Conny W.E.M. Quaedflieg

Introducing the Maastricht Acute Stress Test (MAST): a quick and non-invasive approach to elicit robust autonomic and glucocorticoid stress responses

Stress-related research has employed several procedures to activate the human stress system. Two of the most commonly used laboratory paradigms are the Trier Social Stress Test (TSST) and the Cold Pressor Test (CPT). We combined their most stressful features to create a simple laboratory stress test capable of eliciting strong autonomic and glucocorticoid stress responses. In comparison with the CPT and its variations, our stress tool (labeled the Maastricht Acute Stress Test; MAST) was found to yield superior salivary cortisol responses, while being equally effective in eliciting subjective stress reactions and (systolic and diastolic) blood pressure increases (study 1; N=80). In study 2 (N=20), we directly compared the effectiveness of the MAST and TSST and found that both methods elicited similar subjective, salivary alpha-amylase, and salivary cortisol stress responses. Finally, we developed and evaluated an appropriate no-stress control version of the MAST that was similar to the stress version, although it did not comprise stressful components (study 3; N=40). Collectively, our results confirm the effectiveness of the MAST in terms of subjective, autonomic, and--most importantly--glucocorticoid stress responses. Thus, as a brief and simple stress protocol, the MAST holds considerable promise for future research.

Acute stress differentially affects spatial configuration learning in high and low cortisol-responding healthy adults

Background Stress and stress hormones modulate memory formation in various ways that are relevant to our understanding of stress-related psychopathology, such as posttraumatic stress disorder (PTSD). Particular relevance is attributed to efficient memory formation sustained by the hippocampus and parahippocampus. This process is thought to reduce the occurrence of intrusions and flashbacks following trauma, but may be negatively affected by acute stress. Moreover, recent evidence suggests that the efficiency of visuo-spatial processing and learning based on the hippocampal area is related to PTSD symptoms. Objective The current study investigated the effect of acute stress on spatial configuration learning using a spatial contextual cueing task (SCCT) known to heavily rely on structures in the parahippocampus. Method Acute stress was induced by subjecting participants (N = 34) to the Maastricht Acute Stress Test (MAST). Following a counterbalanced within-subject approach, the effects of stress and the ensuing hormonal (i.e., cortisol) activity on subsequent SCCT performance were compared to SCCT performance following a no-stress control condition. Results Acute stress did not impact SCCT learning overall, but opposing effects emerged for high versus low cortisol responders to the MAST. Learning scores following stress were reduced in low cortisol responders, while high cortisol-responding participants showed improved learning. Conclusions The effects of stress on spatial configuration learning were moderated by the magnitude of endogenous cortisol secretion. These findings suggest a possible mechanism by which cortisol responses serve an adaptive function during stress and trauma, and this may prove to be a promising route for future research in this area.

Time dependent effects of stress prior to encoding on event-related potentials and 24 h delayed retrieval

Stress can exert profound effects on memory encoding. Here, we investigated whether (sub)cortical information processing during encoding and memory retrieval at a 24 h delayed test are affected by the temporal proximity between stress and memory encoding. Sixty-four participants engaged in the Maastricht Acute Stress Test (MAST) or a no-stress control condition either immediately before (i.e., proximate condition) or 30 min before (i.e., distant condition) a picture encoding task. In general, stress decreased the number of freely recalled and recognized pictures and increased the number of false alarms. However, timing of stress exposure did not differentially affect picture recall, recognition or selective attention processes (i.e., LPP). Nevertheless, stress-induced cortisol responses and correctly recognized neutral pictures were positively associated within the proximate stress condition but negatively associated within the distant stress condition. These findings suggest that the time at which a stressor is applied might differentially impact the association between stress-induced cortisol elevations and memory formation and indicate the need for a finer delineation of the time window during which glucocorticoids affect memory formation processes.

