Impaired insight into illness and cognitive insight in schizophrenia spectrum disorders: Resting state functional connectivity

Abstract

Background Impaired 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. Methods Resting 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. Results As 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). Conclusion Increased 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.

Insight in schizophrenia spectrum disorders: relationship with behavior, mood and perceived quality of life, underlying causes and emerging treatments

“…Vohs et al 11 reported robust correlations between metacognitive capacity and multiple domains of clinical insight, as well as the self-certainty domain of cognitive insight, in first-episode psychosis. These findings are consistent with imaging studies which suggest that insight is related to cortical regions and circuits that may support processes necessary for metacognition, including self-consciousness and self-referential processing 102 .…”

“…Consistent with this, studies employing both structural 99 and functional [100][101][102][103][104][105] neuroimaging have implicated a number of areas and networks in the development and maintenance of insight.…”

“…Functional resting state studies also suggest that insight may be related to the default mode network, particularly in the left hemisphere 102 .…”

A Review of the Functional and Anatomical Default Mode Network in Schizophrenia

“…Moreover, chronic schizophrenia is associated with more high-frequency fluctuation and less low-frequency fluctuation in the DMN than healthy volunteers when performing the auditory oddball task [36], which is consistent with the subsequent findings of fluctuation in the DMN they reported in different CSP samples and controls [37]. Work by Gerretsen et al [51] and Table 1 Summary of empirical studies on DMN activity and connectivity in schizophrenia. MSI, multi-source interference; SPT, semantic priming task; FEE, facial emotional expressions; SRT, self-reflection task; SAT, selective attention task; HFF, high-frequency fluctuations; LFF, low-frequency fluctuations; PS, positive symptom; NS, negative symptom; CF: cognitive function; DMN, default mode network; PCC, posterior cingulate cortex; PCUN, precuneus; IFG, inferior frontal gyri; LPL, lateral parietal lobe; IPL, inferior parietal lobe; MPFC, medial prefrontal cortex; PFC, prefrontal cortex; vmPFC, ventromedial prefrontal cortex; DPFC, dorsolateral prefrontal cortex; ACC, anterior cingulate cortex; PHG, parahippocampal gyri; (-) not tested; (:) for resting fMRI, increased activation; for task fMRI, increased deactivation; (;) for resting fMRI, decreased activation; for task fMRI, reduced deactivation; (NS) not significant; (*) relationship between DMN activity/deactivation (or connectivity) and particular behavioral measures; (**) group differences of schizophrenia patients versus controls; (***) patient group includes patients in the early phase of schizophrenia, schizoaffective and schizophreniform disorder; (****)…”

An integrative model of the impairments in insight in schizophrenia: emerging research on causal factors and treatments

“…A similar pattern has been observed in individuals early in the course of schizophrenia, as their ability to recognize and respond to psychological and social challenges was shown to be predictive of clinical insight [30]. These findings are consistent with imaging studies that suggest insight is related to structure and function in brain areas or circuits thought to support processes necessary for metacognition, including self-consciousness, self-other distinction, and self-referential procession [95][96][97][98][99].…”