Peripheral cortisol administration blunts reward arousal but heightens anxiety-like arousal in marmosets

AimsExcess hypothalamic-pituitary-adrenal (HPA) axis activation is common in people with major depression and generalised anxiety disorder. We sought to determine whether higher circulating levels of the glucocorticoid cortisol are causally related to the expression of anhedonia-like and anxiety-like behaviours in marmosets.MethodFour marmosets (two male, two female) took part in the study. Cortisol and saline control injections were administered intramuscularly and salivary cortisol samples were taken before and after injections to determine if circulating cortisol levels changed from pre- to post-injection. To measure anhedonia-like behaviours, we trained marmosets on an appetitive Pavlovian conditioning paradigm, where animals learn to associate two anticipatory auditory cues (conditioned stimulus + or conditioned sitmulus -, CS+ or CS-) with the presence or absence of food reward (unconditioned stimulus + or unconditioned stimulus -, US+ or US-). Using cardiovascular telemetry probes and video cameras, we recorded animals' cardiovascular and behavioural arousal in freely moving conditions, comparing the injection of saline control versus 5mg/kg, 10mg/kg or 20mg/kg intramuscular cortisol. To measure anxiety-like behaviours, we used a human intruder (HI) paradigm, where marmosets are confronted with an unfamiliar human in their home cage. We recorded their behaviour on video cameras after saline control or 20mg/kg intramuscular cortisol. We used an exploratory-factor analysis (EFA) to determine how marmosets' behaviours towards the intruder loaded onto an 'anxiety-like' score. We then compared these scores under saline control versus cortisol conditions. Significance was set at p < 0.05.ResultUnlike saline control, we found that subcutaneous injections of 20 mg/kg cortisol successfully elevated peripheral cortisol concentrations to levels equivalent to peak circadian concentrations (p = 0.023). In the appetitive setting, 5 mg/kg, 10 mg/kg and 20 mg/kg cortisol injections blunted anticipatory (CS+ induced) increases in behavioural arousal (p = 0.004) but did not alter anticipatory cardiovascular arousal. Consummatory behavioural and cardiovascular arousal also remained intact. In the HI test, 20 mg/kg cortisol injections moderately increased anxiety towards the intruder as measured by an increase in marmosets' EFA-derived anxiety-like scores (p = 0.035).ConclusionIn marmosets, elevated peripheral cortisol levels are causally related to the behavioural features of blunted reward anticipation together with elevated anxiety-like behaviours characteristic of mood and anxiety disorders. Future work will characterise the neuroimaging changes induced by elevated peripheral cortisol levels and identify the regions of the prefrontal cortex contributing to HPA axis regulation and dysregulation.

Interoceptive cardiac signals selectively enhance fear memories

Fear is coupled to states of physiological arousal. We tested how learning and memory of threat, i.e. conditioned fear, is influenced by interoceptive signals. Forty healthy individuals were exposed to two threat (CS+, paired with electrocutaneous shocks) and two safety (CS-) stimuli, specifically time-locked to either cardiac ventricular systole (when arterial baroreceptors signal cardiovascular arousal to brainstem), or diastole (when these afferent signals are quiescent). Threat learning was indexed objectively using skin conductance responses (SCRs). During acquisition of threat contingencies, cardiac effects dominated: Stimuli (both CS+ and CS-) presented at systole evoked greater SCR responses, relative to stimuli (both CS+ and CS-) presented at diastole. This difference was amplified in more anxious individuals. Learning of conditioned fear was established by the end of the acquisition phase, which was followed by an extinction phase when unpaired CSs were presented at either the same or switched cardiac contingencies. One day later, electrocutaneous shocks triggered the reinstatement of fear responses. Subsequent presentation of stimuli previously encoded at systole evoked higher SCRs. Moreover, only those participants for whom stimuli had the same cardiac-contingency over both acquisition and extinction phases retained conditioned fear memory (i.e. CS + &gt; CS-). Our findings reveal two important cardiac afferent effects on threat learning and memory: 1) Cardiac signals bias processing towards threat. 2) Cardiac signals are a context for fear memory; altering this context can disrupt the memory. These observations suggest how threat reactivity may be reinforced and maintained by both acute and enduring states of cardiac arousal.

