Marieke Geerte Nynke Bos

The effects of noradrenergic blockade on extinction in humans

The process of reconsolidation has attracted much attention because of its potential application for the treatment of psychiatric disorders. Here, we investigate a possible boundary condition of disrupting reconsolidation with the noradrenergic antagonist propranolol in humans. Reconsolidation can be initiated by retrieval of an acquired fear memory, which is in procedure equivalent to extinction training. If memory retrieval promotes the formation of a novel extinction memory trace, propranolol may interfere with extinction rather than with reconsolidation. Using a differential fear conditioning paradigm, we demonstrate that administration of propranolol (double-blind placebo controlled) prior to repetitive unreinforced CS presentations did not affect extinction at a physiological level (startle reflex and skin conductance). At a cognitive level, propranolol directly impaired extinction learning. These findings indicate that careful selection of timing parameters is essential to ensure that pharmacological agents interfere with the intended memory process to reduce fear.

Noradrenergic Blockade of Memory Reconsolidation: A Failure to Reduce Conditioned Fear Responding

Upon recall, a memory can enter a labile state in which it requires new protein synthesis to restabilize. This two-phased reconsolidation process raises the prospect to directly target excessive fear memory as opposed to the formation of inhibitory memory following extinction training. In our previous studies, we convincingly demonstrated that 40 mg propranolol HCl administration before or after memory reactivation eliminated the emotional expression of fear memory indexed by the fear potentiated startle reflex. To apply this procedure in clinical practice it is important to understand the optimal and boundary conditions of this procedure. As part of a large project aimed at unraveling putative boundary conditions of disrupting reconsolidation of associative fear memory with propranolol HCl, we again tested our memory reconsolidation procedure. Participants (N = 44) underwent a three-day differential fear conditioning procedure. Twenty-four hours after fear acquisition, participants received 40 mg propranolol HCl prior to memory reactivation. The next day, participants were subjected to extinction training and reinstatement testing. In sharp contrast to our previous findings, propranolol HCl before memory reactivation did not attenuate the startle fear response. Remarkably, the startle fear response even persisted during extinction training and did not show the usually observed gradual decline in conditioned physiological responding (startle potentiation and skin conductance) upon repeated unreinforced trials. We discuss these unexpected findings and propose some potential explanations. It remains, however, unclear why we observed a resistance to reduce conditioned fear responding by either disrupting reconsolidation or extinction training. The present results underscore that the success of human fear conditioning research may depend on subtle manipulations and instructions.

Stress enhances reconsolidation of declarative memory

Retrieval of negative emotional memories is often accompanied by the experience of stress. Upon retrieval, a memory trace can temporarily return into a labile state, where it is vulnerable to change. An unresolved question is whether post-retrieval stress may affect the strength of declarative memory in humans by modulating the reconsolidation process. Here, we tested in two experiments whether post-reactivation stress may affect the strength of declarative memory in humans. In both experiments, participants were instructed to learn neutral, positive and negative words. Approximately 24h later, participants received a reminder of the word list followed by exposure to the social evaluative cold pressor task (reactivation/stress group, nexp1=20; nexp2=18) or control task (reactivation/no-stress group, nexp1=23; nexp2=18). An additional control group was solely exposed to the stress task, without memory reactivation (no-reactivation/stress group, nexp1=23; nexp2=21). The next day, memory performance was tested using a free recall and a recognition task. In the first experiment we showed that participants in the reactivation/stress group recalled more words than participants in the reactivation/no-stress and no-reactivation/stress group, irrespective of valence of the word stimuli. Furthermore, participants in the reactivation/stress group made more false recognition errors. In the second experiment we replicated our observations on the free recall task for a new set of word stimuli, but we did not find any differences in false recognition. The current findings indicate that post-reactivation stress can improve declarative memory performance by modulating the process of reconsolidation. This finding contributes to our understanding why some memories are more persistent than others.

Peer rejection cues induce cardiac slowing after transition into adolescence.

The present study examined developmental and gender differences in sensitivity to peer rejection across the transition into adolescence by examining beat-by-beat heart rate responses. Children between the ages of 8 and 14 years were presented with unfamiliar faces of age-matched peers and were asked to predict whether they would be liked by the other person. Their prediction was followed by feedback indicating that the peer had accepted or rejected them. Results revealed cardiac slowing to unexpected peer rejection in 11- to 14-year-olds. The cardiac response to unexpected rejection was most pronounced in girls. This pattern of findings supports the hypothesis of an increase in sensitivity to peer rejection after transition into adolescence and indicates that social rejection may be particularly salient in adolescent girls.

