Annelies Broerse

Parsing cognition in schizophrenia using saccadic eye movements : a selective overview

Eye movements provide a behavioural measure of sensorimotor processing and higher cognitive functions of the brain. With the development of novel paradigms that can be used for the study of various cognitive operations, saccadic eye movements in particular, have become increasingly popular. Patients with schizophrenia have neurocognitive impairments that can be readily investigated with these paradigms. From animal, human lesion and neuroimaging studies, the cerebral centres underlying saccadic eye movements have been identified. The areas of the prefrontal cortex include the dorsolateral prefrontal cortex, the frontal eye fields, the supplementary eye fields, and the anterior cingulate cortex. Pathology of saccadic eye movements, therefore, provides information on the functional status of the underlying neural circuitry in brain disorders such as schizophrenia. In this paper, we evaluate: (i) methodological considerations that are central to the design and application of saccadic paradigms; (ii) brain activation that is associated with saccadic paradigms; (iii) recent findings in healthy subjects and schizophrenic patients; (iv) saccadic abnormalities in other psychiatric and neurological disorders and in individuals at risk for developing schizophrenia.

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, shortterm memory, or salience-map related activity.

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.

Does frontal normality exist in schizophrenia? A saccadic eye movement study

Many observations have supported the general idea of impaired frontal function in schizophrenia. In particular, neuropsychological studies have shown severe frontal deficits. However, other studies found normal cognitive function in a proportion of patients. Since saccadic tasks also provide an index of frontal function, we examined the presence of frontal deficits in patients by means of both neuropsychological and saccadic tasks, and compared the sensitivity of both approaches for frontal impairment. In addition, we examined the relationship between saccadic and neuropsychological measures. Twenty-four schizophrenic patients and twenty healthy controls completed an extensive neuropsychological battery and three saccadic tasks. Based on the neuropsychological battery alone, 42% of the patients showed frontal deficits, whereas combined use of neuropsychological and saccadic tasks resulted in 79% with frontal deficits. The antisaccade task appeared able to detect frontal deficits in patients who were without frontal impairment on the neuropsychological battery. Saccadic deficits were, however, not necessarily accompanied by deficits on frontal neuropsychological measures. This suggests that the saccadic and neuropsychological tasks used in the present study targeted different frontal functions. This view was supported by the lack of correlations between saccadic and frontal neuropsychological measures.

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.

Dopamine and impairment at the executive level

Patients with schizophrenia have an impairment in the inhibition of reflexive saccades, as a consequence of a functional impairment of the prefrontal cortex, which has not yet been encapsulated in terms of a formal model. A number of novel and testable hypotheses can be generated from the framework proposed by Findlay & Walker that will stimulate further research. Their framework therefore marks an important step in the development of a comprehensive functional model of saccadic eye movements. Further advances will be assisted by (1) a recognition of important distinctions in the executive control of volitional saccades and (2) addressing the capacity for cross-model integration of spatial information in the generation of the spatial properties of saccadic eye movements.