Inter-individual variability in neural response to low doses of LSD.

The repeated use of small doses of psychedelics (also referred to as "microdosing") to facilitate benefits in mental health, cognition, and mood is a trending practice. Placebo-controlled studies however have largely failed to demonstrate strong benefits, possibly because of large inter-individual response variability. The current study tested the hypothesis that effects of low doses of LSD on arousal, attention and memory depend on an individual's cognitive state at baseline. Healthy participants (N = 53) were randomly assigned to receive repeated doses of LSD (15 mcg) or placebo on 4 occasions divided over 2 weeks. Each treatment condition also consisted of a baseline and a 1-week follow-up visit. Neurophysiological measures of arousal (resting state EEG), pre-attentive processing (auditory oddball task), and perceptual learning and memory (visual long-term potentiation (LTP) paradigm) were assessed at baseline, dosing session 1 and 4, and follow-up. LSD produced stimulatory effects as reflected by a reduction in resting state EEG delta, theta, and alpha power, and enhanced pre-attentive processing during the acute dosing sessions. LSD also blunted the induction of LTP on dosing session 4. Stimulatory effects of LSD were strongest in individuals with low arousal and attention at baseline, while inhibitory effects were strongest in high memory performers at baseline. Decrements in delta EEG power and enhanced pre-attentive processing in the LSD treatment condition were still present during the 1-week follow-up. The current study demonstrates across three cognitive domains, that acute responses to low doses of LSD depend on the baseline state and provides some support for LSD induced neuroadaptations that sustain beyond treatment.

The moderating role of conscientiousness in the temporal association of stress on sleep.

Personality traits have been associated with sleep problems and stress experience. However, their impact on objective sleep and the temporal relationship of stress on sleep has remained elusive. This study examined whether daytime stress predicts sleep the following night, and the moderating role of neuroticism and conscientiousness in this relationship. To introduce stress variability in natural daily stressors, we measured college students (N = 92) during exams (e.g. high academic stress) and at the start of new course period (e.g. low academic stress). Both objective (actigraphy) and subjective sleep, and daily self-reported stress, were measured for 14 days and personality traits once. Reported daily stress was significantly higher in the exam period compared with baseline, suggesting that our natural manipulation did indeed result in variation in stress levels. Intra-individual daily variations in stress were not associated with the following night's sleep timing, duration or fragmentation, implying that more stress during the day did not affect sleep the following night. Higher levels of neuroticism were associated with poorer daily subjective sleep quality and higher stress levels over the complete period. Neuroticism did not moderate the temporal association of stress on sleep. Conscientiousness moderated the association between intra-individual stress and sleep fragmentation, and intra-individual stress and wake-up time. This implied that highly conscientious participants experienced less sleep fragmentation and woke-up earlier after more stressful days. These results suggest an interconnected relationship among stress, sleep and personality. Focusing on one aspect, like handling stress or enhancing sleep quality, might yield positive effects on the rest.

The Index of Intrusion Control (IIC): Capturing individual variability in intentional intrusion control in the laboratory.

Intrusive memories can be downregulated using intentional memory control, as measured via the Think/No-Think paradigm. In this task, participants retrieve or suppress memories in response to an associated reminder cue. After each suppression trial, participants rate whether the association intruded into awareness. Previous research has found that repeatedly exerting intentional control over memory intrusions reduces their frequency. This decrease is often summarised with a linear index, which may miss more complex patterns characterising the temporal dynamics of intrusion control. The goal of this paper is to propose a novel metric of intrusion control that captures those dynamic changes over time as a single index. Results from a mega-analysis of published datasets revealed that the change in intrusion frequencies across time is not purely linear, but also includes non-linear dynamics that seem best captured by a log function of the number of suppression attempts. To capture those linear and non-linear dynamics, we propose the Index of Intrusion Control (IIC), which relies on the integral of intrusion changes across suppression attempts. Simulations revealed that the IIC best captured the linear and non-linear dynamics of intrusion suppression when compared with other linear or non-linear indexes of control, such as the regression slope or Spearman correlation, respectively. Our findings demonstrate how the IIC may therefore act as a more reliable metric to capture individual differences in intrusion control, and examine the role of non-linear dynamics characterizing the conscious access to unwanted memories.

