Functional Connectivity Of Anterior Insula Research Articles

Brain connectivity-guided, Optimised theta burst transcranial magnetic stimulation to improve Central Pain Modulation in knee Osteoarthritis Pain (BoostCPM): protocol of a pilot randomised clinical trial in a secondary care setting in the UK

IntroductionChronic pain is a common health problem that is not efficiently managed by standard analgesic treatments. There is evidence that treatment resistance may result from maladaptive brain changes in areas...

Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional Constipation.

Functional constipation (FCon) is a common functional gastrointestinal disorder. A considerable portion of patients with FCon is associated with anxiety/depressive status (FCAD). Previous neuroimaging studies mainly focused on patients with FCon without distinguishing FCAD from FCon patients without anxiety/depressive status (FCNAD). Differences in brain functions between these two subtypes remain unclear. Thus, we employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory method to investigate differences in brain network connectivity and topology in 41 FCAD, 42 FCNAD, and 43 age- and gender-matched healthy controls (HCs). FCAD/FCNAD showed significantly lower normalized clustering coefficient and small-world-ness. Both groups showed altered nodal degree/efficiency mainly in the rostral anterior cingulate cortex (rACC), precentral gyrus (PreCen), supplementary motor area (SMA), and thalamus. In the FCAD group, nodal degree in the SMA was negatively correlated with difficulty of defecation, and abdominal pain was positively correlated with nodal degree/efficiency in the rACC, which had a lower within-module nodal degree. The salience network (SN) exhibited higher functional connectivity (FC) with the sensorimotor network (SMN) in FCAD/FCNAD, and FC between these two networks was negatively correlated with anxiety ratings in FCAD group. Additionally, FC of anterior insula (aINS)–rACC was only correlated with constipation symptom (i.e., abdominal pain) in the FCNAD group. In the FCAD group, FCs of dorsomedial prefrontal cortex–rACC, PreCen–aINS showed correlations with both constipation symptom (i.e., difficulty of defecation) and depressive status. These findings indicate the differences in FC of the SN–SMN between FCAD and FCNAD and provide neuroimaging evidence based on brain function, which portrays important clues for improving new treatment strategies.

Increased functional connectivity of anterior insula to anterior cingulate cortex in amnestic mild cognitive impairment: A longitudinal resting‐state fMRI study

AbstractBackgroundThe insula has been reported as a crucial role in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). However, the mechanism and functional connectivity (FC) changes of insula in follow‐up remain unclear. Exploring specific insula network interaction can contribute to a better understanding of integration and segregation patterns of aMCI.MethodTwenty aMCI and twenty healthy controls (HC) participants were recruited and underwent resting‐state functional magnetic resonance imaging (rs‐fMRI) and neuropsychological assessment at baseline and 15 months afterward. Rs‐fMRI data were preprocessed using SPM 12 and CONN software. FC of two insular subregions in each hemisphere were defined as anterior insula connectivity (AIC) and posterior insula connectivity (PIC). Using data driven clustering technique, the insular lobe was subdivided based on whole brain functional connectivity. Two‐way analysis of covariance was used with covariates of gender, age, education, follow‐up interval, volume of gray matter and global correlation (GCOR).ResultWithin group FC maps of HC and aMCI exhibited similar patterns both at baseline and follow‐up. For the left anterior insula, significant connectivity with bilateral anterior cingulate gyrus (ACC), paracingulate gyrus, putamen, frontal orbital cortex, inferior frontal gyrus, and temporal pole were identified. The right anterior insula was positively associated with bilateral insula, ACC, central opercular cortex, frontal orbital cortex, and right junction region of temporal, frontal and parietal lobe. The posterior zone of the insula (both the right and the left) exhibited significant connectivity with the bilateral Insular, ACC, central opercular cortex, precentral gyrus, postcentral gyrus, supramarginal gyrus, parietal operculum cortex, as well as the junction region of temporal, frontal and parietal lobe. For interactive main effects, the right AIC showed significantly increased FC with the left ACC, while the left PIC showed decreased FC with the right precuneous, in aMCI as compared to HC.ConclusionInsula rsFC changes could be potential biomarkers of aMCI and reveal some definite neuropathological mechanism due to pathologic processes in AD. We considered the rsFC increase of AIC with ACC as compensatory and decrease of the PIC with the precuneus as deterioration of follow‐up due to the course of disease.

Increased interregional functional connectivity of anterior insula is associated with improved smoking cessation outcome.

