Trevor J. Crawford

Antisaccades and remembered saccades in Parkinson's disease.

Antisaccades were studied in ten patients with mild to moderate Parkinsons disease and ten age-matched normal controls. Remembered saccades and reflex saccades were assessed for comparison. In the population of patients who showed the previously reported abnormalities of remembered saccades, antisaccades were indistinguishable from those of controls in latency, gain and peak velocity. This finding implies that antisaccades are mediated through pathways which are unaffected by Parkinsons disease, and which are therefore presumably distinct from pathways mediating other voluntary saccades.

Saccadic abnormalities in psychotic patients. I. Neuroleptic-free psychotic patients.

Most of the previous research reporting abnormalities of rapid re-fixation eye movements (saccades) in patients with schizophrenia has used patients receiving neuroleptic medication. In this study non-neuroleptically medicated schizophrenics were compared with other psychiatric patients using a variety of saccadic paradigms to determine the specificity of saccadic dysfunction. The patient groups consisted of schizophrenics (N = 18), bipolar affectives (N = 18), anxiety neurotics (N = 10) and normal controls (N = 31), none of whom had received neuroleptic medication for the preceding 6 months. Four behavioural paradigms, reflexive, predictive, remembered and ANTI were used to elicit saccades. The primary abnormality in the schizophrenic group was a significantly increased rate of distractibility in the ANTI (saccades made towards the target rather than in an opposite direction) and REM (saccades made prior to the imperative cue) paradigms. The major neuropsychological variable predictive of these errors was Wisconsin card sort perseverative errors. These data, in conjunction with findings from previous neurological research, would seem to provide converging evidence towards dysfunction of prefrontal cortex in schizophrenia.

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.

Smooth pursuit and saccadic abnormalities in first-episode schizophrenia.

BACKGROUND Previous studies of oculomotor dysfunction in schizophrenia have tended to concentrate on abnormalities of smooth pursuit eye tracking in chronic medicated patients. We report the results of a study of smooth pursuit, reflexive and antisaccade performance in drug naive and antipsychotic treated first-episode schizophrenic patients. METHODS Smooth pursuit and saccadic eye movements were recorded in 36 first-episode schizophrenic patients and 36 controls matched for age and estimated IQ. The schizophrenic patients were divided into drug-naive (N = 17) and antipsychotic treated groups (N = 19). RESULTS Smooth pursuit velocity gain was significantly lower than controls only in the drug-naive patients. The treated patients did not differ significantly from either the controls or the untreated group. In an antisaccade paradigm both treated and drug-naive schizophrenic patients demonstrated an increased number of errors, but only drug-naive patients also demonstrated an increased latency in initiating correct antisaccades. CONCLUSIONS These impairments are unlikely to be due to a generalized deficit in oculomotor function in the schizophrenic groups, as there were no differences between the groups in saccadic metrics on a reflexive saccade task. The results show that both smooth pursuit and saccadic abnormalities are present at the onset of schizophrenia and are integral to the disorder.

Reliability of smooth pursuit, fixation, and saccadic eye movements.

The present study investigated the reliability and susceptibility to practice effects of oculomotor tasks. Smooth pursuit, fixation, antisaccade, and prosaccade tasks were administered to 31 healthy participants to assess internal consistency (Cronbachs alpha) and within-session practice effects. Twenty-one of these participants were retested after an average interval of 57.86 days to assess temporal stability and between-session practice effects. Internal consistencies were high for most measures, with few within-session performance changes. Test-retest reliabilities of most measures were good. Between-session practice effects were most consistently observed on the antisaccade task, indicated by reduced error rate and improved spatial accuracy at retest. Magnitude of improvement on these measures was related to performance, indicating that poor performers benefited most from repeated assessment. These findings support the trait nature of oculomotor function and point to the need to take into consideration between-session practice effects on the antisaccade task in longitudinal studies.

Inhibitory control of saccadic eye movements and cognitive impairment in Alzheimer’s disease

BACKGROUND This study examined the relationship of inhibitory control and measures of neuropsychological impairment in patients with early Alzheimers disease (AD). Four specific questions were addressed: 1) Which error parameters of saccadic inhibition are sensitive to AD? 2) Which inhibitory deficits are related to cognitive measures of impairment? 3) Is the inhibitory impairment in AD dependent on the initiation of a volitional eye movement? 4) How do the effects of saccadic inhibitory control in AD relate to the normal effects of aging? METHODS Eighteen patients with probable AD and two control groups (seventeen young, and eighteen old participants) completed a battery of neuropsychological tests and four saccadic eye movement paradigms: pro-saccade, NO-GO, GO/NO-GO and anti-saccade. RESULTS Old controls generated increased inhibition errors in comparison to young controls in the GO/NO-GO paradigm. In comparison to old controls, AD generated normal saccades in the pro-saccade paradigm, but showed a higher proportion of inhibition errors in the NO-GO, GO/NO-GO and anti-paradigms. The frequency of uncorrected errors in the anti-saccade paradigm was positively correlated with cognitive measures of dementia. CONCLUSIONS AD patients have an impairment of inhibitory control and error-correction that exceeds the effects of normal aging and is related to the severity of dementia. However, the inhibitory impairment is not contingent on the interaction with a volitional saccade.

