CROSSED-UNCROSSED DIFFERENCE (CUD) ESTIMATES OF INTERHEMISPHERIC TRANSMISSION IN SCHIZOPHRENIA AND ANXIETY DISORDERS

Transcription

1 CROSSED-UNCROSSED DIFFERENCE (CUD) ESTIMATES OF INTERHEMISPHERIC TRANSMISSION IN SCHIZOPHRENIA AND ANXIETY DISORDERS Piotr Wolski a and Gordon Claridge b a Institute of Psychology, Jagiellonian University, Kraków, Poland and b Department of Experimental Psychology, Oxford University, Oxford, UK Running Head: CUD in schizophrenia Address all correspondence to: dr Piotr Wolski Uniwersytet Jagielloñski Instytut Psychologii Kraków ul. Go³êbia 13 pw@phils.uj.edu.pl [ABSTRACT

2 CUD in schizophrenia 2 Performance of 22 patients with DSM III-R schizophrenia in a lateralized simple RT task was compared with that of 58 patients with anxiety disorders and a group of 61 healthy highschool students. Crossed-uncrossed difference (CUD) indexes of interhemispheric transfer were computed for all subjects. We failed to find a significant increase of the CUD in the schizophrenia group predicted by the interhemispheric defect hypothesis of schizophrenia. Paradoxically, we found an increase in CUD in the anxiety disorder group. Both psychopathological groups showed evident speed accuracy trade-off, that was absent in the healthy controls, and both displayed a tendency for a reversal of the RT asymmetries typically observed in the CUD experiments with healthy subjects. We believe that the popular assumption that the CUD reflects the callosal transfer time is valid only for healthy controls; in the psychopathological groups some high-level strategic or cognitive processes are likely to be involved.] Key words: brain hemispheres; inter-hemispheric relations; reaction time; psychopathology

3 CUD in schizophrenia 3 INTRODUCTION Functional and anatomical anomalies of interhemispheric relations have been suggested in schizophrenia for at least two decades. Among the most frequent in the literature have been the propositions of defective interhemispheric transfer and of the left hemisphere dysfunction. (See Woodruff, McManus, & David, 1995; Gruzelier, 1994; Roberts, 1991; Coger & Serafetinides, 1990; Gruzelier, 1987; Walker & McGuire, 1982; Green, 1978 for reviews). Numerous studies have reported changes in the size, structure, or shape of the corpus callosum, that were associated with schizophrenia. These reports have been accompanied by equally abundant observations of impaired performance of patients with schizophrenia in various behavioural tasks that require interhemispheric co-operation. Anatomical changes of the left hemisphere (most notably of the temporal region) as well as departures from the typical pattern of the hemispheric functional asymmetry, suggestive of the left hemisphere dysfunction, have been repeatedly observed in these patients, too. Moreover, several recent studies have correlated behavioural, clinical, and physiological data from the same patients, thus convincingly demonstrating the link between the physiological and the behavioural deficits in schizophrenia (Kareken et al, 1995; Mozley et al, 1994; Rossi et al, 1994; Colombo, Bonfanti, Scarone, 1994; Green, Hugdahl, Mitchell, 1994). The claim of interhemispheric dysfunction in schizophrenia seems well grounded. However, it seems a common view, that in many respects the evidence is still equivocal. The factors of clinical subtype, age, sex, or medication to name but a few are responsible for many interactive effects, and complicate the neuropsychological account of the illness. The research concerning the interhemispheric deficit hypothesis seems to follow two lines: the researchers either test the subjects performance in complex tasks involving interhemispheric co-operation, or they rather attempt to put the corpus callosum to a more direct test. Most behavioural studies naturally conform with the first paradigm. The patients performance is being screened on various cognitive and perceptual tasks involving interhemispheric interaction, for instance, naming objects on the basis of haptic information from the right hand (Dimond, et al, 1979), matching lateralized visual and tactile stimuli (Hatta, Yamamoto & Kawabata, 1984), lateralized Stroop (David 1993) or lexical decision (Blum & Feides, 1995) tasks, and many others. The second approach is restricted almost exclusively to anatomical and electrophysiological studies. Not surprisingly, as direct behavioural testing of the corpus callosum is hardly conceivable. However, one of the simplest interhemispheric tasks a paradigm originated by Poffenberger (1912), usually referred to as Crossed-Uncrossed Difference (CUD), seems to keep the high-level strategic factors at a reasonable minimum. Unlike many other lateralized tasks, the CUD paradigm has been shown to be free of the spatial compatibility effects (Anzola, et al., 1977; Berlucchi et al., 1977), and has been argued to reflect the sheer time of interhemispheric transmission (Bashore, 1981; Milner & Lines, 1982). Therefore, it bears closer relationship to the physiological methods than to the majority of behavioural techniques that reflect mostly high-level interhemispheric co-operation. We decided to test the performance of the patients with schizophrenia in the CUD task. Assuming that the measure reflects (under certain restrictions) the interhemispherictransmission time (ITT), we expected that the patients with schizophrenia should obtain CUDs different from controls. We deliberately use the more secure phrase different from instead of specifying the supposed direction or magnitude of the change: on the one hand, an increase in CUD might be expected in patients with schizophrenia, similar to that observed in the patients with callosal agenesis (Jeeves, 1969; Kinsbourne & Fisher, 1971; Milner, 1982);

