Deep brain stimulation of the subthalamic nucleus transiently enhances loss-chasing behaviour in patients with Parkinson's Disease

Abstract

a b s t r a c t a r t i c l e i n f oDopaminergic treatments are associated with impulse control disorders such as pathological gambling in a subset of patients with Parkinson's Disease. While deep brain stimulation of the subthalamic nucleus has been reported to reduce symptoms of impulse control disorders in some Parkinson's Disease patients, little is known about its specific effects on gambling behaviour. In this experiment, we investigated the effects of deep brain stimulation of the subthalamic nucleus on one of the central features of pathological gambling: the tendency to chase losses. Loss-chasing is associated with impaired control over gambling behaviour and it is one of the most salient features of pathological gambling as it presents in the clinic. Twenty two patients with advanced idiopathic Parkinson's Disease and chronically implanted subthalamic nucleus electrodes for deep brain stimulation completed a simple laboratory model of loss-chasing behaviour twice: once with and once without stimulation. Exploratory analysis indicated that deep brain stimulation of the subthalamic nucleus increased the value of losses chased by patients with Parkinson's Disease when shifting from off-to on-stimulation. These effects were not attributable to changes in state affect or to the motor impairments produced by the withdrawal of deep brain stimulation of the subthalamic nucleus. The effects of the stimulation on the value of losses chased were more pronounced in female than in male patients and reduced in patients taking dopamine receptor agonists. Collectively, these results suggest that deep brain stimulation of the subthalamic nucleus can transiently alter the evaluation of accumulated losses during gambling episodes in idiopathic Parkinson's Disease.

Systemic Administration of 8-OH-DPAT and Eticlopride, but not SCH23390, Alters Loss-Chasing Behavior in the Rat

“…These dilemmas induce risk-seeking behavior in a variety of social and economic contexts (Kahneman and Tversky, 2000). In addition to showing that activity within the anterior cingulate cortex and subthalamic nucleus mediates loss-chasing choices (Campbell-Meiklejohn et al, 2008;Rogers et al, 2011), we have shown that tryptophan depletion reduces decisions to chase in healthy adults. By contrast, single treatments with 176 mg of the D 2 /D 3 receptor agonist, pramipexole, increase the value of losses that participants are prepared to chase but reduce the value of losses surrendered when deciding to quit gambling (Campbell-Meiklejohn et al, 2011).…”

“…Administration of the D 2 receptor antagonist, haloperidol, can enhance the reward value of gambling experiences in pathological gamblers (Zack and Poulos, 2007) and alter betting patterns while playing slot machines (Tremblay et al, 2010). Previously, we found that single doses of pramipexole increased the value of losses that human subjects were prepared to chase (CampbellMeiklejohn et al, 2011) while single doses of methylphenidate blocked the tendency of larger losses to suppress chasing behavior (Campbell-Meiklejohn et al, 2012). This suggests that dopamine activity mediate the evaluation of losses in relation to decisions to keep playing during runs of losing outcomes.…”

“…Finally, following our experiments in human subjects (Campbell-Meiklejohn et al, 2011Rogers et al, 2011), we conducted a final set of tests using only chasing episodes that terminated in either quit responses on the 1st choicepoint, quit responses on the 2nd choice-point, or the maximum of two successive chase responses; that is, we excluded all chasing episodes that ended with winning outcomes in which time-outs were avoided. In this way, our analyses tested rats' chasing behavior during runs of losing outcomes without the random interposition of winning outcomes.…”

A Revision of the Relationship between Gambling Disorder, Attention Deficit Hyperactivity Disorder and Parkinson´s Disease

“…Furthermore, another investigation (n = 22) evaluated subjects with advanced idiopathic pd and implanted electrodes (subthalamic nucleus) for the purpose of exploring the effect of deep brain stimulation on the inclination to chase losses (Rogers et al, 2011). It concluded that temporary stimulation alters the judgment of collected losses during gambling events in idiopathic pd patients.…”

“…On the other hand, dopamine related treatments like high dosages of anti-Parkinsonian drugs (levodopa, dopamine equivalents, levodopa equivalents; Pontieri et al, 2015), levodopa or dopamine agonists (Weintraub et al, 2010), type B monoamine oxidase inhibitors (Pérez-Lloret et al, 2012), increase the incidence of other impulse control disorders in pd patients based on different studies. On the other hand, deep brain stimulation (sub-thalamic nucleus) in advanced stage pd patients alters the judgment during "chasing losses" (Rogers et al, 2011). 2) The incidence of gambling disorder in pd patients can be partially explained by aging effects on cognitive processes, based on the works of Isella et al (2008) and Zamarian et al (2008).…”