Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans

Serotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan—in a double-blind randomised placebo-controlled design—healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.

The disturbance leg-lift response (DLR): an undescribed behavior in bumble bees

Background Bumble bees, primarily Bombus impatiens and B. terrestris, are becoming increasingly popular organisms in behavioral ecology and comparative psychology research. Despite growing use in foraging and appetitive conditioning experiments, little attention has been given to innate antipredator responses and their ability to be altered by experience. In this paper, we discuss a primarily undescribed behavior, the disturbance leg-lift response (DLR). When exposed to a presumably threatening stimulus, bumble bees often react by lifting one or multiple legs. We investigated DLR across two experiments. Methods In our first experiment, we investigated the function of DLR as a prerequisite to later conditioning research. We recorded the occurrence and sequence of DLR, biting and stinging in response to an approaching object that was either presented inside a small, clear apparatus containing a bee, or presented directly outside of the subject’s apparatus. In our second experiment, we investigated if DLR could be altered by learning and experience in a similar manner to many other well-known bee behaviors. We specifically investigated habituation learning by repeatedly presenting a mild visual stimulus to samples of captive and wild bees. Results The results of our first experiment show that DLR and other defensive behaviors occur as a looming object approaches, and that the response is greater when proximity to the object is lower. More importantly, we found that DLR usually occurs first, rarely precedes biting, and often precedes stinging. This suggests that DLR may function as a warning signal that a sting will occur. In our second experiment, we found that DLR can be altered as a function of habituation learning in both captive and wild bees, though the captive sample initially responded more. This suggests that DLR may be a suitable response for many other conditioning experiments.

Does Selection History Influence Attentional Capture by Threat in the Dot-Probe Task?

Threatening stimuli are often thought to have sufficient potency to capture spatial attentional resources over neutral stimuli. But few studies have examined if implicit factors like the selection history of the threatening stimulus influences such cases of capture. Here we tested whether capture by threat in the recent past (i.e., the previous trial) would carryover, or influence capture by threat in the present (i.e., the current trial). In two highly powered dot-probe experiments, we observed a small and a reverse capture effect (sometimes referred to as avoidance) for fearful faces (n = 241) and threatening images (n = 82), respectively. Critically, we found no evidence of carryover effects for either type of threatening stimuli. We conclude that within the standard dot-probe paradigm, capture by threat in healthy adults is not moderated by the selection history for threatening stimuli.

Prelimbic-dependent activation of amygdala somatostatin interneurons signals non-aversive cues to promote discrimination

The amygdala and prelimbic cortex (PL) communicate during fear discrimination retrieval, but how they coordinate to discriminate a non-threatening stimulus is unknown. Here, we show that somatostatin interneurons (SOM) in the basolateral amygdala (BLA) become active specifically during learned non-threatening cues, when they block sensory-evoked phase resetting of theta-oscillations. Further, we show that SOM activation is PL-dependent, and promotes discrimination of non-threat. Thus, fear discrimination engages PL-dependent coordination of BLA SOM responses to non-threatening stimuli.

The specificity of sperm-mediated paternal effects in threespined sticklebacks

Parental effects can help offspring cope with challenging environments, but whether these effects are unique to specific environmental conditions is largely unknown. Parental effects may evolve via a core pathway that generally prepares offspring for risky environments or could be stimuli-specific, with offspring developing phenotypes that are tailored to specific environmental challenges. We exposed threespined sticklebacks (Gasterosteus aculeatus) fathers to a potentially threatening stimulus (net) versus native predator (sculpin). Offspring of sculpin-exposed fathers were more responsive (greater change in activity) to a simulated predator attack, while offspring of net-exposed fathers were less responsive (lower plasma cortisol and fewer antipredator behaviors). To evaluate offspring response to native and non-native stimuli, we sequentially exposed offspring of net-exposed, sculpin-exposed or control fathers to a net, native sculpin model, or non-native trout model. Paternal treatment did not influence offspring response to stimuli; instead, offspring were more responsive to the native sculpin predator compared to nets or non-native trout predator. Collectively, we demonstrate that sperm-mediated paternal effects in response to different, potentially stressful stimuli result in distinct offspring phenotypes. This specificity may be key to understanding the evolution of adaptive parental effects and how parents prime offspring for encountering both evolved and novel environmental stimuli.

How does a threatening stimulus affect the memory of the display?