4 CUD in schizophrenia 4 but on the other hand, atypical values close to zero are also possible if ipsilateral routes were active in schizophrenic patients to compensate for the assumed callosal dysfunction. Although the latter was suggested by Jones & Miller (1981) on the basis of the results that were controversial (Conolly, 1982; Shaw, 1982; Jones, Miller, 1982) and replicated negatively (Shagass, 1983), still the logical possibility remains. The Crossed-Uncrossed Difference is an arithmetic difference between mean reaction times to laterally presented simple light stimuli, measured in two conditions. (Swanson, Ledlow & Kinsbourne, 1978; Bashore, 1981; Milner, 1986; Milner & Rugg, 1989). In the first uncrossed the subject responds to the stimuli with his or her homolateral hand; in the other crossed the response is performed by the hand contralateral to the side of the stimulus presentation. There is no need for interhemispheric exchange of information in the first condition, but in the other, the neural route is believed to involve transfer of a motor command through the corpus callosum (Milner & Lines, 1982; Milner & Rugg, 1989). The validity of the subtractive measure of CUD as an index of ITT has been reported to depend on the paradigm. With choice reaction time (CRT), when the subjects respond either with their left or right hands depending on the side of stimulus presentation, the obtained ITT estimates are much higher than in the simple reaction time (SRT) paradigm, when no uncertainty is involved, and the response does not change with the side of the stimulus presentation. In his review, Bashore (1981) reports the CUD values of the order of ms for the CRT and of 1 to 6 ms (average 3.8 ms) for the SRT paradigm. Only the SRT CUD may be assumed to reflect the time of callosal transmission (Milner & Lines, 1982; Bashore, 1981). The CRT CUD has been shown to change to negative values with crossed hands in a condition that changes the spatial stimulus-response compatibility (Wallace, 1971; Swanson & Kinsbourne, 1976). This makes any anatomical explanation of the CRT CUD inappropriate. The oposite is true for the SRT CUD: the obtained value is not susceptible to changes in the S-R spatial compatibility (Swanson & Kinsbourne, 1976); its observed magnitude is more physiologically plausible; moreover, it increases in congenitally acallosal patients (Jeeves, 1969; Kinsbourne & Fisher, 1971; Milner, 1982). Since we aimed at capturing the behavioural manifestation of the lowest-level of the interhemispheric interchange, the simple reaction time CUD paradigm seemed an obvious choice for our study. METHOD Subjects Schizophrenia group. We tested 46 patients of the Miodowa St. and Symfoniczna St. Out- Patient Wards of the Jagiellonian University Collegium Medicum Psychiatric Clinic. All had the diagnosis of schizophrenia as defined by the DSM-IIIR diagnostic criteria (American Psychiatric Association, 1987). However, to assure maximum homogeneity of the group, we finally included only those patients data, whose diagnosis of DSM-IIIR schizophrenia was independently confirmed by means of the automated diagnostic criteria checklist OPCRIT version 3.3 *. (Williams et al. 1996). Consequently, a subset of data from 22 patients was used in all analyses described further: 11 male and 11 female; aged 23 to 48 (mean 31, S. D. 6.79). The patients were receiving neuroleptic medication, mostly with Leponex, Tisercin, or Haldol in daily doses of 30 to 500 mg of chlorpromazine equivalents (mean 210, S. D. 130). All patients were in a relatively good condition, that allowed for the treatment in an out-patient system. The patients were co-operative, none had difficulties understanding the task demands. * In fact, we repeated all main statistical analyses using the whole set of data from all 46 patients, too; but as the obtained pattern had not actually differed from the one found in the more carefully selected subgroup of 22 patients, we do not report the results.

