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

ABSTRACT: OBJECTIVES: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Ellard KK

PROVIDER: S-EPMC6504612 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Ellard Kristen K KK Gosai Aishwarya K AK Felicione Julia M JM Peters Amy T AT Shea Conor V CV Sylvia Louisa G LG Nierenberg Andrew A AA Widge Alik S AS Dougherty Darin D DD Deckersbach Thilo T

Bipolar disorders 20181122 3

<h4>Objectives</h4>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.<h4>Methods</h4>Functional MRI data were ...[more]

PMID: 30565822

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Project description: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.

Project description:Although it was acknowledged that patients with obsessive-compulsive disorder (OCD) would exhibit cognitive inflexibility, the underlying neural mechanism has not been fully clarified. Therefore, this study aimed to investigate the neural substrates involved in cognitive inflexibility among individuals with OCD. A total of 42 patients with OCD and 48 healthy controls (HCs) completed clinical assessment and functional magnetic resonance imaging (fMRI) data collection during cued task switching. Behavioral performances and fMRI activation were compared between the OCD group and the HC group. Psychophysiological interactions (PPIs) analyses were applied to explore functional connectivity related to task switching. Pearson correlation was used to investigate the relationships among behavioral performance, fMRI activity, and obsessive-compulsive symptoms in OCD. The OCD group had a greater switch cost than HCs (χ2 = 5.89, p < .05). A significant difference in reaction time was found during switch (χ2 = 17.72, p < .001) and repeat (χ2 = 16.60, p = .018) between the two groups, while there was no significant difference in group accuracy. Comparison of group differences showed that the OCD group had increased activation in the right superior parietal cortex (rSPL) during task switching, and exhibited increased connectivity of frontoparietal network/default mode network (FPN-DMN; i.e., middle frontal gyrus [MFG]/inferior parietal cortex-precuneus, MFG-middle/posterior cingulate gyrus) and within the FPN (inferior parietal cortex-postcentral gyrus). In the OCD group, the compulsion score was positively correlated with accuracy during switch (r = .405, p = .008, FDRq <.05), and negatively correlated with activation of rSPL (r = -.328, p = .034, FDRq >.05). Patients with OCD had impaired cognitive flexibility and cautious response strategy. The neural mechanism of cognitive inflexibility in OCD may involve increased activation in the rSPL, as well as hyperconnectivity within the FPN and between the FPN and DMN.

Project description:ObjectiveDaytime cognitive impairment is an essential symptom of primary insomnia (PI). However, the underlying neural substrate remains largely unknown. Many studies have shown that the right anterior insula (rAI) as a key node of salience network (SN) plays a critical role in switching between the executive control network (ECN) and the default mode network (DMN) for better performance of cognitively demanding tasks. Aberrant effective connectivity (directional functional connectivity) of rAI with ECN or DMN may be one reason for daytime cognitive impairment in PI patients. Up to now, no effective connectivity study has been conducted on patients with PI during resting state. Our aim is to investigate the effective connectivity between the rAI and the other voxels in the whole brain in PI.Materials and methodsFifty drug-naive patients with PI and forty age- and sex-matched healthy controls were scanned using resting-state functional MRI. Seed-based Granger causality analysis was used to examine effective connectivity between the rAI, including ventral and dorsal part, and the whole brain. The effective connectivity was compared between the two groups and was correlated with clinical characteristics.ResultsCompared with controls, patients showed decreased effective connectivity from the rAI to the bilateral precuneus, the left postcentral gyrus (extending to bilateral precuneus) and the bilateral cerebellum posterior lobe, and decreased effective connectivity from the bilateral orbitofrontal cortex (OFC) to the rAI (single voxel P < 0.001, AlphaSim corrected with P < 0.01). In addition, effective connectivity from the ventral rAI to the left postcentral gyrus and from the left OFC to the ventral rAI were significantly negatively correlated with Insomnia Severity Index scores (r = -0.28/P = 0.046 and r = -0.29/P = 0.038, respectively).ConclusionThe present study is the first to reveal aberrant effective connectivity between the SN hub (rAI) and the posterior DMN hub (precuneus) as well as decision-making region (OFC) and sensori-motor region in PI. These findings suggest an aberrant salience processing system of the rAI in PI patients.

Dataset Information

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

Publications

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

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