Saccadic abnormalities in psychotic patients. II. The role of neuroleptic treatment

The effects of dopamine-antagonistic neuroleptic (NL) medication on saccadic eye movements were compared in matched groups of 40 NL-treated and 18 NL-free schizophrenic patients and in 18 NL-treated and 14 NL-free bipolar affective patients. Manipulation of the saccadic paradigm yielded data on four types of saccade: those reflexively elicited by novel stimuli (REFLEX saccades), those directed towards the remembered location of a target now extinguished (REM) or towards the location where a predictably alternating target is expected to appear (PRED), or ANTI saccades, directed away from the stimulus to the mirror image location. Extensive psychiatric, neurological and neuropsychological assessments were also carried out on all subjects. The saccades of NL-treated patients, regardless of diagnosis, were less spatially accurate than those of NL-free patients, with a greater tendency to fall short of the target when generated towards the locus of a mentally represented target. This effect was greatest with a predictably alternating target, especially during periods when target visibility was withdrawn, only a temporal cue remaining. This pattern of impairment which is also found in early stages of Parkinsons disease is likely to be due to deficiency of striatal dopamine. Its best clinical predictors were disease duration, and Webster-Parkinsonism scores. Failure to suppress reflexive saccades to the stimulus in the REM and ANTI paradigms were more closely associated with schizophrenia than with NL treatment and were best predicted by negative symptoms and Wisconsin perseverative errors, both of which are widely regarded as indicators of frontal lobe dysfunction.

Smooth pursuit and antisaccade eye movements in siblings discordant for schizophrenia.

Smooth pursuit eye movement (SPEM) and antisaccade deficits have been proposed as endophenotypes in the search for schizophrenia genes. We assessed these measures in 24 schizophrenia patients, 24 of their healthy siblings, and 24 healthy controls closely matched to the siblings. Between-group differences were assessed using a random effects regression model taking into account the relatedness between patients and siblings. Patients showed reduced SPEM gain, increased frequency of saccades during pursuit, increased antisaccade error rate, and reduced antisaccade gain compared to controls. Siblings performed intermediate, i.e. between patients and controls, on most measures, but were particularly characterised by reduced antisaccade gain. SPEM gain at one target velocity was significantly correlated between patients and siblings, highlighting the necessity of taking into account within-family correlations in the statistical analysis of between-group differences. It is concluded that subtle SPEM and antisaccade deficits are observed in clinically unaffected siblings of schizophrenia patients; these deficits may be useful markers of genetic liability to schizophrenia.

The relationship between antisaccades, smooth pursuit, and executive dysfunction in first-episode schizophrenia

BACKGROUND Both oculomotor and neuropsychologic deficits have been used to support the hypothesis that schizophrenia is associated with prefrontal cortex dysfunction, but studies that have specifically investigated the relationships between these deficits have produced inconsistent findings. METHODS We measured both smooth pursuit and antisaccade performance in a large group (n = 109) of patients with first-episode schizophrenia and a group of matched control subjects (n = 59) and investigated the relationship between performance on these tasks and performance on a range of executive tasks. We additionally explored the relationship between these variables and measures of psychopathology at presentation and duration of untreated psychosis. RESULTS Antisaccade errors were significantly correlated with spatial working memory performance. Smooth pursuit gain did not correlate with any neuropsychologic measure. There were no reliable correlations between either oculomotor variables and measures of psychopathology and duration of untreated psychosis. CONCLUSIONS These findings suggest that in schizophrenia working memory and antisaccade performance reflect the same abnormal prefrontal substrates and that smooth pursuit is mediated by a separate neural abnormality.

Saccadic eye movements, schizotypy, and the role of neuroticism

We investigated the relationships of anti- and prosaccades with psychometric schizotypy. One aim was to estimate the role of negative emotionality and general psychopathology (i.e. neuroticism) in this relationship. 115 non-clinical volunteers underwent infrared oculographic assessment of antisaccades and prosaccades. Schizotypy was assessed with the Personality Syndrome Questionnaire (PSQ-80), the Rust Inventory of Schizotypal Cognitions (RISC), and Eysenck Personality Questionnaire-Revised (EPQ-R) Psychoticism. Higher positive schizotypy scores predicted increased antisaccade errors (RISC) and greater prosaccade spatial error (PSQ-80 Unreality). Greater thought disorder (PSQ-80 Activity) predicted shorter prosaccade latencies. EPQ-R Neuroticism was substantially correlated with schizotypy but was not related to saccadic measures and did not account for their relationship with schizotypy. We conclude that saccadic performance patterns in schizotypy are not due to negative emotionality or general psychopathology, but specific to schizophrenia spectrum signs and symptoms.