Different prefrontal areas contribute in distinctly different ways to rule-guided behaviour in the context of a Wisconsin Card Sorting Test (WCST) analog for macaques. For example, causal evidence from circumscribed lesions in NHPs reveals that dorsolateral prefrontal cortex (dlPFC) is necessary to maintain a reinforced abstract rule in working memory, orbitofrontal cortex (OFC) is needed to rapidly update representations of rule value, and the anterior cingulate cortex (ACC) plays a key role in cognitive control and integrating information for correct and incorrect trials over recent outcomes. Moreover, recent lesion studies of frontopolar cortex (FPC) suggest it contributes to representing the relative value of unchosen alternatives, including rules. Yet we do not understand how these functional specializations relate to intrinsic neuronal activities nor the extent to which these neuronal activities differ between different prefrontal regions. After reviewing the aforementioned causal evidence I will present our new data from studies using multi-area multi-electrode recording techniques in NHPs to simultaneously record from four different prefrontal regions implicated in rule-guided behaviour. Multi-electrode micro-arrays (‘Utah arrays’) were chronically implanted in dlPFC, vlPFC, OFC, and FPC of two macaques, allowing us to simultaneously record single and multiunit activity, and local field potential (LFP), from all regions while the monkey performs the WCST analog. Rule-related neuronal activity was widespread in all areas recorded but it differed in degree and in timing between different areas. I will also present preliminary results from decoding analyses applied to rule-related neuronal activities both from individual clusters and also from population measures. These results confirm and help quantify dynamic task-related activities that differ between prefrontal regions. We also found task-related modulation of LFPs within beta and gamma bands in FPC. By combining this correlational recording methods with trial-specific causal interventions (electrical microstimulation) to FPC we could significantly enhance and impair animals performance in distinct task epochs in functionally relevant ways, further consistent with an emerging picture of regional functional specialization within a distributed framework of interacting and interconnected cortical regions.

While most experimental tasks aim at isolating simple cognitive processes to study their neural bases, naturalistic behaviour is often complex and multidimensional. I will present two studies revealing previously uncharacterised neural circuits for decision-making in macaques. This was possible thanks to innovative experimental tasks eliciting sophisticated behaviour, bridging the human and non-human primate research traditions. Firstly, I will describe a specialised medial frontal circuit for novel choice in macaques. Traditionally, monkeys receive extensive training before neural data can be acquired, while a hallmark of human cognition is the ability to act in novel situations. I will show how this medial frontal circuit can combine the values of multiple attributes for each available novel item on-the-fly to enable efficient novel choices. This integration process is associated with a hexagonal symmetry pattern in the BOLD response, consistent with a grid-like representation of the space of all available options. We prove the causal role played by this circuit by showing that focussed transcranial ultrasound neuromodulation impairs optimal choice based on attribute integration and forces the subjects to default to a simpler heuristic decision strategy. Secondly, I will present an ongoing project addressing the neural mechanisms driving behaviour shifts during an evidence accumulation task that requires subjects to trade speed for accuracy. While perceptual decision-making in general has been thoroughly studied, both cognitively and neurally, the reasons why speed and/or accuracy are adjusted, and the associated neural mechanisms, have received little attention. We describe two orthogonal dimensions in which behaviour can vary (traditional speed-accuracy trade-off and efficiency) and we uncover independent neural circuits concerned with changes in strategy and fluctuations in the engagement level. The former involves the frontopolar cortex, while the latter is associated with the insula and a network of subcortical structures including the habenula.