The central role of the Thalamus in psychosis, lessons from neurodegenerative diseases and psychedelics
Open accessAbstract
The PD-DLB psychosis complex found in Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) includes hallucinations, Somatic Symptom/Functional Disorders, and delusions. These disorders exhibit similar presentation patterns and progression. Mechanisms at the root of these symptoms also share similarities with processes promoting altered states of consciousness found in Rapid Eye Movement sleep, psychiatric disorders, or the intake of psychedelic compounds. We propose that these mechanisms find a crucial driver and trigger in the dysregulated activity of high-order thalamic nuclei set in motion by ThalamoCortical Dysrhythmia (TCD). TCD generates the loss of finely tuned cortico-cortical modulations promoted by the thalamus and unleashes the aberrant activity of the Default Mode Network (DMN). TCD moves in parallel with altered thalamic filtering of external and internal information. The process produces an input overload to the cortex, thereby exacerbating DMN decoupling from task-positive networks. These phenomena alter the brain metastability, creating dreamlike, dissociative, or altered states of consciousness. In support of this hypothesis, mind-altering psychedelic drugs also modulate thalamic-cortical pathways. Understanding the pathophysiological background of these conditions provides a conceptual bridge between neurology and psychiatry, thereby helping to generate a promising and converging area of investigation and therapeutic efforts.
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This decoupling could disrupt the comparison between priors and sensory percepts, leading to greater reliance on internally generated content.
“This decoupling could disrupt the comparison between priors and sensory percepts, leading to greater reliance on internally generated content.56”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [56]
A recent proposal views the thalamus as a driver of unbalanced network recruitment, suggesting that it may induce decoupling between the default mode network and task-positive networks.
“a recent proposal56 views the thalamus as a driver of unbalanced network recruitment, suggesting that it may induce decoupling between the default mode network and task-positive networks”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [56]
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“Previous research has shown that the thalamus plays a role in VH in PD 54,55 , and a recent proposal 56 views the thalamus as a driver of unbalanced network recruitment, suggesting that it may induce decoupling between the default mode network and task-positive networks.”
- Authors
- Onofrj, M., Russo, M., Delli Pizzi, S., De Gregorio, D., Inserra, A., Gobbi, G., & Sensi, S. L.
- Affiliations
- University of Chieti-Pescara (IT)
- McGill University (CA)
- Corresponding author
- Onofrj, Marco
- Sensi, Stefano L.
- Venue
- Translational Psychiatry
- Published
- 2023-12-13
- Volume
- 13
- Issue
- 1
- Pages
- 384-384
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC10719401
- OpenAlex
- W4389684661
- Cited by
- 43
- References
- 233
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 11
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Alzheimer's Association (18PTC-19-602325, 18PTC-19-602325 and GEENA-Q-19-596282, GEENA-Q-19-596282, 602325)
- European Commission (HORIZON2020)
- Associazione Italiana Ricerca Alzheimer (18PTC-19-602325, GEENA-Q-19-596282)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- thalamus, psychosis, Parkinson's disease, dementia with Lewy bodies, hallucinations, delusions, somatic symptom disorder, thalamocortical dysrhythmia, default mode network, altered states of consciousness, psychedelics, thalamocortical circuits, neurodegenerative diseases
- MeSH terms
- Hallucinogens, Humans, Parkinson Disease, Psychotic Disorders, Thalamus, Neurodegenerative Diseases, Lewy Body Disease
About these checks
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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