Functional brain imaging in schizophrenia: selected results and methods

Functional brain imaging studies of patients with schizophrenia may be grouped into those that assume that the signs and symptoms of schizophrenia are due to disordered circuitry within a critical brain region and studies that assume that the signs and symptoms are due to disordered connections among brain regions. Studies have investigated the disordered functional brain anatomy of both the positive and negative symptoms of schizophrenia. Studies of spontaneous hallucinations find that although hallucinations are associated with abnormal brain activity in primary and secondary sensory areas, disordered brain activation associated with hallucinations is not limited to sensory systems. Disordered activation in non-sensory regions appear to contribute to the emotional strength and valence of hallucinations, to be a factor underlying an inability to distinguish ongoing mental processing from memories, and to reflect the brain's attempt to modulate the intensity of hallucinations and resolve conflicts with other processing demands. Brain activation studies support the view that auditory/verbal hallucinations are associated with an impaired ability of internal speech plans to modulate neural activation in sensory language areas. In early studies, negative symptoms of schizophrenia were hypothesized to be associated with impaired function in frontal brain areas. In support of this hypothesis meta-analytical studies have found that resting blood flow or metabolism in frontal cortex is reduced in schizophrenia, though the magnitude of the effect is only small to moderate. Brain activation studies of working memory (WM) functioning are typically associated with large effect sizes in the frontal cortex, whereas studies of functions other than WM generally reveal smaller effects. Findings from some functional connectivity studies have supported the hypothesis that schizophrenia patients experience impaired functional connections between frontal and temporal cortex, although the nature of the disordered connectivity is complex. More recent studies have used functional brain imaging to study neural compensation in schizophrenia, to serve as endophenotypes in genetic studies and to provide biomarkers in drug development studies. These emerging trends in functional brain imaging research are likely to help stimulate the development of a general neurobiological theory of the complex symptoms of schizophrenia.