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EQUIPPED TO SURVIVE: COMPREHENSIVE RESPONSE TO THREAT ENABLES OPTIMAL BEHAVIOUR
  1. Guillén Fernández

Abstract

Guillén Fernández is Professor for Cognitive Neuroscience and director of the Donders Center for Neuroscience at the Radboud University Nijmegen Medical Center. He obtained his medical degree, doctorate, and habilitation at Bonn University. He received full training in clinical neurology and cognitive neurosciences in Bonn, Magdeburg, and Stanford. In 2002, he became a founding principal investigator of the Donders Center for Cognitive Neuroimaging in Nijmegen. His area of research is human cognitive neuroscience in which he studies the brain basis of memory, emotion, and their interactions. He applies an interdisciplinary approach integrating cognitive neuroimaging, genetics, pharmacology and diverse clinical disciplines. He is elected member of the Memory Disorder Research Society. He received the Richard-Jung Award of the German Society for Clinical Neurophysiology, the Vici Award of the Dutch Organization for Scientific Research, the Radboud Science Award, and an Advanced Investigator Grant from the European Research Council.

In response to acute environmental adversity, organisms rapidly shift into a state that is optimal to detect and react to imminent threat. To identify underlying neural network dynamics and neuromodulatory mechanisms we combined in a series of studies fMRI with thread based stress induction procedures and pharmacological manipulation. Our data show that acute psychological stress increases responsiveness and interconnectivity within a salience related network as a function of stress response magnitudes. Beta-adrenergic receptor blockade, but not cortisol synthesis inhibition, diminished this increase. These findings reveal that noradrenergic activation during acute stress results in coupling within a distributed network that integrates information exchange between regions involved in autonomic-neuroendocrine control and vigilant, attentional reorienting. This reorientation causes tonic amygdala activity and phasic responses to biologically salient stimuli while the functional connectivity to the locus coeruleus, the medial prefrontal cortex and the anterior insula is enhanced. This response goes along with higher amygdala sensitivity to threatening stimuli, but lower specificity. This heightened sensitivity is critical for survival when an individual is threatened, but cognitive elaboration would slow down appropriate reactions to threat. Accordingly, further experiments show that acute stress leads to elaboration-related working memory impairments and down regulation of associated processes in the prefrontal cortex. This instantaneously occurring reorganization affecting amygdala processing, prefrontal processing, and the connectivity between these regions is normalized by corticosteroid-related mechanisms. Most interestingly, medial temporal and prefrontal effects of cortisol appear to have different time courses, suggesting dynamically changing processes with different underlying molecular mechanisms. This pattern of results reveals basic principles of how we respond when our survival is at stake. It provides a mechanistic account for an acute central nervous stress response and its normalization. Such an account might become instrumental when investigating the pathophysiology of stress-related mental disorders, studying the mechanisms of diverse treatment approaches, and when predicting risk or outcome. Already, our approach to study the neural underpinnings of the acute threat response is capable of delineating mechanisms of how known genetic and environmental factors cause stress vulnerability.

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