, 2007). During intertemporal choice, a number of brain areas thought to be important for attention and episodic memory, such as the precuneus and anterior cingulate cortex, show reduced activation in methamphetamine-dependent individuals,

suggesting that the impaired functions of these brain areas might contribute to Selleckchem GSI-IX more impulsive choices (Hoffman et al., 2008). Although dopamine-related drugs have been shown to influence the steepness of temporal discounting, the results from these behavioral pharmacological studies have not been consistent (Peters and Büchel, 2011). As a result, the precise nature of the neural mechanisms linking the use of addictive drugs and temporal discounting needs to be examined more carefully. In patients with Parkinson’s disease, midbrain dopamine neurons are lost progressively. Since these neurons are a major source of inputs Protein Tyrosine Kinase inhibitor to the basal ganglia, motor deficits found in Parkinson’s patients, such as bradykinesia, rigidity, and tremor, are thought to result from the disruption in the disinhibitory functions of the basal ganglia (DeLong, 1990). In addition, considering the extent to which dopamine neurons contribute to the broad propagation of reward prediction signals in the brain, abilities to improve decision-making strategies through experience might be impaired in patients with Parkinson’s disease.

In fact, given the option of learning from positive or negative outcomes of previous choices, Parkinson’s patients tend to learn more from negative outcomes, and this tendency was ameliorated by medication that increase dopamine levels (Frank et al., 2004). Similarly, striatal activity correlated with reward prediction errors was reduced in Parkinson’s patients (Schonberg et al., 2010). Medication that increases dopamine levels in Parkinson’s patients is not likely to restore the normal pattern of dopamine signals completely and therefore may cause a side-effect in choice behaviors of treated

patients. For example, Parkinson’s patients often get addicted to the drugs used in dopamine replacement therapy (Lawrence et al., 2003). Similar to the mechanisms of other addictive drugs (Redish, 2004), this might Tobramycin result from the amplification of reward prediction error signals, since patients treated with dopaminergic drugs showed higher learning rates during a dynamic foraging task (Rutledge et al., 2009). Patients on dopamine replacement therapy also tend to develop problems with behavioral addictions, such as pathological gambling (Driver-Dunckley et al., 2003; Dodd et al., 2005). Previous studies have also found that compared to normal controls, Parkinson’s patients tend to show steeper temporal discounting during intertemporal choice (Housden et al., 2010; Milenkova et al., 2011). As is the case for the relationship between addiction and temporal discounting, whether and how steeper temporal discounting in Parkinson’s disease is mediated by dopaminergic signaling requires further study (Dagher and Robbins, 2009).