Damage to the insular cortex has been shown to disrupt smoking behavior. However, whether smoking cessation outcomes are associated with abnormal functions of insula and its subregions remains unclear. In this study, we investigated the relationship between insular functions (interregional functional connectivity and regional activity) and treatment outcomes of cigarette smoking. Thirty treatment-seeking smokers were recruited into the treatment study and underwent magnetic resonance imaging (MRI) scans immediately before and after the treatment. Sixteen participants remained abstinent from smoking (quitters), while 14 relapsed to smoking (relapers). Changes in resting-state functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) across groups and visits were assessed using repeated measures ANCOVA. Significant interaction effects were detected: 1) between the left anterior insula and left precuneus; and 2) between the right anterior insula and left precuneus and medial frontal gyrus. Post-hoc region-of-interest analyses in brain areas showing interaction effects indicated significantly increased functional connectivity after treatment compared with before treatment in quitters but opposite longitudinal changes in relapsers. However, no significant effects in fALFF were observed. These novel findings suggest that increased interregional functional connectivity of the anterior insula is associated with improved smoking cessation outcome: individuals with increased functional connectivity of the anterior insula during the treatment would more likely quit smoking successfully. These insular circuits may serve as therapeutic targets for more efficacious treatment of nicotine addiction.

Exploring common changes after acute mental stress and acute tryptophan depletion: Resting-state fMRI studies

Stress and low serotonin levels are important biological factors in depression and anxiety etiologies. Although studies indicate that low serotonin levels, stress, and other factors may interact in depression/anxiety psychopathology, few studies have investigated the potentially shared neural substrates. We conducted resting-state fMRI scans pre- and post-stress task, and under control and tryptophan depletion condition, to explore the common changes induced by acute mental stress (AMS) and acute tryptophan depletion (ATD). The present study targeted regions within core brain networks – default mode network, salience network, executive control network, and emotion network – reported altered in AMS and ATD, and used regional homogeneity (ReHo) and functional connectivity (FC) analyses to explore their overlapped effects. We additionally examined the relationships among core neural networks – operationalized as an index of resource allocation bias that quantifies the shift from internal to external modes of processing. We found both manipulations induced increased ReHo of the amygdala and decreased ReHo of the posterior cingulate cortex (PCC). The PCC-amygdala FC was negatively correlated with the change of negative affect, whereas the right dorsolateral prefrontal cortex and right anterior insula FC was positively associated with anxiety level. In addition, we found that a greater shift to an external mode was correlated with higher anxiety level under both conditions. Common changes induced by acute mental stress and acute tryptophan depletion confirmed our hypothesis that AMS and ATD induce changes in common neural pathways, which in turn might mark vulnerability to depression and anxiety.

Functional Connectivity of Anterior Insula Predicts Recovery of Patients With Disorders of Consciousness.

Background: We hypothesize that the anterior insula is important for maintenance of awareness. Here, we explored the functional connectivity alterations of the anterior insula with changes in the consciousness level or over time in patients with disorders of consciousness (DOC) and determined potential correlation with clinical outcomes.Methods: We examined 20 participants (9 patients with DOC and 11 healthy controls). Each patient underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a standardized Coma Recovery Scale-Revised (CRS-R) assessment on the same day. We categorized the patients according to the prognosis: those who emerged from a minimally conscious state (recovery group, n = 4) and those who remained in the unconscious state (unrecovery group, n = 5). Two rs-fMRI scans were obtained from all patients, and the second scan of patients in the recovery group was obtained after they regained consciousness. We performed seed-based fMRI analysis and selected the left ventral agranular insula (vAI) and dorsal agranular insula (dAI) as the regions of interest. Correlations with CRS-R were determined with the Spearman's correlation coefficient.Results: Compared with healthy controls, the functional connectivity between dAI and gyrus rectus of patients who recovered was significantly increased (p < 0.001, cluster-wise family-wise error rate [FWER] < 0.05). The second rs-fMRI scan of patients who remained with DOC showed a significant decreased functional connectivity between the dAI to contralateral insula, pallidum, bilateral inferior parietal lobule (IPL), precentral gyrus, and middle cingulate cortex (p < 0.001, cluster-wise FWER < 0.05) as well as the functional connectivity between vAI to caudate and cingulum contrast to controls (p < 0.001, cluster-wise FWER < 0.05). Finally, the functional connectivity strength of dAI-temporal pole (Spearman r = 0.491, p < 0.05) and dAI-IPL (Spearman r = 0.579, p < 0.05) were positively correlated with CRS-R scores in all DOC patients. The connectivity of dAI-IPL was also positively correlated with clinical scores in the recovery group (Spearman r = 0.807, p < 0.05).Conclusions: Our findings indicate that the recovery of consciousness is associated with an increased connectivity of the dAI to IPL and temporal pole. This possibly highlights the role of the insula in human consciousness. Moreover, longitudinal variations in dAI-IPL and dAI-temporal pole connectivity may be potential hallmarks in the outcome prediction of DOC patients.

