The flexibly ordered brain

Abstract

I investigate the human brain systems involved in the cognitive control of behaviour. Using novel cognitive paradigms and brain imaging, I identify brain systems that support the flexible structuring of behaviour. I then observe how these systems are implicated in patients with depression as they respond to psilocybin therapy. In the first of three experiments, I observe the changes in healthy adult brain activation that are associated with task-switching. This demonstrated that remapping rules introduces a switching-cost to response speed and activates the multiple-demand (MD) network. Critically, switching-costs and MD activation were greater when the rules being remapped were of an abstract and higher-order nature. Going deeper, in the second experiment, I investigate how healthy adult brains mitigate switching-costs by structuring behaviour into efficient routines. I observe that learning to optimise and structure behaviour covaries with changes in MD and default mode network (DMN) activation alongside increases in between-network connectivity. These concurrent behavioural and neural adaptations imply that cognitive demand is minimised when behavioural routines are structured. Indeed, these mechanisms are known to have broad roles in flexibly adapting behaviour and, subsequently, they have been implicated in disorders such as depression. Using these insights, in the third experiment, I examine the neural basis of the treatment response to psilocybin in patients with depression. In two clinical trials, I find that treatment response covaried with global increases in between-network connectivity. Converging functional cartography measures indicated that this global shift in network organisation related to increased dynamic flexibility and integration of the MD and DMN. Together, the findings in this thesis indicate that a ‘flexibly ordered brain’, the adaptive sequencing of neurocognitive states, is a necessary feature of well-being and for successfully navigating the demands of daily life.