What we imagine is what we do? A critical overview about mental imagery as a strategy to study human defensive responses.

There is not a single and perfect instinctive behavior to react to threatening situations. However, the study of particular features of these situations suggests the existence of prototypical emotional reactions and associated defensive behaviors. Since all living beings are subjected to common evolutionary pressures, such as predation and conspecific competition, it is plausible that there is conservation of some basic defensive responses in their behavioral repertoire. The choice for approaching or withdrawing from a given situation depends, among others things, on environmental features, including the threat intensity and the distance from the source of the threat. If these basic responses were conserved in humans, they should be expressed in ways similar to those observed in non-human animals. Due to ethical reasons and easy application, mental imagery has been used to test this hypothesis. The studies included in this review point to the validity of this method, with both self-report and neurophysiological findings corroborating the hypothesis under scrutiny. Despite the need for additional investigation to deal with some limitations, the information obtained with this method can help to a better understanding of the conditions that provoke specific defensive behaviors and related emotions. This knowledge may also contribute to identify vulnerability factors for fear/anxiety-related disorders.

µ-Opioid and 5-HT1A receptors in the dorsomedial hypothalamus interact for the regulation of panic-related defensive responses.

The dorsomedial hypothalamus (DMH) and the dorsal periaqueductal gray (DPAG) have been implicated in the genesis and regulation of panic-related defensive behaviors, such as escape. Previous results point to an interaction between serotonergic and opioidergic systems within the DPAG to inhibit escape, involving µ-opioid and 5-HT1A receptors (5-HT1AR). In the present study we explore this interaction in the DMH, using escape elicited by electrical stimulation of this area as a panic attack index. The obtained results show that intra-DMH administration of the non-selective opioid receptor antagonist naloxone (0.5 nmol) prevented the panicolytic-like effect of a local injection of serotonin (20 nmol). Pretreatment with the selective µ-opioid receptor (MOR) antagonist CTOP (1 nmol) blocked the panicolytic-like effect of the 5-HT1AR agonist 8-OHDPAT (8 nmol). Intra-DMH injection of the selective MOR agonist DAMGO (0.3 nmol) also inhibited escape behavior, and a previous injection of the 5-HT1AR antagonist WAY-100635 (0.37 nmol) counteracted this panicolytic-like effect. These results offer the first evidence that serotonergic and opioidergic systems work together within the DMH to inhibit panic-like behavior through an interaction between µ-opioid and 5-HT1A receptors, as previously described in the DPAG.

Behavioral and neuroimaging responses induced by mental imagery of threatening scenarios.

Functional neuroimaging studies have shown that actual situations of uncertain or distant threats increase the activity of forebrain regions, whereas proximal threats increase the activity of the dorsal midbrain. This experiment aimed at testing the hypothesis that brain activity elicited by imagined scenarios of threats with two different magnitudes, potential and imminent, resembles that found in response to actual threats. First, we measured subjective responses to imagined scenarios of potential and imminent threats compared with neutral and pleasant scenarios. The same scenarios were used as a paradigm in a functional magnetic resonance imaging experiment. Behavioral results show that the scenarios draw a gradient of hedonic valence and arousal dimensions. Both potential and imminent threat scenarios increased subjective anxiety; the imminent threat scenario also increased feelings of discomfort and bodily symptoms. The functional magnetic resonance imaging results revealed modulations of BOLD signal in the ventromedial prefrontal cortex by potential threat and in the periaqueductal gray matter by imminent threat. These results agree with previously reported evidence using actual threat situations, indicating that mental imagery is a reliable method for studying the functional neuroanatomy of relevant behavioral processes.