Marianne Moran

Does pursuit abnormality in schizophrenia represent a deficit in the predictive mechanism

Although an abnormality of smooth pursuit eye movement has been consistently noted in schizophrenia, the underlying ocular motor pathophysiology is unknown. It is unclear whether the abnormality represents deficits in processing of information provided by the moving target, generation of pursuit eye movements, or other ocular motor and related cognitive processes. To evaluate the ability to process information provided by a moving target, saccadic accuracies were studied in step-ramp and single step tasks. Schizophrenic (with and without tardive dyskinesia [TD]) and normal subjects made equally accurate initial corrective saccades to the moving target. Thus, when the target jumped and then smoothly moved (creating a position and a velocity error on the retina), the patients were able to process retinal motion information and generate a normally accurate saccadic response. After the initial corrective saccade, both groups followed the target with a combination of pursuit eye movements and occasional catch-up saccades. During this period, the retinal velocity error is minimal because the eye approximates the target motion, and the major source of target motion information both for the smooth pursuit and saccadic responses is extra-retinal (i.e., predictive mechanism). The accuracies of catch-up saccades were significantly lower in the schizophrenic patients than in the normal subjects. During this period, overall pursuit performance, measured by pursuit gain, was also significantly worse in the patients. Accuracies of subsequent catch-up saccades, but not initial corrective saccades, significantly predicted the pursuit gain. Low pursuit gain was associated with high numbers of saccades per time spent in pursuit, which were similar in both schizophrenic subgroups (i.e., with and without TD), but were only significantly higher in the patients with TD than in the normal subjects. These preliminary data suggest that schizophrenic patients are able to process retinal motion information but have difficulties in using extra-retinal motion information to generate an appropriate saccadic response.

TOBACCO SMOKING INCREASES SQUARE-WAVE JERKS DURING PURSUIT EYE MOVEMENTS

Smooth-pursuit eye-movement (SPEM) abnormalities have been consistently observed in schizophrenia. The SPEM changes in schizophrenia are not thought to be an artifact of voluntary attention or medication, although a number of nondisease factors are known to affect SPEM. However, cigarette smoking has recently been reported to deteriorate SPEM in both smokers and nonsmokers. This finding is particularly relevant to schizophrenia, because schizophrenic patients smoke cigarettes considerably more than do normals, and none of the previous studies in this patient group have controlled for smoking. The current study was initiated to examine the effects of smoking on a number of oculomotor measures, including SPEM in smoker and nonsmoker normal volunteers. The results of this study suggest that cigarette smoking induces or significantly increases square-wave jerks, especially during smooth pursuit in normals. However, the effect is small and the global qualitative SPEM score is not affected. Other eye movements such as latencies for reflex and volitional saccades and saccadic distractibility are also unaffected by smoking. No differences were apparent between chronic smokers and nonsmokers under nonsmoking conditions in any of the eye-movement measures.

Shifts in covert visual attention in schizophrenic patients and normal controls

Attentional deficits have been consistently demonstrated in schizophrenic patients (Nuecherlein and Dawson 1984). Recently, Posner et al (1988) identified a specific visual attention deficit involving an increased difficulty in shifting covert visual attention, independent of eye movements, when visual attention was invalidly summoned to the left visual field and a target appeared in the right visual field. These investigators also found that the advantage of valid cuing as compared to invalid cuing was less for left visual field targets in schizophrenic patients. However, as the cue served to both alert and spatially orient the subject, their findings may have been due to nonspecific arousal deficits rather than an impaired ability to shift attention. Furthermore, the differences in reaction times in the different cuing conditions may have been due to differences in the perceived brightness or size of the target, as cue and target occurred in close proximity during the valid cuing condition but not in the invalid or uncued condition. Tc examine these alternative possibilities, three modifications were made in the Posner task. First, a 0 msec interval was included as a control

GABA agonist-induced changes in motor, oculomotor, and attention measures correlate in schizophrenics with tardive dyskinesia

Saccadic distractibility, Stroop color-word scores, and serial dyskinesia assessments were obtained on 10 schizophrenic patients with tardive dyskinesia during a pharmacologic challenge with placebo or 7 mg muscimol, a potent, direct-acting GABA agonist. Although no significant difference in the measures was evident between conditions, a significant correlation was found between GABA agonist-induced changes in saccadic distractibility and dyskinesia scores where no correlation existed between these measures on placebo. Improvement in saccadic distractibility was also correlated with reduction in attention performance, as measured by Stroop. These effects are not due to sedation. The correlation between dyskinesia and saccadic distractibility is consistent with a model of parallel motor and oculomotor cortico-striatal-thalamic circuits in humans. This work supports the hypothesis that a dysfunction in GABA-mediated neurotransmission may be the basis for tardive dyskinesia.

Abnormal Electroretinography in Schizophrenic Patients with a History of Sun Gazing

Electroretinographic (ERG) measurements were performed in 9 schizophrenic patients and in 13 control subjects. The measurements of schizophrenic patients as a group did not differ from those of normals. However, 6 schizophrenic patients who had a past history of sun gazing showed a decrease in retinal responsiveness under conditions of light adaptation. These results suggest that a subgroup of schizophrenic patients, who show deviant light-related behavior, have abnormal ERG. We postulate that an abnormality in retinal dopaminergic neurons, which are known to reduce light responsiveness of horizontal and ganglion cells, is the underlying pathophysiology of this clinical finding.

Reversibility and irreversibility of tardive dyskinesia following neuroleptic withdrawal

being assessed by means of the Abnormal Involuntary Movement Scale (AIMS). In a preliminary evaluation we analyzed the data from the first 16 patients that completed the study (6 male, IO female, age S1.6* 18.6 years). We found a significant improvement in older patients (age> 40 years) on alpha-tocopherol as compared to the placebo group (p < 0.05). No therapeutic effects of alphatocopherol were observed in the younger patients (age<40 years). Up to now age is the only valid risk factor which increases vulnerability for TD. Because the content of alpha-tocopherol in the brain is known to decrease with age, it is tempting to speculate that (1) the decrease of brain alpha-tocopherol with age enhances the susceptibility of elder individuals to the damaging effects of free radicals, resulting in increased susceptibility to neuroleptic-induced TD, and that (2) therefore these elder patients might benefit from high-dose alpha-tocopherol therapy, as found in the present study. However, this working hypothesis certainly needs confirmation in a larger sample before any definite conclusion can be drawn.

Oculomotor assessment in individuals with personality disorder

test). In contrast, group amplitudes at T4 (SZ mean: 2.48 pV, NL mean: 4.69 pV) were not statistically significant. The mean P300 peak latency in unmedicated SZ (mean: 439 milliseconds) differed from NL (mean: 381 milliseconds, p C .03, MW), in contrast to no difference in previous groups; however, the left/right differences persisted with integrated voltages adjusted for individual latency differences.