Heart's tale of trauma: Fear-conditioned heart rate changes in post-traumatic stress disorder

The study of emotional memories in neuroscience is now more than ever linked to the use of fear conditioning paradigms, which represent a direct and controlled way to study this phenomenon in humans. Repeated pairings of a neutral stimulus with a negative consequence leads to the creation of a transiently threatening entity, which can be used to assess explicit and implicit ratings of fear. In fact, the use of psychophysiological indices (i.e., skin conductance responses, fear potentiated startle, pupillary responses) represents a less biased tool compared with verbal ratings, as they are harder to control voluntarily. Among those, the use of heart rate (HR) responses is on the rise, as it reveals the presence of fear-induced bradycardia, a phenomenon by which a conditioned stimulus elicits a brief cardiac deceleration upon its presentation. This stems from an intricate interplay among the central and the peripheral nervous systems, by means of the vagus nerve which extends to the heart. The neurovisceral integration model of fear (NVI-f) proposes that high level cognitive structures (i.e., prefrontal cortex) influence both the amygdala and the hippocampus, generating neurovisceral responses via projections that govern heart behaviour. Compromised functioning of those high-level structures can, thus, engender aberrant fear conditioning, which is known to lead to the development of different psychiatric disorders, including post-traumatic stress disorder (PTSD). As these populations of patients show differences from the norm in their conditioned responses when measured by more widely used techniques, it is possible to assume that the same would be true for HR responses. This hypothesis has been investigated with a particular focus on PTSD patients (see Table 1 for a summary). Here, we aim at discussing in a single work the research endeavours made in this field. Moreover, our goal is to provide an interpretation of the various results taken together. PTSD is tightly related to second-order conditioning, a phenomenon by which a conditioned stimulus (CS) can acquire the properties of an unconditioned stimulus (US) and become a US by itself. Moreover, the affective properties of the CS can be further transferred to a second stimulus. This is actually relevant for these patients since cues related to the traumatic event can serve as a US and negatively impact on everyday life. Accordingly, to study this phenomenon, Wessa and Flor recruited trauma exposed individuals, some of which suffered from PTSD, and healthy controls. They had them undergo a fear conditioning paradigm during which one geometrical shape was followed by a picture of an airplane crash, while the other never was. Crucially, HR results showed no differences between the two CSs, in none of the groups, revealing how fear bradycardia does not emerge in situations where the US causes cognitive distress instead of a painful physical sensation. Similarly, Orr et al recruited trauma exposed individuals to partake in a fear conditioning experiment. Some of the participants satisfied the criteria for PTSD, while others did not develop the condition. Differently from the study by Wessa and Flor, the US consisted of a painful physical sensation, namely a shock delivered to the hand. The results of this experiment revealed that PTSD patients showed greater differential responses to the two CS, while non-PTSD patients did not. More specifically, PTSD patients displayed faster HR to the CS+. The authors suggest that this higher conditionability constitutes an explanation for the development of this disorder. Valuable insights can stem even from studies that consider populations with PTSD-related problems instead of the fully fledged condition. Notably, Costanzo et al focused their study not on patients but on war veterans with subthreshold PTSD. Authors hypothesised that given the characteristics of the disorder, higher symptom severity would be associated with greater conditioned responses during both acquisition and extinction. Therefore, they recruited war veterans and split them in two groups based on symptom levels, forming a low and a high symptom group. They underwent a conditional discrimination paradigm, where three different visual stimuli were presented in pairs to participants. During acquisition, the ‘threat’ pairs were presented with an air blast, and the ‘safety’ pair represented the CS . During the inhibition phase, a pair comprised of a stimulus from both previous pairs was presented to assess the ability to associate a safety signal to a threatening cue. Finally, during the extinction phase, both ‘threat’ and ‘safety’ pairs were presented unreinforced. Results revealed that during the acquisition phase, the high symptom group Received: 8 May 2023 Revised: 7 July 2023 Accepted: 23 July 2023