7p/trial and CA|ER = .79. KD started on an increasing dose of ropinirole, an agonist acting largely D2 and D3 dopamine receptors. By contrast, l-dopa would have a balanced effect across all these receptors by increasing synaptic dopamine. On 4 mg ropinirole daily there was marked improvement in KD’s apathy. He was far more spontaneous in conversation, reported better social interactions and

was more interested in events around him. He managed to secure a job and now scored in the normal range (4/12) on the initiative and interest subscales of the Apathy Inventory (Robert et al., PARP inhibitor 2002). On the directional reward-sensitivity task, saccades were generally faster, but those to the RS were significantly faster (RS = 183 msec vs US = 208 msec; p < .001), far

larger than in controls ( Fig. 7). On the TLT by week four (on 4 mg ropinirole daily) KD demonstrated much greater early responding (45.2%). However, this was at the expense of greater numbers of errors (17.8% vs control mean = 24.2%) so the CA|ER (1.54) was not as high as on l-dopa. Despite this, mean reward (27.3p/trial) Selleckchem CX5461 exceeded that achieved on l-dopa, matching the highest performing individual healthy control. Thus KD showing increased willingness to anticipate frequently and take risks, an effect that persisted over 12 weeks on ropinirole ( Fig. 5D). We used novel probes of oculomotor decision-making to demonstrate relative insensitivity to reward in an individual with apathy following bilateral GPi lesions. Our TLT (Adam et al., 2012) requires reward sensitivity and motivation or effort to succeed, combined with fast reaction times and the ability to update behaviour in response to positive and negative feedback. A reactive response – simply waiting for the green light – is less well rewarded than an anticipatory response prepared in advance of the green signal. KD initially made very few anticipatory responses compared with age-matched controls. However, dopaminergic therapy, first with levodopa and then with ropinirole, increased anticipatory responses to within the normal range. The

directional saccade reward-sensitivity task, originally developed for the study of reward sensitivity in macaque monkeys (Hong Metformin clinical trial and Hikosaka, 2008), demonstrated that KD had SRTs within the normal range but showed no speeding to the rewarded side (RS), unlike healthy volunteers. Treatment with levodopa led to reward sensitivity, with speeding of responses to the RS and slowing to the unrewarded side (US) compared to baseline. Off medication, the difference in SRTs to rewarded and unrewarded targets became non-significant, while subsequently on ropinirole, a direct dopamine D2/D3 receptor agonist, KD again demonstrated reward sensitivity, as well as generalized speeding. These effects on dopaminergic medication were associated with clinical improvement – reduction of apathy and increased motivation to find work and in social interactions – most prominently while on the dopamine agonist.