Every time you learn from a mistake or change your mind based on new information, a network of frontal brain circuits is at work—and this project will map exactly how those circuits control learning and decision-making. The problem is that many psychiatric conditions—from addiction to obsessive-compulsive disorder—involve people making bad choices and failing to learn from them. Current treatments are blunt because we don't understand which specific brain circuits are failing, or how frontal regions should be regulating them. This project targets that gap by studying five key circuits, using macaque models to make precise lesions in frontal areas and then scanning the rest of the brain with fMRI to see how the network responds. If successful, this fundamental science will reveal the wiring diagram of how frontal brain regions govern learning and decision-making. The researchers will also use diffusion-weighted MRI to track how white matter pathways physically change as animals learn to make better choices. While this work has no immediate clinical application, understanding these circuit-level mechanisms could eventually help design targeted brain stimulation therapies for conditions where learning and decision-making are impaired—treatments that currently don't exist because we don't know which circuits to target.
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The aim of the current proposal is to look at the neural mechanisms of learning and decision making. Learning, the acquisition of new behaviours and information, and decision making, the ability to act on that information, are two of the most fundamental cognitive operations that are called into play throughout our lives. Impairments in learning and decision making are often central to psychiatric conditions; maladaptive choices are not just made in the first place but they are also not adjusted as a result of experience. It is important to emphasize that not only do we investigate basic aspects of learning and decision making but, for example, we also attempt to understand such processes in the social domain. Learning and decision making do not depend on a single brain region but on the interactions that occur between many regions. Our aim is to investigate these interactions in five key circuits. The focus will be on the parts of the five circuits that are located in the frontal lobes of the brain and the aim is to test whether and how the frontal components of these circuits regulate activity in the rest of the circuits of which they are parts. The interactions within brain circuits will be investigated in two principal ways. First, we will attempt to manipulate and alter activity in one component of each circuit and then record the consequences for behaviour and for activity recorded in other parts of the circuits. This can be done by making a selective lesion in a brain area and for this reason it is necessary to use animal models. In the current case the brain areas are only present in a few species and so the macaque is the model species. The lesion?s effect on other parts of the network can be investigated by using a non-invasive brain scanner technique, functional magnetic resonance imaging (fMRI), to record the blood oxygen level dependent (BOLD) signal that provides an index of brain activity. The second way that we can look at brain circuits is by using the brain scanner to acquire a different type of MRI data, diffusion weighted MRI (DW-MRI). DW-MRI scans provide information about the white matter pathways that run between different component parts of brain circuits. We plan to look at how the pathways linking brain circuits change during learning to make decisions in the most effective manner possible.
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