Controlling intrusive thoughts of future fears under stress.

Negative outlooks of our future may foster unwanted and intrusive thoughts. To some extent, individuals have control over their ability to suppress intrusions and downregulate their frequency. Acute stress impairs intentional suppression, leading to an increased frequency of intrusions. The aim of this study was to gain insight into the mechanism underlying stress-induced impairments in intentional suppression of intrusions by investigating the combined and independent roles of the two major stress hormones, noradrenaline and cortisol. Healthy participants (N = 181) were administered propranolol (to block the noradrenergic response), metyrapone (to block the cortisol response), or a placebo before being exposed to the Maastricht Acute Stress Test. Intrusive thoughts of autobiographical future fears were then measured via the Imagine/No-Imagine task. Results demonstrated that the stress response was successfully altered because of the drug and stress manipulations. In all groups, repeated suppression of future fears reduced intrusions. Across the sample, an enhanced decrease over time was associated with greater attenuation of anxiety towards the related fears. The groups did not differ in the total frequency of intrusions. Though, trait anxiety increased the total number of intrusions. Our findings show that stress hormones did not influence the ability to suppress intrusions. However, our results do add support to previous research linking anxiety to memory control deficits. When using autobiographical content, future research should focus on the quality and characteristics of the individual memories to explain more of the variation observed in intentional memory control.

Does stress consistently favor habits over goal-directed behaviors? Data from two preregistered exact replication studies.

Instrumental learning is controlled by two distinct parallel systems: goal-directed (action-outcome) and habitual (stimulus-response) processes. Seminal research by Schwabe and Wolf (2009, 2010) has demonstrated that stress renders behavior more habitual by decreasing goal-directed control. More recent studies yielded equivocal evidence for a stress-induced shift towards habitual responding, yet these studies used different paradigms to evaluate instrumental learning or used different stressors. Here, we performed exact replications of the original studies by exposing participants to an acute stressor either before (cf. Schwabe and Wolf, 2009) or directly after (cf. Schwabe and Wolf, 2010) an instrumental learning phase in which they had learned that distinct actions led to distinct, rewarding food outcomes (i.e., instrumental learning). Then, following an outcome devaluation phase in which one of the food outcomes was consumed until participants were satiated, action-outcome associations were tested in extinction. Despite successful instrumental learning and outcome devaluation and increased subjective and physiological stress levels following stress exposure, the stress and no-stress groups in both replication studies responded indifferently to valued and devalued outcomes. That is, non-stressed participants failed to demonstrate goal-directed behavioral control, thereby rendering the critical test of a shift from goal-directed to habitual control in the stress group inapt. Several reasons for these replication failures are discussed, including the rather indiscriminate devaluation of outcomes that may have contributed to indifferent responding during extinction, which emphasize the need to further our understanding of the boundary conditions in research aimed at demonstrating a stress-induced shift towards habitual control.

Neural Correlates of Impaired Self-awareness of Deficits after Acquired Brain Injury: A Systematic Review.

Self-awareness is essential for the process and outcome of rehabilitation but is often affected by acquired brain injury (ABI). While many studies investigated the psychological aspects of self-awareness deficits, the biological underpinnings are not well understood. The aim of this systematic review was to identify the neural correlates of self-awareness after ABI. Results indicate that anticipation of future problems is associated with lesions and decreased neural functioning in the right frontal lobe, as well as increased diffusivity throughout the white matter of the brain. Poor behavioral adjustment on implicit awareness tasks is associated with less functional connectivity of anterior cingulate cortex and right or middle inferior frontal gyri to the fronto-parietal control network, as well as more activation in the left insula and left parietal operculum during error processing. Recognition of mistakes is associated with internetwork connectivity of anterior or posterior default mode network to salience network. In conclusion, after ABI, different results in brain activation and connectivity are found depending on level of awareness measured. Future studies are necessary to confirm these findings.

