Biology subjects

de Voogd, L. D.

Publications and source records attributed to de Voogd, L. D..

9 recordsLinked to original sources

bioRxiv2025

Spine-brain dynamics during human defensive threat-reactions

Synchrony between central and autonomic nervous system responses during threat rely on spine-brain interactions. Activation of the parasympathetic autonomic nervous system during acute threat has been linked to optimized action preparation and longer-term stress-resilience. However, it is unclear how this is orchestrated by spine-brain interactions during our widely used models of threat conditioning. Here we used a well-established threat conditioning procedure to test whether freezing-related bradycardia modulates the strength of motor- and sensory-relevant spinal-brain connectivity patterns. Conditioning elicited the expected autonomic and psychophysiological responses, with significant bradycardia and heightened differentiation between conditioned stimuli. Heart rate bradycardia modulated activity in the cingulate cortex and spinal cord, emphasizing their role in freezing. Notably, bradycardia-modulated spinal cord activity during threat was functionally coupled with motor cortex activity, suggesting a preparatory response for defensive actions. Establishing these effects for the first time in humans helps discovery of biomarkers for threat coping-relevant body-brain interactions, essential for clinical evaluations.

neuroscience↗

bioRxiv2024

Defensive freezing sharpens threat-reward information processing during approach-avoidance decision making

People regularly face approach-avoidance dilemmas which require minimization of potential threat whilst maximizing potential reward. Defensive reactions to threat, such as transient states of freezing, influence integration of reward/threat information in the dorsal Anterior Cingulate Cortex (dACC). However, the mechanism of this integration between internal state and external value (state-value integration) remains unknown. Here, we decoded approach-avoidance decisions under threat using high-precision magnetoencephalography (MEG). Threat-induced cardiac deceleration (indicative of defensive freezing) was trial-by-trial associated with more pronounced effects of reward and threat magnitudes on approach-avoidance choices. Time-resolved decoding of threat-reward information from neural signals predicted approach-avoidance choices several seconds before the actual response. Crucially, during freezing, 6-12 Hz coherence between threat-reward information and dACC neural activity increased, suggesting that defensive freezing sharpens threat/reward processing during approach-avoidance decision making. These findings provide a potential neural mechanism by which threat-induced freezing can facilitate information integration, essential for optimal decision making under threat.

neuroscience↗

bioRxiv2023

The neurocomputational link between defensive cardiac states and approach-avoidance arbitration under threat

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 are linked to the neurocomputational underpinnings of approach-avoidance arbitration when facing varying reward and threat magnitudes. Bradycardia was not only linked to aversive value-related avoidance decisions but also to value comparison (a stronger tendency to approach vs. avoid when expected reward outweighs potential threat). An amygdala-striatal-prefrontal neural circuit supported approach-avoidance arbitration under threat, with specific involvement of the amygdala and dorsal anterior cingulate (dACC) in integrating subjective outcome values and bradycardia states. These findings highlight the role of human freezing states in value-based decision making, relevant for optimal threat coping. They point to a specific role for amygdala/dACC in state-value integration under threat.

neuroscience↗

bioRxiv2022

Assessing pupil size as an index of activation of subcortical ascending arousal system nuclei during rest

Neuromodulatory nuclei that are part of the ascending arousal system (AAS) play a crucial role in regulating cortical state and optimizing task performance. Pupil diameter, under constant luminance conditions, is increasingly used as an index of activity of these AAS nuclei. Indeed, task-based functional imaging studies in humans have begun to provide evidence of stimulus-driven pupil-AAS coupling. However, whether there is such a tight pupil-AAS coupling during rest is not clear. To address this question, we examined simultaneously acquired resting-state fMRI and pupil-size data from 74 participants, focusing on six AAS nuclei: the locus coeruleus, ventral tegmental area, substantia nigra, dorsal and median raphe nuclei, and cholinergic basal forebrain. Activation in all six AAS nuclei was optimally correlated with pupil size at 0-to 2-second lags, suggesting that spontaneous pupil changes were almost immediately followed by corresponding BOLD-signal changes in the AAS. These results suggest that spontaneous changes in pupil size that occur during states of rest can be used as a noninvasive general index of activity in AAS nuclei. Importantly, the nature of pupil-AAS coupling during rest appears to be vastly different from the relatively slow canonical hemodynamic response function that has been used to characterize task-related pupil-AAS coupling.

neuroscience↗

bioRxiv2022

Gamma Oscillations and Emotional Memory

Increased visual gamma band activity is known to relate to memory and encoding in cognitive tasks and has been shown to be present during arousing compared to neutral stimulus processing. Here, we set out to investigate whether gamma activity is stronger for later remembered compared to later forgotten emotional pictures. Thirty-two healthy participants underwent a passive viewing task in which they viewed 208 (104 arousing (52 pleasant and 52 unpleasant) and 104 neutral) pictures from the International Affective Picture System (IAPS) database while we simultaneously recorded their electroencephalogram (EEG). Immediately after, they performed a recognition task including the 208 target pictures they saw before and 104 new pictures (52 arousing (26 pleasant and 26 unpleasant) and 52 neutral) as lures. We found that arousing pictures (unpleasant ones in particular) were better remembered compared to neutral pictures. Importantly, gamma activity was enhanced for remembered compared to forgotten pictures and this effect was stronger for arousing pictures. We conclude that previous findings regarding enhanced gamma as a signature of subsequent memory generalizes to emotional memory. Our findings therefore shed new light on the role of visual gamma band activity in arousal and memory formation.

