Distributed anatomical circuits for decision-making, inference, and learning

Every day we make decisions about what to do next. We do this because we are constantly monitoring and evaluating how well things are going. As a consequence we adjust our behaviour so it is appropriate for the current context or we decide to take one course of action rather than another. Sometimes we are aware of making these evaluations and decisions but often we are not. Nevertheless, however much we take these abilities for granted, it is striking when they are altered in psychological illnesses such as depression.

The aim of this proposal is to undertake work to understand what the brain does to enable us to behave in the way that we do. Our focus is on parts of the brain called the prefrontal and cingulate cortex. We already know that these brain regions are especially important for the behaviour we are interested in but what we do not know is how they accomplish the role they play. We want to find out the mechanisms by which they operate and the way in which they interact with the rest of the brain.

A key part of the work is designing behavioural tasks to probe cognitive operations in a precise way to reveal their mechanistic basis. A second component is recording brain activity and seeing how it relates to behaviour. We do this by using a magnetic resonance imaging (MRI) scanner, usually by taking what are called functional MRI (fMRI) scans. FMRI scans tell us about blood oxygenation in the brain. This is useful because the blood oxygen level dependent (BOLD) signal tracks the activity of the brain's cells -- neurons -- in a very precise way. It is, for example, possible to estimate changes in distribution of BOLD signal in specific brain areas from moment to moment as a decision is made or as feedback is provided to enable adjustments and changes in behaviour.

We conduct the fMRI recording in animals because we also want to examine the consequences of manipulating the activity we record. This is essential for finding out what activity patterns are causally driving behaviours. We can test causation by making precise and circumscribed interventions in the brain. We do this under anaesthesia in the same way that it would be done with human patients. When the animals recover we monitor changes in behaviour. Usually there are no obvious changes in behaviour because the interventions we carry out are subtle. If, however, we have designed our behavioural tasks with care so as to precisely probe specific cognitive processes, then we may be able to pick up equally subtle alterations in behaviour. They can then be measured and quantified. We use macaques because they provide a model of many features of human prefrontal and cingulate cortex. Most other animals lack these features so they cannot be used as models.

One of the questions that we are examining concerns how quickly we should change and adjust our behaviour. There is evidence that in some psychological illnesses, such as bipolar depression, our behaviour becomes too responsive to each minor piece of feedback; the behaviour becomes too volatile. We are also interested in how, when we receive feedback for a choice, we attribute that feedback correctly to the event that really caused it. There is evidence that we do not always manage this simple job well and when we are very poor at it we may draw odd conclusions about what we are, and are not, responsible for. Again this may be a feature of psychological illnesses. A third process we are interested in is inference. Often neuroscientists have studied the neural mechanisms that mediate learning about particular events or actions. Once the learning is done a good decision can be made next time the event is encountered or the action is needed. However, often in the real world we make inferences about what to do next on the basis of experience of some situations with some similar component elements. We will attempt to understand how such inferences are made.

We will investigate the neural basis of decision making, learning, behavioural change, and inference in PFC and ACC. Neural activity will be recorded in macaques with fMRI and probed with a range of interventions including lesions, focal ultrasound neurostimulation, and possibly microstimulation. Effects on behaviour and neural activity will be measured.

The aim of each project is not simply to assess involvement of brain areas in cognitive processes of interest but instead it is to derive a mechanistic understanding of the way in which the areas operate and the way in which they interact with other brain areas. With careful task design it is possible to identify neural activity covarying with quantitative estimates of choice value and value comparison. It is then possible to determine the nature of PFC and ACC representations when a decision is made between choices, when an inference is made about a choice's value on the basis of past experience, and when estimates of choice values or behaviour values are being updated during learning.

Computational models will be used to guide analyses. The models will be used to make quantitative predictions of behaviour and neural activity that can be contrasted with actual observations.

We will investigate: 1) simultaneous representation of multiple learning rates in dACC; 2) different reward representations in lOFC and amygdala in relation to credit assignment; 3) independent versus interactive nature of vmPFC and dACC during decision making; 4) hippocampus-dependent map-like representation to guide decision making in vmPFC and pgACC; 5) model-based versus model-free reward learning mediated by lPFC and vmPFC interaction; 6) activation and suppression of stimulus-reward representations in OFC; 7) a mechanism for determining speed, accuracy, and task engagement dependent on average reward and temporal structure of the environment; 8) distinct representations of surprise and prediction error in PFC and striatum.

If awarded the grant would make it possible to conduct eight projects into different aspects of the function of the prefrontal cortex and anterior cingulate cortex. The focus is on fundamental aspects of behaviour including decision making, learning, and inference. The aim is to provide a mechanistic account of the operations of specific brain regions in relation to specific cognitive operations such as setting the rate at which behaviour changes or linking outcomes of decisions to the events and choices that caused them.

Decision making and learning mechanisms are of broad interest to many researchers working in psychology, neuroscience, and the computational modelling of behaviour. They will inform understanding and modelling of these processes.

The experiments will record neural activity in animal models using functional magnetic resonance imaging (fMRI). This will mean that the results will form a bridge between single neuron recordings made in animal models and fMRI studies (a non-invasive technique) in humans. The aim is to link specific neural signals to particular behaviour events and to understand the interrelationships between activity in prefrontal cortex and anterior cingulate cortex.

The focus is on understanding neural mechanisms in the healthy brain but the brain areas and the behavioural processes being investigated are ones that are known to be changed in many psychological illnesses such as depression. The applicants have collaborations with researcher in the Psychiatry Department, University of Oxford and related hypotheses will inform investigations in clinical populations. In addition to recording neural activity the applicants intend to measure the impact of manipulating and disrupting activity in the brain circuits they investigate. This will also enhance their ability to understand dysfunction as well as function in prefrontal and cingulate cortex.

The results will be published in peer-reviewed scientific journals and discussed at international scientific meetings that the applicants regularly attend.

The applicants have explained some of their work to non-scientific audiences at university open days and on non-specialist courses. Their research has been featured in a range of national and international radio and newspaper news articles.