Caudate serotonin signaling during social exchange distinguishes essential tremor and Parkinson’s disease patients
Dynamic changes in dopamine, noradrenaline, and serotonin release are believed to causally contribute to the neural computations that support reward-based decision making. Accordingly, changes in signaling by these systems are hypothesized to underwrite multiple cognitive and behavioral symptoms observed in many neurological disorders. Here, we characterize the release of these neurotransmitters measured concurrently in the caudate of patients with Parkinson's disease or essential tremor undergoing deep brain stimulation surgery as they played a social exchange game. We show that violations in the expected value of monetary offers are encoded by opponent patterns of dopamine and serotonin release in essential tremor, but not Parkinson's disease, patients. We also demonstrate that these changes in serotonin signaling comprise a neurochemical boundary that subsegments these two neuromotor diseases. Our combined results point to a neural signature of altered reward processing that can be used to understand the signaling deficiencies that underwrite these diseases.
Authors
- Alexandra G. DiFeliceantonio (ORCID: https://orcid.org/0000-0002-7155-6060)
- Rebecca Calafiore (ORCID: https://orcid.org/0000-0003-1567-1942)
- Mark R. Witcher (ORCID: https://orcid.org/0000-0001-6877-2670)
- Seth R. Batten (ORCID: https://orcid.org/0000-0001-8147-4301)
- Kenneth T. Kishida (ORCID: https://orcid.org/0000-0002-7394-8922)
- Terry Lohrenz (ORCID: https://orcid.org/0000-0002-1581-0765)
- Dan Bang (ORCID: https://orcid.org/0000-0001-7446-7090)
- Adrian W. Laxton (ORCID: https://orcid.org/0000-0002-4631-5476)
- Jason P. White (ORCID: https://orcid.org/0000-0003-1754-3768)
- Stephen B. Tatter (ORCID: https://orcid.org/0000-0002-1063-0431)
- L. Paul Sands (ORCID: https://orcid.org/0009-0003-1552-5504)
- William M. Howe (ORCID: https://orcid.org/0000-0003-0433-6591)
- P. Read Montague (ORCID: https://orcid.org/0000-0002-8967-0339)
- Arian Kolahi Sohrabi (ORCID: https://orcid.org/0000-0002-9289-9222)
- Alec Hartle (ORCID: https://orcid.org/0000-0002-4089-5473)
- Leonardo S. Barbosa (ORCID: https://orcid.org/0009-0003-3412-2567)
Institutions
- Wellcome Centre for Human Neuroimaging (GB)
- Aarhus University (DK)
- Virginia Cooperative Extension (US)
- Biomedical Research Institute (US)
- Professional Education and Research Institute (US)
- University College London (GB)
- Wake Forest University (US)
- Carilion Clinic (US)
- Virginia Tech (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-02
- DOI
- https://doi.org/10.1038/s41467-025-63079-w
- Citations
- 2
- Primary Topic
- Neurological disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 2.78
Funders
- Bill and Melinda Gates Foundation
- Lundbeckfonden
- H. Lundbeck A/S
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- National Center for Advancing Translational Sciences