Floris Klumpers

Radboud University | RU

Based on studies in rodents, the basolateral amygdala (BLA) is considered a key site for experience-dependent neural plasticity underlying the acquisition of conditioned fear responses. In humans, very few studies exist of subjects with selective amygdala lesions and those studies have only implicated the amygdala more broadly leaving the role of a...

The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute...

Real-life shooting decisions typically occur under acute threat and require fast switching between vigilant situational assessment and immediate fight-or-flight actions. Recent studies suggested that freezing facilitates action preparation and decision-making but the neurocognitive mechanisms remain unclear. We applied functional magnetic resonance...

The commentary by Luyck and colleagues on our paper provides many stimulating viewpoints and interpretations of our original study on dissociable responses in the amygdala and bed nucleus of the stria terminalis in threat processing. Here, we reply to some of the points raised and while agreeing with most of the comments also provide some alternati...

Healthy and successful living involves carefully navigating rewarding and threatening situations by balancing approach and avoidance behaviors. Excessive avoidance to evade potential threats often leads to forfeiting potential rewards. However, little is known about how reward and threat information is integrated neurally to inform approach or avoi...

Adequate control over evolutionary engrained bodily stress reactions is essential to avoid23 disproportionate responses during highly arousing situations in police. This regulation can be trained24 via heart rate variability (HRV)-biofeedback, a widely used intervention aiming to improve stress25 regulation, but typically conducted under passive, l...

Avoidance, a hallmark of anxiety-related psychopathology, often comes at a cost; avoiding threat may forgo the possibility of a reward. Theories predict that optimal approach-avoidance arbitration depends on threat-induced psychophysiological states, like freezing-related bradycardia. Here we used model-based fMRI analyses to investigate whether an...

Healthy and successful living involves carefully navigating rewarding and threatening situations by balancing approach and avoidance behaviours. Excessive avoidance to evade potential threats often leads to forfeiting potential rewards. However, little is known about how reward and threat information is integrated neurally to inform either approach...

Fearful avoidance is a hallmark of anxiety disorders and often comes at a cost. It reduces the probability of threat and of obtaining rewards. Theoretical models predict that threat-induced psychophysiological states, such as freezing-related bradycardia, facilitate arbitration of approach-avoidance decisions. We indeed show that bradycardia states...

Introduction Police are at risk of trauma and related mental health outcomes. Sleep disturbances and fatigue predict poor mental health in other populations, thus it is critical we determine whether they represent risk factors for mental health problems in first responders. We examined if pre-trauma sleep and fatigue experienced by police recruits...

One of the hallmarks of post-traumatic stress disorder (PTSD) is abnormalities in the HPA-axis. This includes alterations in its negative feedback regulation. Although altered glucocorticoid receptor (GR) mRNA expression is thought to play a crucial role herein, direct longitudinal evidence in humans is lacking to support this assumption. The curre...

[This corrects the article DOI: 10.1371/journal.pone.0260952.].

Substantial individual differences exist in how acute stress affects large-scale neurocognitive networks, including salience (SN), default mode (DMN), and central executive networks (CEN). Changes in the connectivity strength of these networks upon acute stress may predict vulnerability to long-term stress effects, which can only be tested in prosp...

It is widely recognized that police performance may be hindered by psychophysiological state changes during acute stress. To address the need for awareness and control of these physiological changes, police academies in many countries have implemented Heart-Rate Variability (HRV) biofeedback training. Despite these trainings now being widely delive...

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain...

Freezing to impending threat is a core defensive response. It has been studied primarily using fear conditioning in non-human animals, thwarting advances in translational human anxiety research that has used other indices, such as skin conductance responses. Here we examine postural freezing as a human conditioning index for translational anxiety r...

It is widely recognized that police performance may be hindered by psychophysiological state changes during acute stress. To address the need for awareness and control of these physiological changes, police academies in many countries have implemented Heart-Rate Variability (HRV) biofeedback training. Despite these trainings now being widely delive...

The anticipation of threat facilitates innate defensive behaviours including freezing reactions. Freezing in humans is characterised by reductions in body sway and heart rate. Limited evidence suggests that individual differences in freezing reactions are associated with predictors of anxiety-related psychopathology including trait anxiety and hypo...