5 CUD in schizophrenia 5 Anxiety disorder group. 58 patients of the Psychotherapy Unit of the Jagiellonian University Collegium Medicum Psychiatric Clinic (11 male, 47 female), aged 19 to 53 (mean 34, S. D. 10,25) constituted the other psychopathological group. We selected those patients whose diagnoses fell within the DSM-IIIR Anxiety Disorder category. The original diagnoses were done by screening psychiatrists, on the basis of interviews and symptom questionnaires. The diagnoses were then further confirmed by independently checking for the presence of strong anxiety or panic complaints in the recorded interviews and case notes. Most of the patients were tested during their initial screening period, prior to the beginning of the proper psychotherapy. As a rule, the patients were unmedicated, but we estimate that about 30% of the group might have been using occasionally mild doses (2-5 mg) of diazepam or equivalent anxiolitic. Non-psychiatric control group. 62 general profile high school students (38 male, 24 female), aged 19, were tested as non-psychiatric control group. In all groups, we selected only those subjects, who were right-handed (according to selfreport), had normal or corrected to normal vision (-4 to +2 dioptries), and in the two psychiatric groups no organic brain disease of any kind in the hospital record. The subjects were unpaid. Although they were not volunteers as such, each time it was made clear that the participation in the study was not compulsory, and indeed few students, two patients with schizophrenia, and one patient with anxiety neurosis refused to participate. Most of the subjects in the control and schizophrenia groups seemed well motivated by the very opportunity to check one s response speed that we offered. Though no such suggestion was explicitly made, the patients in the anxiety neurosis group seemed generally to take the test as just another of the set of the screening tests. Stimuli and apparatus Two arrays of green light emitting diodes (LEDs) were used for stimulus display and a single red LED served as a fixation point. Each of the two stimulus display arrays was a square mm matrix of 16 round LEDs placed tightly in 4 columns (or rows) of 4 diodes. The stimuli used in the present experiment were thick vertical bars, that is shapes obtained by lighting all 8 lights of the second and third LED columns together. Although the shapes in fact consisted of separate light dots, when viewed peripherally, they seemed solid vertical bars of green light. The choice of the shapes was quite arbitrary, but we do not think it was very significant, because, by definition, simple RT tasks rely on sheer detection of the stimulus with no need of discrimination. We used the described shape mostly because of it s total luminance that allowed for easy perception in daylight conditions. Same stimuli were used in the two visual hemifields. The stimuli were displayed at an eccentricity of 6 degrees, at a distance of 1500 mm from the subject s eyes. A very short stimulus duration of only 25 ms was used in order to put the risk of non-peripheral perception to a minimum. Due to superb timing characteristics of the light emitting diodes, one can use such short exposures at no cost in visibility. The nominal luminosity of the stimuli LED was 1.5 mcd each, and that of the fixation point: 1.8 mcd. A small mm rectangular pad with two micro switches (of which only one was used throughout each block of trials) was utilised to register the responses. The switches had round buttons of 10 mm diameter; their travelling distance was 7 mm, and they had a fallback ( clicking ) mechanical characteristic with a depression force of ca. 0,1 N. The pad was being placed on the table so as to keep the responding hand centrally with respect to the subject s body axis.

