Neural correlates of aversive conditioning: development of a functional imaging paradigm for the investigation of anxiety disorders

Abstract

The purpose of the present study was to establish a short paradigm for the examination of classical aversive conditioning processes for application in patients with anxiety disorders. We measured behavioral, autonomic and neural correlates of the paradigm in healthy subjects, applying functional magnetic resonance imaging (fMRI) and measurement of skin conductance. Therefore, neutral visual stimuli were paired with an unpleasant white noise as unconditioned stimulus. Twenty healthy subjects performed three experimental phases of learning: familiarization, acquisition and extinction. Subjective ratings of valence and arousal after each phase of conditioning as well as skin conductance measurement indicated successful conditioning. During acquisition, fMRI results showed increased activation for the conditioned stimulus (CS+(unpaired)) when compared with the non-conditioned stimulus (CS-) in the right amygdala, the insulae, the anterior cingulate cortex and the parahippocampal gyrus, all regions known to be involved in emotional processing. In addition, a linearly decreasing activation in the right amygdala/hippocampus for the CS- across the acquisition phase was found. There were no significant differences between CS+ and CS- during extinction. In conclusion, the applicability of this paradigm for the evaluation of neural correlates in conditioning and extinction processes has been proven. Thus, we present a promising paradigm for the examination of the fear-circuit in patients with anxiety disorders and additionally effects of cognitive-behavioral interventions.

Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing

“…The task design and analyses has been described in detail elsewhere 51,52 . Briefly, we employed a differential fear conditioning task that consisted of three phases (familiarisation (F); acquisition (A) and extinction (E)), each subdivided into an early and a late phase.…”

“…A Monte Carlo simulation was conducted to establish an appropriate voxel contiguity threshold 53 . Thus, for all analyses voxels with a significance level of p < 0.005 uncorrected belonging to clusters with at least 142 voxels are reported (see also 51,52,54,55 ). Whole-brain analysis was carried out first.…”

Understanding mental disorders from neuronal networks to glial cells and proteomics

“…Looking for the neural correlates of aversive conditioning, Reinhardt et al [1] are searching for a functional imaging paradigm to investigate a basis of anxiety disorders. Likewise searching for a suitable phenotype of disturbed neuronal development, several research groups have focussed on the analysis of gyral pattern.…”

Neural Correlates of Procedural Variants in Cognitive-Behavioral Therapy: A Randomized, Controlled Multicenter fMRI Study

“…Parallel versions of a previously validated differential conditioning paradigm were applied during fMRI data acquisition (details in Kircher et al [1] and Reinhardt et al [36]) before and after CBT. The time course of the fMRI paradigm consisted of 3 phases: familiarization, acquisition and extinction [36], each subdivided into an early and a late phase [1].…”

“…Brain imaging studies have related fear conditioning in healthy subjects to a neural network including the amygdalae, hippocampi, insulae, anterior cingulate and medial frontal cortices [1,29,31,32,33,34,35,36,37]. This network has substantial overlap with fear circuitry structures that have been reported to show dysactivation across different anxiety disorders [38,39].…”