Regulating social emotional actions is essential for coping with life stressors and is associated with control by the anterior prefrontal cortex (aPFC) over the amygdala. However, it remains unclear to what extent prefrontal emotion regulation capacities contribute to resilience against developing post-traumatic stress disorder (PTSD) symptoms. Her...

Substantial individual differences exist in how acute stress affects large-scale neurocognitive networks, including Salience (SN), Default Mode (DMN) and Central Executive Networks (CEN). These network-level changes upon acute stress may predict vulnerability to long-term stress effects, which can only be tested in prospective longitudinal studies....

Successful responding to acutely threatening situations requires adequate approach–avoidance decisions. However, it is unclear how threat-induced states—like freezing-related bradycardia—impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models...

Freezing to impending threat is a core defensive response. It has been studied primarily using fear-conditioning in non-human animals, thwarting advances in translational human anxiety-research. Here we examine postural freezing as a human conditioning-index for translational anxiety-research. We show (n=28) that human freezing is highly sensitive...

Acutely challenging or threatening situations frequently require approach-avoidance decisions. Acute threat triggers fast autonomic changes that prepare the body to freeze, fight or flee. However, such autonomic changes may also influence subsequent instrumental approach-avoidance decisions. Since defensive bodily states are often not considered in...

As part of the Dutch national science program “Professional Games for Professional Skills” we developed a stress-exposure biofeedback training in virtual reality (VR) for the Dutch police. We aim to reduce the acute negative impact of stress on performance, as well as long-term consequences for mental health by facilitating physiological stress reg...

Successful responding to acutely threatening situations requires adequate approach-avoidance decisions. However, it is unclear how threat-induced states -like freezing-related bradycardia- impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our model...

Early interventions to improve resilience require the identification of objective risk biomarkers for PTSD symptom development. Although altered hippocampal and amygdala volumes are consistently observed in PTSD, it remains currently unknown whether they represent a predisposing vulnerability factor for PTSD symptom development or an acquired conse...

The bed nucleus of the stria terminalis (BNST) plays a critical modulatory role in driving fear responses. Part of the so-called extended amygdala, this region shares many functions and connections with the substantially more investigated amygdala proper. In this chapter, we review contributions of the BNST and amygdala to subjective, behavioral, a...

Excessive avoidance behaviour is a cardinal symptom of anxiety disorders. Avoidance is not only associated with the benefits of avoiding threats, but also with the costs of missing out on rewards upon exploration. Psychological and psychophysiological mechanisms contributing to these costly avoidance decisions in prospect of mixed outcomes remain u...

Acute stress induces large‐scale neural reorganization with relevance to stress‐related psychopathology. Here, we applied a novel supervised machine learning method, combining the strengths of a priori theoretical insights with a data‐driven approach, to identify which connectivity changes are most prominently associated with a state of acute stres...

Stressors induce physiological changes in the brain and periphery that support adaptive defensive responses. The consequences of psychological stress on cognitive functioning are often measured in laboratory settings using experimentally induced stress that leads to mainly negative subjective feelings. There is a need for verification of these stud...

Susceptibility to stress-related psychopathology is associated with reduced expression of the serotonin transporter (5-HTT), particularly in combination with stress exposure. Aberrant physiological and neuronal responses to threat may underlie this increased vulnerability. Here, implementing a cross-species approach, we investigated the association...

Anxiety disorders are prevalent in the population and costly for society, while current treatment is not effective in all individuals. A central symptom of anxiety is avoidance behaviour, with excessive avoidance being predictive of poor clinical outcomes. Appetitive motivation could play a role in decreasing avoidance behaviour by increasing the p...

Although police officers are carefully selected for their high emotion-regulation abilities, excessive aggression in police officers has been reported, particularly in socially challenging situations known to elicit high state testosterone levels. Adequate regulation of emotional actions depends on the prefrontal cortex’s control over the amygdala....

Active adaptation to acute stress is essential for coping with daily life challenges. The stress hormone cortisol, as well as large scale re-allocations of brain resources have been implicated in this adaptation. Stress-induced shifts between large-scale brain networks, including salience (SN), central executive (CEN) and default mode networks (DMN...

