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Insight and psychosis: Functional and anatomical brain connectivity and self-reflection in Schizophrenia.

ABSTRACT: Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self-reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty-five schizophrenia patients and 19 healthy subjects performed a self-reflection task during fMRI, and underwent diffusion tensor imaging. Using dynamic causal modelling we observed increased effective connectivity from the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and dorsal mPFC (dmPFC) towards the vmPFC with poorer insight and decrease from vmPFC to the IPL. Stronger connectivity from the PCC to vmPFC during judgment of traits related to self was associated with poorer insight. We found small-scale significant changes in white matter integrity associated with clinical insight. Self-reflection may be influenced by synaptic changes that lead to the observed alterations in functional connectivity accompanied by the small-scale but measurable alterations in anatomical connections. Our findings may point to a neural compensatory response to an impairment of connectivity between self-processing regions. Similarly, the observed hyper-connectivity might be a primary deficit linked to inefficiency in the component cognitive processes that lead to impaired insight. We suggest that the stronger cognitive demands placed on patients with poor insight is reflected in increased effective connectivity during the task in this study.

SUBMITTER: Curcic-Blake B

PROVIDER: S-EPMC6869637 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Insight and psychosis: Functional and anatomical brain connectivity and self-reflection in Schizophrenia.

Ćurčić-Blake Branislava B van der Meer Lisette L Pijnenborg Gerdina H M GH David Anthony S AS Aleman André A

Human brain mapping 20151015 12

Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self-reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty-five schizophrenia patients and 19 healthy subjects performed a self-reflection task during fMRI, and underwent dif ...[more]

PMID: 26467308

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Project description:BackgroundInsight is impaired in the majority of schizophrenia patients. The exact neural correlates of impaired insight remain unclear. We assume that the ability to regulate emotions contributes to having good clinical insight, as patients should be able to regulate their emotional state in such a way that they can adapt adequately in order to cope with impaired functioning and negative stigma associated with a diagnosis of schizophrenia. Numerous studies have shown emotional dysregulation in schizophrenia. We investigated the association between insight and brain activation and connectivity during emotion regulation.MethodsBrain activation during emotion regulation was measured with functional MRI in 30 individuals with schizophrenia. Two emotion regulation strategies were examined: cognitive reappraisal and expressive suppression. Clinical insight was measured with the Schedule for the Assessment of Insight - Expanded, and cognitive insight was measured with the Beck Cognitive Insight Scale. Whole brain random effects multiple regression analyses were conducted to assess the relation between brain activation during emotion regulation and insight. Generalized psychophysiological interaction (gPPI) was used to investigate the relation between task-related connectivity and insight.ResultsNo significant associations were found between insight and neural correlates of cognitive reappraisal. For clinical insight and suppression, significant positive associations were found between symptom relabeling and activation in the left striatum, thalamus and insula, right insula and caudate, right pre- and postcentral gyrus, left superior occipital gyrus and cuneus and right middle and superior occipital gyrus and cuneus. Furthermore, reduced clinical insight was associated with more connectivity between midline medial frontal gyrus and right middle occipital gyrus. For cognitive insight and suppression, significant positive associations were found between self-reflectiveness and activation in pre- and postcentral gyrus and left middle cingulate gyrus.ConclusionsOur results suggest an association between the capacity to relabel symptoms and activation of brain systems involved in cognitive-emotional control and visual processing of negative stimuli. Furthermore, poorer self-reflectiveness may be associated with brain systems subserving control and execution.

Project description:Schizophrenia is hypothesized to involve disordered connectivity between brain regions. Currently, there are no direct measures of brain connectivity; functional and structural connectivity used separately provide only limited insight. Simultaneous measure of anatomical and functional connectivity and its interactions allow for better understanding of schizophrenia-related alternations in brain connectivity.Twenty-seven schizophrenia patients and 27 healthy control subjects underwent magnetic resonance imaging with resting state functional magnetic resonance imaging and diffusion tensor imaging. Separate functional and anatomical connectivity maps were calculated and combined for each subject. Global, regional, and voxel measures and K-means network analysis were employed to identify group differences and correlation with clinical symptoms.A global connectivity analysis indicated that patients had lower anatomical connectivity and lower coherence between the two imaging modalities. In schizophrenia these group differences correlated with clinical symptom severity. Although anatomical connectivity nearly uniformly decreased, functional connectivity in schizophrenia was lower for some connections (e.g., middle temporal gyrus) and higher for others (e.g., cingulate and thalamus). Within the default mode network (DMN) two separate subsystems can be identified. Schizophrenia patients showed decoupling between structural and functional connectivity that can be localized to networks originating in posterior cingulate cortex as well as in the task-positive network and one of the DMN components.Combining two measures of brain connectivity provides more comprehensive descriptions of altered brain connectivity underlying schizophrenia. Patients show deficits in white matter anatomy, but functional connectivity alterations are more complex. Fusion of both methods allows identification of subsystems showing both increased and decreased functional connectivity.

Project description:BackgroundImpaired insight into illness (clinical insight) in schizophrenia has negative effects on treatment adherence and clinical outcomes. Schizophrenia is described as a disorder of disrupted brain connectivity. In line with this concept, resting state networks (RSNs) appear differentially affected in persons with schizophrenia. Therefore, impaired clinical, or the related construct of cognitive insight (which posits that impaired clinical insight is a function of metacognitive deficits), may reflect alterations in RSN functional connectivity (fc). Based on our previous research, which showed that impaired insight into illness was associated with increased left hemisphere volume relative to right, we hypothesized that impaired clinical insight would be associated with increased connectivity in the DMN with specific left hemisphere brain regions.MethodsResting state MRI scans were acquired for participants with schizophrenia or schizoaffective disorder (n=20). Seed-to-voxel and ROI-to-ROI fc analyses were performed using the CONN-fMRI fc toolbox v13 for established RSNs. Clinical and cognitive insight were measured with the Schedule for the Assessment of Insight-Expanded Version and Beck Cognitive Insight Scale, respectively, and included as the regressors in fc analyses.ResultsAs hypothesized, impaired clinical insight was associated with increased connectivity in the default mode network (DMN) with the left angular gyrus, and also in the self-referential network (SRN) with the left insula. Cognitive insight was associated with increased connectivity in the dorsal attention network (DAN) with the right inferior frontal cortex (IFC) and left anterior cingulate cortex (ACC).ConclusionIncreased connectivity in DMN and SRN with the left angular gyrus and insula, respectively, may represent neural correlates of impaired clinical insight in schizophrenia spectrum disorders, and is consistent with the literature attributing impaired insight to left hemisphere dominance. Increased connectivity in the DAN with the IFC and ACC in relation to cognitive insight may facilitate enhanced mental flexibility in this sample.

Dataset Information

Insight and psychosis: Functional and anatomical brain connectivity and self-reflection in Schizophrenia.

Publications

Insight and psychosis: Functional and anatomical brain connectivity and self-reflection in Schizophrenia.

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