Barone, J. | bioRxiv Science

bioRxiv2019

The rate of de novo CNVs in healthy controls

BackgroundCopy number variation (CNV) is an important cause for human disease. Due to relatively high selection pressure operating against pathogenic CNVs, their rate is maintained in the population by de novo formation. The rates of de novo CNVs are increased in neurodevelopmental disorders. However only a few studies have been performed on relatively healthy individuals, making it problematic to calculate the magnitude of this increased rate. MethodsThe UK Biobank recruited about half a million randomly selected middle-aged members of the general population of the UK. We re-constructed family relationships from the genotypic data and identified 923 parent-offspring trios that passed out quality control filters. Potential de novo CNVs of >100 kb in size were identified and the log R ratios (LRR) and B allele frequency (BAF) traces of the trio members were visually inspected for those regions. We had no opportunity to validate CNVs with a laboratory method, but the traces appeared conclusive. Results and DiscussionWe identified 10 CNVs >100kb in size, a rate of 1.1%. These rates are very similar to those in previous large studies. Using previous large studies, we provide overall rates among 4844 trios for different size ranges that are expected in relatively healthy populations. These rates can be used for comparison in studies on disease populations.

genomics↗

bioRxiv2019

Reward certainty and preference bias selectively shape voluntary decisions

Choosing between equally valued options can be a conundrum, for which classical decision theories predicted a prolonged response time (RT). Paradoxically, a rational decision-maker would need no deliberative thinking in this scenario, as outcomes of alternatives are indifferent. How individuals choose between equal options remain unclear. Here, we characterized the neurocognitive processes underlying such voluntary decisions, by integrating advanced cognitive modelling and EEG recording in a probabilistic reward task, in which human participants chose between pairs of cues associated with identical reward probabilities at different levels. We showed that higher reward certainty accelerated RT. At each certainty level, participants preferred to choose one cue faster and more frequently over the other. The behavioral effects on RT persisted in simple reactions to reward cues. By using hierarchical Bayesian parameter estimation for an accumulator model, we showed that the certainty and preference effects were independently associated with the rate of evidence accumulation during decisions, but not with visual encoding or motor execution latencies. Time-resolved multivariate pattern classification of EEG evoked response identified significant representations of reward certainty and preference choices as early as 120 ms after stimulus onset, with spatial relevance patterns maximal in middle central and parietal electrodes. Furthermore, EEG-informed computational modelling showed that the rate of change between N100 and P300 event-related potentials reflected changes in the model-derived rate of evidence accumulation on a trial-by-trial basis. Our findings suggested that reward certainty and preference collectively shaped voluntary decisions between equal options, providing a mechanism to prevent indecision or random behavior.

neuroscience↗