Animal to human translational paradigms relevant for approach avoidance conflict decision making

Abstract

Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work.

Keywords: Anxiety; Approach-avoidance conflict; Decision-making; Fear; Translational.

Fig. 1. Animal punishment-induced conflict paradigms and translational human approach-avoidance conflict paradigms in which the punishment is affective or painful in nature

(A) A1 and A2 are pictorial representations of the Vogel and Geller-Seifter conflict tests, respectively. For these tests, rodents are delivered a shock after a specific number of water licks (Vogel) or level presses for food (Geller-Seifter). (B) B1 is a figure reprinted with permission from Talmi et al. (2009). How humans integrate the prospects of pain and reward during choice. Journal of Neuroscience, 29(46). This task presented participants with choices between two faces associated with either high or low probability of tactile (shock or touch) stimulation combined with a monetary gain or loss. B2 is a figure reprinted with permission from Schlund et al. (2016). The tipping point: Value differences and parallel dorsaleventral frontal circuits gating human approacheavoidance behavior. NeuroImage, 136, p. 97. This task presented participants with a binary choice to approach or avoid a potential $.10 outcome that was paired with varying threat (probability) of losing $1.00 and hearing an aversive female scream. B3 is a task developed by one of tShe current authors (Aupperle et al., 2011) in which participants are presented with choices between two outcomes on either side of a runway and during conflict trials, one of these outcomes consists of a negative affective image/sound combined with point reward while the other outcome consists of a positive affective image/sound combined with no points. (C) A summary of behavioral and functional magnetic resonance imaging (fMRI) findings for each human paradigm are provided.

Fig. 2. Animal exploratory paradigms and translational human exploratory paradigms

(A) A1 is pictorial representation of the elevated plus maze task in which rodents are placed on a center platform of a maze with two open arms and two enclosed arms. A2 is a pictorial representation of the light-dark box in which rodents are placed into a box divided into equal black/enclosed and white/glass compartments. A3 is a pictorial representation of the open field test in which the rodent is placed in an open field area to explore. A4 is a pictorial representation of the rodent behavioral pattern monitor (a type of activity chamber) consisting of a chamber with rearing touchplates on the walls and holes in the floors and walls to invite exploration. (B) B1 is a figure reprinted from Kallai et al. (2007). Cognitive and affective aspects of thigmotaxis strategy in humans. Behavioral Neuroscience, 121(1). Investigators used both a computer-generated circular arena (not pictured) and a real arena maze, consisting of a large circular timber wall arena with eight navigation objects placed throughout. Participants goal is to find a target platform while wearing opaque swimming glasses. B2 is a figure reprinted with permission from Walz et al. (2016). A Human Open Field Test Reveals Thigmotaxis Related to Agoraphobic Fear frontal circuits gating human approacheavoidance behavior. Biological Psychiatry, 80(5). This task consists of a 166 m × 79 m unlined soccer field that participants are asked to walk on in any way they chose for 15 minutes. B3 is a human behavioral pattern monitor developed by one of the current authors (Young et al., 2007; Perry et al., 2009) in which participants are asked to wait for 15 minutes in a room (designed to appear as an “office in transition”), with objects placed around the room to invite exploration.