Hippocampal Representation of Threat Features and Behavior in a Human Approach–Avoidance Conflict Anxiety Task

Abstract

Decisions under threat are crucial to survival and require integration of distinct situational features, such as threat probability and magnitude. Recent evidence from human lesion and neuroimaging studies implicated anterior hippocampus (aHC) and amygdala in approach-avoidance decisions under threat, and linked their integrity to cautious behavior. Here we sought to elucidate how threat dimensions and behavior are represented in these structures. Twenty human participants (11 female) completed an approach-avoidance conflict task during high-resolution fMRI. Participants could gather tokens under threat of capture by a virtual predator, which would lead to token loss. Threat probability (predator wake-up rate) and magnitude (amount of token loss) varied on each trial. To disentangle effects of threat features, and ensuing behavior, we performed a multifold parametric analysis. We found that high threat probability and magnitude related to BOLD signal in left aHC/entorhinal cortex. However, BOLD signal in this region was better explained by avoidance behavior than by these threat features. A priori ROI analysis confirmed the relation of aHC BOLD response with avoidance. Exploratory subfield analysis revealed that this relation was specific to anterior CA2/3 but not CA1. Left lateral amygdala responded to low and high, but not intermediate, threat probability. Our results suggest that aHC BOLD signal is better explained by avoidance behavior than by threat features in approach-avoidance conflict. Rather than representing threat features in a monotonic manner, it appears that aHC may compute approach-avoidance decisions based on integration of situational threat features represented in other neural structures.

The anxiety‐specific hippocampus–prefrontal cortex pathways links to procrastination through self‐control

“…Moreover, direct reciprocal connections between anterior HPC and the amygdala, insula, as well as medial PFC conspired to offer it a privileged interface with affect, especially anxiety and stress (Zeidman & Maguire, 2016). For example, human studies showed activation in the anterior HPC occurred in the paradigms like contextual fear conditioning (i.e., a spatial location associated with aversive stimulus; Pohlack, Nees, Ruttorf, Schad, & Flor, 2012), and approach‐avoidance conflict anxiety task which was central to the genesis of anxiety (Abivardi, Khemka, & Bach, 2020; Loh et al, 2017). Taken together, these findings indicated why it was the left rostral hippocamps, rather than its caudal zone, that anatomically functioned with the prefrontal regions to anxiety‐processing.…”

Mental Resilience and Coping With Stress: A Comprehensive, Multi-level Model of Cognitive Processing, Decision Making, and Behavior

“…This is an example of accentuated alarm-to-threat stage by rigid binary cognitive strategy, whereas improving cognitive flexibility by configural associative learning could be a key element in the psychotherapeutical approach. Another example is that strong fear can elicit avoidance behavior related to the left lateral amygdala and anterior hippocampal hyperactivity (Abivardi et al, 2020). In other words, ''cold'' executive functioning is set to prioritize the most reliable decision-making to avoid danger when confronting a threat, yet it limits attention and flexibility.…”

Cross-species anxiety tests in psychiatry: pitfalls and promises

“…This tendency is reduced in persons with surgical and acute inflammatory hippocampus lesions [ 18 ]. Furthermore, gamma oscillations in HC and theta HC-PFC coupling increase with predator probability [ 33 ], and hippocampus (particularly CA2/3) BOLD signal increases with increased avoidance [ 39 ]. In N = 41 participants, self-reported trait anxiety [ 83 ] was related to behaviour in a non-linear way [ 40 ].…”

“…Indeed, cross-species anxiety tests have led to remarkable insights into the basic neurobiology and cognitive mechanisms of threat avoidance behaviour in healthy individuals. Expanding on the classic septo-hippocampal model established in the 1980s [14,15], more recent research has highlighted the contribution of various additional brain regions to avoidance behaviour, such as amygdala [16][17][18], nucleus accumbens [19,20], area 25 [21], as well as striatum and anterior cingulate cortex (ACC) [22][23][24][25][26][27]; how they communicate by neural oscillations [28][29][30][31][32][33][34]; the more finegrained role of hippocampal subfields [35][36][37][38][39]; and the computational mechanisms that underly behaviour under threat [40][41][42][43] as well as their neural implementation [44]. Despite these fascinating insights, however, we argue that the field is yet to deliver on the three clinical promises.…”