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Logo of neurologyNeurologyAmerican Academy of Neurology
 
Neurology. Nov 9, 2010; 75(19): 1711–1716.
PMCID: PMC3033606
Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD(e Pub ahead of print)
T. van Eimeren, MD, G. Pellecchia, PhD, R. Cilia, MD, B. Ballanger, PhD, T.D.L. Steeves, MD, S. Houle, MD, J.M. Miyasaki, MD, M. Zurowski, MD, A.E. Lang, MD, and A.P. Strafella, MD, PhD
From the Division of Brain, Imaging and Behaviour-Systems Neuroscience, BIB-SN (T.v.E., G.P., R.C., B.B., A.P.S.), Toronto Western Research Institute; Movement Disorders Centre (T.D.L.S., J.M., M.Z., A.E.L., A.P.S.), Toronto Western Hospital; and CAMH-PET Centre (T.v.E., G.P., R.C., B.B., S.H., A.P.S.), University of Toronto, Canada.
Abstract
Objective:
Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls).
Methods:
Following overnight withdrawal of antiparkinsonian medication, patients were studied with H2 15O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback.
Results:
We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity.
Conclusions:
We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions—outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)—together with restricted access of those areas to executive control (external pallidum)—may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.
GLOSSARY
ANOVA = analysis of variance;
DA = dopamine agonist;
G-SAS = Gambling Symptom Assessment Scale;
GPe = external pallidum;
MNI = Montréal Neurological Institute;
OFC = orbitofrontal cortex;
PD = Parkinson disease;
rCBF = regional cerebral blood flow;
RCZ = rostral cingulated zone;
UPDRS = Unified Parkinson's Disease Rating Scale.

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