Impaired Visuomotor Function in Schizophrenic Patients Compared With Control Subjects Henry Silver, M.B.B.S., B.Med.Sci., D.P.M., F.R.A.N.Z.C.P. Nili Shlomo, M.D. Miguel Schwartz, M.D. Shraga Hocherman, Ph.D. Visuomotor function was studied in 36 schizophrenic patients treated with atypical antipsychotics and in 22 control subjects. Patients showed signiﬁcant disturbances in ability to control movement direction when tracing objects on screen and in keeping pace with a moving target in tracking tests. The impairments were not related to medication dose or to extrapyramidal side effects. Visuomotor impairment may be part of illness-related pathology in schizophrenia. (The Journal of Neuropsychiatry and Clinical Neurosciences 2002; 14:72–76)
eurological abnormalities are common in schizophrenia1 and discriminate between patients and healthy subjects2 irrespective of treatment. Medicationinduced extrapyramidal side effects may further impair neurological function. Disturbances in pursuit and saccadic eye movements are also common in schizophrenia and may be trait markers for the illness.3–6 Such disturbances may impair the ability to manually track moving visual targets. In addition to normal ocular control, eye–hand coordination requires intact frontal-parietal-temporal connections,7–9 which are postulated to be disturbed in schizophrenia.10,11 Hence it can be predicted that visuomotor impairment, too, may be a part of the illness process. We tested this prediction by studying visuomotor coordination in patients with schizophrenia, using a sensitive visuomotor testing system (VMT) developed for detection of early Parkinson’s disease.12 To minimize potential confounds from drug-induced extrapyramidal side effects, only patients treated with atypical antipsychotics were studied and compared with normal control subjects.
Received July 7, 2000; revised October 10, 2000; accepted October 19, 2000. From Flugelman (Mazra) Psychiatric Hospital, Mobile Post Ashrat, Israel; and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel. Address correspondence to Dr. Silver, Sha’ar Menashe Mental Health Center, Mobile Post Hefer 38814, Israel. E-mail: [email protected]
. Copyright 䉷 2002 American Psychiatric Publishing, Inc.
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METHODS Subjects 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: n⳱12, mean dose⳱4.3Ⳳ1.5 mg; olanzapine: n⳱17, mean dose⳱14.7Ⳳ3.7 mg; clozapine: n⳱7, mean dose⳱350Ⳳ153 mg) for at least 6 weeks. Ten patients also received biperiden (mean dose⳱3.6Ⳳ1.6 mg), and 6 received trihexyphenidyl (mean dose⳱10.8Ⳳ4.9 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 (meanⳲSD: 40.6Ⳳ10.7 years vs. 55.3Ⳳ12.0 years, P⬍0.01). There was no signiﬁcant difference in gender distribution between the groups (chi-square, Fisher’s exact test, P⳱0.1). The sociodemographic and illness characteristics of the patient population are shown in Table 1. Clinical Assessment The same experienced rater (N.S.) performed clinical assessment for all patients. General psychopathology was assessed with the Brief Psychiatric Rating Scale,13 scored
Demographic and clinical characteristics of the patient population
Age, years Age at ﬁrst hospital admission Number of hospital admissions Length of current admission, years Cumulated time as inpatient, years Duration of illness, years BPRS SANS SA AIMS
40.6Ⳳ10.7 26.9Ⳳ9.2 4.6Ⳳ4.5 4.1Ⳳ5.5 7.6Ⳳ7.7 13.8Ⳳ11.3 18.9Ⳳ8.5 38.0Ⳳ18.2 3.0Ⳳ3.7 1.1Ⳳ2.5
Note: BPRS⳱Brief Psychiatric Rating Scale; SANS⳱Scale for the Assessment of Negative Symptoms; SA⳱Neurological Rating Scales for Extrapyramidal Side Effects; AIMS⳱Abnormal Involuntary Movement Scale.
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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 Instrumentation 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. Tests Tracing: 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. Tracking: 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 (minimum⳱16 mm/s at the curved peaks, maximum⳱22 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. Paths: 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
VISUOMOTOR FUNCTION IN SCHIZOPHRENIA 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. Scores Performance was evaluated ofﬂine by use of the following measures: 1. 2. 3.
Mean total time (MnTrkT) of tracking test performance. Mean distance (MnDist) between the model path and the path traversed by the hand. The directional error (DirEr) of hand movement. This consisted of the instantaneous movement component heading in a direction perpendicular to the model path, expressed as percentage of the total movement vector. The percentage of movement time during which the DirEr exceeded a level of 50% (PT50%) was calculated. This number expressed the relative test time during which movement advanced in a direction more perpendicular than parallel to the model path. Mean hand movement velocity during tracing (MnVtrc). The mean number of tracking interruptions (MnNints).
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 performance18 according to the following equation: GPM⳱Z[(MnPT50%)2Ⳮ (MnNints)2]. Procedure 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. Statistical Analysis 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.
RESULTS 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: r⳱–0.17 right hand, r⳱–0.11 left hand, not signiﬁcant; GPM vs. AIMS score: r⳱0.12 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 (r⳱0.37, P⳱0.03). 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: r⳱0.37, P⳱0.03), illness duration (except for correlation with MnDist left hand: r⳱0.44, P⳱0.008), number of admissions, and accumulated time in hospital (except for correlation with PT50% right hand: r⳱0.34, P⳱⬍0.05, and MnDist right hand: r⳱0.49, P⳱0.003). 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. DISCUSSION 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.
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SILVER et al. TABLE 2.
Visuomotor coordination in schizophrenia patients versus control subjects MeanⴣSD
PT50% PT50% MnNints MnNints MnTrkT MnTrkT MnDist MnDist MnVTrc MnVTrc GPM GPM
Right Left Right Left Right Left Right Left Right Left Right Left
22.15Ⳳ13.03 21.36Ⳳ12.85 28.22Ⳳ24.16 23.70Ⳳ17.67 27.46Ⳳ11.23 26.20Ⳳ9.14 3.36Ⳳ2.27 3.12Ⳳ1.64 16.24Ⳳ7.93 17.31Ⳳ9.42 37.83Ⳳ24.59 33.39Ⳳ19.41
12.91Ⳳ8.23 10.97Ⳳ5.08 6.80Ⳳ6.02 5.73Ⳳ5.76 18.15Ⳳ2.98 17.43Ⳳ2.13 1.62Ⳳ0.81 1.48Ⳳ0.72 13.80Ⳳ4.06 13.58Ⳳ4.40 15.24Ⳳ9.14 13.06Ⳳ6.38
8.80 13.04 16.53 21.21 14.37 19.47 11.78 19.49 1.77 3.05 16.99 22.47
0.004 0.001 0.0001 0.0001 0.0001 0.0001 0.001 0.0001 0.19 0.09 0.0001 0.0001
Note: One patient with incomplete data on some tests was excluded. PT50%⳱percentage of movement time during which the directional error of hand movement exceeded a level of 50%; MnTrkT⳱mean total time of tracking test performance; MnDist⳱mean distance between the model path and the path traversed by the hand; MnVtrc⳱mean hand movement velocity during tracing; MnNints⳱mean number of tracking interruptions; GPM⳱global measure of performance.
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 regions10,11 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 processes19 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 ad-
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dition, 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 cortex26 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.
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