Thirty-six patients (25 males, 11 females) and 22 control subjects (10 males, 12 females) were compared. Patients were recruited from inpatient and day patient populations of the Flugelman (Mazra) psychiatric hospital. All were physically healthy.
Patients fulfilled the DSM-IV criteria for chronic schizophrenia (10 paranoid type, 25 disorganized type, and 1 residual type) and were treated with atypical antipsychotics (risperidone: n=12, mean dose=4.3±1.5 mg; olanzapine: n=17, mean dose=14.7±3.7 mg; clozapine: n=7, mean dose=350±153 mg) for at least 6 weeks. Ten patients also received biperiden (mean dose=3.6±1.6 mg), and 6 received trihexyphenidyl (mean dose=10.8±4.9 mg).
Control subjects were drawn from hospital staff. All were neurologically healthy, had no psychiatric disorders, and received no psychoactive medication.
All subjects gave written informed consent after a full explanation of study procedures. The study was approved by the institutional ethics committee.
Patients were significantly younger than control subjects (mean±SD: 40.6±10.7 years vs. 55.3±12.0 years,
P<0.01). There was no significant difference in gender distribution between the groups (chi-square, Fisher's exact test,
P=0.1). The sociodemographic and illness characteristics of the patient population are shown in
+Table 1.
The same experienced rater (N.S.) performed clinical assessment for all patients. General psychopathology was assessed with the Brief Psychiatric Rating Scale,
+13 scored 0—6; negative symptoms with the Scale for the Assessment of Negative Symptoms (SANS);
+14 positive symptoms with the Scale for the Assessment of Positive Symptoms (SAPS);
+15 and extrapyramidal side effects with the Neurological Rating Scales for Extrapyramidal Side Effects (SA)
+16 and the Abnormal Involuntary Movement Scale (AIMS).
+17
All visuomotor tests employed a computerized system consisting of a digitizing tablet and a PC. The tablet was placed at a lower chest level and hidden from the subject's view by an overlying board, positioned 16 cm above it and supporting a computer monitor on which paths for tracing and for tracking were displayed. A screen cursor represented the location of an unseen dome-shaped manipulandum, containing the digitizer's stylus, which could be moved freely over the surface of the digitizing tablet. The location of the manipulandum was read every 10 ms, with a resolution of 0.05 mm. A one-to-one correspondence between movements of the manipulandum and movements of the screen cursor was maintained.
A path (described below) and a cursor were displayed on screen. The subjects brought the cursor to a designated starting point from which they moved it along the entire path, as accurately as possible, by use of the unseen manipulandum. No demands on speed were made, but the tracing test was stopped automatically 64 seconds after it started even if not completed entirely.
The same path and cursor were used. A 1-cm target circle was programmed to move along the path at a predetermined speed of 22 mm/s (square and circular path) and 19 mm/s (minimum=16 mm/s at the curved peaks, maximum=22 mm/s at the straight middles) along the sine-wave path. The subject needed to maintain the cursor within the target in order to keep it moving. Whenever the cursor left the target, the latter stopped moving (tracking interruption) until the cursor was returned into it.
Three path types were used: sine-wave, square, and circle. This combination affords the VMT a wide range of task difficulties, from simple straight movements (square path) through a constant change in direction (circular path) to a variable change in direction and speed (sine-wave path). Regarding the square path, the data recorded at the corners (i.e., at the points of directional change) were ignored. All three path types were used with each hand for tracing and for tracking. The VMT results (below) are given as grand averages across all path types.
Performance was evaluated offline by use of the following measures:
In addition, a global measure of performance (GPM) was constructed, consisting of the PT50% in all tracing tests and MnNints in all tracking tests, as two independent cardinal measures of performance
+18 according to the following equation: GPM=√[(MnPT50%)
2+(MnNints)
2].
Each subject was tested on tracking of the sine-wave path with the right hand and then with the left hand. The subjects then traced the same path with each hand. The same sequence was repeated using the square path and then, again, with the circular path. Before actual testing began, each subject performed a trial session of tracking along a sine-wave path with the right and left hand.
For statistical analyses we used SPSS software. Performance differences between patients and control subjects were assessed by analysis of variance.
The relationship of test performance to independent clinical and treatment variables was determined through linear regression using Pearson's r. Two-tailed significance was used throughout.
