Neural correlates of trait anxiety in fear extinction.

BACKGROUND: Fear conditioning involves the amygdala as the main neural structure for learning fear responses whereas fear extinction mainly activates the inhibitory prefrontal cortex (PFC). In this study we investigated whether individual differences in trait anxiety affect amygdala and dorsal anterior cingulate cortex (dACC) activation during fear conditioning and extinction. METHOD: Thirty-two healthy subjects were investigated by functional magnetic resonance imaging (fMRI) at 3 T while performing a cued fear-conditioning task. All participants completed the trait version of the State-Trait Anxiety Inventory (STAI-T). Activations of the amygdala and the dACC were examined with respect to the effects of trait anxiety. RESULTS: Analysis of the fMRI data demonstrated enhanced activation in fear-related brain areas, such as the insula and the ACC, during both fear conditioning and extinction. Activation of the amygdala appeared only during the late acquisition phase whereas deactivation was observed during extinction. Regression analyses revealed that highly trait-anxious subjects exhibited sustained amygdala activation and reduced dACC involvement during the extinction of conditioned responses. CONCLUSIONS: This study reveals that high levels of trait anxiety are associated with both increased amygdala activation and reduced dACC recruitment during the extinction of conditioned fear. This hyper-responsivity of the amygdala and the deficient cognitive control during the extinction of conditioned fear in anxious subjects reflect an increased resistance to extinct fear responses and may thereby enhance the vulnerability to developing anxiety disorders.

ERP indices for response inhibition are related to anxiety-related personality traits.

Anxiety is often associated with impaired cognitive control and avoidance behaviour. The aim of this study was to investigate the effect of anxiety-related personality traits, such as anxiety sensitivity and trait anxiety, on event-related potentials of response inhibition in a standard Go/Nogo-paradigm. We focused on the Nogo-N2 and Nogo-P3 components, which probably represent different sub-processes of response inhibition. The Nogo-N2 was mainly influenced by trait anxiety, while it was slightly affected by anxiety sensitivity. In contrast, the Nogo-P3 was significantly associated with anxiety sensitivity, but was less affected by trait anxiety. Thus, anxious subjects seem to maintain a higher level of cognitive control to prepare and to monitor the outcome of their actions, which is differentially reflected in Nogo-N2 and Nogo-P3 potentials. Our results show that anxiety-related personality traits modulate electrophysiological responses related to cognitive control processes and should be taken into consideration in studies investigating response inhibition.

Association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set shifting in healthy individuals.

Set-shifting and maintenance are complex cognitive processes, which are often impaired in schizophrenia. The genetic basis of these processes is poorly understood. We aimed to investigate the association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set-shifting in healthy individuals. The relationship between 14 selected single nucleotide polymorphisms (SNPs) of the GRM3 gene and cognitive set-shifting as measured by perseverative errors using the modified card sorting test (MCST) was analysed in a sample of N = 98 young healthy individuals (mean age in years: 22.7 +/- 0.19). Results show that SNP rs17676277 is related to the performance on the MCST. Subjects with the TT genotype showed significantly less perseverative errors as compared with the AA (P = 0.025) and AT (P = 0.0005) and combined AA/AT genotypes (P = 0.0005). Haplotype analyses suggest the involvement of various SNPs of the GRM3 gene in perseverative error processing in a dominant model of inheritance. The findings strongly suggest that the genetic variation (rs17676277 and three haplotypes) in the metabotropic GRM3 is related to cognitive set-shifting in healthy individuals independent of working memory. However, because of a relatively small sample size for a genetic association study, the present results are tentative and require replication.