Stronger top-down and weaker bottom-up frontotemporal connections during sensory learning are associated with severity of psychotic phenomena
Open accessAbstract
Recent theories in computational psychiatry propose that unusual perceptual experiences and delusional beliefs may emerge as a consequence of aberrant inference and disruptions in sensory learning. The current study investigates these theories and examines the alterations that are specific to schizophrenia spectrum disorders vs those that occur as psychotic phenomena intensify, regardless of diagnosis. We recruited 66 participants: 22 schizophrenia spectrum inpatients, 22 nonpsychotic inpatients, and 22 nonclinical controls. Participants completed the reversal oddball task with volatility manipulated. We recorded neural responses with electroencephalography and measured behavioral errors to inferences on sound probabilities. Furthermore, we explored neural dynamics using dynamic causal modeling (DCM). Attenuated prediction errors (PEs) were specifically observed in the schizophrenia spectrum, with reductions in mismatch negativity in stable, and P300 in volatile, contexts. Conversely, aberrations in connectivity were observed across all participants as psychotic phenomena increased. DCM revealed that impaired sensory learning behavior was associated with decreased intrinsic connectivity in the left primary auditory cortex and right inferior frontal gyrus (IFG); connectivity in the latter was also reduced with greater severity of psychotic experiences. Moreover, people who experienced more hallucinations and psychotic-like symptoms had decreased bottom-up and increased top-down frontotemporal connectivity, respectively. The findings provide evidence that reduced PEs are specific to the schizophrenia spectrum, but deficits in brain connectivity are aligned on the psychosis continuum. Along the continuum, psychotic experiences were related to an aberrant interplay between top-down, bottom-up, and intrinsic connectivity in the IFG during sensory uncertainty. These findings provide novel insights into psychosis neurocomputational pathophysiology.
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Compared to healthy controls, schizophrenia patients showed stronger functional connectivity between orbitofrontal and visual cortex, and between the right and left superior temporal gyrus.
“Compared to HC, patients with SCZ showed stronger functional connectivity between orbitofrontal and vi sual cortex, and between the right and left superior temporal gyrus.”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Dzafic et al., 2021
In schizophrenia, reduced connectivity between several brain areas was found in tasks involving movements: precuneus and medial prefrontal cortex during predictable motion; left frontal pole, superior frontal gyrus, and paracingulate gyrus during random motion; right cerebellum, left superior frontal gyrus, and paracingulate gyrus during arbitrary motion.
“Reduced connectivity between several brain areas was found in tasks involving movements, such as precuneus and medial prefrontal cortex during predictable motion; left frontal pole, superior frontal gyrus, and paracingulate gyrus during random motion; right cerebellum, left superior frontal gyrus, and par acingulate gyrus during arbitrary motion (Dzafic et al., 2021; Scheliga et al., 2022”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Dzafic et al., 2021
In schizophrenia, reduced connectivity between the left and right hemispheres was observed for the inferior/superior frontal gyrus and primary auditory cortex during prediction tasks.
“Conversely, reduced connectivity between the left and right hemi spheres was observed for the inferior/superior frontal gyrus and primary auditory cortex during prediction tasks.”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Dzafic et al., 2021
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Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review.
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“…prefrontal cortex during predictable motion; left frontal pole, superior frontal gyrus, and paracingulate gyrus during random motion; right cerebellum, left superior frontal gyrus, and par-acingulate gyrus during arbitrary motion (Dzafic et al., 2021; Scheliga et al., 2022; Schmack et al., 2017).”
- Authors
- Dzafic, I., Larsen, K. M., Darke, H., Pertile, H., Carter, O., Sundram, S., & Garrido, M. I.
- Affiliations
- The University of Queensland (AU)
- University of Copenhagen (DK)
- The University of Melbourne (AU)
- Monash Medical Centre (AU)
- Corresponding author
- Dzafic, Ilvana
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-01-06
- Volume
- 47
- Issue
- 4
- Pages
- 1039-1047
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC8266649
- OpenAlex
- W3119608760
- Cited by
- 24
- References
- 50
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 6 · 2021: 2
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Schizophrenia Bulletin (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Queensland (2016000071)
- Queensland Government
- Australian Research Council (FT140100807)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Keywords
- schizophrenia spectrum disorders, psychotic experiences
- MeSH terms
- Auditory Cortex, Humans, Learning, Perception, Psychotic Disorders, Case-Control Studies, Prefrontal Cortex, Patient Acuity
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