6 CUD in schizophrenia 6 A simple, Intel Z80-based microcomputer (Amstrad/Schneider CPC 6128), equipped with an extra I/O ports was adapted to control the experiment. Stimulus display, reaction recording, and the timing were controlled by a machine code subroutine. This allowed for 1 ms resolution and much greater accuracy. Procedure We employed a randomized-trials simple RT CUD paradigm, as described in the metaanalytic reviews of Marzi, Bisiacchi, and Nicoletti, 1991, and Bashore, Because with randomized-trials technique (as opposed to the blocked-trials), the side of the stimulus presentation changes unpredictably between trials, the subject s optimal strategy for quick and accurate responses is to keep firmly his or her gaze right at the fixation point. This paradigm is therefore safer with respect to the most important assumption of the laterality experiments: that of parafoveal perception of the stimuli. Each subject completed two blocks of 100 trials each. Same hand was used for responding throughout a block. Half of the subjects started with left hand blocks, and half with right hand blocks of trials. At the beginning of each block, the subjects were asked to rest their index fingers lightly on the left (in the left hand block) or right (in the right hand block) button of the reaction pad, and to press it as soon as the stimulus appeared. We encouraged quick responses but not at the cost of accuracy. The task was very simple, and no prior training was necessary. Every stimulus was preceded by a visual warning signal turning on the fixation point LED. The time lag between the warning signal and the stimulus onset was randomized within the range of 1 to 2.5 s. For one second after the stimulus display, the computer waited for a key press. Lack of the reaction within this period or a reaction longer than that were recorded as a miss. We chose such timing on the basis of our previous experience that showed only occasional reactions exceeding 700 ms and virtually none longer than 1000 ms. The pace of the experiment did not depend upon the subject s response: the computer always waited the whole 1 s interval after the stimulus onset, regardless of when (or if) the reaction occurred. A fixed 1s interval preceded the start of the next trial the onset of the warning signal. The overall presentation rate was approximately one trial per four seconds. Each hand and visual field combination was tested 50 times in every subject. RTs from spatially discordant hand and VF combinations were used to calculate the crossed RT and RTs from the concordant ones provided the uncrossed RT. The crossed-uncrossed differences (CUDs) were then calculated by subtracting these two. Raw data transformations Some subjects missed the first, and some even the second trial of the experiment. Starting with the trial number three, the incidence of omission errors was low and uniform. To correct for that, we decided to ignore the first two trials of each hand and visual field combination. This cut down the total number of trials per person from 200 to 192. As typical in simple reaction time studies, our RT data showed slight tendency for rightskewed distributions. The Kolmogorow-Smirnov test, however, did not show a significant departure from normality for neither of the four RT variables. Nevertheless, because the logtransformed data slightly better approximated the normal distribution, we repeated the basic analyses after log-transformation, too. The pattern of results in the two analyses was the same. Hence we report only the results of the untransformed data analyses. Error-rates RESULTS

7 CUD in schizophrenia 7 All reaction times shorter than 140 ms were excluded as anticipation errors, while those that exceeded 999 ms were treated as omissions. On the average, the omission errors made 1.5% of the total number of trials. Between-group differences were small and non-significant (χ 2 = 3.5; df=2; p = 0.17). The rate of the anticipation errors was clearly lower in the anxiety group than in the other two. Anxiety patients showed 0.2% error-rate, while the error-rates in the two remaining groups were: 1.0% in schizophrenia group, and 1.2% in non-psychiatric controls. The effect of group was statistically significant: χ 2 = 14.9; df=2; p < Global reaction times and crossed-uncrossed differences We performed a four-factor ANOVA of mean individual reaction times with repeated measures on two factors: Visual Field, and Hand. There were two between-subjects factors: Group, and Gender. To check for a potential influence of the fact that the three groups differed in their mean ages, we repeated all computations applying an ANCOVA model, with the subjects age as a co-variate. The results closely matched the original ANOVA. One should note however, that the interpretation of the ANCOVA results is restricted by zero variance of the subjects ages in the non-psychiatric control group, as well as by the nonrandom assignment of subjects to the three groups. The latter is a universal weakness of all comparative psychopathological research where the researcher can not obey strictly the first rule of randomisation. Below, we report only the ANOVA results. The compared groups differed in their general response speed: mean reaction times were longest in the schizophrenia group, intermediate in the anxiety patients, and shortest in the non-psychiatric control group. [F (2,136) = 14.5; p < 0.001]. All differences between the pairs of means were significant on post-hoc Scheffé tests Table 1 about here We succeeded replicating the basic CUD phenomenon that has been frequently described in the literature: reaction times were significantly longer in the crossed than in the uncrossed condition; see Table 1. The respective ANOVA effect was highly significant [Visual Field Hand: F (1,136) = 30.1; p < 0.001]. Contrary to our expectations, the CUD value was highest not in the schizophrenia but in the anxiety group. In the non-psychiatric control group the CUDs showed, as expected, the lowest values. However, the differences were not statistically significant [interaction of Visual Field Hand Group: F (2, 136) = 2.1; p = 0.13] Lateral asymmetries As in 13 out of 16 studies meta-analyzed by Marzi, Bisiacchi, and Nicoletti (1991), in the non-psychiatric control group, we too obtained faster right hand than left hand responses. Interestingly, in contrast to that, both psychiatric groups performed faster with their left hands. However, the respective ANOVA effect has not reached the threshold of significance [Group Hand: F (2, 136) = 2,8; p = 0.06] Table 2 about here

