The Representation of Decision Variables in the Parietal and Prefrontal Cortex and its Modulation by Dopamine D1 Receptors

Abstract

Everyday decision-making requires us to collect, evaluate and integrate multiple pieces of evidence. For example, when we get dressed, we consider daily activities, weather forecast and personal preferences. In this thesis, we made use of a task that aimed to mimic the components of an everyday decision, but that was sufficiently simplified to be studied in an animal model: the Sequential Probability Ratio Task (SPRT). We trained two rhesus macaques on the SPRT and measured each monkeys’ baseline behaviour and found that both monkeys performed the task in different ways. In addition, we recorded neural activity from the Lateral Intraparietal area (LIP) and Dorsolateral Prefrontal Cortex (DLPFC). Activity in LIP has been related to the accumulation and integration of evidence into a decision variable (DV), however whether its role is causal has been of debate. Given its noted role in working memory and reward processing, we recorded from DLPFC with the aim of addressing any similarities and or differences in its activity, compared to LIP. To date, this is the only study that has recorded, simultaneously, activity from LIP and DLPFC in response to the SPRT. Both areas behaved largely similarly, but again with inconsistencies across monkeys. We further manipulated the availability of dopamine (DA) D1 receptors (D1Rs), through the systemic administration of selective D1R agonists (stimulation) and antagonists (inhibition). DA exerted different modulatory effects over the behaviour of each monkey. But one consistency lends insight into the debate surrounding the causal role of reward, providing supporting evidence for the Incentive Salience (IC) hypothesis. DA-ergic effects on neural activity were few and only observed in DLPFC. Deficits of decision-making are notable in neuropsychiatric disorders whose aetiology is characterised by a dysfunction of the neuromodulator dopamine (DA) (e.g., Parkinson’s Disease). Thus, our results are translational to patient populations.