The effects of ketamine and risperidone on eye movement control in healthy volunteers.

The non-competitive N-methyl-D-aspartate receptor antagonist ketamine leads to transient psychosis-like symptoms and impairments in oculomotor performance in healthy volunteers. This study examined whether the adverse effects of ketamine on oculomotor performance can be reversed by the atypical antipsychotic risperidone. In this randomized double-blind, placebo-controlled study, 72 healthy participants performed smooth pursuit eye movements (SPEM), prosaccades (PS) and antisaccades (AS) while being randomly assigned to one of four drug groups (intravenous 100 ng ml(-1) ketamine, 2 mg oral risperidone, 100 ng ml(-1) ketamine plus 2 mg oral risperidone, placebo). Drug administration did not lead to harmful adverse events. Ketamine increased saccadic frequency and decreased velocity gain of SPEM (all P < 0.01) but had no significant effects on PS or AS (all P > or = 0.07). An effect of risperidone was observed for amplitude gain and peak velocity of PS and AS, indicating hypometric gain and slower velocities compared with placebo (both P < or = 0.04). No ketamine by risperidone interactions were found (all P > or = 0.26). The results confirm that the administration of ketamine produces oculomotor performance deficits similar in part to those seen in schizophrenia. The atypical antipsychotic risperidone did not reverse ketamine-induced deteriorations. These findings do not support the cognitive enhancing potential of risperidone on oculomotor biomarkers in this model system of schizophrenia and point towards the importance of developing alternative performance-enhancing compounds to optimise pharmacological treatment of schizophrenia.

Instrumental responding for rewards is associated with enhanced neuronal response in subcortical reward systems.

The response of human reward systems to different reinforcers, including food, drugs and money, has been investigated in a number of recent functional neuroimaging studies. They have varied, however, in terms of whether or not a behavioural response was required to obtain rewards. The aim of the present study was to determine whether neuronal responses to financial reward are significantly modulated by the requirement to make a behavioural response. Twelve subjects were scanned using functional magnetic resonance imaging (fMRI) while performing a simple target detection task. Certain targets acted as cues predicting financial reinforcement; some additionally required that a movement be executed, while others did not. There were also targets that required a movement but were not predictive of reward. We observed, as expected, responses within motor and reward systems associated with main effects of movement and reward, respectively. Critically, the reward responses were significantly modulated by the requirement to make an intervening behavioural response. Blood oxygenation level-dependent (BOLD) responses in the amygdala and striatum were significantly enhanced when a movement was required, while reward-related response in the orbitofrontal cortex was independent of movement. These results suggest important dissociations within human reward systems, reflecting different properties of rewards. The striatum and amygdala may mediate the function of rewards in eliciting goal-directed behaviour, while the orbitofrontal cortex mediates incentive value.