CLINICAL HANDBOOK OF SCHIZOPHRENIA

40 I. CORE SCIENCE AND BACKGROUND INFORMATIONphenomena to localize areas of neuronal activity. Specifically, when oxygen is deliveredby the blood to working neurons, it is not immediately consumed. Thus, there is excessvascular oxygen in the area near the active neurons. Because hemoglobin that is bound tooxygen causes less magnetic disruption than deoxyhemoglobin, the local signal is strongerin the areas of high activity. This is the basis of the blood oxygen level–dependent(BOLD) signal most commonly measured in fMRI. fMRI has several advantages overPET and SPECT imaging, including better temporal and spatial resolution, greater repeatability,and ability to collect functional and structural images in the same apparatus.One disadvantage relative to PET is that BOLD fMRI cannot quantify blood flow in absoluteunits; rather, it relies on a contrasting signal between two conditions. Thus, BOLDfMRI studies typically compare brain response between a baseline condition and an experimentalcondition. Although there are fMRI techniques that permit absolute quantificationof blood flow using arterial spin labeling, these methods have not yet been appliedto the study of schizophrenia.fMRI studies in schizophrenia to date have generally focused on frontal and temporallobe function, and on brain response to executive, language, and working and episodicmemory tasks. Two main issues make summarizing the results of such studies complicated.First, even within particular information-processing domains, the specificcognitive challenge tasks vary greatly in terms of stimuli, instructions, and difficulty level.Second, fMRI studies, as well as most recent PET and SPECT studies, generally analyzeevery volume element (voxel) in the brain and report the location and size of voxel clustersthat reach a significant threshold in terms of volume and magnitude. Thus, if twostudies both report clusters within the left prefrontal cortex, but in slightly different locations,it is difficult to know whether the studies are replicating the same finding or haveidentified two separate areas of abnormality. In the area of working memory, however, inwhich only a small number of similar tasks have been used, some summary statementscan be made. Although many studies have found less response of the dorsolateralprefrontal cortex during working memory tasks in patients with schizophrenia comparedto controls, others have either failed to find a difference or have found hyperactivity.There is some evidence that this may be partly due to discrepancies between studies in thedifficulty (i.e., working memory load) of the task. If there is an inverted-U curve that relatesprefrontal activation to working memory load and prefrontal deficits in schizophreniaresult in a shift of this curve to the left relative to controls, then patient–control comparisonswill yield different, even opposite, results depending on the load used. Althoughmost working memory tasks have focused on findings in the prefrontal cortex, other regionsare sometimes found to be involved and overactivated, such as the anterior cingulatecortex. The general finding that there are areas of both hypo- and hyperactivationrelative to controls within a certain information-processing domain is frequently observedin fMRI studies in schizophrenia. This suggests that there may be abnormal functionalconnections between regions, but very few studies to date have used multivariatetechniques to examine this hypothesis directly using fMRI data.Electroencephalography and MagnetoencephalographyA major limitation of fMRI as a functional imaging technique is that it only measures thefunctioning of neurons indirectly, through the effects of activity on blood flow and/orsubsequent blood oxygenation changes. This means that the temporal resolution of fMRIis necessarily limited by the sluggishness of the hemodynamic response to neural events.Because methods such as EEG and magnetoencephalography (MEG), which measure theelectrical or magnetic signal resulting from coordinated firing of collections of neurons,do not have this problem, they are able to resolve much more precise timing of neural