatively correlated with pain intensity. In this cluster, patients with TN had concurrent cortical thickness reductions but unaltered cortical surface area. Meanwhile, LGI of this cluster was not correlated with overlying cortical thickness or surface area but was positively correlated with the fractional anisotropy of 2 nearby white matter clusters, suggesting that insular LGI reductions may be primarily driven by microstructural abnormalities of the underlying white matter tracts, rather than by abnormalities in cortical thickness and surface area. In addition, patients with TN exhibited increased insula functional connectivity to the left posterior cingulate cortex and thalamus, which was positively correlated with disease duration. These findings provide new evidence for the involvement of insular abnormalities in the pathophysiology of TN.

Impaired insula functional connectivity associated with persistent pain perception in patients with complex regional pain syndrome.

Given that the insula plays a contributory role in the perception of chronic pain, we examined the resting-state functional connectivity between the insular cortex and other brain regions to investigate neural underpinnings of persisting perception of background pain in patients with complex regional pain syndrome (CRPS). A total of 25 patients with CRPS and 25 matched healthy controls underwent functional magnetic resonance imaging at rest. With the anterior and posterior insular cortices as seed regions, we compared the strength of the resting-state functional connectivity between the two groups. Functional connectivity between the anterior and posterior insular cortices and the postcentral and inferior frontal gyri, cingulate cortices was reduced in patients with CRPS compared with controls. Additionally, greater reductions in functional connectivity between the anterior insula and right postcentral gyrus were associated with more severe sensory pain in patients with CRPS (short-form McGill Pain Questionnaire sensory subscores, r = -.517, P = .023). The present results imply a possible role of the insula in aberrant processing of pain information in patients with CRPS. The findings suggest that a functional derangement of the connection between one of the somatosensory cortical functions of perception and one of the insular functions of awareness can play a significant role in the persistent experience of regional pain that is not confined to a specific nerve territory.

Investigating the relationship between multiple grip forces and BOLD signal in the Cerebellum and dentate nuclei of MS subjects

Investigating the relationship between multiple grip forces and BOLD signal in the Cerebellum and dentate nuclei of MS subjects

Human Posterior Insula Functional Connectivity Differs Between Electrical Pain and the Resting State.

The objective in this study was to directly compare MRI-based functional connectivity between conditions of rest and painful electrical nerve stimulation for key regions involved in pain processing: the anterior and posterior insula and the anterior cingulate cortex. Electric nerve stimulation, rated 7/10 for pain, was delivered to the right index finger of 14 healthy pain-free adult volunteers in four 30-sec blocks and continuously for 2 min. Functional connectivity maps obtained at rest and during both pain tasks were compared using seed time courses from the left anterior and posterior insula and anterior cingulate. Significant Pain versus Rest connectivity differences were consistently shown for the posterior insula, notably to the posterior cingulate and precuneus, while minimal and inconsistent differences were observed for the anterior insula and anterior cingulate. This study reinforces the known differences that can occur with changes in seed region selection in functional connectivity analysis. It also presents preliminary evidence that functional connectivity for the left posterior insula can potentially differentiate the presence of acute right-sided electrical pain from the nonpainful resting state.

Abnormal interhemispheric resting state functional connectivity of the insula in heroin users under methadone maintenance treatment

Abnormal interhemispheric functional connectivity is attracting more and more attention in the field of substance use. This study aimed to examine 1) the differences in interhemispheric functional connections of the insula with the contralateral insula and other brain regions between heroin users under methadone maintenance treatment (MMT) and healthy controls, and 2) the association between heroin users' interhemispheric insular functional connectivity using resting functional magnetic resonance imaging (fMRI) and the results of urine heroin analysis. Sixty male right-handed persons, including 30 with heroin dependence under MMT and 30 healthy controls, were recruited to this study. Resting fMRI experiments and urine heroin analysis were performed. Compared with the controls, the heroin users had a significantly lower interhemispheric insular functional connectivity. They also exhibited lower functional connectivity between insula and contralateral inferior orbital frontal lobe. After controlling for age, educational level and methadone dosage, less deviation of the interhemispheric insula functional connectivity was significantly associated with a lower risk of a positive urine heroin analysis result. Our findings demonstrated that the heroin users under MMT had abnormal long-range and interhemispheric resting functional connections. Those with a less dysfunctional interhemispheric insula functional connectivity had a lower risk of a positive urine heroin test.

Brain dynamics of post-task resting state are influenced by expertise: Insights from baseball players.

