McGovern, D. P. | Search bioRxiv

bioRxiv2018

Inflammatory bowel disease microbiotas alter gut CD4 T-cell homeostasis and drive colitis in mice

To examine the functional contribution of Inflammatory Bowel Disease (IBD) microbes to immune homeostasis and colitis, we colonized unchallenged and colitis-susceptible germ-free mice with over twenty human intestinal microbiotas from healthy and IBD donors. Compared to healthy microbiotas, IBD microbiotas led to expanded ROR{gamma}t+Th17 cells and reduced ROR{gamma}t+Treg in the gut of unchallenged gnotobiotic mice and increased disease severity in colitis-susceptible mice. The proportions of ROR{gamma}t+Th17 and ROR{gamma}t+Treg induced by each microbiota were highly predictive of the human disease status and strongly correlated with disease severity in colitis-susceptible mice colonized with the same human microbiotas. The transmittable functional potential of IBD microbes suggests a mechanism for a microbial contribution to IBD pathogenesis and a potential route for its treatment and prevention.

immunology↗

bioRxiv2017

Reconciling age-related changes in behavioural and neural indices of human perceptual decision making

Ageing impacts on decision making behaviour across a wide range of cognitive tasks and scenarios. Computational modeling has proven highly valuable in providing mechanistic interpretations of these age-related differences; however, the extent to which model parameter differences accurately reflect changes to the underlying neural computations has yet to be tested. Here, we measured neural signatures of decision formation as younger and older participants performed motion discrimination and contrast-change detection tasks, and compared the dynamics of these signals to key parameter estimates from fits of a prominent accumulation-to-bound model (drift diffusion) to behavioural data. Our results indicate marked discrepancies between the age-related effects observed in the model output and the neural data. Most notably, while the model predicted a higher decision boundary in older age for both tasks, the neural data indicated no such differences. To reconcile the model and neural findings, we used our neurophysiological observations as a guide to constrain and adapt the model parameters. In addition to providing better fits to behaviour on both tasks, the resultant neurally-informed models furnished novel predictions regarding other features of the neural data which were empirically validated. These included a slower mean rate of evidence accumulation amongst older adults during motion discrimination and a beneficial reduction in between-trial variability in accumulation rates on the contrast-change detection task, which was linked to more consistent attentional engagement. Our findings serve to highlight how combining human brain signal measurements with computational modelling can yield unique insights into group differences in neural mechanisms for decision making.

neuroscience↗