Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

Recent studies have shown that cognitive therapy is an effective treatment for panic disorder. However, little is known about how cognitive therapy compares with other psychological and pharmacological treatments. To investigate this question 64 panic disorder patients were initially assigned to cognitive therapy, applied relaxation, imipramine (mean 233 mg/day), or a 3-month wait followed by allocation to treatment. During treatment patients had up to 12 sessions in the first 3 months and up to three booster sessions in the next 3 months. Imipramine was gradually withdrawn after 6 months. Each treatment included self-exposure homework assignments. Cognitive therapy and applied relaxation sessions lasted one hour. Imipramine sessions lasted 25 minutes. Assessments were before treatment/wait and at 3, 6, and 15 months. Comparisons with waiting-list showed all three treatments were effective. Comparisons between treatments showed that at 3 months cognitive therapy was superior to both applied relaxation and imipramine on most measures. At 6 months cognitive therapy did not differ from imipramine and both were superior to applied relaxation on several measures. Between 6 and 15 months a number of imipramine patients relapsed. At 15 months cognitive therapy was again superior to both applied relaxation and imipramine but on fewer measures than at 3 months. Cognitive measures taken at the end of treatment were significant predictors of outcome at follow-up.

These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.

A series of editorials in this Journal have argued that psychiatry is in the midst of a crisis. The various solutions proposed would all involve a strengthening of psychiatry's identity as essentially 'applied neuroscience'. Although not discounting the importance of the brain sciences and psychopharmacology, we argue that psychiatry needs to move beyond the dominance of the current, technological paradigm. This would be more in keeping with the evidence about how positive outcomes are achieved and could also serve to foster more meaningful collaboration with the growing service user movement.