Spatio-temporal theta pattern dissimilarity in the right centro-parietal area during memory generalization.

Generalization across past events may guide our action in novel situations. Although generalization is a fundamental memory process, its neural underpinnings are not fully understood yet. In the present experiment, we combinedElectroencephalography(EEG) with multivariate representational similarity analysis (RSA) to examine in particular the role of spatio-temporal patterns of theta oscillations known to be important for associative memory processes, in memory generalization. We recorded EEG while healthy participants (n = 56) performed an acquired equivalence task. In this task, participants first acquired multiple associations among antecedent and consequent stimuli before they were required to transfer the acquired knowledge to novel stimulus pairs, thus probing memory generalization. Our behavioural data indicated that participants learned the initial associations well and transferred these associations successfully to novel test stimuli, demonstrating successful memory generalization. Our neural data revealed that, compared to mere memory retrieval, generalization was associated with significantly increased pattern dissimilarity of theta activity in the right centro-parietal area (electrodes P4 and P6). This pattern was specific to theta oscillations and not observed in other frequency bands. Our findings suggest an important role of theta oscillations in memory generalization, potentially serving the reactivation and integration of distinct events that enable the generalization across experiences.

Cortisol reactivity impairs suppression-induced forgetting.

To some extent, we can shape our recollections by intentionally remembering certain experiences while trying to forget others, for example, by intentional suppression. Acute stress impairs suppression-induced forgetting of memories. It is unclear, however, whether these deficits are a direct consequence of the acute stress-induced cortisol response. The present study was designed to examine the stress-induced impairment in suppression-induced forgetting in a subgroup of cortisol responders. We exposed healthy participants to a stress (n = 55) or no-stress control (n = 32) version of the Maastricht Acute Stress Test before they performed the Think / No-Think task. Here, participants aimed to repeatedly retrieve or suppress memories of previously learned cue-target video clips to mimic the complexity of episodic memories. Results on the subsequent memory test revealed that, while the no-stress controls and cortisol non-responders demonstrated suppression-induced forgetting, this effect was absent in cortisol responders. Moreover, the magnitude of suppression-induced forgetting was negatively correlated to stress-induced cortisol increases. The current study extends findings on stress-induced impairments in suppression-induced forgetting by specifically focusing on cortisol reactivity. Furthermore, our findings show the importance of individual differences in cortisol responses as a driving mechanism behind stress-induced alterations in our capacity to actively control our memory.

Volume and Connectivity Differences in Brain Networks Associated with Cognitive Constructs of Binge Eating.

Bulimia nervosa (BN) and binge eating disorder (BED) are characterized by episodes of eating large amounts of food while experiencing a loss of control. Recent studies suggest that the underlying causes of BN/BED consist of a complex system of environmental cues, atypical processing of food stimuli, altered behavioral responding, and structural/functional brain differences compared with healthy controls (HC). In this narrative review, we provide an integrative account of the brain networks associated with the three cognitive constructs most integral to BN and BED, namely increased reward sensitivity, decreased cognitive control, and altered negative affect and stress responding. We show altered activity in BED/BN within several brain networks, specifically in the striatum, insula, prefrontal cortex (PFC) and orbitofrontal cortex (OFC), and cingulate gyrus. Numerous key nodes in these networks also differ in volume and connectivity compared with HC. We provide suggestions for how this integration may guide future research into these brain networks and cognitive constructs.

Examining the effect of stress on the flexible updating of avoidance responses.

