GABAergic modulation of performance in response inhibition and interference control tasks.

BACKGROUND: Inhibitory control is a crucial executive function with high relevance to mental and physical well-being. However, there are still unanswered questions regarding its neural mechanisms, including the role of the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA). AIMS: This study examined the effects of lorazepam (0.5 mg and 1 mg), a positive allosteric modulator at the GABAA receptor, on response inhibition and interference control. We also explored the heterogeneity of inhibitory control and calculated delta plots to explore whether lorazepam affects the gradual build-up of inhibition and activation over time. METHODS: N = 50 healthy participants performed antisaccade, Eriksen flanker and Simon tasks in a within-subjects, placebo-controlled, double-blind randomized design. RESULTS: Lorazepam increased reaction time (RT) and error rates dose dependently in all tasks (p ⩽ 0.005). In the antisaccade and Simon tasks, lorazepam increased congruency effects for error rate (p ⩽ 0.029) but not RT (p ⩾ 0.587). In the Eriksen flanker task, both congruency effects were increased by the drug (p ⩽ 0.031). Delta plots did not reflect drug-induced changes in inhibition and activation over time. Delta plots for RT in the Simon task were negative-going, as expected, whereas those for the antisaccade and flanker tasks were positive-going. CONCLUSIONS: This study provides evidence for GABAergic involvement in performance on response inhibition and interference control tasks. Furthermore, our findings highlight the diversity of the broader construct of inhibitory control while also pointing out similarities between different inhibitory control tasks. In contrast to RT and error rates, the cognitive processes indexed by delta plots may not be sensitive to GABAergic modulation.

Effects of lorazepam on prosaccades and saccadic adaptation.

BACKGROUND: Benzodiazepines have reliable adverse effects on saccadic eye movements, but the impact of sex as a potential modulator of these effects is less clear. A recent study reported stronger adverse effects on the spatial consistency of saccades in females, which may reflect sex differences in cerebellar mechanisms. AIMS: We aimed to further examine the role of sex as a potential modulator of benzodiazepine effects by employing the saccadic adaptation paradigm, which is known to be sensitive to cerebellar functioning. METHODS: A total of n=50 healthy adults performed a horizontal step prosaccade task and a saccadic adaptation task under 0.5 mg lorazepam, 1 mg lorazepam and placebo in a double-blind, within-subjects design. RESULTS: In the prosaccade task, lorazepam had adverse effects on measures of peak velocity, latency and spatial consistency. The administration of 0.5 mg lorazepam led to significant reductions in gain-decrease adaptation, while a dose of 1 mg did not impair adaptation learning. Gain-increase adaptation was generally less pronounced, and unaffected by the drug. There were no significant drug×sex interactions in either task. CONCLUSIONS: We conclude that a low dose of lorazepam impairs gain-decrease adaptation independent of sex. At higher doses, however, increasing fatigue may facilitate adaptation and thus counteract the adverse effects observed at lower doses. With regards to prosaccades, our findings confirm peak velocity as well as latency and spatial measures as sensitive biomarkers of GABAergic effects.

The Role of Personality, Political Attitudes and Socio-Demographic Characteristics in Explaining Individual Differences in Fear of Coronavirus: A Comparison Over Time and Across Countries.

Since the emergence of the SARS-CoV-2 pandemic in December 2019 about 500,000 people died within the first 6 months. The virus itself, as well as the related political decisions, intensified an increasing feeling of fear in billions of people worldwide. However, while some people remained unperturbed, others experienced panic over the current situation. In order to investigate individual differences in the perceptions, emotions and behaviors in response to the Coronavirus pandemic, an online survey was conducted between 6th and 27th of March 2020. Participants included 7309 individuals from 96 countries, who provided information on socio-demographics, personality, political orientation and general life satisfaction. To determine the specificity of fear of Coronavirus, we also investigated fear related to two other current political issues: the refugee and the climate crises. Overall, in parallel with the escalation of the pandemic, fear of Coronavirus increased significantly over the 22-day period, with the strongest predictors being the personality variable neuroticism, as well as education, sex and being an at-risk person. A detailed longitudinal analysis of the largest sample, Germany, revealed that political orientation was also an important predictor of fear of Coronavirus. Specifically, conservatives were more afraid of Coronavirus than liberals. However, as the perceived threat of the virus increased, the influence of political orientation disappeared, whereas personality remained a stable predictor. The pattern of results regarding the perceived threat of the refugee and climate crises painted a different picture: political orientation was by far the best predictor, more important even than personality. Conservatives were more worried about the refugees, and liberals about climate change. Cross-cultural analyses showed pronounced differences between countries, dependent on the crisis. Nonetheless, the importance of personality for the prediction of fear of Coronavirus remained stable over time and across the world within the investigated 22-day period.

Differentiating anxiety from fear: an experimental-pharmacological approach.

