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Cotton, R. J.

Publications and source records attributed to Cotton, R. J..

2 recordsLinked to original sources

A neural basis of probabilistic computation in visual cortex

Bayesian models of behavior suggest that organisms represent uncertainty associated with sensory variables. However, the neural code of uncertainty remains elusive. A central hypothesis is that uncertainty is encoded in the population activity of cortical neurons in the form of likelihood functions. We studied the neural code of uncertainty by simultaneously recording population activity from the primate visual cortex during a visual categorization task in which trial-to-trial uncertainty about stimulus orientation was relevant for the decision. We decoded the likelihood function from the trial-to-trial population activity and found that it predicted decisions better than a point estimate of orientation. This remained true when we conditioned on the true orientation, suggesting that internal fluctuations in neural activity drive behaviorally meaningful variations in the likelihood function. Our results establish the role of population-encoded likelihood functions in mediating behavior, and provide a neural underpinning for Bayesian models of perception.

neuroscience

Connecting genetic risk to disease endpoints through the human blood plasma proteome

Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence for mapping disease associations and translating them into clinical applications. However, although hundreds of genetic risk variants have been associated with complex disorders, the underlying molecular pathways often remain elusive. Associations with intermediate traits across multiple chromosome locations are key in establishing functional links between GWAS-identified risk-variants and disease endpoints. Here, we describe a GWAS performed with a highly multiplexed aptamer-based affinity proteomics platform. We quantified associations between protein level changes and gene variants in a German cohort and replicated this GWAS in an Arab/Asian cohort. We identified many independent, SNP-protein associations, which represent novel, inter-chromosomal links, related to autoimmune disorders, Alzheimer's disease, cardiovascular disease, cancer, and many other disease endpoints. We integrated this information into a genome-proteome network, and created an interactive web-tool for interrogations. Our results provide a basis for new approaches to pharmaceutical and diagnostic applications.

genetics