Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review

Abstract

Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm.A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending on specific design parameters. These include stronger hippocampal activation in trace conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli enhance activation of pain related, motor, and somatosensory areas.Differences concerning experimental factors may partly explain the variance between neuroimaging investigations on human fear conditioning and extinction and should, therefore, be taken into serious consideration in the planning and the interpretation of research projects.

Oxytocin Facilitates Pavlovian Fear Learning in Males

“…This response is not surprising owing to previous findings showing that the ACC has a crucial role within a general neural fear circuit (Hariri et al, 2003) as well as within the framework of Pavlovian fear conditioning (see reviews by Milad et al, 2007;Sehlmeyer et al, 2009). Furthermore, OXT has been found to moderate ACC activity (Gorka et al, 2015;Scheele et al, 2014a), and the ACC is characterized by a high OXT receptor density (Boccia et al, 2013).…”

“…We predicted that OXT IN would facilitate rather than inhibit Pavlovian fear conditioning. We expected this to be evident in psychophysiology as well as in fear-related neural networks (Sehlmeyer et al, 2009). These networks include the amygdala as well as middle and anterior parts of the cingulate cortex, which are involved in negative affect (Vogt, 2005) and whose activations have been found to be susceptible to OXT IN (Eckstein et al, 2014a, b;Preckel et al, 2014;Scheele et al, 2014a, b).…”

“…Experimentally, Pavlovian fear conditioning is established by repeatedly coupling a neutral stimulus (CS+) with an aversive stimulus (UCS), which leads to a conditioned response (CR) to the CS+ alone (Sehlmeyer et al, 2009). However, whether or not Pavlovian fear conditioning benefits from human sociality has received less attention from neurobiology.…”

Plasticity of human auditory-evoked fields induced by shock conditioning and contingency reversal

“…1C). Thus, the pupil CR did not undergo reversal, in terms of tone affiliation, after contingency reversal, but rather "extinguished" then (23)(24)(25)(26). This remains the case even when considering only later parts of phase 3.…”

The time course of attentional bias to cues of threat and safety

“…Bekhterev, 1913;Kim & Jung, 2006;Pape & Pare, 2010;Pape & Stork, 2003), and has also long been proven effective in humans (e.g. Fendt & Fanselow, 1999;LaBar, Gatenby, Gore, LeDoux, & Phelps, 1998;Sehlmeyer et al, 2009;Watson & Rayner, 1920). In a classic fear-conditioning paradigm, an initially neutral stimulus (CS) such as a sound is associated with an aversive unconditioned stimulus (US) such as an electrical shock, while another neutral stimulus remains unpaired (CS−) (Maren, 2001;Pavlov, 1927).…”