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Peer-reviewedCC BYNature Mental Health

Patient-specific functional networks track early cognitive alterations and minor hallucinations in Parkinson’s disease

  • Sara Stampacchia1
  • Fosco Bernasconi1
  • Dimitri Van De Ville2,3
  • Enrico Amico4,5
  • Lada Kohoutová1
  • John‐Paul Taylor6
  • Alan J. Thomas6
  • Javier Pagonabarraga7,8,9,10
  • Jaime Kulisevsky7,8,9,10
  • Olaf Blanke11,1
11 affiliations
  1. 1Laboratory of Cognitive Neuroscience (LNCO), Neuro-X Institute and Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
  2. 2Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland
  3. 3Neuro X Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
  4. 4Centre for Human Brain Health, University of Birmingham, Birmingham, UK
  5. 5School of Mathematics, University of Birmingham, Birmingham, UK
  6. 6Translational and Clinical Research Institute, Newcastle University, Newcastle, UK
  7. 7Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain
  8. 8Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
  9. 9Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Barcelona, Spain
  10. 10Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
  11. 11Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland
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Abstract

Minor hallucinations (MHs) affect up to 40% of patients with Parkinson's disease (PD) and are early indicators of cognitive decline. Unlike previous group-level studies, connectome-based brain fingerprinting enables the capture of individualized neural features. Leveraging this framework in a cross-sectional cohort of patients with Parkinson's disease with and without MHs using resting-state functional magnetic resonance imaging, here we show that each patient exhibits a unique brain fingerprint, irrespective of MH status. The most individualized features were associated with clinically relevant measures such as motor-symptom severity and cognitive performance. Patients with MHs showed a loss of individual-specific features in brain networks linked to cognitive health, whereas the cerebellar-to-cortex connectivity-typically less distinctive-became more prominent, emphasizing the role of somatosensory and motor integration in MH pathogenesis. Moreover, MH-related fingerprint regions mapped onto cortical territories with lower densities of neurotransmitter systems implicated in hallucinations. Overall, our fully data-driven findings reveal a distinct, patient-specific signature that differentiates patients with Parkinson's disease and MHs.

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Cite

BibTeXRIS
BibTeX
@article{stampacchia2026patientspecific,
  title = {{Patient-specific functional networks track early cognitive alterations and minor hallucinations in Parkinson’s disease}},
  author = {Sara Stampacchia and Fosco Bernasconi and Dimitri Van De Ville and Enrico Amico and Lada Kohoutová and John‐Paul Taylor and Alan J. Thomas and Javier Pagonabarraga and Jaime Kulisevsky and Olaf Blanke},
  journal = {Nature Mental Health},
  year = {2026},
  month = jun,
  doi = {10.1038/s44220-026-00657-x},
  url = {https://doi.org/10.1038/s44220-026-00657-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Patient-specific functional networks track early cognitive alterations and minor hallucinations in Parkinson’s disease
AU  - Sara Stampacchia
AU  - Fosco Bernasconi
AU  - Dimitri Van De Ville
AU  - Enrico Amico
AU  - Lada Kohoutová
AU  - John‐Paul Taylor
AU  - Alan J. Thomas
AU  - Javier Pagonabarraga
AU  - Jaime Kulisevsky
AU  - Olaf Blanke
PY  - 2026
DA  - 2026/06/08
JO  - Nature Mental Health
DO  - 10.1038/s44220-026-00657-x
UR  - https://doi.org/10.1038/s44220-026-00657-x
AB  - Minor hallucinations (MHs) affect up to 40% of patients with Parkinson's disease (PD) and are early indicators of cognitive decline. Unlike previous group-level studies, connectome-based brain fingerprinting enables the capture of individualized neural features. Leveraging this framework in a cross-sectional cohort of patients with Parkinson's disease with and without MHs using resting-state functional magnetic resonance imaging, here we show that each patient exhibits a unique brain fingerprint, irrespective of MH status. The most individualized features were associated with clinically relevant measures such as motor-symptom severity and cognitive performance. Patients with MHs showed a loss of individual-specific features in brain networks linked to cognitive health, whereas the cerebellar-to-cortex connectivity-typically less distinctive-became more prominent, emphasizing the role of somatosensory and motor integration in MH pathogenesis. Moreover, MH-related fingerprint regions mapped onto cortical territories with lower densities of neurotransmitter systems implicated in hallucinations. Overall, our fully data-driven findings reveal a distinct, patient-specific signature that differentiates patients with Parkinson's disease and MHs.
SN  - 2731-6076
ER  -