Cited by 43Hallucinations in medical conditionsPsychedelics and Drug StudiesFunctional Brain Connectivity Studies

The central role of the Thalamus in psychosis, lessons from neurodegenerative diseases and psychedelics

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Onofrj, Marco, Russo, Mirella, Delli Pizzi, Stefano, De Gregorio, Danilo, Inserra, Antonio, Gobbi, Gabriella, Sensi, Stefano L.·2023·Translational Psychiatry

Abstract

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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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)
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
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

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