Acute stress has been found to impair the flexible updating of stimulus - outcome associations. However, there is a lack of studies investigating the effect of acute stress on the flexible updating of stimulus-response associations, like active avoidance responses. The current study used an avoidance reversal learning paradigm to address this question. Sixty-one participants learned that a red dot was associated with an aversive sound, whereas a green dot was not (Pavlovian Acquisition phase). Next, they were trained to avoid the aversive stimulus by selectively pressing a button in response to the red, but not the green, dot (Avoidance Acquisition phase). Subsequently, participants either underwent a stress induction task or a no-stress control task. The flexible updating of expectancies of the US and avoidance responses were assessed after reversal of the original contingencies (Reversal Test). Acute stress did not impair the flexible updating of avoidance responses during the Reversal Test. In contrast, results showed that in the stress group the expectancies of the aversive sound were more in accordance with the reversed contingencies compared to the ratings of control participants. Additionally, cortisol responders avoided less often in comparison to cortisol non-responders. Increased noradrenergic activity in stressed participants was related to impairments in the flexible updating of avoidance responses after contingency reversal, while this association was absent in the control participants. In conclusion, our results suggest that the autonomic response might account for shifting the balance toward inflexible updating of stimulus-outcome awareness while stress does not impair flexible updating of avoidance responses.

Stress enhances emotional memory-related theta oscillations in the medial temporal lobe.

Stressful events impact memory formation, in particular for emotionally arousing stimuli. Although these stress effects on emotional memory formation have potentially far-reaching implications, the underlying neural mechanisms are not fully understood. Specifically, the temporal processing dimension of the mechanisms involved in emotional memory formation under stress remains elusive. Here, we used magnetoencephalography (MEG) to examine the neural processes underlying stress effects on emotional memory formation with high temporal and spatial resolution and a particular focus on theta oscillations previously implicated in mnemonic binding. Healthy participants (n = 53) underwent a stress or control procedure before encoding emotionally neutral and negative pictures, while MEG was recorded. Memory for the pictures was probed in a recognition test 24 h after encoding. In this recognition test, stress did not modulate the emotional memory enhancement but led to significantly higher confidence in memory for negative compared to neutral stimuli. Our neural data revealed that stress increased memory-related theta oscillations specifically in medial temporal and occipito-parietal regions. Further, this stress-related increase in theta power emerged during memory formation for emotionally negative but not for neutral stimuli. These findings indicate that acute stress can enhance, in the medial temporal lobe, oscillations at a frequency that is ideally suited to bind the elements of an ongoing emotional episode, which may represent a mechanism to facilitate the storage of emotionally salient events that occurred in the context of a stressful encounter.

Dopaminergic and noradrenergic modulation of stress-induced alterations in brain activation associated with goal-directed behaviour.

BACKGROUND: Acute stress is thought to reduce goal-directed behaviour, an effect purportedly associated with stress-induced release of catecholamines. In contrast, experimentally increased systemic catecholamine levels have been shown to increase goal-directed behaviour. Whether experimentally increased catecholamine function can modulate stress-induced reductions in goal-directed behaviour and its neural substrates, is currently unknown. AIM: To assess whether and how experimentally induced increases in dopamine and noradrenaline contribute to the acute stress effects on goal-directed behaviour and associated brain activation. METHODS: One hundred participants underwent a stress induction protocol (Maastricht acute stress test; MAST) or a control procedure and received methylphenidate (MPH) (40 mg, oral) or placebo according to a 2 × 2 between-subjects design. In a well-established instrumental learning paradigm, participants learnt stimulus-response-outcome associations, after which rewards were selectively devalued. Participants' brain activation and associated goal-directed behaviour were assessed in a magnetic resonance imaging scanner at peak cortisol/MPH concentrations. RESULTS: The MAST and MPH increased physiological measures of stress (salivary cortisol and blood pressure), but only MAST increased subjective measures of stress. MPH modulated stress effects on activation of brain areas associated with goal-directed behaviour, including insula, putamen, amygdala, medial prefrontal cortex, frontal pole and orbitofrontal cortex. However, MPH did not modulate the tendency of stress to induce a reduction in goal-directed behaviour. CONCLUSION: Our neuroimaging data suggest that MPH-induced increases in dopamine and noradrenaline reverse stress-induced changes in key brain regions associated with goal-directed behaviour, while behavioural effects were absent. These effects may be relevant for preventing stress-induced maladaptive behaviour like in addiction or binge eating disorder.

