A Perceptual Inference Mechanism for Hallucinations Linked to Striatal Dopamine

Clifford M. Cassidy, Peter D. Balsam, Jodi J. Weinstein, Rachel J. Rosengard, Mark Slifstein, Nathaniel D. Daw, Anissa Abi-Dargham, Guillermo Horga

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Hallucinations, a cardinal feature of psychotic disorders such as schizophrenia, are known to depend on excessive striatal dopamine. However, an underlying cognitive mechanism linking dopamine dysregulation and the experience of hallucinatory percepts remains elusive. Bayesian models explain perception as an optimal combination of prior expectations and new sensory evidence, where perceptual distortions such as illusions and hallucinations may occur if prior expectations are afforded excessive weight. Such excessive weight of prior expectations, in turn, could stem from a gain-control process controlled by neuromodulators such as dopamine. To test for such a dopamine-dependent gain-control mechanism of hallucinations, we studied unmedicated patients with schizophrenia with varying degrees of hallucination severity and healthy individuals using molecular imaging with a pharmacological manipulation of dopamine, structural imaging, and a novel task designed to measure illusory changes in the perceived duration of auditory stimuli under different levels of uncertainty. Hallucinations correlated with a perceptual bias, reflecting disproportional gain on expectations under uncertainty. This bias could be pharmacologically induced by amphetamine, strongly correlated with striatal dopamine release, and related to cortical volume of the dorsal anterior cingulate, a brain region involved in tracking environmental uncertainty. These findings outline a novel dopamine-dependent mechanism for perceptual modulation in physiological conditions and further suggest that this mechanism may confer vulnerability to hallucinations in hyper-dopaminergic states underlying psychosis. Cassidy et al. induced auditory illusions to test a dopamine-dependent cognitive mechanism for hallucinations. Unmedicated schizophrenia patients with auditory hallucinations perceived tone durations in a way similar to what was expected, even when expectations were imprecise, and this perceptual bias related to excess dopamine function.

Original languageEnglish (US)
Pages (from-to)503-514.e4
JournalCurrent Biology
Volume28
Issue number4
DOIs
StatePublished - Feb 19 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • Bayesian inference
  • PET imaging
  • amphetamine
  • dopamine
  • hallucinations
  • illusion
  • predictive coding
  • psychosis
  • schizophrenia
  • sensory learning

Fingerprint Dive into the research topics of 'A Perceptual Inference Mechanism for Hallucinations Linked to Striatal Dopamine'. Together they form a unique fingerprint.

Cite this