neuroscience↗

bioRxiv2021

Defensive freezing and its relation to approach-avoidance decision-making under threat

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 of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach-avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia interacted with subjective value, depending on the action-context (i.e., passive vs. active). Specifically, in action-contexts incongruent with participants intrinsic action-tendencies, strong freezers showed diminished effects of subjective value on choice. These findings illustrate the relevance of testing approach-avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach-avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporating internal psychophysiological states and external action-contexts into models of approach-avoidance decision-making.

neuroscience↗

bioRxiv2020

Meta-analytic evidence for downregulation of the amygdala during working memory maintenance

The amygdala is a region critically implicated in affective processes. Downregulation of the amygdala is therefore one of the hallmarks of successful emotion regulation. Downregulation is thought to be established through top-down control of the executive control network over the amygdala. Such a reciprocal relationship, however, is not exclusive to cognitive regulation of emotion. It has recently been noted that any cognitively demanding task may downregulate the amygdala, including a standard working memory task. Here, using a coordinate-based meta-analysis based on an activation likelihood estimation (ALE), we examined whether a standard working memory task (i.e., a 2-back task) downregulates the amygdala similarly to a cognitive reappraisal task. Following the PRISMA guidelines, we included a total of 66 studies using a 2-back working memory task and 65 studies using a cognitive reappraisal task. We found that a standard 2-back working memory task indeed systematically downregulates the amygdala, and that deactivated clusters strongly overlap with those observed during a cognitive reappraisal task. This finding has important consequences for the interpretation of the underlying mechanism of the effects of cognitive reappraisal on amygdala activity: downregulation of amygdala during cognitive reappraisal might be due to the cognitively demanding nature of the task and not per se by the act of the reappraisal itself. Moreover, it raises the possibility of applying working memory tasks in a clinical setting as an alternative emotion regulation strategy.

neuroscience↗

bioRxiv2019

The role of hippocampal spatial representations in contextualization and generalization of fear

Using contextual information to predict aversive events is a critical ability that protects from generalizing fear responses to safe contexts. Animal models have demonstrated the importance of spatial context representations within the hippocampal formation in contextualization of fear learning. The ventromedial prefrontal cortex (vmPFC) is known to play an important role in safety learning, possibly also through the incorporation of context information. However, if contextual representations are related to context-dependent expression of fear memory in humans remains unclear. Twenty-one healthy participants underwent functional MRI combined with a cue-context conditioning paradigm within a self-navigated virtual reality environment. The environment included two buildings (Threat and Safe context), which had distinct features outside but were identical inside. Within each context, participants saw two cues (CS+, CS-). The CS+ was consistently (100% reinforcement rate) paired with an electric shock in the Threat context, but never in the Safe context. The CS- was never paired with a shock. We found robust differential skin conductance responses (SCRs; CS+ > CS-) in the Threat context, but also within the Safe context, indicating fear generalization. Within the Safe context, vmPFC responses to the CS+ were larger than those in the Threat context. We furthermore found environment-specific representantions for the two contexts in the training paradigm (i.e., before conditioning took place) in the hippocampus to be related to fear expression and generalization. Namely, participants with a weak context representation (z-score < 1.65) showed stronger fear generalization compared to participants with a strong context representation (z-score > 1.65). Thus, a low neural representation of spatial context may explain overgeneralization of memory to safe contexts. In addition, our findings demonstrate that context-dependent regulation of fear expression engages ventromedial prefrontal pathways suggesting this involves a similar mechanism that is known to be involved in retrieval of extinction memory.

neuroscience↗

bioRxiv2018

Eye-movement intervention enhances extinction via amygdala deactivation

Improving extinction learning is essential to optimize psychotherapy for persistent fear-related disorders. In two independent studies (both n=24), we found that goal-directed eye movements activate a dorsal fronto-parietal network and transiently deactivate the amygdala. Connectivity analyses revealed this down-regulation engages a ventromedial prefrontal pathway known to be involved in cognitive regulation of emotion. Critically, when eye movements followed memory reactivation during extinction learning, this reduced spontaneous fear recovery 24 hours later. Stronger amygdala deactivation furthermore predicted a stronger reduction in subsequent fear recovery after reinstatement. In conclusion, we show that extinction learning can be improved with a non-invasive eye-movement intervention that triggers a transient suppression of the amygdala. Our finding that another task which taxes working memory leads to a similar amygdala suppression furthermore indicates that this effect is likely not specific to eye movements, which is in line with a large body of behavioral studies. This study contributes to the understanding of a widely used treatment for traumatic symptoms by providing a parsimonious account for how working memory tasks and goal-directed eye movements can enhance extinction-based psychotherapy, namely through neural circuits similar to those that support cognitive control of emotion.\n\nSignificant statementFear-related disorders represent a significant burden on individual sufferers and society. There is a high need to optimize treatment, in particular via non-invasive means. One potentially effective intervention is execution of eye movements following trauma recall. However, a neurobiological understanding of how eye movements can reduce traumatic symptoms is lacking. We demonstrate that goal-directed eye-movements, like working memory tasks, deactivate the amygdala, the core neural substrate of fear learning. Effective connectivity analyses revealed amygdala deactivation engaged dorsolateral and ventromedial prefrontal pathways. When applied during safety learning, this deactivation predicts a reduction in later fear recovery. These findings provide a parsimonious and mechanistic account of how behavioral manipulations taxing working memory and suppress amygdala activity can alter retention of emotional memories.

neuroscience↗