Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness

Objective: Theories of human behavior from Plate to Freud have repeatedly e mphasized links between emotion and reason, a relationship now commonly att ributed to pathways connecting phylogenetically "old" and "new" brain regio ns. Expanding on this theory, this study examined functional interactions b etween specific limbic and neocortical regions accompanying normal and dise ase-associated shifts in negative mood state. Method: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patie nts were examined with two positron emission tomography techniques: [O-15]w ater and [F-18]fluorodeoxyglucose, respectively. Results: With sadness, inc reases in limbic-paralimbic blood flow (subgenual cingulate, anterior insul a) and decreases in neocortical regions (right dorsolateral prefrontal, inf erior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen-limbic metabolic decreases a nd neocortical increases. A significant inverse correlation between subgenu al cingulate and right dorsolateral prefrontal activity was also demonstrat ed in both conditions. Conclusions: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional recip rocity between these regions with shifts in mood in either direction sugges ts that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both norm al and pathological conditions. The bidirectional nature of this limbic-cor tical reciprocity provides additional evidence of potential mechanisms medi ating cognitive ("top-down"), pharmacological (mixed), and surgical ("botto m-up") treatments of mood disorders such as depression.