Abstract
Acute stress has an important impact on higher-order cognitive functions supported by the prefrontal cortex (PFC) such as working memory (WM). In rodents, such effects are mediated by stress-induced alterations in catecholaminergic signaling, but human data in support of this notion is lacking. A common variation in the gene encoding Catechol-O-methyltransferase (COMT) is known to affect basal catecholaminergic availability and PFC functions. Here, we investigated whether this genetic variation (Val158Met) modulates effects of stress on WM-related neural activity in humans. In a counterbalanced crossover design, 41 healthy young men underwent functional magnetic resonance imaging (fMRI) while performing a numerical N-back WM task embedded in a stressful or neutral context. Moderate psychological stress was induced by a well-controlled procedure involving viewing strongly aversive (versus emotionally neutral) movie material in combination with a self-referencing instruction. Acute stress resulted in genotype-dependent effects on WM performance and WM-related activation in the dorsolateral PFC, with a relatively negative impact of stress in COMT Met-homozygotes as opposed to a relatively positive effect in Val-carriers. A parallel interaction was found for WM-related deactivation in the anterior medial temporal lobe (MTL). Our findings suggest that individuals with higher baseline catecholaminergic availability (COMT Met-homozygotes) appear to reach a supraoptimal state under moderate levels of stress. In contrast, individuals with lower baselines (Val-carriers) may reach an optimal state. Thus, our data show that effects of acute stress on higher-order cognitive functions vary depending on catecholaminergic availability at baseline, and thereby corroborate animal models of catecholaminergic signaling that propose a non-linear relationship between catecholaminergic activity and prefrontal functions.
Highlights
Acute stress has an important impact on higher-order cognitive function such as working memory (WM)
We found a main effect of stress [F(1, 74) = 46.62, p < 0.001], and further t-tests confirmed that heart rate (HR) was consistently higher during all three phases of the experiment in the stress condition [all t(38) > 2.29, p < 0.03]
More important for the question at issue, we found a suprathreshold cluster in the right dorsolateral prefrontal cortex (PFC) for the interactive effect of stress and genotype (COMT Met-homozygotes vs. Val-Carriers) on this contrast
Summary
Acute stress has an important impact on higher-order cognitive function such as working memory (WM). The COMT-Val transgenic mice (Val-like genotype) are associated with inferior WM performance at baseline, but are less sensitive to stress (Papaleo et al, 2008) Based on these findings and the aforementioned inverted U-shaped relationship between catecholaminergic signaling and neurocognitive functioning, one may hypothesize that effects of experimentally induced moderate stress on WM-related prefrontal activity in humans would exhibit a similar genotype-dependency, with stronger detrimental effects of stress in COMT Met-homozygotes. To test this hypothesis, 41 healthy young men underwent functional magnetic resonance imaging (fMRI) while performing a numerical N-back WM task (including 2- and 0-back conditions). Because WM-related activation of the dorsolateral PFC is normally accompanied by deactivation in the medial temporal lobe (MTL), and adaptive changes in reciprocal organization of dorsal executive and ventral affective brain areas under arousal and stressful circumstance (Dolcos and McCarthy, 2006; Oei et al, 2011; Cousijn et al, 2012), we conjectured a corresponding genotype-dependent effect in the MTL
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