Thigmotaxis in a virtual human open field test

Abstract

Animal models are used to study neurobiological mechanisms in mental disorders. Although there has been significant progress in the understanding of neurobiological underpinnings of threat-related behaviors and anxiety, little progress was made with regard to new or improved treatments for mental disorders. A possible reason for this lack of success is the unknown predictive and cross-species translational validity of animal models used in preclinical studies. Re-translational approaches, therefore, seek to establish cross-species translational validity by identifying behavioral operations shared across species. To this end, we implemented a human open field test in virtual reality and measured behavioral indices derived from animal studies in three experiments ($$\textit{N}=31$$ N = 31 , $$\textit{N}=30$$ N = 30 , and $$\textit{N}=80$$ N = 80 ). In addition, we investigated the associations between anxious traits and such behaviors. Results indicated a strong similarity in behavior across species, i.e., participants in our study—like rodents in animal studies—preferred to stay in the outer region of the open field, as indexed by multiple behavioral parameters. However, correlational analyses did not clearly indicate that these behaviors were a function of anxious traits of participants. We conclude that the realized virtual open field test is able to elicit thigmotaxis and thus demonstrates cross-species validity of this aspect of the test. Modulatory effects of anxiety on human open field behavior should be examined further by incorporating possible threats in the virtual scenario and/or by examining participants with higher anxiety levels or anxiety disorder patients.

A comparative analysis of Danionella cerebrum and zebrafish (Danio rerio) larval locomotor activity in a light-dark test

“…Thigmotaxis or centrophobism, i.e., the tendency of animals to avoid the center area of an open field or arena and instead to spend more time in its periphery, is a behavioral response that is evolutionary conserved from Drosophila ( Besson and Martin, 2005 ; Mohammad et al, 2016 ) to zebrafish ( Colwill and Creton, 2011 ; Richendrfer et al, 2012 ; Schnörr et al, 2012 ; Pietri et al, 2013 ; Zhang et al, 2017 ; Xu and Guo, 2020 ) and mammals ( Hall, 1934 ; Denenberg, 1969 ; Treit and Fundytus, 1988 ; Prut and Belzung, 2003 ), including humans ( Walz et al, 2016 ; Gromer et al, 2021 ). Although a natural behavioral tendency across species, it has been suggested that thigmotaxis is indicative of an anxiety-like state in both larval and adult zebrafish ( Maximino et al, 2010 ; Richendrfer et al, 2012 ; Schnörr et al, 2012 ; Pietri et al, 2013 ; Zhang et al, 2017 ; Abreu et al, 2020 ; Xu and Guo, 2020 ).…”

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

“…The use of virtual environments has allowed for additional assessments of humans on similar learning and memory tasks used in rodents. Using a virtual open field task, Gromer et al (2021) investigated human movement behavior as analogous to animal studies and showed a strong similarity across species ( Gromer et al, 2021 ). Biedermann et al (2017) re-translated the elevated plus maze to a human virtual reality test and reported the predicted open-arm avoidance ( Biedermann et al, 2017 ).…”

Preclinical and clinical evidence on the approach-avoidance conflict evaluation as an integrative tool for psychopathology

“…This approach should build a more solid basis to develop novel tools to help clinical diagnosis and maximise the predictive validity of AAC preclinical paradigms used to test pharmacological interventions for humans (Belzung and Lemoine, 2011 ). Cross-species behavioural tests to assess AAC mainly exploit paradigms of exploration (Gromer et al ., 2021 ). Mammals' functioning is indeed based on an innate exploratory drive for territorial recognition, food supply and reproduction, which are in turn associated with a significant reward (Kidd and Hayden, 2015 ).…”