Regional Brain Atrophy and Functional Disconnection in Broca's Area in Individuals at Ultra-High Risk for Psychosis and Schizophrenia

Abstract

Background: Abnormalities in cognitive abilities such as verbal fluency and in cognitive-related brain regions, particularly Broca's area, have been reported in patients with schizophrenia. Additionally, previous studies have demonstrated that structural and functional abnormalities in Broca's area were associated with clinical symptoms and cognitive deficits in patients with schizophrenia, suggesting that deficits in this area may reflect the core pathology of schizophrenia. Thus, it is important to understand how the structural volume and functional connectivity in this area changes at rest according to the course of the illness. Methods/Principal Findings: We used magnetic resonance imaging (MRI) to measure the structural volume of Broca's area as a region of interest in 16 schizophrenia, 16 ultra-high risk (UHR), and 23 healthy matched controls. We also assessed verbal fluency and analyzed differences across groups in the functional connectivity patterns using resting-state functional MRI. The UHR group showed significantly reduced structural volume in Broca's area and significantly reduced functional connectivity between Broca's area and the lateral and medial frontal cortex as well as decreased cognitive performance. Altered functional connectivity in patients was correlated with their positive symptoms. Conclusions/Significance: Our results suggest the existence of functional disconnections in Broca's area, even during resting-states, among those with schizophrenia as well as those at UHR for this disorder. These alterations may contribute to their clinical symptoms, suggesting that this is one of the key regions involved in the pathophysiology of schizophrenia.