Associations of resting-state perfusion and auditory verbal hallucinations with and without emotional content in schizophrenia.

Auditory Verbal Hallucinations (AVH) are highly prevalent in patients with schizophrenia. AVH with high emotional content lead to particularly poor functional outcome. Increasing evidence shows that AVH are associated with alterations in structure and function in language and memory related brain regions. However, neural correlates of AVH with emotional content remain unclear. In our study (n = 91), we related resting-state cerebral perfusion to AVH and emotional content, comparing four groups: patients with AVH with emotional content (n = 13), without emotional content (n = 14), without hallucinations (n = 20) and healthy controls (n = 44). Patients with AVH and emotional content presented with increased perfusion within the amygdala and the ventromedial and dorsomedial prefrontal cortex (vmPFC/ dmPFC) compared to patients with AVH without emotional content. In addition, patients with any AVH showed hyperperfusion within the anterior cingulate gyrus, the vmPFC/dmPFC, the right hippocampus, and the left pre- and postcentral gyrus compared to patients without AVH. Our results indicate metabolic alterations in brain areas critical for the processing of emotions as key for the pathophysiology of AVH with emotional content. Particularly, hyperperfusion of the amygdala may reflect and even trigger emotional content of AVH, while hyperperfusion of the vmPFC/dmPFC cluster may indicate insufficient top-down amygdala regulation in patients with schizophrenia.

Resting-state perfusion in motor and fronto-limbic areas is linked to diminished expression of emotion and speech in schizophrenia.

Negative symptoms (NS) are a core component of schizophrenia affecting community functioning and quality of life. We tested neural correlates of NS considering NS factors and consensus subdomains. We assessed NS using the Clinical Assessment Interview for Negative Symptoms and the Scale for Assessment of Negative Symptoms. Arterial spin labeling was applied to measure resting-state cerebral blood flow (rCBF) in 47 schizophrenia patients and 44 healthy controls. Multiple regression analyses calculated the relationship between rCBF and NS severity. We found an association between diminished expression (DE) and brain perfusion within the cerebellar anterior lobe and vermis, and the pre-, and supplementary motor area. Blunted affect was linked to fusiform gyrus and alogia to fronto-striatal rCBF. In contrast, motivation and pleasure was not associated with rCBF. These results highlight the key role of motor areas for DE. Considering NS factors and consensus subdomains may help identifying specific pathophysiological pathways of NS.

Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia.

Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.