Habitual behavior and dopamine cell vulnerability in Parkinson disease

The cardinal features of Parkinson disease (PD) often begin focally, typically in one limb, and may remain relatively restricted to one side of the body for many years. It is now well established that dopaminergic neurons in the ventro-lateral tier of the substantia nigra pars compacta (SNpc), which project mainly to the caudal putamen, are the first to degenerate in the initial phase of PD (Fearnley and Lees, 1991; Halliday et al., 2008; Blesa et al., 2010) indicating differential vulnerability. The caudal region of the striatum (dorsolateral striatum in rodents) has been associated with habitual (or automatic) behavior (Redgrave et al., 2010), consequently the differential loss of dopamine (DA) from this region provides the pathophysiological substrate for the early impairment of automatic movements (walking, writing, . . . ) in early PD. The brain has two major systems for controlling behavior: a goal directed mechanism (GD) and a mechanism mediating stimulus-response habits (Figure 1). The goal directed system entails conscious, voluntary control of actions aimed toward obtaining rewards or avoiding punishments. Action selection is determined by competitions between relative outcome values, i.e. if outcome A is more valuable than outcome B, then learned behavior that will lead to outcome A will be selected. Examples of goal-directed control would be: heading to the fridge or going to a restaurant when we are hungry, taking the elevator or taking the stairs back to the apartment. This goaldirected process engages the prefrontal cortex and dorsolateral striatum (Yin et al., 2004).On the other hand, the habitual system detects well-learned cues that have been associated with specific responses, and therefore elicit automatic stimulus-response behavior via the re-entrant loop that connect sensorimotor cortical areas with the posterior putamen (dorsolateral striatum in rodents) (Barnes et al., 2005). Habits are established gradually over time. They evolve after many repetitions of a task being performed under flexible goal-directed learning and depend heavily on the statistical regularities between specific stimuli and consequent responses. Examples of habitual control would be, walking, riding a bike or driving. The critical test for habits is that they are resistant to outcomedevaluation (Adams andDickinson, 1981). Inappropriate habitual responses are frequently difficult to eradicate and have to be corrected by goal-directed interventions after they fail to achieve their original intention. In this Opinion article we put forward the hypothesis that a significant factor that confers vulnerability to the ventro-lateral tier of SNpc at the onset of PD may reside in the key functional role that these neurons play in the performance of habitual behavior, switching between habitual and goal-directed control, and engaging both goal-directed and habitual control when carrying out multiple tasks simultaneously.