Brain Circuit Tied to Gambling Risk in Parkinson Disease Identified

Some of the drugs used to treat Parkinson disease (PD) increase the risk for pathological gambling.  This can have a significant economic adverse effect on some individuals.  I have previous posted on the use of amantadine in reducing pathological gambling in PD.  Although some medications may reduce the risk of pathological gambling, there is a need to further understand the mechanism of drug-related gambling behavior.

Cilia and colleagues from the University of Toronto as well as Italy recently published a study examining the neural network in a series of patients with PD and pathological gambling.   The research team used a brain imaging technique called SPECT.  SPECT is an earlier technology that measures brain anatomical blood flow.  In contrast to functional MRI, SPECT requires an intravenous injection of contrast agent.  In this study, the authors conducted a correlational analysis between regional cerebral blood flow and a measure of gambling severity from a psychometric instrument called the South Oaks Gambling Screen.   A series of subjects with PD  with pathological gambling were compared to a matched PD group without pathological gambling and a matched group without PD.   Using a complicated statistical analysis strategy called path analysis, they estimated effective brain connectivity (circuitry) associated with pathological gambling behavior.

High pathological gambling scores were associated with the reduced blood flow in the following brain regions (inpartial list):

• Right ventrolateral prefrontal cortex (VLPFC)
• Right anterior cingulate cortex (ACC)
• Right posterior cingulate cortex (PCC)
• Right medial frontopolar cortex (mPFC)
• Bilateral anterior insula
• Left striatum

The authors summarize why these specific regions and connections could affect the risk for development of pathological gambling behaviors.

Right VLPC: this brain region is involved with behavioral response inhibition, impulsivity and “risk-taking choices during decision making under conflict”.   Studies of damage to this region produces a “blunted reaction to aversive outcome and risk-taking behavior. 

ACC and striatum:  In healthy individuals, the authors note the ACC in a region involved in monitoring and processing negative outcomes.  The ACC regulates behavioral adjustments in scenarios where outcome predictability is low.  The ACC becomes activated in detecting errors after inhibition fails.   The striatum has previously been shown to be dysfunctional in problem gamblers without PD.  Dopamine (a neurotransmitter target of many PD drugs) is rich in the striatum and dopamine signaling mediates the “computation of reward prediction error and outcome expectation from future choices”.

The authors suggest that in PD gamblers, a disconnection develops between the ACC and striatum.  This may explain why they have difficulty with perserveration of behavior (continued gambling) despite continued monetary losses.

The authors note a weakness of their study is a reliance on correlational resting data.  A more powerful design would be to activate the brain regions involved in gambling with a task and study the anatomical and connectivity changes in those with PD associated with gambling and controls.  I suspect we will see such a study in the near future.

Image of Anterior Cingulate Cortex (ACC) Brain Region from 3D Brain Screen Shot Courtesy of Yates Photography.

Cilia R, Cho SS, van Eimeren T, Marotta G, Siri C, Ko JH, Pellecchia G, Pezzoli G, Antonini A, & Strafella AP (2011). Pathological gambling in patients with Parkinson's disease is associated with fronto-striatal disconnection: A path modeling analysis. Movement disorders : official journal of the Movement Disorder Society PMID: 21284039