RESEARCH ASPECTS PSYCHIATRY 7:10 430 © 2008 Published by Elsevier Ltd. Functional neuro-imaging in schizophrenia Chiara Nosarti Sukhi S Shergill Abstract Although extensively investigated, the specific neurophysiological basis of schizophrenia remains unclear. The study of neuronal activity using functional neuro-imaging techniques provides the opportunity to improve understanding of the neuropathological processes associated with schizo- phrenia and to ascertain differences in the degree, profile and specificity of possible impairments in this group. Functional neuro-imaging studies have demonstrated abnormalities in several brain areas in schizophrenia during cognitive operations and the experience of behavioural phenomena associated with the disorder, including cortical and subcortical structures such as the prefrontal cortex, hippocampus, temporal lobe, cingulate gyrus, thalamus and cerebellum. Study of the functional brain correlates of the core symptoms of psychosis may aid the understanding of both their cogni- tive and their biological basis, and is essential in informing the design and implementation of psychological and biological remediation strategies. Keywords delusion; executive function; fMRI; hallucination; PET; schizophrenia; self-monitoring Despite being a disabling condition with an estimated preva- lence of 1%, the specific neurophysiological basis of schizophre- nia remains unclear. Alterations in several key structural brain regions have been documented 1 that may cause functional brain changes in distributed systems, underlying the complex symp- tomatology and cognitive profile of individuals with the disorder. The typical characteristics of schizophrenia, such as altered per- ceptions, hearing voices (hallucinations), assigning bizarre sig- nificance or meaning to ordinary events, and having fixed false beliefs (delusions), as well as cognitive deficits, have implicated a dysfunction of fronto-subcortical circuits and abnormalities in Chiara Nosarti MSc PhD is a Lecturer in Mental Health Studies and Neuroimaging and is based in the Cognition Schizophrenia and Imaging Laboratory (CSI Lab), Division of Psychological Medicine at the Institute of Psychiatry. Her research focuses on the study of processes of brain plasticity following perinatal injury and the mechanisms responsible for the development and symptoms of psychotic illness, using a variety of neuroimaging techniques. Sukhi S Shergill BSc MBBS FRCPsych PhD is is a Reader in Psychiatry, Head of the Cognition, Schizophrenia and Imaging Lab at the Institute of Psychiatry, and Honorary Consultant Psychiatrist to the National Psychosis Unit at the Maudsley Hospital London. His research interests are the physiological and psychological mechanisms underlying psychotic illness. dopamine neurotransmission. Recent developments in functional neuro-imaging techniques, based on measures of blood oxygen- ation and flow, have enabled the in vivo monitoring of brain activation changes in key brain structures and assessment of the neuro-anatomical substrates of healthy, as well as pathological, cognitive and behavioural processes, providing a window into the brain organization of individuals with schizophrenia. This article provides a brief overview of the basic principles of the most widely used functional neuro-imaging techniques, and then highlights how these techniques have been used to examine symptoms and relevant cognitive mechanisms in schizophrenia. Basic principles of functional neuro-imaging The most commonly used functional neuro-imaging techniques in schizophrenia are functional magnetic resonance imaging (fMRI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET). fMRI is a relatively new method that can be used to map changes in brain haemo- dynamics that correspond to mental operations. During a typical experiment, several images of the brain are repeatedly acquired while participants are presented with specific stimuli or are required to complete a psychological task. fMRI provides mea- sures of the neural activity detected by a blood oxygen level- dependent (BOLD) signal, which is a measure of the increase in blood flow to the local blood vessels that normally accompanies neural activity in the brain. This increase in blood flow produces a localized change in the ratio of oxygenated to deoxygenated blood, which can be detected using fMRI and demonstrated as a colour change in voxels that contain vessels of interest (Figure 1). Thus, changes in oxygenation in the blood are detected as the signal changes. PET and SPECT can be used to study the function of neu- rotransmitters implicated in schizophrenia, such as dopamine and glutamate, and involve the use of radioactive nuclides. A radiopharmaceutical substance introduced into the bloodstream is used as a tracer and its absorption in selective brain region(s) is studied. SPECT is used to measure regional cerebral blood flow and employs a radiopharmaceutical substance that ema- nates gamma rays, as opposed to positron emitters employed in PET. SPECT radioisotopes often have long half-lives, which helps to keep their cost low. However, SPECT is regarded as being inferior to the other neuro-imaging modalities in terms of both spatial and temporal resolution, sensitivity, and quantification capability. PET measures regional cerebral perfusion, oxygen extraction fraction, oxygen consumption and blood volume. In PET, mol- ecules of biological interest are labelled with a positron emitter before being introduced into the bloodstream. Subsequently, the positron travels a short distance before colliding with an elec- tron. The annihilation of the two particles creates photon pairs with energy of 511 keV. A tomographic reconstruction algorithm applied to the acquired data provides a three-dimensional distribu- tion of the absolute concentration of positron emitter in the brain. Behavioural symptomatology In recent years, functional neuro-imaging techniques have allowed the investigation of the neural substrates of the most