Frontal cortical interactions during decision-making and social valuation

Psychological illnesses affect many people in the UK and other countries. Many illnesses, such as autism, depression, and obsessive compulsive disorder are associated with changes in social interaction and altered patterns of decision-making. For example, depression is often associated with a decrease in the value given to social interaction and with the allocation of undue weight to negative feedback when making a decision and choosing what to do next. In such illnesses changes do not just occur at the behavioural level, they also occur at the level of the brain. Two regions may be particularly important – prefrontal cortex and anterior cingulate cortex (PFC and ACC). What is not clear is how and whether the brain changes lead to changes at the behavioural level. The proposal is to use animal models in which dysfunction is induced in small regions of PFC and ACC. The effect of dysfunction can then be assessed by taking careful measurements of behaviour. How the changes occur can be assessed by using two types of brain imaging techniques. The first brain imaging approach is called diffusion weighted imaging and it looks at the interconnexion patterns of the PFC and ACC with other brain areas and tells us the routes within the brain by which the PFC and ACC reach and influence other brain areas and thereby affect behaviour. Such connexion routes are increasingly becoming the focus for medical attempts to treat the most severe forms of psychological illness. The second brain imaging approach is called functional magnetic resonance imaging and it measures activity levels in the brain. By measuring the activity levels in other brain areas it is possible to ascertain the impact of dysfunction in PFC and ACC on the working of those other brain areas. If such changes are found then it suggests that small initial changes in PFC and ACC can have wider consequences for how the rest of the brain works. This may in turn reveal how patterns of decision-making and social interaction come to change during psychological illnesses.

The aim of the current proposal is to examine how prefrontal (PFC) and anterior cingulate cortical (ACC) areas interact with other regions of the primate brain during decision-making and social appraisal. The proposal is submitted in response to the MRC/ESRC ?highlight? call for submissions linking basic neuroscience and social behaviour. The work is important, first, because it will investigate fundamental aspects of PFC and ACC function. Second, it is anticipated that results will be relevant to the understanding of neurological causes and correlates of psychological illness.
There are changes both in social interaction and in decision-making in several psychological illnesses, such as autism, depression, and obsessive compulsive disorder. For example the value given to social interaction decreases in depression and undue weight is given to the possible negative outcomes of decisions. The proposal will exploit animal models of social valuation and decision-making we have developed and findings that these processes are affected by dysfunction in two brain areas, the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). We will now contrast the distinct contributions made by subdivisions of each of these brain regions and by the white matter connexions pathways near these brain areas. This will be done by taking careful and automated measurements of behaviour after brain dysfunction is induced in each region. In addition we will use magnetic resonance imaging (MRI) approaches in combination with our animal model. First, MRI will be used to guide and measure the induction of brain dysfunction. Second, MRI will be used to obtain diffusion weighted images and, by using tractography algorithms developed in Oxford, it will be possible to establish probabilistic estimates of the white matter connexion pathways to, from, and adjacent to PFC and ACC areas. Third, it is hoped that functional magnetic resonance imaging (fMRI) will be used to obtain estimates of activity patterns in brain areas shown to be connected to PFC and ACC areas. Whether PFC or ACC dysfunction induces changes in activity patterns in these areas will be investigated.
In combination the methods make it possible to measure the causal importance of PFC and ACC areas for behaviours that are compromised in psychological illnesses. In addition it is hoped that the studies will begin to explain how PFC and ACC dysfunction can impact on other brain regions and affect behaviour.