The functional role of individual-alpha based frontal asymmetry in stress responding

Asymmetry in frontal electrical activity has been suggested to index tendencies in affective responding and thus may be associated with hormonal stress responses. To assess the functional role of frontal asymmetry (FA) in stress, we measured FA at rest and following exposure to acute stress induced with the Maastricht Acute Stress Task (MAST; N=70) in the standard 8-13Hz band as well as based on individual alpha frequency (IAF) band. IAF-based resting FAF4-F3 was associated with the stress-induced neuroendocrine response, such that left individual frontal activity predicted smaller total cortisol increases in response to the MAST. Like previous studies, we found resting left-sided FAF8-F7 to predict trait behavioural activation measured with the BIS/BAS scales. FA remained unaffected by stress-induced cortisol response. These findings suggest that individual FA might reflect a trait-like characteristic that moderates the stress response. Our results underscore the utility of IAF in studying individual differences in stress responding.

Temporal Dynamics of Stress-Induced Alternations of Intrinsic Amygdala Connectivity and Neuroendocrine Levels

Stress-induced changes in functional brain connectivity have been linked to the etiology of stress-related disorders. Resting state functional connectivity (rsFC) is especially informative in characterizing the temporal trajectory of glucocorticoids during stress adaptation. Using the imaging Maastricht Acute Stress Test (iMAST), we induced acute stress in 39 healthy volunteers and monitored the neuroendocrine stress levels during three runs of resting state functional magnetic resonance imaging (rs-fMRI): before (run 1), immediately following (run 2), and 30min after acute stress (run 3). The iMAST resulted in strong increases in cortisol levels. Whole-brain analysis revealed that acute stress (run 2 - 1) was characterized by changes in connectivity of the amygdala with the ventrolateral prefrontal cortex (vlPFC), ventral posterior cingulate cortex (PCC), cuneus, parahippocampal gyrus, and culmen. Additionally, cortisol responders were characterized by enhanced amygdala - medial prefrontal cortex (mPFC) connectivity. Stress recovery (run 3 - 2) was characterized by altered amygdala connectivity with the dorsolateral prefrontal cortex (dlPFC), ventral and dorsal anterior cingulate cortex (ACC), anterior hippocampal complex, cuneus, and presupplementary motor area (preSMA). Opposite to non-responders, cortisol responders were characterized by enhanced amygdala connectivity with the anterior hippocampal complex and parahippocampal gyrus, and reduced connectivity with left dlPFC, dACC, and culmen during early recovery. Acute stress responding and recovery are thus associated with changes in the functional connectivity of the amygdala network. Our findings show that these changes may be regulated via stress-induced neuroendocrine levels. Defining stress-induced neuronal network changes is pertinent to developing treatments that target abnormal neuronal activity.

The role of frontal EEG asymmetry in post-traumatic stress disorder

Frontal alpha asymmetry, a biomarker derived from electroencephalography (EEG) recordings, has often been associated with psychological adjustment, with more left-sided frontal activity predicting approach motivation and lower levels of depression and anxiety. This suggests high relevance to post-traumatic stress disorder (PTSD), a disorder comprising anxiety and dysphoria symptoms. We review this relationship and show that frontal asymmetry can be plausibly linked to neuropsychological abnormalities seen in PTSD. However, surprisingly few studies (k = 8) have directly addressed frontal asymmetry in PTSD, mostly reporting that trait frontal asymmetry has little (if any) predictive value. Meanwhile, preliminary evidence suggest that state-dependent asymmetry during trauma-relevant stimulation distinguishes PTSD patients from resilient individuals. Thus, exploring links between provocation-induced EEG asymmetry and PTSD appears particularly promising. Additionally, we recommend more fine-grained analyses into PTSD symptom clusters in relation to frontal asymmetry. Finally, we highlight hypotheses that may guide future research and help to fully apprehend the practical and theoretical relevance of this biological marker.

Frontal EEG asymmetry as predictor of physiological responses to aversive memories

Evidence suggests that asymmetry in frontal electrical activity predicts responses to aversive experiences, such that higher left-sided activity might dampen responses to trauma reminders. We measured frontal asymmetry at rest and during viewing of a trauma film, and assessed startle responses to film-reminder images. To explore potential moderators, we compared two films (Study 1; N = 64) and modulated reappraisal (Study 2; N = 72). As expected, left frontal activation during film viewing predicted dampened responses in individuals who viewed a staged road accident. However, this effect tended to be reversed when a genocide documentary was used. In Study 2, all participants viewed the genocide film. Left frontal activity at rest again predicted higher startle responses, while reappraisal did not moderate the effects. Thus, the type of trauma film plays a crucial role in the effects of frontal asymmetry, which warrants further critical investigation.