8 CUD in schizophrenia 8 Somewhat similar pattern of group differences can be seen with the visual field asymmetries: again we found small differences in the non-psychiatric group that were reversed in the two psychiatric groups. On the one hand, the statistical evidence is weak: although the overall Visual Field Group effect was significant [F (2, 136) = 3.3; p < 0.04], the post-hoc Scheffé comparisons of the VF differences within the three groups were not. On the other hand, the direction and magnitude of the differences again matched the dominating trend for VF differences found by Marzi, Bisiacchi, and Nicoletti (1991) in their metaanalysis. Gender differences Men were generally faster in all three groups. (See table 3). Though the main effect of gender was statistically significant [F (1, 136) = 10.8; p = 0.01], and so was the Gender Group interaction [F (2, 136) = 7.7; p = 0.007], on post-hoc comparisons only the gender difference in the schizophrenia group was significant (Scheffé; p = 0.003). There were no interactions of gender with laterality factors or CUD. The main part of the variance seems attributable to much poorer performance of women than men in the schizophrenia group Table 3 about here DISCUSSION We failed to confirm our hypothesis of a greater CUD in schizophrenia. Even if we attributed the lack of statistically significant between-group effects to insufficient sample size, the results would rather suggest elevated CUDs in anxiety not in schizophrenia. This however is not likely to be the case. Unlike in schizophrenia, where abundant reports of inter-hemispheric anomalies exist, to our knowledge no such deficits have been found in the anxiety neurosis. In fact, the anxiety patients were used as controls in studies of neuropsychological abnormalities in schizophrenia just because of that (Crow et al. 1989; Hunter, Green, 1985; Shaw, Colter, Resek, 1983). Our patients with schizophrenia obtained the much smaller CUD values than the commisurotomized patients (Clarke and Zaidel, 1989) or callosal agenesis cases (Jeeves, 1960; Kinsbourne and Fisher, 1971; Milner, 1982). This too is very unlikely to change even with much greater sample. One might attribute the lack of the expected CUD increase in schizophrenia to a normalizing effect of medication. However, we found no reports that would suggest an improvement in the hemispheric interaction under neuroleptic medication. Several studies have independently shown cessation of pathological left-hemispheric asymmetries after farmacological intervention (Tomer, 1990; Roemer & Shagass, 1990; Tomer & Flor-Henry, 1989; Hammond & Gruzelier, 1978), but none seems to report analogous improvement of interhemispheric communication. An unpublished first author s results suggest low psychometric reliability of the CUD measure. The technique, however, is reliable enough to capture the most severe cases of callosal dysfunction, as shown by the CUD results in callosal agenesis and callosotomy. Then, our present results suggest that the interhemispheric abnormalities in schizophrenia are not likely due to a severe organic callosal dysfunction. Their cause is probably more subtle, and the CUD, being a relatively insensitive measure, can not detect it. The observed response asymmetry the shorter reaction times to the right-visual-field stimuli concords with the popular left hemisphere over-activation hypothesis (see e.g.

9 CUD in schizophrenia 9 Woodruff, McManus, and David, 1995). One must note, however, that the right hand reactions in the patients were not faster than those of the left hand. In fact, they were even slightly slower. Paradoxically, even this result can be explained by the left-hemisphere overactivation if one postulates additionally, that the over-activation facilitates perception, but deteriorates motor output. This draws attention to a basic problem of the over-activation hypothesis: as long as we can not be sure if the alleged over-activation increases or decreases the speed of processing, in fact no observed behavioral asymmetries can reliably confirm it nor falsify. What is more, we can not be sure if what we regard a right visual field improvement was not actually a left visual field handicap indicative of a relative deficiency of the right not the left hemisphere. With all that in mind, we would rather put off any explanations until additional data is collected. For instance, with the normalization of asymmetries under neuroleptic medication, some interesting additional evidence could be provided by measuring the CUDs of the patients untreated pharmacologically. Resolving this question definitely requires further research.

