Inhibitory attentional control in anxiety: Manipulating cognitive load in an antisaccade task

Theorists have proposed that heightened anxiety vulnerability is characterised by reduced attentional control performance and have made the prediction in turn that elevating cognitive load will adversely impact attentional control performance for high anxious individuals to a greater degree than low anxious individuals. Critically however, existing attempts to test this prediction have been limited in their methodology and have presented inconsistent findings. Using a methodology capable of overcoming the limitations of previous research, the present study sought to investigate the effect of manipulating cognitive load on inhibitory attentional control performance of high anxious and low anxious individuals. High and low trait anxious participants completed an antisaccade task, requiring the execution of prosaccades towards, or antisaccades away from, emotionally toned stimuli while eye movements were recorded. Participants completed the antisaccade task under conditions that concurrently imposed a lesser cognitive load, or greater cognitive load. Analysis of participants’ saccade latencies revealed high trait anxious participants demonstrated generally poorer inhibitory attentional control performance as compared to low trait anxious participants. Furthermore, conditions imposing greater cognitive load, as compared to lesser cognitive load, resulted in enhanced inhibitory attentional control performance across participants generally. Crucially however, analyses did not reveal an effect of cognitive load condition on anxiety-linked differences in inhibitory attentional control performance, indicating that elevating cognitive load did not adversely impact attentional control performance for high anxious individuals to a greater degree than low anxious individuals. Hence, the present findings are inconsistent with predictions made by some theorists and are in contrast to the findings of earlier investigations. These findings further highlight the need for research into the relationship between anxiety, attentional control, and cognitive load

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

BACKGROUND AND PURPOSE: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. METHODS: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. RESULTS: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. CONCLUSION: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability

Large‐scale collaboration in ENIGMA‐EEG: A perspective on the meta‐analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity.

Background and purpose The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. Methods We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. Results We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. Conclusion The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability

Supplementary Material for: Brain Arousal Regulation in Carriers of Bipolar Disorder Risk Alleles

<br><strong><em>Objectives:</em></strong> Recent genome-wide association studies identified a number of chromosomal risk loci for bipolar disorder (BD, ‘manic-depressive illness'). According to the vigilance regulation model, the regulation of brain arousal (referred to as ‘vigilance') when assessed via EEG is an emerging biomarker linked to the pathogenesis of manic and depressive episodes. On this basis, the present study aimed to assess whether carriers of BD risk alleles differ in brain arousal regulation. <b><i>Methods:</i></b> Healthy participants of the population-based Leipzig Health Care Study (LIFE) underwent a 20-min eyes-closed resting EEG paradigm. Brain arousal was assessed applying the computer-based Vigilance Algorithm Leipzig (VIGALL). The primary sample (n = 540) was genotyped for ten of the most reliable BD risk variants, of which two qualified for replication (n = 509). <b><i>Results:</i></b> Primary sample analyses revealed Bonferroni-adjusted significance for rs1006737 in CACNA1C (encoding a calcium channel subunit), with risk allele carriers exhibiting relatively steep brain arousal declines. Further, carriers of two risk alleles of rs472913 at 1p32.1 showed generally lower brain arousal levels for the duration of the resting paradigm. However, both associations failed replication. <b><i>Conclusion:</i></b> Although our initial findings are in line with the vigilance regulation model and convincing in view of the previously reported notable role of ion channelopathies in BD, our results do not provide consistent evidence for a link between BD risk variants and brain arousal regulation. Several between-sample differences may account for this inconsistency. The molecular genetics of brain arousal regulation remain to be clarified

Effects of COMT genotype and tolcapone on lapses of sustained attention after sleep deprivation in healthy young men

Tolcapone, a brain penetrant selective inhibitor of catechol-O-methyltransferase (COMT) devoid of psychostimulant properties, improves cognition and cortical information processing in rested volunteers, depending on the genotype of the functional Val158Met polymorphism of COMT. The impact of this common genetic variant on behavioral and neurophysiological markers of increased sleep need after sleep loss is controversial. Here we investigated the potential usefulness of tolcapone to mitigate consequences of sleep deprivation on lapses of sustained attention, and tested the hypothesis that dopamine signaling in the prefrontal cortex (PFC) causally contributes to neurobehavioral and neurophysiological markers of sleep homeostasis in humans. We first quantified in 73 young male volunteers the impact of COMT genotype on the evolution of attentional lapses during 40 h of extended wakefulness. Subsequently, we tested in an independent group of 30 young men whether selective inhibition of COMT activity with tolcapone counteracts attentional and neurophysiological markers of elevated sleep need in a genotype-dependent manner. Neither COMT genotype nor tolcapone affected brain electrical activity in wakefulness and sleep. By contrast, COMT genotype and tolcapone modulated the sleep loss-induced impairment of vigilant attention. More specifically, Val/Met heterozygotes produced twice as many lapses after a night without sleep than Met/Met homozygotes. Unexpectedly, tolcapone further deteriorated the sleep loss-induced performance deficits when compared to placebo, particularly in Val/Met and Met/Met genotypes. The findings suggest that PFC dopaminergic tone regulates sustained attention after sleep loss according to an inverse U-shaped relationship, independently of neurophysiological markers of elevated sleep need