Facing stress: No effect of acute stress at encoding or retrieval on face recognition memory.

Eyewitnesses may experience stress during a crime and when attempting to identify the perpetrator subsequently. Laboratory studies can provide insight into how acute stress at encoding and retrieval affects memory performance. However, previous findings exploring this issue have been mixed. Across two preregistered experiments, we examined the effects of stress during encoding and retrieval on face and word recognition performance. We used the Maastricht Acute Stress Test (MAST) to induce stress and verified the success of the stress manipulation with blood pressure measures, salivary cortisol levels, and negative affect scores. To examine differences in stressor timing, participants encoded target faces or words both when confronted with the stressor and during the subsequent cortisol peak and retrieved these stimuli 24 h later. We found neither effects of acute stress on face recognition memory during encoding or retrieval (Experiments 1 and 2), nor effects of encoding stress on word recognition memory (Experiment 2). Bayesian analyses largely provided substantial or strong evidence for the null hypotheses. We emphasize the need for well-powered experiments using contemporary methodology for a more complete understanding of the effect of acute stress on face recognition memory.

The effects of acute stress on eyewitness memory: an integrative review for eyewitness researchers.

The eyewitness and fundamental memory research fields have investigated the effects of acute stress at encoding on memory performance for decades yet results often demonstrate contrasting conclusions. In this review, we first summarise findings on the effects of acute encoding stress on memory performance and discuss how these research fields often come to these diverging findings regarding the effects of encoding stress on memory performance. Next, we critically evaluate methodological choices that underpin these discrepancies, emphasising the strengths and limitations of different stress-memory experiments. Specifically, we elaborate on choice of stressors and stimuli, stress manipulation checks, stressor timing, and the interval between encoding and retrieval and discuss how methodological shortcomings in both the eyewitness and fundamental memory fields have limited our understanding of how encoding stress may affect eyewitness memory performance. Finally, we propose several recommendations for researchers interested in this topic, such as confirming stress inductions with physiological measures, implementing sufficient retrieval intervals to isolate the memory phase of interest and using ecologically valid memory paradigms. We conclude that the best progress can be made if researchers are responsive to the methodologies and findings reported in other research fields and encourage collaborations between the different disciplines.

Mitigating the negative effects of retrieval stress on memory: an arousal reappraisal intervention.

In a preregistered experiment, we examined the efficacy of arousal reappraisal as an intervention for reducing the negative effects of stress at retrieval on memory. Participants (N = 177) were semi-randomly assigned to one of three conditions: a Stress-intervention condition, a Stress-placebo condition, and a No-stress-placebo control condition. Participants viewed four images of complex, mildly negatively valenced scenes. One day later, they received an arousal reappraisal intervention or placebo before exposure to a laboratory stressor (or a control version for the No-stress condition). Participants were then tested on their memory of the images using a free recall instruction and multiple-choice recognition questions. As expected, negative affect and blood pressure increased for the stress conditions but not the control condition. Contrary to our hypotheses, memory performance did not statistically significant differ between the Stress-placebo condition and the No-stress-placebo control condition, indicating a lack of negative effects of acute retrieval stress on memory. Furthermore, we also found no statistically significant differences between the Stress-intervention condition and Stress-placebo condition in terms of memory performance, suggesting that the intervention did not assist with enhancing memory. We integrate interpretations of the findings from this study with a discussion of avenues for future research in this area.

The effects of stress on eyewitness memory: A survey of memory experts and laypeople.