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.

Individual differences in socioemotional sensitivity are an index of salience network function

Connectivity in intrinsically connected networks (ICNs) may predict individual differences in cognition and behavior. The drastic alterations in socioemotional awareness of patients with behavioral variant frontotemporal dementia (bvFTD) are presumed to arise from changes in one such ICN, the salience network (SN). We examined how individual differences in SN connectivity are reflected in overt social behavior in healthy individuals and patients, both to provide neuroscientific insight into this key brain–behavior relationship, and to provide a practical tool to diagnose patients with early bvFTD. We measured SN functional connectivity and socioemotional sensitivity in 65 healthy older adults and 103 patients in the earliest stage [Clinical Dementia Rating (CDR) Scale score ≤1] of five neurodegenerative diseases [14 bvFTD, 29 Alzheimer's disease (AD), 20 progressive supranuclear palsy (PSP), 21 semantic variant primary progressive aphasia (svPPA), and 19 non-fluent variant primary progressive aphasia (nfvPPA)]. All participants underwent resting-state functional imaging and an informant described their responsiveness to subtle emotional expressions using the Revised Self-Monitoring Scale (RSMS). Higher functional connectivity in the SN, predominantly between the right anterior insula (AI) and both “hub” cortical and “interoceptive” subcortical nodes, predicted socioemotional sensitivity among healthy individuals, showing that socioemotional sensitivity is a behavioral marker of SN function, and particularly of right AI functional connectivity. The continuity of this relationship in both healthy and neurologically affected individuals highlights the role of socioemotional sensitivity as an early diagnostic marker of SN connectivity. Clinically, this is particularly important for identification of patients in the earliest stage of bvFTD, where the SN is selectively vulnerable.

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.

Visual deprivation selectively reshapes the intrinsic functional architecture of the anterior insula subregions

The anterior insula (AI) is the core hub of salience network that serves to identify the most relevant stimuli among vast sensory inputs and forward them to higher cognitive regions to guide behaviour. As blind subjects were usually reported with changed perceptive abilities for salient non-visual stimuli, we hypothesized that the resting-state functional network of the AI is selectively reorganized after visual deprivation. The resting-state functional connectivity (FC) of the bilateral dorsal and ventral AI was calculated for twenty congenitally blind (CB), 27 early blind (EB), 44 late blind (LB) individuals and 50 sighted controls (SCs). The FCs of the dorsal AI were strengthened with the dorsal visual stream, while weakened with the ventral visual stream in the blind than the SCs; in contrast, the FCs of the ventral AI of the blind was strengthened with the ventral visual stream. Furthermore, these strengthened FCs of both the dorsal and ventral AI were partially negatively associated with the onset age of blindness. Our result indicates two parallel pathways that selectively transfer non-visual salient information between the deprived “visual” cortex and salience network in blind subjects.

Altered resting state functional connectivity of anterior insula in young smokers.

The insula has been implicated in cognitive control and craving, all of which are critical to the clinical manifestations of nicotine dependence. However, little evidence exists about the abnormalities in resting state functional connectivity (RSFC) of the insula in young smokers, which might improve our understanding of the neural mechanisms of nicotine dependence. Due to the structural and functional heterogeneity of the insula, the RSFC patterns of both left and right anterior (AI) and posterior insula (PI) were investigated in young smokers and non-smokers. Meanwhile, the relationship was assessed between the neuroimaging findings and clinical information (pack-years, FTND, and craving) as well as cognitive control deficits measured by Stroop task performance. Compared with non-smokers, young smokers showed reduced RSFC between right AI and anterior cingulate cortex (ACC), ventromedial prefrontal cortex (VMPFC), amygdala, left dorsolateral prefrontal cortex, and dorsal striatum. Additionally, left AI showed reduced RSFC with ACC. Both left and right PI network differences were not observed between two groups. Moreover, in young smokers, FTND and incongruent errors in the Stroop task were negatively correlated with the RSFC between AI and ACC. Craving scores showed a significantly negative relationship with the RSFC strength between right AI and left VMPFC. These results provide a more thorough network-level understanding the role of insula in cigarette smoking. The findings provide new insights into the roles of AI-ACC circuit in cognitive control deficits and right AI-VMPFC circuit relevant to the craving of nicotine dependence for young smokers.