Ample research has suggested that visual attention is biased towards threat and it was argued that this bias is an essential component of survival and implicated in anxiety. However, it is less clear how this bias is translated into memory, and specifically into the memory of items presented near a threatening stimulus. Here, we investigated this issue by testing how well people remember neutral and threatening images presented under various task demands. On each trial, observers saw two images before performing a dot-probe task (Experiment 1), a colour discrimination task (Experiment 2), a global or local attention task (Experiment 3), or no task at all (Experiment 4). A recognition memory test was performed at the end of each experiment to assess how the presence of a threatening image influences the memory of both images presented in the display. In all experiments, overall memory was enhanced as more threatening images were presented in the display. However, this enhancement did not occur at the expense of the processing of the surroundings. That is, with the exception of the dot-probe task, memory performance was not affected by an adjacent threatening image. Together, these findings challenge trade-off accounts, which predict that the processing of a threatening stimulus should take place at the expense of the processing of nearby items. Instead, these findings suggest that any effect of threat on the visual processing of the display is short-lived and more limited than previously thought.

Manipulating the Perceived Shape and Color of a Virtual Limb Can Modulate Pain Responses

Changes in body representation may affect pain perception. The effect of a distorted body image, such as the telescoping effect in amputee patients, on pain perception, is unclear. This study aimed to investigate whether distorting an embodied virtual arm in virtual reality (simulating the telescoping effect in amputees) modulated pain perception and anticipatory responses to pain in healthy participants. Twenty-seven right-handed participants were immersed in virtual reality and the virtual arm was shown with three different levels of distortion with a virtual threatening stimulus either approaching or contacting the virtual hand. We evaluated pain/discomfort ratings, ownership, and skin conductance responses (SCRs) after each condition. Viewing a distorted virtual arm enhances the SCR to a threatening event with respect to viewing a normal control arm, but when viewing a reddened-distorted virtual arm, SCR was comparatively reduced in response to the threat. There was a positive relationship between the level of ownership over the distorted and reddened-distorted virtual arms with the level of pain/discomfort, but not in the normal control arm. Contact with the threatening stimulus significantly enhances SCR and pain/discomfort, while reduced SCR and pain/discomfort were seen in the simulated-contact condition. These results provide further evidence of a bi-directional link between body image and pain perception.

Influence of Pairing Startling Acoustic Stimuli with Postural Responses Induced by Light Touch Displacement

The first exposure to an unexpected, rapid displacement of a light touch reference induces a balance reaction in naïve participants, whereas an arm-tracking behaviour emerges with subsequent exposures. The sudden behaviour change suggests the first trial balance reaction arises from the startling nature of the unexpected stimulus. We investigated how touch-induced balance reactions interact with startling acoustic stimuli. Responses to light touch displacements were tested in 48 participants across six distinct combinations of touch displacement (DISPLACEMENT), acoustic startle (STARTLE), or combined (COMBINED) stimuli. The effect of COMBINED depended, in part, on the history of the preceding stimuli. Participants who received 10 DISPLACEMENT initially, produced facilitated arm-tracking responses with subsequent COMBINED. Participants who received 10 COMBINED initially, produced facilitated balance reactions, with arm-tracking failing to emerge until the acoustic stimuli were discontinued. Participants who received five DISPLACEMENT, after initially habituating to 10 STARTLE, demonstrated re-emergence of the balance reaction with the subsequent COMBINED. Responses evoked by light touch displacements are influenced by the startling nature of the stimulus, suggesting that the selection of a balance reaction to a threatening stimulus is labile and dependent, in part, on the context and sensory state at the time of the disturbance.

Patients with dorsolateral prefrontal cortex lesions are capable of discriminatory threat learning but appear impaired in cognitive regulation of subjective fear

Humans are able to cognitively regulate emotions by changing their thoughts. Neuroimaging studies show correlations between dorsolateral prefrontal cortex (dlPFC) activity and cognitive regulation of emotions. Here our objective was to investigate whether dlPFC damage is associated with impaired cognitive regulation of emotion. We therefore tested the ability of patients with dlPFC lesions (N = 6) and matched control participants (N = 19) to utilize a laboratory version of cognitive regulation training (CRT) to regulate subjective fear and autonomic threat responses following Pavlovian threat conditioning. We found that patients with dlPFC lesions were able to acquire conditioned threat but seemed impaired in their ability to utilize CRT to cognitively regulate subjective fear to a threatening stimulus. Despite inclusion of a limited number of lesion patients, our results suggest that the dlPFC is important for the cognitive regulation of subjective fear.