Does testosterone impair mens' cognitive empathy? Evidence from two large-scale randomized controlled trials Supplementary material, bioRxiv, 2019-01-13
The capacity to infer the mental states of others (known as cognitive empathy) is essential for social interactions, and a well-known theory proposes that it is negatively affected by intrauterine testosterone exposure. Furthermore, previous studies reported that testosterone administration impaired cognitive empathy in healthy adults, and that a biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small-sample studies with mixed evidence. We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men (N=243 and N=400), using two different testosterone administration protocols. We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.
biorxiv neuroscience 200-500-users 2019Does testosterone impair men’s cognitive empathy? Evidence from two large-scale randomized controlled trials, bioRxiv, 2019-01-13
AbstractThe capacity to infer others’ mental states (known as “mind reading” and “cognitive empathy”) is essential for social interactions across species, and its impairment characterizes psychopathological conditions such as autism spectrum disorder and schizophrenia. Previous studies reported that testosterone administration impaired cognitive empathy in healthy humans, and that a putative biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small-sample studies with mixed evidence. We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men (N=243 and N=400), using two different testosterone administration protocols. We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.
biorxiv neuroscience 200-500-users 2019Highly-accurate long-read sequencing improves variant detection and assembly of a human genome, bioRxiv, 2019-01-13
AbstractThe major DNA sequencing technologies in use today produce either highly-accurate short reads or noisy long reads. We developed a protocol based on single-molecule, circular consensus sequencing (CCS) to generate highly-accurate (99.8%) long reads averaging 13.5 kb and applied it to sequence the well-characterized human HG002NA24385. We optimized existing tools to comprehensively detect variants, achieving precision and recall above 99.91% for SNVs, 95.98% for indels, and 95.99% for structural variants. We estimate that 2,434 discordances are correctable mistakes in the high-quality Genome in a Bottle benchmark. Nearly all (99.64%) variants are phased into haplotypes, which further improves variant detection. De novo assembly produces a highly contiguous and accurate genome with contig N50 above 15 Mb and concordance of 99.998%. CCS reads match short reads for small variant detection, while enabling structural variant detection and de novo assembly at similar contiguity and markedly higher concordance than noisy long reads.
biorxiv genomics 200-500-users 2019False-positive neuroimaging Undisclosed flexibility in testing spatial hypotheses allows presenting anything as a replicated finding, bioRxiv, 2019-01-09
AbstractHypothesis testing in neuroimaging studies relies heavily on treating named anatomical regions (e.g., “the amygdala”) as unitary entities. Though data collection and analyses are conducted at the voxel level, inferences are often based on anatomical regions. The discrepancy between the unit of analysis and the unit of inference leads to ambiguity and flexibility in analyses that can create a false sense of reproducibility. For example, hypothesizing effects on “amygdala activity” does not provide a falsifiable and reproducible definition of precisely which voxels or which patterns of activation should be observed. Rather, it comprises a large number of unspecified sub-hypotheses, leaving room for flexible interpretation of findings, which we refer to as “model degrees of freedom.” From a survey of 135 functional Magnetic Resonance Imaging studies in which researchers claimed replications of previous findings, we found that 42.2% of the studies did not report any quantitative evidence for replication such as activation peaks. Only 14.1% of the papers used exact coordinate-based or a priori pattern-based models. Of the studies that reported peak information, 42.9% of the ‘replicated’ findings had peak coordinates more than 15 mm away from the ‘original’ findings, suggesting that different brain locations were activated, even when studies claimed to replicate prior results. To reduce the flexible and qualitative region-level tests in neuroimaging studies, we recommend adopting quantitative spatial models and tests to assess the spatial reproducibility of findings. Techniques reviewed here include permutation tests on peak distance, Bayesian MANOVA, and a priori multivariate pattern-based models. These practices will help researchers to establish precise and falsifiable spatial hypotheses, promoting a cumulative science of neuroimaging.
biorxiv neuroscience 200-500-users 2019Optical clearing of living brains with MAGICAL to extend in vivo imaging, bioRxiv, 2019-01-09
To understand brain functions, it is important to observe directly how multiple neural circuits are performing in living brains. However, due to tissue opaqueness, observable depth and spatiotemporal resolution are severely degraded in vivo. Here, we propose an optical brain clearing method for in vivo fluorescence microscopy, termed MAGICAL (Magical Additive Glycerol Improves Clear Alive Luminance). MAGICAL enabled two-photon microscopy to capture vivid images with fast speed, at cortical layer V and hippocampal CA1 in vivo. Moreover, MAGICAL promoted conventional confocal microscopy to visualize finer neuronal structures including synaptic boutons and spines in unprecedented deep regions, without intensive illumination leading to phototoxic effects. Fluorescence Emission Spectrum Transmissive Analysis (FESTA) showed that MAGICAL improved in vivo transmittance of shorter wavelength light, which is vulnerable to optical scattering thus unsuited for in vivo microscopy. These results suggest that MAGICAL would transparentize living brains via scattering reduction.
biorxiv neuroscience 200-500-users 2019