Caudate serotonin signaling during social exchange distinguishes essential tremor and Parkinson’s disease patients

Alec E. Hartle (), Kenneth T. Kishida, L. Paul Sands, Seth R. Batten, Leonardo S. Barbosa, Dan Bang, Terry Lohrenz, Jason P. White, Arian K. Sohrabi, Rebecca L. Calafiore, Alexandra G. DiFeliceantonio, Adrian W. Laxton, Stephen B. Tatter, Mark R. Witcher, P. Read Montague () and W. Matt Howe ()
Additional contact information
Alec E. Hartle: Virginia Tech
Kenneth T. Kishida: Wake Forest University
L. Paul Sands: Virginia Tech
Seth R. Batten: Virginia Tech
Leonardo S. Barbosa: Virginia Tech
Dan Bang: Virginia Tech
Terry Lohrenz: Virginia Tech
Jason P. White: Virginia Tech
Arian K. Sohrabi: Wake Forest University School of Medicine
Rebecca L. Calafiore: Wake Forest University School of Medicine
Alexandra G. DiFeliceantonio: Virginia Tech
Adrian W. Laxton: Wake Forest University School of Medicine
Stephen B. Tatter: Wake Forest University School of Medicine
Mark R. Witcher: Virginia Tech
P. Read Montague: Virginia Tech
W. Matt Howe: Virginia Tech

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-63079-w

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