Gunther, F. | Search bioRxiv

bioRxiv2019

Effects of mid-frontal brain stimulation on sustained attention

Sustained attention is defined as the ability to maintain attention over longer periods of time, which typically declines with time on task (i.e., the vigilance decrement). Previous studies have suggested an important role for the dorsomedial prefrontal cortex (mPFC) in sustained attention. In two experiments, we aimed to enhance sustained attention by applying transcranial electrical current stimulation over the mPFC during a sustained attention task. In the first experiment, we applied transcranial direct current stimulation (tDCS) in a between-subject design (n=97): participants received either anodal, cathodal, or sham stimulation. Contrary to our prediction, we found no effect of stimulation on the vigilance decrement. In the second experiment, participants received theta and alpha transcranial alternating current stimulation (tACS) in two separate sessions (n=47, within-subject design). Here, we found a frequency-dependent effect on the vigilance decrement, such that contrary to our expectation, participants performance over time became worse after theta compared to alpha stimulation. However, this result needs to be interpreted with caution given that this effect could be driven by differential side effects between the two stimulation frequencies. To conclude, across two studies, we were not able to reduce the vigilant decrement using tDCS or theta tACS.

neuroscience↗

bioRxiv2019

Maximum likelihood method quantifies the overall contribution of gene-environment interaction to complex traits: an application to obesity traits

As genome-wide association studies (GWAS) increased in size, numerous gene-environment interactions (GxE) have been discovered, many of which however explore only one environment at a time and may suffer from statistical artefacts leading to biased interaction estimates. Here we propose a maximum likelihood method to estimate the contribution of GxE to complex traits taking into account all interacting environmental variables at the same time, without the need to measure any. This is possible because GxE induces fluctuations in the conditional trait variance, the extent of which depends on the strength of GxE. The approach can be applied to continuous outcomes and for single SNPs or genetic risk scores (GRS). Extensive simulations demonstrated that our method yields unbiased interaction estimates and excellent confidence interval coverage. We also offer a strategy to distinguish specific GxE from general heteroscedasticity (scale effects). Applying our method to 32 complex traits in the UK Biobank reveals that for body mass index (BMI) the GRSxE explains an additional 1.9% variance on top of the 5.2% GRS contribution. However, this interaction is not specific to the GRS and holds for any variable similarly correlated with BMI. On the contrary, the GRSxE interaction effect for leg impedance [Formula] is significantly (P < 10-56) larger than it would be expected for a similarly correlated variable [Formula]. We showed that our method could robustly detect the global contribution of GxE to complex traits, which turned out to be substantial for certain obesity measures.

epidemiology↗