Dopaminergic and glutamatergic contribution to the formation of decision variables in fronto-parietal brain circuits

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We make innumerable decisions every day. Decision making requires accumulation of evidence for or against a proposition and ultimately for a specific action. However, it is not sufficient to simply accumulate evidence, the evidence must be evaluated. How useful it is? When is enough enough? Many of these aspects of decision making have been studied at the psychological and, to some extent, the neuronal level. Accumulation of evidence has been studied in the context of value based decisions, social decisions, economic decisions, gambling decisions, memory-based decisions, and, importantly, perceptual decisions. These studies have provided a rich theoretical background within which decision making can be explained, and they have generated tools to delineate the different cognitive components that are involved in decision making. At the neuronal level, signatures of decision making have been found in various cortical and subcortical areas. Neurons in these areas gradually alter their activity as evidence in favor or against a proposition is gathered, and they retain the representation of accumulated evidence even when the evidence is removed, i.e. a memory trace of evidence exists. Finally, many of these neurons convert the evidence into a categorical decision, when sufficient evidence has been gathered, or when urgency so dictates. Despite these insights, we currently do not understand how brain areas involved in decision making exchange information, or how the process of evidence accumulation, evidence evaluation, and categorization is made possible. Specifically we do not understand which brain chemicals (transmitters and their related receptors) are critical in enabling these processes. An understanding thereof is essential to understand decision making at a mechanistic level, and to understand how deficits in decision making come about in mental disorders such as Schizophrenia, Impulsive compulsive disorders, or Parkinson (for example). We aim to study these questions in macaque monkeys, the most appropriate animal model to relate neuronal data to human conditions. Neuronal signatures of decision making are best understood in the domain of perceptual decisions. In the laboratory, this is studied by confronting subjects with noisy sensory stimuli, who have to discriminate what stimulus has been presented. We will exploit well established paradigms which have helped understand the neural computations involved in perceptual decision making, namely a reaction time version of a coherent motion discrimination task, and a task where sequential information about the likely choice location has to be integrated over time. In the coherent motion task the subject is confronted with noisy motion stimuli and has to decide what direction of motion is present. In the sequential sampling task, monkeys are presented with different symbols which indicate a likelihood that a given choice location will yield a reward. We will record neuronal activity in the parietal and the frontal cortex, which have been studied in the context of these tasks. We intentionally copy existing paradigms and record in areas where the basic response properties are well delineated, as this allows to test specific predictions how different brain chemicals support different components of the decision making process. We focus on the dopaminergic and the glutamatergic system, as these have been implicated with different cognitive dysfunctions that affect decision making (e.g. working memory, evidence accumulation, evidence evaluation), but their contribution at the neuronal level remains poorly understood. We will determine how these systems contribute to evidence accumulation, evidence evaluation, and threshold setting to form a categorical decision.The study will generate a better understanding of the neuronal mechanisms of decision making in health and disease, aiming to help improve therapeutic approaches in the future.