Elsevier

NeuroImage

Volume 29, Issue 3, 1 February 2006, Pages 1007-1012
NeuroImage

Rapid Communication
Contingency awareness in human aversive conditioning involves the middle frontal gyrus

https://doi.org/10.1016/j.neuroimage.2005.09.011Get rights and content

Abstract

In contrast to the wealth of data describing the neural mechanisms underlying classical conditioning, we know remarkably little about the mechanisms involved in acquisition of explicit contingency awareness. Subjects variably acquire contingency awareness in classical conditioning paradigms, in which they are able to describe the temporal relationship between a conditioned cue and its outcome. Previous studies have implicated the hippocampus and prefrontal cortex in the acquisition of explicit knowledge, although their specific roles remain unclear. We used functional magnetic resonance imaging to track the trial-by-trial acquisition of explicit knowledge in a concurrent trace and delay conditioning paradigm. We show that activity in bilateral middle frontal gyrus and parahippocampal gyrus correlates with the accuracy of explicit contingency awareness on each trial. In contrast, amygdala activation correlates with conditioned responses indexed by skin conductance responses (SCRs). These results demonstrate that brain regions known to be involved in other aspects of learning and memory also play a specific role, reflecting on each trial the acquisition and representation of contingency awareness.

Introduction

Learning about aversive stimuli in the environment is necessary for an organism's success. One of the simplest and best studied mechanisms by which this is realized is classical conditioning, whereby a predictive association is learned between a neutral stimulus (the conditioned stimulus or CS) and a biologically meaningful signal (the unconditioned stimulus or US) (Pavlov, 1906, Cook and Harris, 1937, Wilensky et al., 1999, Buchel and Dolan, 2000, Maren, 2001, Clark et al., 2002, LeDoux, 2003, Maren and Quirk, 2004). Typically, after repeated pairings of CS and US, the CS comes to elicit a response that is appropriate to the anticipated US. In aversive conditioning, this conditioned response (CR) will often be a change in heart rate or skin conductance, and is taken as an implicit measure of successful conditioning in experimental studies.

It is possible to become consciously aware of the predictive contingency between CS and US, a phenomenon referred to as contingency awareness. An individual can acquire both implicit associations and contingency awareness or either may be acquired independently (Bechara et al., 1995) indicating some degree of dissociation between the two systems. Currently, a major question in conditioning (and consciousness) research is the extent, and mechanism, of contingency awareness effects in conditioning (Hilgard et al., 1937, Cole, 1939, Dawson and Furedy, 1976, Lovibond and Shanks, 2002, Wiens and Ohman, 2002, Olsson and Phelps, 2004). A better understanding of contingency awareness and how it can facilitate or inhibit implicit associations is critical for a rational treatment of phobias, placebo effects, and anxiety disorders (Grillon, 2002, Quirk and Gehlert, 2003, Colloca and Benedetti, 2005).

The acquisition of contingency awareness and its interaction with conditioning differ across conditioning protocols (Clark and Squire, 1998, Ohman and Soares, 1998, Knuttinen et al., 2001, Han et al., 2003). For instance, in trace conditioning, in which there is temporal separation between CS and US, contingency awareness has been shown to correlate positively with the amplitude of conditioned responses(Clark and Squire, 1998). Those subjects in a trace conditioning experiment who do not display contingency knowledge fail to be trace conditioned. By contrast, in delay conditioning, in which there is no separation between the CS and US, no correlation between contingency awareness and successful conditioning has been observed; either can be acquired in the absence of the other. However, the simplicity of the delay protocol often results in immediate acquisition of explicit knowledge, making separation of explicit from implicit processes using a delay paradigm alone difficult.

In this study, we used functional magnetic resonance imaging (fMRI) to identify brain regions that were specifically related to the explicit acquisition of contingency awareness during both delay and trace conditioning, independent of individual protocols. We simultaneously conditioned human subjects to predict an aversive electrical stimulus (US) from arbitrary visual cues (CS) with concurrent delay and trace protocols (see Figs. 1a, b). The use of simultaneous conditioning allowed us to identify brain responses specifically correlated with contingency awareness and distinct from responses associated with measures of implicit knowledge. To assess contingency awareness, subjects reported their shock expectancy on each trial (Figs. 1c, d), and in addition filled out a post-experimental questionnaire. These measures were then used to identify brain responses that correlated with accurate contingency awareness. We predicted that activity in dorsolateral prefrontal cortex and hippocampus would correlate with these measures of explicit knowledge based on evidence that these structures are involved in working memory (Leung et al., 2002), memory formation (Fanselow, 2000), and revaluation (Corlett et al., 2004), as well as from lesion studies of trace conditioning deficits (Compton et al., 1997, Clark and Squire, 1998, Kronforst-Collins and Disterhoft, 1998, McEchron et al., 1998).

Section snippets

Participants

We recruited 16 healthy right-handed subjects. Two were excluded: one because of excessive movement-related artifact precluding image analysis, and another subject who did not have at least one significant skin conductance response (SCR) for each trial type, precluding study of the time course of learning. The remaining subjects are reported in the analysis: 9 male and 5 female, age range 19–31 (mean 24.7). All subjects gave prior informed consent. This study was approved by the Joint Ethics

Conditioned skin conductance responses

We recorded skin conductance responses associated with visual cues to provide an implicit measure of conditioning. Activity in the left amygdala (−27, −3, −12) correlated with the trial-by-trial time course of conditioning, indexed by the level of discriminatory skin conductance responses (P < 0.01 corrected, see Methods and Table 1a). This result confirms previous findings (Buchel et al., 1998a, Buchel et al., 1999, Knight et al., 2004) and in addition demonstrates that amygdala activity

Discussion

Our data indicate a clear role for the middle frontal gyrus in contingency awareness during conditioning, correlated specifically with the acquisition of awareness on a trial-by-trial basis. To our knowledge, this is the first time such a trial-by-trial link has been demonstrated during conditioning. The role of the middle frontal gyrus in contingency awareness is contrasted with involvement of the amygdala which we show to reflect the acquisition of implicit knowledge, as indexed by autonomic

Acknowledgments

This work was supported by grants from the Gordon Moore Foundation, the National Science Foundation, Sandia National Laboratory, and the Wellcome Trust Programme Grant to RJD. RMC would like to thank N. Tsuchiya, C. Hofstötter, and K. Watson for discussions and comments on the manuscript.

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