A perceptual inference mechanism for hallucinations linked to striatal dopamine
Open accessAbstract
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.
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Structural MRI revealed that schizophrenia patients showed reduced gray matter in the dorsolateral anterior cingulate cortex and striatum.
“Finally, structural MRI revealed that SCZ patients showed reduced gray matter in the dorsolateral anterior cingulate cortex (i.e., involved in uncertainty adaptation and decision-making), and striatum (i.e., involved in temporal precision and statistical regularities) (Cassidy et al., 2018).”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Cassidy et al., 2018
The Study 2 Results report that smaller gray-matter volume in a region encompassing the dorsal anterior cingulate cortex correlated with reduced uncertainty adjustment, including among healthy controls. The same passage explicitly says the MRI analysis found no significant group differences; it does not report reduced gray matter in schizophrenia patients in either the cingulate cortex or striatum. Page number is unavailable in our copy. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredDopamine release in the associative striatum is associated with increased weighting of prior predictions.
“Indeed, dopamine release in the associative striatum, a key area of disruption in psychosis (49) is associated with increased weighting of prior predictions (97).”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [97]
The Results (Study 2; page not provided) link greater associative-striatal dopamine release capacity to reduced adjustment for uncertainty, which the authors interpret as failing to dampen the influence of predictions when uncertainty is higher. They also report that the overall context-mean effect was not correlated with release capacity, so the source does not establish a general increase in the weighting of prior predictions. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPatients with auditory hallucinations put more weight on predictions than on sensory evidence when compared with healthy individuals.
“Several studies reported that patients with auditory hallucinations put more weight on predictions than on sensory evidence when compared with healthy individuals (14, 15).”
From A Predictive Coding Perspective on Mismatch Negativity Impairment in Schizophrenia (2020) · cites this paper as [15]
The Discussion reports a stronger bias toward expected sounds with greater hallucination severity, particularly under uncertainty. In Study 2’s Results, patients with active hallucinations showed greater bias than healthy controls in the high-variance condition, but the authors call this comparison preliminary and say it would not survive correction for multiple comparisons. The unqualified claim of a patient–control difference therefore overstates the finding. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDopamine appears to be involved in encoding the precision of perceptual predictions.
“Moreover, dopamine also appears to be involved in encoding the precision of perceptual predictions (19, 20, 97).”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [97]
The impact of priors on perception may be enhanced in those with hallucinations.
“However, recent neural data suggest that they do (72, 73), and that the impact of priors on perception may be enhanced in those with hallucinations (74–76).”
From The Predictive Coding Account of Psychosis (2018) · cites this paper as [75]
Computational modelling indicates that patients with hallucinations have more heavily weighted priors than non-hallucinators, and that this is associated with striatal dopamine function.
“Auditory hallucinations are a common psychotic symptom and computational modelling indicates that patients with hallucinations have more heavily weighted priors than non-hallucinators (97, 98), and that this is associated with striatal dopamine function (97).”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [97]
In SCZ, hallucinations correlate with a greater perceptual bias toward expected stimuli.
“Hallucinations also correlated with a greater perceptual bias toward expected stimuli (Cassidy et al., 2018).”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Cassidy et al., 2018
The dopamine hypothesis (excessive dopamine activity in the thalamocorticostriatal network) has been mechanistically linked with hallucinations by causing a perceptual bias towards prior top-down expectation.
“The dopamine hypothesis characterized by excessive dopamine activity in the thalamocorticostriatal network 97 has been mechanistically linked with hallucinations by causing a perceptual bias towards prior (top-down) expectation.”
From Towards an Integrative Account of Potential Mechanisms Mediating the Path From Sleep Dysfunction to Hallucinations (2025) · cites this paper as [98]
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The Predictive Coding Account of Psychosis
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“Another recent study investigated the perception of auditory stimuli under different levels of uncertainty (75).”
BackgroundSchizophrenia, dopamine and the striatum: From biology to symptoms
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Self-citationHallucinations and strong priors
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Self-citationForms of prediction in the nervous system
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“Several studies reported that patients with auditory hallucinations put more weight on predictions than on sensory evidence when compared with healthy individuals (14, 15).”
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“Finally, structural MRI revealed that SCZ patients showed reduced gray matter in the dorsolateral anterior cingulate cortex (i.e., involved in uncertainty adaptation and decision-making), and striatum (i.e., involved in temporal precision and statistical regularities) (Cassidy et al., 2018).”
Relating glutamate, conditioned, and clinical hallucinations via 1H-MR spectroscopy
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Rethinking Predictive Processing
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- Authors
- Cassidy, C. M., Balsam, P. D., Weinstein, J. J., Rosengard, R. J., Slifstein, M., Daw, N. D., Abi-Dargham, A., & Horga, G.
- Affiliations
- University of Ottawa (CA)
- Columbia University Irving Medical Center (US)
- Stony Brook University (US)
- Princeton University (US)
- Corresponding author
- Horga, Guillermo
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 28
- Issue
- 4
- Pages
- 503-514.e4
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC5820222
- OpenAlex
- W2787581258
- Cited by
- 176
- References
- 99
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 15 · 2023: 20 · 2022: 20 · 2021: 28 · 2020: 26 · 2019: 16 · 2018: 7
- FWCI
- 15.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K23-MH101637, P50-MH086404, R21-MH099509, R01MH068073)
- Fonds de Recherche du Québec, Santé
- Sidney R. Baer Jr. Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- hallucinations, schizophrenia, striatal dopamine, Bayesian inference, perceptual inference, gain control, prior expectations, auditory perception, duration perception, uncertainty, dorsal anterior cingulate cortex, amphetamine, dopamine release, psychosis vulnerability
- MeSH terms
- Adult, Bayes Theorem, Brain, Corpus Striatum, Dopamine, Female, Gyrus Cinguli, Hallucinations, Humans, Illusions, Male, Perception, Perceptual Distortion, Psychotic Disorders, Schizophrenia
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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