The validity of individual frontal alpha asymmetry EEG neurofeedback

Frontal asymmetry in alpha oscillations is assumed to be associated with psychopathology and individual differences in emotional responding. Brain-activity-based feedback is a promising tool for the modulation of cortical activity. Here, we validated a neurofeedback protocol designed to change relative frontal asymmetry based on individual alpha peak frequencies, including real-time average referencing and eye-correction. Participants (N = 60) were randomly assigned to a right, left or placebo neurofeedback group. Results show a difference in trainability between groups, with a linear change in frontal alpha asymmetry over time for the right neurofeedback group during rest. Moreover, the asymmetry changes in the right group were frequency and location specific, even though trainability did not persist at 1 week and 1 month follow-ups. On the behavioral level, subjective stress on the second test day was reduced in the left and placebo neurofeedback groups, but not in the right neurofeedback group. We found individual differences in trainability that were dependent on training group, with participants in the right neurofeedback group being more likely to change their frontal asymmetry in the desired direction. Individual differences in trainability were also reflected in the ability to change frontal asymmetry during the feedback.

Individual differences in spatial configuration learning predict the occurrence of intrusive memories

The dual-representation model of posttraumatic stress disorder (PTSD; Brewin, Gregory, Lipton, & Burgess, Psychological Review, 117, 210-232 2010) argues that intrusions occur when people fail to construct context-based representations during adverse experiences. The present study tested a specific prediction flowing from this model. In particular, we investigated whether the efficiency of temporal-lobe-based spatial configuration learning would account for individual differences in intrusive experiences and physiological reactivity in the laboratory. Participants (N = 82) completed the contextual cuing paradigm, which assesses spatial configuration learning that is believed to depend on associative encoding in the parahippocampus. They were then shown a trauma film. Afterward, startle responses were quantified during presentation of trauma reminder pictures versus unrelated neutral and emotional pictures. PTSD symptoms were recorded in the week following participation. Better configuration learning performance was associated with fewer perceptual intrusions, r = −.33, p < .01, but was unrelated to physiological responses to trauma reminder images (ps > .46) and had no direct effect on intrusion-related distress and overall PTSD symptoms, rs > −.12, ps > .29. However, configuration learning performance tended to be associated with reduced physiological responses to unrelated negative images, r = −.20, p = .07. Thus, while spatial configuration learning appears to be unrelated to affective responding to trauma reminders, our overall findings support the idea that the context-based memory system helps to reduce intrusions.

Negative mood-induction modulates default mode network resting-state functional connectivity in chronic depression

BACKGROUND The aim of this study was to investigate the effects of sad mood on default mode network (DMN) resting-state connectivity in persons with chronic major depressive disorder (cMDD). METHODS Participants with a diagnosis of cMDD (n=18) and age, gender and education level matched participants without a diagnosis of depression (n=18) underwent a resting-state fMRI scan, before and after a sad mood induction. The posterior cingulate cortex (PCC) was used as a seed for DMN functional connectivity across the two resting-state measurements. RESULTS Mood ratings decreased in both groups following the sad mood induction procedure. PCC connectivity with the parahippocampal gyrus, the superior temporal gyrus and the anterior inferior temporal cortex increased in cMDD patients following the sad mood induction, whereas it decreased in non-patient controls. PCC connectivity with the anterior prefrontal cortex and the precuneus decreased in cMDD patients following the sad mood induction, whereas it increased in non-patient controls. LIMITATIONS Limitations of this study include the relatively small sample size and lack of a clinical control group. CONCLUSIONS These findings are in line with neurobiological models of depression suggesting that the observed changes in DMN connectivity following the sad mood induction might reflect a failure to exert cognitive control over negative memory retrieval in patients with cMDD.