+Table 2 shows the performance of patients and control subjects on the five parameters tested. Schizophrenic patients performed significantly worse than control subjects on all measures except velocity of tracing. VMT performance was not influenced by age or sex. In the patient group there was no significant correlation between VMT measures and extrapyramidal side effects or involuntary movements. (GPM vs. SA score:
r=—0.17 right hand,
r=—0.11 left hand, not significant; GPM vs. AIMS score:
r=0.12 for both hands, not significant). There was no significant correlation between VMT measures and scale scores, except for BPRS, which showed a correlation with PT50% right hand (
r=0.37,
P=0.03).
There was no consistent significant correlation between VMT performance and illness parameters. These included age at first admission (except for correlation with PT50% left hand: r=0.37, P=0.03), illness duration (except for correlation with MnDist left hand: r=0.44, P=0.008), number of admissions, and accumulated time in hospital (except for correlation with PT50% right hand: r=0.34, P=<0.05, and MnDist right hand: r=0.49, P=0.003).
Right hand performance was worse than left in both groups.
There was no difference in VMT performance in patients taking different atypical antipsychotics or between patients with or without anticholinergic treatment.
The main finding of the present study was that schizophrenic patients showed impaired visuomotor function compared with normal subjects. The deficits were mainly in the ability to control movement direction when tracing simple patterns and in keeping pace with a moving target in tracking tests. Velocity of movement, however, was not impaired.
The patients' impairment was not due to extrapyramidal side effects: the patients were on atypical antipsychotics, they had no or few extrapyramidal symptoms (EPS) as measured on the SA scale, and there was no relationship between SA scores and VMT performance. Likewise, anticholinergic co-administration did not influence results. Nonetheless, the possibility that subtle effects of medication not detected by scales contributed to the findings cannot be entirely excluded.
There was no consistent relationship between VMT performance and illness characteristics such as age at first admission, length of illness, or cumulative hospitalization time, although some correlations were noted. Nor was there an overall significant relationship with levels of positive or negative symptoms.
The lack of relationship to these illness variables suggests that visuomotor deficit may be a traitlike characteristic in schizophrenia, linked to basic CNS pathology similar to eye movement abnormalities.
+5 However, the possibility that factors related to illness chronicity contributed to the findings cannot be excluded. In this regard, nonspecific factors such as poor motivation or generalized motor slowing did not appear to be significant confounds, since the patients cooperated willingly and their movement velocity on tracing tests did not differ from that of control subjects.
Of the many changes that underlie and accompany schizophrenia, the reduced connectivity between remote cortical regions
+10,+11 is likely to be a major factor in reducing visuomotor capabilities. As already noted, normal visuomotor function depends on availability of visuospatial information, processed in posterior parietal and superior temporal areas, to premotor regions.
+7—+9 Reduced corticocortical connectivity is likely to attenuate this information flow to a level that impairs performance. Similarly, reduced interhemispheric cross-talk may result in greater manual asymmetry during execution of tasks that are controlled preferentially by one hemisphere or the other. Visuomotor coordination is thought to be related to right hemisphere processes
+19 and is therefore likely to be more impaired in the right hand when interhemispheric communication is disrupted. However, we did not perform a detailed assessment of performance by hand.
Impaired control of eye movements, well documented in schizophrenia,
+20—+22 may also contribute to visuomotor deficits. Normal control of eye movements is necessary for successful visually guided hand movements. In addition, the same neural pathology causing abnormal saccades and visual tracking may be involved in reduced coordination,
+23 so that impaired eye movements may interfere with visuomanual coordination directly and through a shared neural abnormality.
There is evidence that eye movement dysfunction, in particular the characteristic deficit in velocity discrimination,
+5,+24,+25 may be localized to motion-sensitive areas of the parietal lobe, middle temporal (MT), and medial superior temporal (MST) areas and their associated networks,
+5,+24,+25 including in the prefrontal cortex
+26 and the occipital lobe.
+27 It is possible that defects in these areas may also underlie VMT abnormalities.
Impaired attention, common in schizophrenia,
+28,+29 may also reduce VMT. Lowered attentional resources are likely to increase the number of tracking interruptions and may be manifested in greater distance from the desired path during tracing. Our results show that patients with schizophrenia perform much worse than normal subjects on both variables.
In summary, the present study shows a marked reduction in the visuomotor capabilities of individuals with schizophrenia, despite the absence of extrapyramidal side effects and despite treatment with atypical neuroleptics. The possibility that this deficit may be a core attribute of schizophrenia that can be related to other well-documented functional changes in this disease merits further study.
The authors acknowledge the competent assistance of Henia Ben David and thank Rena Kurs for assistance in preparation of the manuscript.