Sala, F. | bioRxiv Science

bioRxiv2019

Mendelian Randomization with Instrumental Variable Synthesis (IVY)

Mendelian Randomization (MR) is an important causal inference method primarily used in biomedical research. This work applies contemporary techniques in machine learning to improve the robustness and power of traditional MR tools. By denoising and combining candidate genetic variants through techniques from unsupervised probabilistic graphical models, an influential latent instrumental variable is constructed for causal effect estimation. We present results on identifying relationships between biomarkers and the occurrence of coronary artery disease using individual-level real-world data from UK-BioBank via the proposed method. The approach, termed Instrumental Variable sYnthesis (IVY) is proposed as a complement to current methods, and is able to improve results based on allele scoring, particularly at moderate sample sizes.

bioinformatics↗

bioRxiv2019

A study of parietal-motor connectivity by intraoperative dual cortical stimulation

the function of the primates posterior parietal cortex in sensorimotor transformations is well-established, though in humans its complexity is still challenging. Well-established models indicate that the posterior parietal cortex influences motor output indirectly, by means of connections to the premotor cortex, which in turn is directly connected to the motor cortex. The possibility that the posterior parietal cortex could be at the origin of direct afferents to M1 has been suggested in humans but has never been confirmed directly. In the present work we assessed during intraoperative monitoring of the corticospinal tract in brain tumour patients the existence of short-latency effects of parietal stimulation on corticospinal excitability to the upper limb. We identified several foci within the inferior parietal lobule that drove short-latency influences on cortical motor output. Active foci were distributed along the postcentral gyrus and clustered around the anterior intraparietal area and around the parietal operculum. For the first time in humans, the present data show direct evidence in favour of a distributed system of connections from the posterior parietal cortex to the ipsilateral primary motor cortex.

neuroscience↗