Risky choices link the subthalamic nucleus with pathological gambling in Parkinson's disease

Abstract

A commonly recognized feature of Parkinson’s disease (PD) is a deficit in movement initiation and execution, which is considered a problem of “energization.” However, excessive inhibition (eg freezing of gait) or disinhibition (eg levodopa [L-dopa]-induced dyskinesias) are also frequent manifestations. Moreover, in a sense, bradykinesia and akinesia could be considered as representing excessive inhibition of movement initiation/execution. Impulsivity, which is one of the symptoms associated with inhibitory deficits, can take many forms. Responding fast without taking time for reflection (reflection impulsivity), a preference for immediate small rewards rather than delayed larger rewards (aversion to delayed gratification), delayed inhibition of responses to a prepotent stimulus (delayed motor inhibition), and engaging in more risky decision making (risk taking) are some of the characteristics of impulsive individuals. 1,2 Until recently, there have been two separate strands of research on failure of inhibitory control and impulsivity in relation to PD. The first has been related to the development of impulse control disorders (ICDs), including hypersexuality, pathological gambling (PG) and shopping, overeating, hobbyism, and punding. Together, these ICDs occur in about 14% of patients with PD and are associated with dopamine agonist therapy, particularly ropinirole and pramipexole as well as L-dopa. 3 ICDs have been related to dysfunction of the mesolimbic dopamine pathways with their reward-related functions. For PG, which is a behavioral addiction associated with monetary risk taking, this was supported by evidence from a raclopride imaging study in which, during performance of a gambling task, there was greater release of dopamine in the ventral striatum in patients with PG versus those without PG. 4 Furthermore, during a gambling task, dopamine induced a reduction of activation in brain areas implicated in impulse control and response inhibition, namely, the lateral orbitofrontal cortex (OFC), rostral cingulate area, amygdala, and external segment of the pallidum, in patients who had PD with PG, which was not observed in those without PG. 5 A previous functional magnetic resonance imaging study by the same group established that, on a probabilistic reward task, the dopamine agonist pramipexole, similar to L-dopa, reduced reward processing in the ventral striatum compared with off medication but resulted in higher outcome-induced activation of the lateral OFC compared with L-dopa or off medication, a change that was associated with greater risk taking on a balloon analogue