The pattern of striatal dopaminergic denervation explains sensorimotor synchronization accuracy in Parkinson's disease.

Abstract

The basal ganglia are thought to play a critical role in duration perception and production. However, experimental evidence for impaired temporal processing in Parkinson's disease (PD) patients is mixed. This study examined the association between striatal dopaminergic denervation in PD patients and sensorimotor synchronization. Twenty-eight mild-to-moderate stage PD patients synchronized finger taps to tone sequences of either 500 ms, 1000 ms or 1500 ms time intervals while ON levodopa (l-DOPA) or placebo pill (on separate test days) with the index finger of their more and less affected hands. We measured the accuracy and variability of synchronization. In a separate session, patients underwent (11)C-dihydrotetrabenazine ((11)C-DTBZ) PET scanning to measure in vivo striatal dopaminergic denervation. Patients were less accurate synchronizing to the 500 ms target time interval, compared to the 1000 ms and 1500 ms time intervals, but neither medication state nor hand affected accuracy; medication state, hand nor the target time interval affected synchronization variability. Regression analyses revealed no strong relationships between synchronization accuracy or variability and striatal dopaminergic denervation. We performed a cluster analysis on the degree of dopaminergic denervation to determine whether patient subgroup differences underlie our results. Three patient subgroups showed behavioral differences in synchronization accuracy, but not variability, paralleling their pattern of denervation. These findings provide further evidence for the role of the basal ganglia and dopamine in duration production and suggest that the degree of striatal dopaminergic denervation may explain the heterogeneity of performance between PD patients on the sensorimotor synchronization task.

• Authors: Nathaniel S Miller, Youngbin Kwak, Nicolaas I Bohnen, Martijn L T M Müller, Praveen Dayalu, Rachael D Seidler
• Journal: Behavioural brain research (Behav Brain Res) Vol. 257 Pg. 100-10 (Nov 15 2013) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 24076152 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Antiparkinson Agents
• Carbon Isotopes
• dihydrotetrabenazine
• Levodopa
• Dopamine
• Tetrabenazine

Topics

• Aged
• Aged, 80 and over
• Antiparkinson Agents (pharmacology, therapeutic use)
• Carbon Isotopes (pharmacokinetics)
• Cluster Analysis
• Corpus Striatum (diagnostic imaging, drug effects, metabolism)
• Dopamine (metabolism)
• Female
• Humans
• Levodopa (pharmacology, therapeutic use)
• Male
• Middle Aged
• Motor Activity (drug effects)
• Parkinson Disease (diagnostic imaging, drug therapy, pathology, physiopathology)
• Positron-Emission Tomography
• Psychomotor Performance (drug effects, physiology)
• Tetrabenazine (analogs & derivatives, pharmacokinetics)
• Time Factors
• Time Perception (drug effects, physiology)