The detection and anticipation of threat facilitates innate defensive behaviours including freezing reactions. Freezing in humans is characterized by reductions in body sway and heart rate and limited evidence suggests that individual differences in freezing reactions are associated with hypothalamic-pituitary-adrenal (HPA) axis activity and anxiet...

Rodent research delineates how the basolateral amygdala (BLA) and central amygdala (CeA) control defensive behaviors, but translation of these findings to humans is needed. Here, we compare humans with natural-selective bilateral BLA lesions to rats with a chemogenetically silenced BLA. We find, across species , an essential role for the BLA in the...

The ability to regulate emotional actions is essential for adequate social behavior and largely depends on control from the prefrontal cortex (PFC) over the amygdala [1]. Optimal functioning of this circuitry is especially important for police officers, who regularly face emotionally challenging situations. Trait aggression has been associated with...

Depression during pregnancy is highly prevalent and has a multitude of potential risks of the offspring. Among confirmed consequences is a higher risk of psychopathology. However, it is unknown how maternal depression may impact the child's brain to mediate this vulnerability. Here we studied amygdala functioning, using task-based functional MRI, i...

Background: Control over automatic tendencies is often compromised in challenging situations when people fall back on automatic defensive reactions, such as freeze–fight–flight responses. Stress-induced lack of control over automatic defensive responses constitutes a problem endemic to high-risk professions, such as the police. Difficulties control...

Background: Childhood adversity (CA) leads to greater vulnerability for psychopathology by causing structural as well as functional brain abnormalities. Recent findings on gray matter effects point towards the importance of identifying CA outcome as a function of different CA types, varying in the dimensions of threat and deprivation. Using diffus...

Memory recall is facilitated when retrieval occurs in the original encoding context. This context dependency effect likely results from the automatic binding of central elements of an experience with contextual features (i.e., memory “contextualization”) during encoding. However, despite a vast body of research investigating the neural correlates o...

Background Healthy aging has been associated with stable emotional well-being and attenuated brain responses to negative stimuli. At the same time, depressive symptoms are common in older adults. The neural mechanisms behind this paradox remain to be clarified. We hypothesized that acute stress could alter emotion processing in healthy aging brain...

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodent...

Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to differences in (the risk for) affective disorders that...

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is HPA-axis function. Here we studied how inter-individual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in ne...

Childhood adversity (CA) has been associated with long-term structural brain alterations and an increased risk for psychiatric disorders. Evidence is emerging that subtypes of CA, varying in the dimensions of threat and deprivation, lead to distinct neural and behavioral outcomes. However, these specific associations have yet to be established with...

In the commentary by Bianchi and Laurent (2015), the authors suggest that depressive symptoms should be controlled for when examining the neurobiology associated with trait neuroticism. We fully agree that the relation between neuroticism and symptoms of stress-related psychiatric disorders, such as major depressive disorder and anxiety disorders,...

Fear learning in stressful situations is highly adaptive for survival by steering behavior in subsequent situations, but fear learning can become disproportionate in vulnerable individuals. Despite the potential clinical significance, the mechanism by which stress modulates fear learning is poorly understood. Memory theories state that stress can c...

Processing of emotional stimuli can either hinder or facilitate ongoing working memory (WM); however, the neural basis of these effects remains largely unknown. Here we examined the neural mechanisms of these paradoxical effects by implementing a novel emotional WM task in an fMRI study. Twenty-five young healthy participants performed an N-back ta...

Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine in mediating the shift towards the salience network and improving vigilance processing, while the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been s...

Deep brain stimulation (DBS) of the ventral internal capsule is effective in treating therapy refractory obsessive–compulsive disorder (OCD). Given the close proximity of the stim-ulation site to the stria terminalis (BNST), we hypothesized that the striking decrease in anxiety symptoms following DBS could be the result of the modulation of context...

Background Excessive anticipatory reactions to potential future adversity are observed across a range of anxiety disorders but the neurogenetic mechanisms driving inter-individual differences are largely unknown. We aimed to discover and validate a gene-brain-behaviour pathway by linking presumed genetic risk for anxiety-related psychopathology, ke...