Post‐task resting state dynamics can be viewed as a task‐driven state where behavioral performance is improved through endogenous, non‐explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post‐task resting state dynamics that promote learning. We measured simultaneous fMRI/EEG and DTI in Division‐1 collegiate baseball players and compared to a group of controls, examining differences in both functional and structural connectivity. Participants performed a surrogate baseball pitch Go/No‐Go task before a resting state scan, and we compared post‐task resting state connectivity using a seed‐based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Although both groups were equally trained on the task, the experts showed differential activity in their post‐task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA–L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD‐alpha oscillation correlations between groups suggests variability in modulatory attention in the post‐task state, and (3) group differences between BOLD‐beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find that brain dynamics in the post‐task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity. Hum Brain Mapp 37:4454–4471, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Aberrant Insular Functional Network Integrity in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is accompanied by tissue injury to the insular cortices, areas that regulate autonomic pain, dyspnea, and mood, all of which are affected in the syndrome. Presumably, the dysregulation of insular-related functions are mediated by aberrant functional connections with other brain regions; however, the integrity of the functional connectivity (FC) to other sites is undescribed. Our aim was to examine resting-state FC of the insular cortices to other brain areas in OSA, relative to control subjects. We collected resting-state functional magnetic resonance imaging (MRI) data from 67 newly diagnosed, treatment-naïve OSA and 75 control subjects using a 3.0-Tesla MRI scanner. After standard processing, data were analyzed for the left and right insular FC. OSA subjects showed complex aberrant insular FC to several brain regions, including frontal, parietal, cingulate, temporal, limbic, basal ganglia, thalamus, occipital, cerebellar, and brainstem regions. Areas of altered FC in OSA showed linear relationships with magnitudes of sleep related and neuropsychologic-related variables, whereas control subjects showed no such relationships with those measures. Brain functional connections from insular sites to other brain regions in OSA subjects represent abnormal autonomic, affective, sensorimotor, and cognitive control networks that may affect both impaired parasympathetic and sympathetic interactions, as well as abnormal sensorimotor integration, affected in the condition. The functional changes likely result from the previously reported structural changes in OSA subjects, as demonstrated by diverse neuroimaging studies.

Decreased interhemispheric functional connectivity in insula and angular gyrus/supramarginal gyrus: Significant findings in first-episode, drug-naive somatization disorder

Neuroimaging data have demonstrated brain functional alterations in patients with somatization disorder (SD). However, there is little information on interhemispheric resting-state functional connectivity (FC) in SD. In this study, resting-state functional magnetic resonance imaging (fMRI) and voxel-mirrored homotopic connectivity (VMHC) were applied to examine the changes of interhemispheric FC of the whole brain in patients with SD. A total of 25 first-episode, medication-naive SD patients and 28 age-, sex-, education-matched healthy controls (HC) underwent resting-state fMRI, and the data were analyzed by VMHC. Compared with HC, patients had lower VMHC in the angular gyrus/supramarginal gyrus (AG/SG) and insula. The reproducibility of the results was validated using the split-half and leave-one-out validations. No significant correlation was found between the VMHC in AG/SG or insula and clinical variables. Our findings indicate that the interhemispheric FC in the AG/SG and insula is decreased in first-episode, treatment-naive patients with SD, and thus provide new insight for disruption of interhemispheric FC in the pathophysiological mechanism of SD.

Functional Connectivity of Insula, Basal Ganglia, and Prefrontal Executive Control Networks during Hypoglycemia in Type 1 Diabetes.

The major factor limiting improved glucose control in type 1 diabetes is the significant increase in hypoglycemia associated with insulin treatment. Repeated exposure to hypoglycemia alters patients' ability to recognize the autonomic and neuroglycopenic symptoms associated with low plasma glucose levels. We examined brain resting state networks during the induction of hypoglycemia in diabetic and control subjects and found differences in networks involved in sensorimotor function, cognition, and interoceptive awareness that were related to chronic levels of glycemic control. These findings identify brain regions that are sensitive to variations in plasma glucose levels and may also provide a basis for understanding the mechanisms underlying the increased incidence of cognitive impairment and affective disorders seen in patients with diabetes.

Optimizing and Interpreting Insular Functional Connectivity Maps Obtained During Acute Experimental Pain: The Effects of Global Signal and Task Paradigm Regression.

The insula is uniquely located between the temporal and parietal cortices, making it anatomically well-positioned to act as an integrating center between the sensory and affective domains for the processing of painful stimulation. This can be studied through resting-state functional connectivity (fcMRI) imaging; however, the lack of a clear methodology for the analysis of fcMRI complicates the interpretation of these data during acute pain. Detected connectivity changes may reflect actual alterations in low-frequency synchronous neuronal activity related to pain, may be due to changes in global cerebral blood flow or the superimposed task-induced neuronal activity. The primary goal of this study was to investigate the effects of global signal regression (GSR) and task paradigm regression (TPR) on the changes in functional connectivity of the left (contralateral) insula in healthy subjects at rest and during acute painful electric nerve stimulation of the right hand. The use of GSR reduced the size and statistical significance of connectivity clusters and created negative correlation coefficients for some connectivity clusters. TPR with cyclic stimulation gave task versus rest connectivity differences similar to those with a constant task, suggesting that analysis which includes TPR is more accurately reflective of low-frequency neuronal activity. Both GSR and TPR have been inconsistently applied to fcMRI analysis. Based on these results, investigators need to consider the impact GSR and TPR have on connectivity during task performance when attempting to synthesize the literature.