Psychophysiological Response Patterns to Affective Film Stimuli

Psychophysiological research on emotion utilizes various physiological response measures to index activation of the defense system. Here we tested 1) whether acoustic startle reflex (ASR), skin conductance response (SCR) and heart rate (HR) elicited by highly arousing stimuli specifically reflect a defensive state and 2) the relation between resting heart rate variability (HRV) and affective responding. In a within-subject design, participants viewed film clips with a positive, negative and neutral content. In contrast to SCR and HR, we show that ASR differentiated between negative, neutral and positive states and can therefore be considered as a reliable index of activation of the defense system. Furthermore, resting HRV was associated with affect-modulated characteristics of ASR, but not with SCR or HR. Interestingly, individuals with low-HRV showed less differentiation in ASR between affective states. We discuss the important value of ASR in psychophysiological research on emotion and speculate on HRV as a potential biological marker for demarcating adaptive from maladaptive responding.

Personality predicts individual variation in fear learning: a multilevel growth modeling approach

Although fear-learning research has tended to focus on typical responses, there is substantial individual variation in response to threat. Here, we investigated how personality is related to variability in associative fear learning. We used multilevel growth curve modeling to examine the unique and interactive effects of Stress Reaction (SR) and Harmavoidance (HA; Multidimensional Personality Questionnaire scales) and their corresponding higher-order factors on differential fear conditioning (n = 225) and extinction (n = 109; 24–48 hr later). Fear was indexed by fear potentiation of the eyeblink startle reflex. Our findings demonstrated weaker discrimination between threat and safety with high levels of SR. Subsequently, both retention of differential fear acquisition and extinction were weaker with high levels of SR and HA, thereby indicating maladaptive fear learning, whereas they were stronger with low levels of SR and high levels of HA, which suggests efficient fear learning. These findings illustrate how specific personality traits may operate to confer vulnerability or resilience for anxiety disorders.

Muscle or Motivation? A Stop-Signal Study on the Effects of Sequential Cognitive Control

Performance on cognitive control tasks deteriorates when control tasks are performed together with other control tasks, that is, if simultaneous cognitive control is required. Surprisingly, this is also observed if control tasks are preceded by other control tasks, that is, if sequential cognitive control is required. The typical explanation for the latter finding is that previous acts of cognitive control deplete a common resource, just like a muscle becomes fatigued after repeated usage. An alternative explanation, however, is that previous acts of cognitive control reduce motivation to match allocated resources to required resources. In this paper we formalize these muscle and motivation accounts, and show that they yield differential predictions regarding the interaction between simultaneous and sequential cognitive control. These predictions were tested using a paradigm where participants had to perform multiple stop-signal tasks, which varied in their demands on simultaneous and sequential control. Results of two studies supported predictions derived from the motivation account. Therefore, we conclude that the effects of sequential cognitive control are best explained in terms of a reduction of motivation to match allocated to required resources.

Cortisol response mediates the effect of post-reactivation stress exposure on contextualization of emotional memories

Retrieval of traumatic experiences is often accompanied by strong feelings of distress. Here, we examined in healthy participants whether post-reactivation stress experience affects the context-dependency of emotional memory. First, participants studied words from two distinctive emotional categories (i.e., war and disease) presented against a category-related background picture. One day later, participants returned to the lab and received a reminder of the words of one emotional category followed by exposure to a stress task (Stress group, n=22) or a control task (Control group, n=24). Six days later, memory contextualization was tested using a word stem completion task. Half of the word stems were presented against the encoding context (i.e., congruent context) and the other half of the word stems were presented against the other context (i.e., incongruent context). The results showed that participants recalled more words in the congruent context than in the incongruent context. Interestingly, cortisol mediated the effect of stress exposure on memory contextualization. The stronger the post-reactivation cortisol response, the more memory performance relied on the contextual embedding of the words. Taken together, the current findings suggest that a moderate cortisol response after memory reactivation might serve an adaptive function in preventing generalization of emotional memories over contexts.