This survey examined lay and expert beliefs about statements concerning stress effects on (eyewitness) memory. Thirty-seven eyewitness memory experts, 36 fundamental memory experts, and 109 laypeople endorsed, opposed, or selected don't know responses for a range of statements relating to the effects of stress at encoding and retrieval. We examined proportions in each group and differences between groups (eyewitness memory experts vs. fundamental memory experts; experts vs. laypeople) for endorsements (agree vs. disagree) and selections (don't know vs. agree/disagree). High proportions of experts from both research fields agreed that very high levels of stress impair the accuracy of eyewitness testimony. A majority of fundamental experts, but not eyewitness experts, endorsed the idea that stress experienced during encoding can enhance memory. Responses to statements regarding moderating factors such as stressor severity and detail type provided further insight into this discrepancy. Eyewitness memory experts more frequently selected the don't know option for neuroscientific statements regarding stress effects on memory than fundamental memory experts, although don't know selections were substantial among both expert groups. Laypeople's responses to eight of the statements differed statistically from expert answers on topics such as memory in children, in professionals such as police officers, for faces and short crimes, and the existence of repression, providing insight into possible 'commonsense' beliefs on stress effects on memory. Our findings capture the current state of knowledge about stress effects on memory as reflected by sample of experts and laypeople, and highlight areas where further research and consensus would be valuable.

Balancing Between Goal-Directed and Habitual Responding Following Acute Stress.

Instrumental learning is regulated by two memory systems: a relatively rigid but efficient habit system and a flexible but resource-demanding goal-directed system. Previous work has demonstrated that exposure to acute stress may shift the balance between these systems toward the habitual system. In the current study, we used a 2-day outcome devaluation paradigm with a 75% reward contingency rate and altered food reward categories to replicate and extend our previous findings. Participants learned neutral stimulus-response-reward associations on the first day. On the second day, rewards were devalued by eating to satiety. Subsequently, acute stress was induced in half of the participants using the Maastricht Acute Stress Test, while the other half engaged in a nonstressful control task. Finally, relative goal-directed versus habitual behavior was evaluated in a slips-of-action phase, where more slips-of-action indicate a shift toward the habitual system. Results showed that participants successfully acquired the stimulus-response-reward associations, that devaluation was effective, and that stressed participants displayed significant increases in cortisol and blood pressure. Stress led participants to commit more slips-of-action compared with nonstressed controls. The current study extends previous work, showing that the employed paradigm and outcome devaluation procedure are boundary conditions to the stress-induced shift in instrumental responding.

Acute stress - but not aversive scene content - impairs spatial configuration learning.

Contextual learning pervades our perception and cognition and plays a critical role in adjusting to aversive and stressful events. Our ability to memorise spatial context has been studied extensively with the contextual cueing paradigm, in which participants search for targets among simple distractor cues and show search advantages for distractor configurations that repeat across trials. Mixed evidence suggests that confrontation with adversity can enhance as well as impair the contextual cueing effect. We aimed to investigate this relationship more systematically by devising a contextual cueing task that tests spatial configuration learning within complex visual scenes that were emotionally neutral or negative (Study 1) and was preceded by the Maastricht Acute Stress Test (MAST) or a no-stress control condition (Study 2). We demonstrate a robust contextual cueing effect that was comparable across negative and neutral scenes (Study 1). In Study 2, acute stress disrupted spatial configuration learning irrespective of scene valence and endogenous cortisol reactivity to stress. Together with the emerging evidence in the literature, our findings suggest that spatial configuration learning may be subject to complex regulation as a function of spatial or temporal proximity to a stressor, with potential implications for the development of stress-related psychopathology.

The interaction between stress and chronic pain through the lens of threat learning.

Stress and pain are interleaved at multiple levels - interacting and influencing each other. Both are modulated by psychosocial factors including fears, beliefs, and goals, and are served by overlapping neural substrates. One major contributing factor in the development and maintenance of chronic pain is threat learning, with pain as an emotionally-salient threat - or stressor. Here, we argue that threat learning is a central mechanism and contributor, mediating the relationship between stress and chronic pain. We review the state of the art on (mal)adaptive learning in chronic pain, and on effects of stress and particularly cortisol on learning. We then provide a theoretical integration of how stress may affect chronic pain through its effect on threat learning. Prolonged stress, as may be experienced by patients with chronic pain, and its resulting changes in key brain networks modulating stress responses and threat learning, may further exacerbate these impairing effects on threat learning. We provide testable hypotheses and suggestions for how this integration may guide future research and clinical approaches in chronic pain.