Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity

Abstract

Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a ’recovery’ pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies.

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

“…Hence, differential connectivity patterns between the amygdala and the hippocampus may provide a neural model underlying the increased risk of stress-related disorders in T homozygotes. Crucially, this coupling has been demonstrated to increase after stress (Ghosh et al 2013;Vaisvaser et al 2013), which is in line with the prolonged stress response in T homozygotes (Binder 2009). …”

“…The amygdala-hippocampus connection has been demonstrated to be critically involved in the formation of emotional memory (Hooker et al 2008;Phelps 2004). Moreover, amygdala-hippocampus connectivity has been shown to be influenced by stress exposure (Ghosh et al 2013;Vaisvaser et al 2013). …”

Amygdala–Hippocampal Connectivity Changes During Acute Psychosocial Stress: Joint Effect of Early Life Stress and Oxytocin

“…Amygdala activity and connectivity signal the emotional significance of the perceived stimuli and prepare our brain and body for suitable responses (LeDoux, 2000). Changes in functional connectivity (FC) between amygdala and other limbic-prefrontal regions have been demonstrated during and after stress induction (Hermans et al, 2011;Vaisvaser et al, 2013;Veer et al, 2011). Particularly, enhanced amygdala-hippocampal FC has been found both in the immediate responses to and in the prolonged aftermath of stress (Vaisvaser et al, 2013).…”

“…Changes in functional connectivity (FC) between amygdala and other limbic-prefrontal regions have been demonstrated during and after stress induction (Hermans et al, 2011;Vaisvaser et al, 2013;Veer et al, 2011). Particularly, enhanced amygdala-hippocampal FC has been found both in the immediate responses to and in the prolonged aftermath of stress (Vaisvaser et al, 2013). The hippocampus inhibits the hypothalamic-pituitary-adrenal (HPA) axis and receives negative feedback from its hormonal end product cortisol (Herman et al, 2005).…”

Altered Structural-functional Maturation of the Right Amygdala in Healthy Adolescents Exposed to Traumatic Events

“…While many have reported volumetric reductions in the hippocampus [15][16][17] or amygdala [18], others have found no change in either hippocampal or amygdala volume [19,20]. Resting-state functional imaging studies have also produced varied results, with some research reporting increased amygdala-hippocampal connectivity associated with greater levels of self-reported trauma symptoms [21] or following stress induction [22], and other work reporting no trauma-related connectivity changes [18]. Variability in type of trauma exposure, and imaging analysis may play a role in explaining these discrepancies.…”