Box 1 | Prefrontal cortical versus amygdala circuits: the switch from non-stress to stress conditions

From the following article:

Stress signalling pathways that impair prefrontal cortex structure and function

Amy F. T. Arnsten

Nature Reviews Neuroscience 10, 410-422 (June 2009)


The prefrontal cortex (PFC) has extensive connections with other cortical and subcortical regions that are organized in a topographical manner, such that regions that regulate emotion are situated ventrally and medially (green area in part a of the figure) and regions that regulate thought and action are situated more dorsally and laterally (blue and blue–green areas in part a). The dorsolateral PFC (DLPFC) has extensive connections with sensory and motor cortices and is key for regulating attention, thought and action163. In humans, the right inferior PFC (rIPFC) seems to be specialized for inhibiting inappropriate motor responses4. By contrast, the ventromedial PFC (VMPFC) has extensive connections with subcortical structures (such as the amygdala, the nucleus accumbens and the hypothalamus) that generate emotional responses and habits164, 165, 166 and is thus able to regulate emotional responses. Finally, the dorsomedial PFC (DMPFC) has been associated with error monitoring9 and, in human functional MRI studies, reality testing167. These PFC regions extensively interconnect to regulate higher-order decision making and to plan and organize for the future. Under non-stress conditions (see part a of the figure), the extensive connections of the PFC orchestrate the brain's activityfor intelligent regulation of behaviour, thought and emotion. The PFCalso has direct and indirect connections to monoamine cell bodies in the brainstem, such as the locus coeruleus (LC) (where noradrenaline projections arise) and the substantia nigra (SN) and ventral tegmental area (VTA) (where the major dopamine projections originate), and thus can regulate its own catecholamine inputs. Optimal levels of catecholamine release in turn enhance PFC regulation, thus creating a 'delicious cycle'. Under conditions of psychological stress (see part b of the figure) the amygdala activates stress pathways in the hypothalamus and brainstem, which evokes high levels of noradrenaline (NA) and dopamine (DA) release. This impairs PFC regulation but strengthens amygdala function, thus setting up a 'vicious cycle'. For example, high levels of catecholamines, such as occur during stress, strengthen fear conditioning mediated by the amygdala168. By contrast, stress impairs higher-order PFC abilities such as working memory and attention regulation. Thus, attention regulation switches from thoughtful 'top-down' control by the PFC that is based on what is most relevant to the task at hand to 'bottom-up' control by the sensory cortices, whereby the salience of the stimulus (for example, whether it is brightly coloured, loud or moving) captures our attention5. The amygdala also biases us towards habitual motor responding rather than flexible, spatial navigation14. Thus, during stress, orchestration of the brain's response patterns switches from slow, thoughtful PFC regulation to the reflexive and rapid emotional responses of the amygdala and related subcortical structures.

Stress signalling pathways that impair prefrontal cortex structure and function