Antipsychotics and single-cell activity in the rat superior colliculus.

Schizophrenic patients have problems with saccadic eye movements that can be characterized as a loss of control over the saccadic system. Preliminary clinical results suggest that antipsychotics can either disrupt or improve saccadic performance. The brain mechanism through which antipsychotics might affect saccades is the subject of study. The superior colliculus (SC) is crucially involved in the generation of saccades. Previous experimental studies showed that the substantia nigra reticulata (SNr), a structure with profound inhibitory influence on the SC, is differentially affected by classical and atypical antipsychotics. In this study, we investigated the potential effects of atypical antipsychotics (clozapine, olanzapine, and risperidone) and a classical antipsychotic (haloperidol) on the firing rate of SC cells in the rat. In anesthetized rats, we performed extracellular recordings on spontaneous active neurons in the intermediate and deep layers of the SC. After subcutaneous injection of an antipsychotic drug, changes in firing rate were compared with responses upon saline injection. Olanzapine (1.0 mg/kg), risperidone (0.3 and 1.0 mg/kg), and haloperidol (0.5 mg/kg) did not significantly alter cell activity, but clozapine (10.0 mg/kg) induced a short-lasting but significant decrease. Except for clozapine, the effects of antipsychotics on the SC were nonsignificant and therefore independent of the effects in the SNr. Our results support the notion that clozapine is different from the other atypical antipsychotics.

A goal activation approach to the study of executive function: an application to antisaccade tasks.

We argue that a general control process, responsible for the activation and maintenance of task goals, is central to the concept of executive function. Failures of this process can become manifest as goal neglect: disregard of a task requirement even though it has been understood (Duncan, 1995). We discuss the results of several published and new experiments using various versions of the antisaccade task in order to investigate the circumstances under which goal neglect is likely to occur. Potentially conflicting results in the literature on adaptive control of saccadic eye movements are argued to be attributable to the extent to which different task versions elicit goal neglect. The results suggest an increased susceptibility to goal neglect of high-functioning older adults (Experiment 1) and of first-episode schizophrenia patients (Experiment 2), but not of patients with obsessive-compulsive disorder (Experiment 3). However, the degree to which such differences in susceptibility become manifest in task performance, is shown to be strongly influenced by manipulations of the relative saliency of task requirements. Theoretical and methodological implications for the study of executive function are discussed.

Event-related fMRI responses in the human frontal eye fields in a randomized pro- and antisaccade task.

We examined whether the frontal eye fields (FEF) are involved in the suppression of reflexive saccades. Simultaneous recording of horizontal eye movements and functional magnetic resonance imaging enabled us to perform a randomized pro- and antisaccade task and to sort blood oxygenation level dependent (BOLD) time series on the basis of task performance. Saccadic reaction time distributions were comparable across tasks indicating a similar effort in preprocessing of the saccades. Furthermore, we found similar BOLD activation in FEF during both correctly performed pro- and antisaccades. Frontal eye field activation started prior to target presentation and saccade generation. While we observed only few erroneous antisaccades, these were associated with a decrease in BOLD activity prior to target presentation, and increased BOLD activity after target presentation relative to correctly performed antisaccades. These findings are consistent with a role of the FEF in the suppression of reflexive saccades. The increase in activity after target presentation for antisaccade errors can only be indirectly linked to such a role but may also reflect activity related to the generation of a correction saccade. Frontal eye field BOLD activity may further represent general arousal, preparatory set, short-term memory, or salience-map related activity.