One example of such self-analytical self-focus is rumination. Unlike analytical self-focus, subjects in an experiential self-focus mode pay attention to their feeling and emotional experience, regardless of the causes or consequences of that experience. Depression and cognitive homestasis Mayberg and Fossati2 further postulate that depression is not simply the result of selective Inhibitors,research,lifescience,medical regional or pathway dysfunction, but also involves failure of the remaining systems to maintain homeostatic emotional control in times of increased cognitive demands. From this point of view, normal individuals

have limited cognitive resources (or limited capacity to process information) and mental operations may differ in the amount of attention or cognitive resources they require. Depression interferes with effortful cognitive processes – processes accomplished in sequence and restricted by the short-term memory capacity – leaving intact automatic processes in several domains such as learning,

memory, problem-solving, reading, and speed processing (for review see ref 17). The effortful-deficit Inhibitors,research,lifescience,medical hypothesis in depression predicts impairment in the actions requiring attentional and executive resources such as complex goal-directed behaviors. We suggest that deficits of depressed patients on effortful tasks are preceded by increasing efforts to maintain a high level of performance. The progressive exhaustion Inhibitors,research,lifescience,medical of cognitive resources preceding the deficits of depressed patients Inhibitors,research,lifescience,medical and the reduction of cognitive resources is a final by-product of the failure of depressed patients to constantly adapt to cognitive and emotional demands. Recent fMRI data support this hypothesis. In a recent fMRI study,18 we compared 10 depressed subjects and 10 normal controls on a verbal n-back task. The n-back task is a working memory task that requires both maintenance of the n-stimuli and updating of these stimuli each time a new stimulus occurs. The working memory load was manipulated Inhibitors,research,lifescience,medical across the experiment (1,2,AZD8055 order 3-back) to increase the cognitive demands. We selected, a priori, depressed patients with normal performance on

the n-back task, and no difference between groups was found for both Isotretinoin performance and reaction times for each levels of complexity of the n-back task. Both groups, depressed patients and controls, showed bilateral activation of DLPFC (BA 9/46), premotor and SMA (BA 6/8), Broca’s area, dorsal anterior cingulate cortex (ACC), and parietal cortex during n-back tasks. Activation of these regions was modulated by the complexity of the task. Within this n-back neural network, depressed patients showed greater activation of the DLPFC and dorsal ACC than normal controls. Since this seminal work, three fMRI studies have used an n-back task or a working memory task in depressed patients. Two of these three studies replicated our original findings, and showed a hyperactivation in the left DLPFC in depressed patients as compared with normal controls (see refs 19-21).