Elsevier

Psychiatry Research

Volume 143, Issue 1, 30 June 2006, Pages 77-88
Psychiatry Research

Evidence from increased anticipation of predictive saccades for a dysfunction of fronto-striatal circuits in obsessive–compulsive disorder

https://doi.org/10.1016/j.psychres.2005.08.020Get rights and content

Abstract

In obsessive–compulsive disorder (OCD), a dysfunction of neuronal circuits involving prefrontal areas and the basal ganglia is discussed that implies specific oculomotor deficits. Performance during reflexive and predictive saccades, antisaccades and predictive smooth pursuit was compared between patients with OCD (n = 22), patients with schizophrenia (n = 21) and healthy subjects (n = 24). Eye movements were recorded by infrared reflection oculography. In both patient groups, higher frequencies of anticipatory saccades with reduced amplitudes in the predictive saccade task were observed. Additionally, reduced smooth pursuit eye velocity and increased frequencies of saccadic intrusions during smooth pursuit as well as increased error rates in the antisaccade task were demonstrated for patients suffering from schizophrenia. Patients with OCD and schizophrenia revealed different patterns of oculomotor impairment: whereas increased anticipation of predictive saccades provides evidence for a dysfunction of the circuit between the frontal eye field and the basal ganglia in both groups, results from the antisaccade task imply additional deficits involving the dorsolateral prefrontal cortex in schizophrenic patients. Furthermore, the cortical network for smooth pursuit (especially the frontal eye field) is also assumed to be disturbed in schizophrenia.

Introduction

Obsessive–compulsive disorder (OCD) is characterized by repetitive obsessive thoughts or actions. In one explanation, a deficit in inhibitory control of reflexive responses is assumed. Normally, inhibitory control relies on frontal pathways including prefrontal areas, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex, as well as the basal ganglia (Baxter, 1992). Results from neuroimaging studies support the hypothesis that prefrontal areas and their connecting fibres to the basal ganglia are particularly greatly involved in the pathophysiology of OCD (Busatto et al., 2000). However, many questions remain to be resolved.

Since the neuronal circuits that control oculomotor responses also rely on frontal subcortical pathways, an investigation of oculomotor function may help to characterize the pathomechanisms underlying OCD, such as those that have been demonstrated in schizophrenia (Levy et al., 2000). The oculomotor network controls saccadic and smooth pursuit eye movements amongst other eye movements (Fig. 1):

Reflexive saccades are fast eye movements (peak velocity up to 400–500°/s) and serve to fixate objects with the fovea that enter the field of vision. The parietal eye field in the posterior parietal cortex (PPC) is regarded as the main cortical area for the generation of reflexive saccades; see Fig. 1. Lesions of the PPC lead to a marked reduction in the amplitude of reflexive saccades (Gaymard et al., 1998). In contrast, after lesions in the frontal eye field (FEF), visually guided saccades are only slightly affected, and the control of visually guided saccades quickly recovers (Gaymard et al., 1998, Broerse et al., 2001).

In predictive saccade tasks, the timing, amplitude and direction of the target step are all predictable. Healthy subjects are able to develop predictive behaviour within a few target presentations, as demonstrated by reductions in latency times. Primate studies and clinical lesion studies identified the FEF, supplementary eye field (SEF), and the basal ganglia as the most relevant cortical areas for predictive saccades (Gaymard et al., 1998, Broerse et al., 2001). Lesions in the FEF and the basal ganglia lead to saccadic hypometria and prolonged latencies (Ventre et al., 1992). The FEF plays an important role in the short-term memorization of saccades that provides the internal representation of the target's position (Gaymard et al., 1999, Broerse et al., 2001). The SEF is assumed to be responsible for the initiation and timing of predictive saccades (Gaymard et al., 1993).

In the antisaccade task, subjects must suppress a reflexive saccade and generate a saccade with the same amplitude in the opposite direction of the target. The main cortical area responsible for reflexive saccade inhibition and transformation of visuo-spatial information to the mirror image projection is the DLPFC (Gaymard et al., 1999, Broerse et al., 2001). Furthermore, it has also been suggested that the PPC controls visual spatial working memory (Broerse et al., 2001). Although the FEF has been shown to be involved with antisaccades (Olk et al., 2005), its role seems to be of minor importance (Broerse et al., 2001). In primates with FEF lesions, the performance of antisaccades remains unaffected (Gaymard et al., 1999).