Imagined Interactions and Inner Speech

Similarities and differences between inner speech and imagined interactions (IIs) are discussed. Selected studies in both areas are reviewed. Inner speech originally was conceptualized as a stage in language acquisition and the process of thought. It reflects speaking to oneself in the form of monologue. It has been referred to as verbal thinking, inner speaking, covert self-talk, internal monologue, and internal dialogue as people talk to themselves in silence. IIs are similar, yet different in that imaginary dialogue reflects talking to another person while monologue is self-talk. IIs are a type of daydreaming, social cognition, and mental imagery in which people experience cognitive representations of conversation with accompanying verbal and nonverbal features. We highlight relevant studies in the areas of daydreaming, public speaking, rumination, cardiovascular arousal, and road rage. We conclude with two suggestions for future research.

Impact of cardiac interoception cues on voluntary decisions to make or withhold action in an intentional inhibition task

Interoceptive signals concerning the internal physiological state of the body influence motivational feelings and action decisions. Cardiovascular arousal may facilitate inhibition to mitigate risks of impulsive actions. Baroreceptor discharge at ventricular systole underpins afferent signalling of cardiovascular arousal. We used a modified Go/NoGo task to demonstrate that decisions to make or withhold actions on ‘Choose’ trials were not, in fact, influenced by cardiac phase. However, cardiac interoceptive awareness (insight) predicted how frequently participants chose to act: Participants with higher awareness tended to withhold actions, while those with lower awareness tended to execute actions. Moreover, on a scale of impulsive behaviour, self-reported urgency correlated negatively with intentional inhibition rates. Individual differences in heart rate variability did not predict intentional inhibition. These findings suggest that lower insight into bodily signals is linked to urges to move the body, putatively by engendering noisier sensory input into motor decision processes eliciting reactive behaviour.

Response inhibition on the stop signal task improves during cardiac contraction

Motor actions can be facilitated or hindered by psychophysiological states of readiness, to guide rapid adaptive action. Cardiovascular arousal is communicated by cardiac signals conveying the timing and strength of individual heartbeats. Here, we tested how these interoceptive signals facilitate control of motor impulsivity. Participants performed a stop signal task, in which stop cues were delivered at different time points within the cardiac cycle: at systole when the heart contracts, or at diastole between heartbeats. Response inhibition, indexed by a shorter stop signal reaction time (SSRT) and longer stop signal delay (SSD), was better at systole. Furthermore, parasympathetic control of cardiovascular tone, and subjective sensitivity to interoceptive states, predicted response inhibition efficiency. This suggests that response inhibition capacity is influenced by interoceptive physiological cues, such that people are more likely to express impulsive actions during putative states of lower cardiovascular arousal, when frequency and strength of cardiac afferent signalling is reduced.

High cardiorespiratory fitness in early to late middle age preserves the cortical circuitry associated with brain-heart integration during volitional exercise

This study tested the hypothesis that high cardiorespiratory fitness (peak oxygen uptake) preserves the cortical circuitry associated with cardiac arousal during exercise in middle- to older-aged individuals. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 52 healthy, active individuals (45–73 yr; 16 women, 36 men) across a range of fitness (26–66 ml·kg−1·min−1). Seven repeated bouts of isometric handgrip (IHG) at 40% maximal voluntary contraction force were performed with functional magnetic resonance imaging at 3 T, with each contraction lasting 20 s and separated by 40 s of rest. HR responses to IHG showed high variability across individuals. Linear regression revealed that cardiorespiratory fitness was not a strong predictor of the HR response ( r2 = 0.09). In a region-of-interest analysis both the IHG task and the HR time course correlated with increased cortical activation in the bilateral insula and decreased activation relative to baseline in the anterior and posterior cingulate and medial prefrontal cortex (MPFC). t-Test results revealed greater deactivation at the MPFC with higher fitness levels beyond that of guideline-based activity. Therefore, whereas high cardiorespiratory fitness failed to affect absolute HR responses to IHG in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal. NEW & NOTEWORTHY Our first observation suggests that fitness does not strongly predict the heart rate (HR) response to a volitional handgrip task in middle- to older-aged adults. Second, the BOLD response associated with the handgrip task, and with the HR time course, was associated with response patterns in the cortical autonomic network. Finally, whereas high cardiorespiratory fitness failed to affect absolute HR responses to isometric handgrip in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal, beyond that achieved through healthy active living.