Influence of glutamatergic and GABA-ergic neurotransmission on perception and decision making: a novel pharmacological approach based on computational models.

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Two central hypotheses concerning theoretical models of human cognition have linked processes of perception and decision making to network effects of both glutamatergic and GABA-ergic (gamma-aminobutyric acid) activity. Thus, glutamatergic cortical activity is supposed to generate top-down predictions about perceptions and related decisions. And GABA-ergic activity is assumed to be required for the bottom-up control relating the generated predictions to encoded memories. Although these hypotheses are widely accepted in the field of cognitive neuroscience, neuropharmacological evidence has yet to be collected concerning both hypotheses. Under randomized and double-blind conditions participants receive a set of pharmacological agents (D-Cycloserine, Dextromethorphane, Lorazepam, Flunarizine, Placebo), which efficiently modulate glutamatergic and GABA-ergic network activity. The influence of the pharmacological interventions on perception and decision making will be assessed combining two established tasks (probabilistic-reaction-time task; urn task) and two computational bayesian models (Hierarchical-Gaussian-Filter, Markow-decision-processes). Thus, the research proposal presents a step toward understanding the glutamatergic and GABA-ergic network effects on perception and decision making in a human in-vivo model. Establishing the outlined translational research-framework is key to enable future research projects on patients with schizophrenia, where pathological dysfunction of glutamatergic and GABA-ergic networks as well as impairments in decision making and perception have repeatedly been described. The research proposal therefore constitutes the foundation to adress future research issues in schizophrenia patients using the outlined novel research approach.