Guillermo Horga, MD, PhD

Associate Professor of Psychiatry

Columbia University

Bridging neurobiology, computation, and phenomenology of psychosis

Psychotic symptoms of schizophrenia, including auditory hallucinations, are a paradigmatic example of altered subjective experience in mental illness. While auditory hallucinations are consistently linked to elevated (dorsal) striatal dopamine and perceptual biases in signal-detection tasks, an underlying computational mechanism grounded in plausible biology remains elusive. Such mechanism has been obscured by functional heterogeneity in dopamine signals across striatal subregions. I will discuss our efforts to develop a normative circuit model in which corticostriatal plasticity depends on distinct dopaminergic learning signals across modules: plasticity in the ventral striatum is modulated by reward prediction errors to drive reinforcement learning while that in the sensory-dorsal striatum is modulated by sensory prediction errors derived from internal belief to drive self-supervised learning. I will present initial validations of key predictions of this model using dopamine recordings across striatal subregions in mice, as well as human behavior across various tasks including a new hybrid learning task. Finally, I will present evidence that changes in learning resulting from optogenetic stimulation of the sensory-dorsal striatum in mice and individual variability in hallucinations in humans are best explained by selectively enhancing dopamine levels in the model sensory-dorsal striatum. These findings identify plasticity mechanisms underlying biased learning of sensory expectations as a biologically plausible link between excess dopamine and hallucinations, illustrating the utility of computational circuit models as a translational bridge between neurobiology and phenomenology.

Relevant Publications:

A corticostriatal learning mechanism linking excess striatal dopamine and auditory hallucinations

An integrative framework for perceptual disturbances in psychosis

Tuesdays@10 is a signature Zuckerman Institute initiative that aims to expose researchers at all levels to high-quality science and stimulate scientific discourse. The speakers featured in this series represent various fields and techniques in neuroscience, and include invited guests of the Columbia Neuroscience Seminars, the Zuckerman Institute's Local Circuits Affiliates Program, and other special seminar series through a combined, collaborative effort of one or more of the following: Columbia's Zuckerman Institute, the Center for Precision Psychiatry, the Center for Theoretical Neuroscience, the Department of Neuroscience, the Doctoral Program in Neurobiology and Behavior and the Columbia Translational Neuroscience Initiative, and with support from the Kavli Institute for Brain Science. 

More information and a full schedule can be found here.