Thesis defense Hein van Marle (Donders Series 70)

The amygdala on alert: A neuroimaging investigation into amygdala function during acute stress and its aftermath

Acutely stressful events like a robbery at gun point or a car crash can hugely impact a person’s life. Yet, to date we know very little about what happens in the brain when we experience such events. In my thesis I combine neuroimaging (fMRI), experimental stress induction, pharmacological manipulation, and various neurocognitive tasks probing emotional processing and memory, in an initial attempt to translate some important stress principles coming from animal research to the systems level in humans.

In doing so, I specifically focus on the amygdala, a small subcortical structure that is primarily involved in threat detection and the regulation of vigilance, rendering it to some extent the gatekeeper to the brain. In healthy participants I show that the exposure to a single stressful event results in a profound state change of amygdala functioning, augmenting its gatekeeper function and putting it on high alert both during acute stress and the different consecutive phases of the aftermath. I show that under acutely stressful conditions the amygdala adopts a better-safe-than-sorry mode of functioning, and that it continues to put up its guard in the immediate aftermath of the stressful event. Cortisol administration during first post-encoding sleep then benefits the factual memory consolidation of emotional or stress-related memory traces while simultaneously depotentiating their affective charge, leading to an attenuated alarm function of amygdala during subsequent retrieval. Finally, in case of stress-related disease, like posttraumatic stress disorder, there is a constant state of augmented alert with both excessive and needless amygdala alarms. In the final chapter I show that under the influence of a drug that targets these pathological end-points of stress, the amygdala is downregulated in its function as gatekeeper, even in healthy participants. I end the thesis with a discussion on how these fundamental insights into the neural and neuroendocrine basis of the stress response in the human brain, possibly, and purely on a speculative basis, hold some heuristic value with respect to the inception, and therefore prevention, of psychological trauma.