Smooth pursuit eye movements can keep moving objects stable on the fovea up to velocities of between 60°/s and 80°/s (Ilg, 1997). The oculomotor command for smooth pursuit eye movements is generated with the participation of the FEF and the SEF. These areas receive input from the DLPFC as well as from the PPC and the motion-sensitive area V5 in the occipito–parietal–temporal region (see Fig. 1). Different smooth pursuit sub-functions have been deduced from studies on patients with specific cortical lesions (Heide et al., 1996): lesions of the FEF lead to deficient initiation and maintenance of smooth pursuit eye movements, lesions of the SEF are associated with a delayed reversal of smooth pursuit direction (with periodic stimuli such as triangle wave stimuli), dysfunctions of the PPC are accompanied by reduced smooth pursuit velocity with structured backgrounds, and lesions of area V5 lead to impaired smooth pursuit initiation, maintenance and motion perception.

In summary, the control of different types of eye movements is accomplished by different cortical networks (see Fig. 1). A given pattern of eye movement dysfunction may assist in the identification of the brain regions involved. In an earlier study on eye movement response to unpredictable foveofugal and foveopetal step-ramp stimuli, our results supported an impairment of frontal subcortical networks in patients with OCD, schizophrenia and affective disorder with different patterns and degrees of pursuit impairment for the patient groups. In contrast, parameters for reflexive saccades remained unaltered (Lencer et al., 2004). Using an explorative approach, the present study aims to further characterize the hypothesized frontal neuronal dysfunction in OCD by studying the saccadic and the smooth pursuit system. Based on the knowledge that cortical areas driving predictive saccades overlap with circuits involved in the pathophysiology of OCD (i.e. pathways from prefrontal areas to the basal ganglia), we were primarily interested in predictive saccade performance where abnormalities in this task were expected in OCD patients. A reflexive saccade task was used to control for the integrity of the basic neuronal saccade mechanisms. We did not expect any abnormality in OCD patients. Antisaccade performance was investigated to obtain information about any dysfunction related to the DLPFC. Predictive smooth pursuit was assessed to explore whether the smooth pursuit maintenance deficit observed with unpredictable stimuli in OCD patients could be confirmed.

Patients with OCD were not just compared to healthy subjects, but also to schizophrenic patients. The sample included 18 of 22 OCD-patients, 16 of 21 schizophrenic patients and 23 of 24 healthy subjects who had already participated in our earlier study (Lencer et al., 2004).

Section snippets

Subjects

The study was approved by the local ethics committee, and every subject agreed by written consent after being informed in detail about the study. Patients were inpatients and outpatients of the Department of Psychiatry and Psychotherapy of the University of Luebeck. They underwent a clinical examination and participated in structured psychiatric interviews. Patients had to be psychopathologically stable for at least 1 week. Healthy control subjects were recruited by personal contact. Patients

Clinical characterization

General psychiatric symptom severity assessed by the BPRS was low and did not differ between groups (OCD patients: 37.0 ± 11.1, schizophrenic patients: 34.9 ± 8.9; Overall and Gorham, 1962). A mean Y-BOCS score of 20.1 ± 7.7 in OCD patients indicated that obsessive–compulsive symptom severity was moderate (Goodman et al., 1989). In schizophrenic patients, a mean percentile rank of 26.9 ± 26.3 for positive symptoms and a mean percentile rank of 45.3 ± 66.5 for negative symptoms indicated moderate symptom

Discussion

The main purpose of this study was to investigate whether specific oculomotor dysfunctions can be observed in patients with OCD so that more detailed information can be acquired about the hypothesized frontal neuronal dysfunction underlying OCD. In addition to healthy subjects, we also included a group of schizophrenic patients for whom oculomotor abnormalities are suggested to reflect a frontal-subcortical impairment (MacAvoy and Bruce, 1995, Sweeney et al., 1998). Although from a

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (DFG), grant Ar 234/1-1 and the University of Luebeck, grant FUL J 25-00. We thank Björn Fiedler for assistance in assessing the data.

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