Inconsistent analytic strategies reduce robustness in fear extinction via skin conductance response

Robustness of fear conditioning and extinction paradigms has become increasingly important for many researchers interested in improving the study of anxiety and trauma disorders. We recently illustrated the wide variability in data analysis techniques in this paradigm, which we argued may result in lack of robustness. In the current study, we resampled data from six of our own fear acquisition and extinction datasets, with skin conductance as the outcome. In the resampled and original datasets, we found that effect sizes that were calculated using discrepant statistical strategies, sourced from a non-exhaustive search of high-impact articles, were often poorly correlated. The main contributors to poor correlations were selection of trials from different stages of each experimental phase and use of averaged compared to trial-by-trial analysis. These findings reinforce the importance of focusing on robustness in psychophysiological measurement of fear acquisition and extinction in the laboratory and may guide prospective researchers in which decisions may most impact the robustness of their results

Polymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans

This work was supported by the Australian Research Council [DE140100750 to I.B.].Learning is one of our most adaptive abilities, allowing us to adjust our expectations about future events. Aberrant learning processes may underlie disorders such as anxiety, motivating the search for the neural mechanisms that underpin learning. Animal studies have shown that the neurotransmitter GABA is required for the computation of prediction errors, the mismatches between anticipated and experienced outcomes, which drive new learning. Given that evidence from human studies is lacking, we sought to determine whether these findings extend to humans. Here, in two samples of Caucasian individuals, we investigated whether genetically determined individual differences in GABA neurotransmission predict the P3 event-related potential, an EEG component known to reflect prediction error processing. Consistent with the results of animal studies, we show that a weighted genetic risk score computed from the number of GABRB2 rs1816072 A alleles (associated with increased expression of the GABAA receptor β2 subunit gene) and the number of ErbB4 rs7598440 T alleles (associated with increased GABA concentration) predicts optimal prediction error processing during aversive classical conditioning with both visual (Experiment 1, N = 90; p = .010) and auditory (Experiment 2; N = 92; p = .031) unconditioned stimuli. Our finding that optimal processing of aversive prediction errors is reduced in individuals genetically predisposed towards decreased GABA neurotransmission suggests a potential mechanism linking GABA and anxiety. Specifically, reduced GABA signalling via GABAA receptors could result in aberrant learning from aversive experiences and vulnerability to anxiety disorders