Mesocorticolimbic reinforcement learning of reward representation and value provides an integrated mechanistic account for schizophrenia

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Abstract

Mesocorticolimbic dopamine projections are crucial for value learning, motivational control, and cognitive functions, but their precise neurocomputational roles remain elusive. Based on recent experimental and theoretical findings, we constructed a neural circuit model where dopamine neuronal populations receive differential inputs from individual rewards and encode heterogeneous reward prediction errors, which train cortical and striatal neurons to learn reward-associated state representation and value. Learning is achieved via simultaneous ‘alignments’ of the cortical and striatal downstream connections to the mesocorticolimbic dopamine projections, and inhibition-dominance in the cortical recurrent network is a key for successful learning. Excessive excitation, whether pre-existing or induced by manipulations, leads to aberrant activity, which disrupts the alignments and even causes anti-alignment. This impairs both reward-specific motivational control and credit assignment, potentially explaining the negative and positive symptoms of schizophrenia, respectively. Our model thus provides a mechanistic account for schizophrenia, integrating the different causes and symptoms, with testable predictions.

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last seen: 2026-05-20T01:45:00.602351+00:00