Gray's theory of personality postulates that fear and anxiety are distinct emotional systems with only the latter being sensitive to anxiolytic drugs. His work was mainly based on animal research, and translational studies validating his theory are scarce. Previous work in humans showed an influence of the benzodiazepine lorazepam on both systems, however, dependent on dosage (1 and 2 mg) and personality differences in negative emotionality. The present study aims to replicate these findings, and in addition tests the drug threshold effect by introducing a lower dosage of 0.5 mg lorazepam. Fifty healthy adults (23 males, agemean 22.40, SD ± 3.68) participated in an experimental threat-avoidance paradigm designed to dissociate risk assessment intensity (RAI, reflecting anxiety) and flight intensity (FI, reflecting fear) and completed two self-report questionnaires assessing facets of negative emotionality (Spielberger State Trait Anxiety Inventory and Fear Survey Schedule). In a randomized placebo-controlled within-subjects design, 0.5 and 1 mg of lorazepam were applied per os. Saccadic peak velocity was assessed by means of eye-tracking in order to control for sedating drug effects. Results showed the expected and specific anxiolytic effect of lorazepam on RAI, however, only in the 0.5 mg condition. FI was not influenced by lorazepam, and previous findings of interaction effects of lorazepam with self-reported negative emotionality could not be corroborated. Overall, this study demonstrates anxiolytic effects of lorazepam in dosages ≤1 mg in the absence of a drug effect on fear using a translational behavioural task. However, a putative moderating role of personality on defensive behaviour has to be clarified in future research.

Neural correlates of proactive and reactive inhibition of saccadic eye movements.

Although research on goal-directed, proactive inhibitory control (IC) and stimulus-driven, reactive IC is growing, no previous study has compared proactive IC in conditions of uncertainty with regard to upcoming inhibition to conditions of certain upcoming IC. Therefore, we investigated effects of certainty and uncertainty on behavior and blood oxygen level dependent (BOLD) signal in proactive and reactive IC. In two studies, healthy adults performed saccadic go/no-go and prosaccade/antisaccade tasks. The certainty manipulation had a highly significant behavioral effect in both studies, with inhibitory control being more successful under certain than uncertain conditions on both tasks (p ≤ 0.001). Saccadic go responses were significantly less efficient under conditions of uncertainty than certain responding (p < 0.001). Event-related functional magnetic resonance imaging (fMRI) (one study) revealed a dissociation of certainty- and uncertainty-related proactive inhibitory neural correlates in the go/no-go task, with lateral and medial prefrontal and occipital cortex showing stronger deactivations during uncertainty than during certain upcoming inhibition, and lateral parietal cortex being activated more strongly during certain upcoming inhibition than uncertainty or certain upcoming responding. In the antisaccade task, proactive BOLD effects arose due to stronger deactivations in uncertain response conditions of both tasks and before certain prosaccades than antisaccades. Reactive inhibition-related BOLD increases occurred in inferior parietal cortex and supramarginal gyrus (SMG) in the go/no-go task only. Proactive IC may imply focusing attention on the external environment for encoding salient or alerting events as well as inhibitory mechanisms that reduce potentially distracting neural processes. SMG and inferior parietal cortex may play an important role in both proactive and reactive IC of saccades.

Variation on the CRH Gene Determines the Different Performance of Opioid Addicts and Healthy Controls in the IOWA Gambling Task.

BACKGROUND: The hypothalamus-pituitary-adrenal (HPA) axis, the biological substrate of stress reactivity, and related genetic variations play a crucial role in the initiation and maintenance of drug addiction. On the behavioral level, substance abusers are characterized by impulsivity and the inability to pursue long-term goals. The neural substrate of these behaviors is assumed to be related to the ventromedial prefrontal cortex (VMPFC). One of the most established paradigms to assess VMPFC deficiency is the IOWA gambling task (IGT). AIMS: The aim of this study was to investigate the interplay between the HPA axis-related genetic variation on corticotropin-releasing hormone (CRH; secreted from the hypothalamus and constituting the starting point of the HPA axis) gene and opioid addiction, with respect to IGT performance. There is some evidence that stress and pathological HPA axis hyperactivity, in the same way as drug addiction, is related to a poorer IGT performance. METHODS: In total, 138 long-term opioid addicts (mean age 38.63 years [SD 9.15]) and 160 healthy controls (mean age 22.57 years [SD 5.86]) performed the IGT and were genotyped for 6 SNPs covering the CRH gene and adjacent regions (rs3176921, rs6999780, rs7816410, rs1870393, rs1814583, and rs11996294). The first 5 of these 6 SNPs build a haplotype block spanning 15 kb on the CRH gene. RESULTS: We found a significant group difference in the total IGT score, with higher scores in controls than in opioids. Most interestingly, there was a 3-way interaction, group × haplotype × block. Carriers homozygous for the TGTAA-haplotype differed in IGT performance dependent on group. In the control group, carriers homozygous for the TGTAA-haplotype showed a linear learning curve across blocks of trials, which was not observed in participants without this homozygosity. There were diametric effects in opioid addicts. Controlling for age and gender did not change the findings. CONCLUSION: This study provides genetic evidence for the interplay between stress, decision-making, and opioid addiction.