Functional imaging

Functional neuroimaging assesses neural function in different brain regions by measuring metabolism (such as glucose utilisation) or blood flow, both of which are thought to be closely coupled to neural activation. Most studies of resting activity have described hypo-frontality, particularly in the dorsolateral prefrontal and anterior cingulate cortices, and several groups have also described decreased activity in the basal ganglia (see Fu et al., 2003, for review). However, criticisms of these studies include the difficulty in standardising what the brain is actually doing in the resting state (Sheline & Minyun, 2002).

This has led to the use of functional neuroimaging while subjects undertake neuropsy-chological tasks; as well as standardising what the brain is doing, this allows particular areas of the brain, or particular psychological functions, relevant to depression to be probed. In depression, this approach has uncovered impaired activation in, among other areas, the left anterior cingulate, right prefrontal cortex, and left caudate (Fu et al., 2003). Induction of low mood in normals can induce similar changes to depressed subjects. More recently, Elliott and colleagues used a cognitive task with emotional valence (happy, neutral, or sad). They found that depressed subjects demonstrated an attenuated response to neutral or happy objects, but an enhanced one to sad objects, again focused in anterior cingulate and pre-frontal cortical regions (Elliott et al., 2002). Thus, there may be a definable neural substrate underlying the perceptual cognitive bias in depression.

It should also be noted that many of these changes are not specific to depression, and indeed can be seen in other psychiatric states. It has been suggested that changes in brain regions are more likely to be related to specific psychological dysfunctions rather than diagnoses. Thus, specific patterns of changes have been ascribed to the presence of, for example, psychomotor retardation or depressive pseudo-dementia (Fu et al., 2003).

A number of studies have investigated the response to treatment in depression. Many show that pretreatment abnormalities reverse with treatment. The most consistent finding has been in the subgenual prefrontal cortex: activity is increased activation during an acute depressive state, and this decreases following effective antidepressant treatment (Fu et al., 2003; Mayberg et al., 2000).

Finally, rather than simply looking at one part of the brain in isolation, it may be most important to look at the various networks of the brain and how they are interlinked. These functional connections may be disrupted in the depressed state. Thus, one study revealed a complex picture of cortical and subcortical changes associated with treatment response to fluoxetine, with increases in the dorsal prefrontal cortex but decreases in the hippocampus (Mayberg et al., 2000). The study of changes in brain connectivity by path analysis and other statistical methods may yield more understanding of the clearly complex pathways in brain neurocircuitry.

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