Subgenual Prefrontal Cortex Activity Predicts Individual Differences in Hypothalamic-Pituitary-Adrenal Activity Across Different Contexts

Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
Biological psychiatry (Impact Factor: 10.26). 10/2009; 67(2):175-81. DOI: 10.1016/j.biopsych.2009.07.039
Source: PubMed


Hypothalamic-pituitary-adrenal (HPA) system activation is adaptive in response to stress, and HPA dysregulation occurs in stress-related psychopathology. It is important to understand the mechanisms that modulate HPA output, yet few studies have addressed the neural circuitry associated with HPA regulation in primates and humans. Using high-resolution F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in rhesus monkeys, we assessed the relation between individual differences in brain activity and HPA function across multiple contexts that varied in stressfulness.
Using a logical AND conjunctions analysis, we assessed cortisol and brain metabolic activity with FDG-PET in 35 adolescent rhesus monkeys exposed to two threat and two home-cage conditions. To test the robustness of our findings, we used similar methods in an archival data set. In this data set, brain metabolic activity and cortisol were assessed in 17 adolescent male rhesus monkeys that were exposed to three stress-related contexts.
Results from the two studies revealed that subgenual prefrontal cortex (PFC) metabolism (Brodmann's area 25/24) consistently predicted individual differences in plasma cortisol concentrations regardless of the context in which brain activity and cortisol were assessed.
These findings suggest that activation in subgenual PFC may be related to HPA output across a variety of contexts (including familiar settings and novel or threatening situations). Individuals prone to elevated subgenual PFC activity across multiple contexts may be individuals who consistently show heightened cortisol and may be at risk for stress-related HPA dysregulation.

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    • "In addition, because the subgenual ACC (sgACC) is specifically linked to escapable threat [Amat et al., 2005; Jahn et al., 2010; Mobbs et al., 2007, 2009], but is not included in the salience network mask, we included a separate mask for this region. We used the mask of Brodmann area 25 from the WFU Pickatlas as it corresponds to this region. "
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    • "The medial prefrontal cortex (mPFC) has been of particular interest because subregions of the mPFC show marked changes in neural activity in depressed patients compared to healthy controls. For instance, the ventral mPFC (vmPFC) of MDD patients exhibits increased cerebral blood flow (Drevets et al., 1992) and metabolism (Mayberg, 1997), while the subgenual anterior cingulate cortex (sgACC) (Drevets et al., 1997; Jahn et al., 2010; Ongür et al., 1998; van Tol et al., 2010), shows increases in glucose metabolism in depression (Drevets et al., 1997, 2008) that normalize with successful antidepressant treatment, including deep-brain stimulation near this area (Mayberg et al., 2000, 2005). "
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