10 CUD in schizophrenia 10 ACKNOWLEDGEMENTS We thank for their helpful co-operation: the personnel and the patients of the Miodowa St. and Symfoniczna St. Out-Patient Wards and of the Psychotherapy Unit all of the Jagiellonian University Collegium Medicum Psychiatric Clinic in Kraków; the Head and students of the XIVth General Profile High-School in Kraków. The research was supported by a grant number 1047/H01/95/09 from the Polish Ministry of Education.

11 CUD in schizophrenia 11 REFERENCES 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Third Edition.Revised. American Psychiatric Association, Washington, Anzola, G. P., Bertoloni, G., Buchtel, H. A., and Marzi, C. A. Spatial compatibility and anatomical factors in simple and choice reaction time. Neuropsychologia 15, , Bashore, T. R. Vocal and manual reaction time estimates of interhemispheric transmission time. Psychol. Bull. 99, , Berlucchi, G., Crea, F., Di Stefano, M. and Tassinari, G. Influence of spatial stimulusresponse compatibility on reaction time of ipsilateral and contralateral hand to lateralized light stimuli. J. Exp. Psychol.: H. P. P. 3, , Blum, N. A. and Freides, D. Investigating thought disorder in schizophrenia with the lexical decision task. Schizophr.-Res. 16, , Coger, R. W. and Serafetinides E. A. Schizophrenia, corpus callosum, and interhemispheric communication: A review. Psychiat.Res. 34, , Colombo, C., Bonfanti, A. and Scarone, S. Anatomical characteristics of the corpus callosum and clinical correlates in schizophrenia. Eur. Arch. Psychiat. Clin. Neurosci. 243, , Conolly, J. F. The Corpus Callosum and Brain Function in Schizophrenia. Correspondence. Brit. J. Psychiat. 140, , Crow, T. R., Colter, N., Frith, C. D. and Johnstone, E. C. Developmental arrest of cerebral asymmetries in early onset schizophrenia. Psychiat. Res. 29, , David, A. S. Callosal transfer in schizophrenia: Too much or too little? J. Abn. Psychol. 102, , Dimond, S. J., Scammell, R. E., Pruce, I. G., Huws, D. and Gray, C. Callosal transfer and left-hand anomia in schizophrenia. Biol. Psychiat. 14, , Green, M. F, Hugdahl, K., and Mitchell, S. Dichotic listening during auditory hallucinations in patients with schizophrenia. Am. J. Psychiat. 151, , Green, P. Defective interhemispheric transfer in schizophrenia. J. Abn. Psychol. 87, , Gruzelier, J. H. Cerebral laterality and schizophrenia: A review of the interhemispheric disconnection hypothesis. In Individual differences in hemispheric specialization, W. A. Glass. (Editor), NATO ASI series A: Life Sciences. 130, pp Plenum Press, New York, Gruzelier, J. H. Syndromes of schizophrenia and schizotypy, hemispheric imbalance and sex differences: Implications for developmental psychopathology. Special Issue: Developmental psychophysiology. Int. J. Psychophysiol. 18, , Hammond, N. V. and Gruzelier, J. H. Laterality, attention and rate effects in the auditory temporal discrimination of chronic schizophrenics: The effect of treatment with chlorpromazine. Quart. J. Exp. Psychol. 30, , Hatta, T., Yamamamoto, M. and Kawabata, Y. Functional hemispheric differences in schizophrenia: Interhemispheric transfer deficit or selective hemispheric dysfunction? Biol. Psychiat. 19, , Hinrichs, H. and Machleidt, W. Basic emotions reflected in EEG-coherences. Int. J. Psychophysiol. 13, , Hunter, M. and Green, P. Abnormal interhemispheric integration and schizophrenia. Special issue: Schizophrenia. Int. Rev. App. Psychol. 34, , 1985.

12 CUD in schizophrenia Jones, G. and Miller, J. J. Functional tests of the corpus callosum in schizophrenia. Brit. J. Psychiat. 139, , Jones, G. and Miller, J. J. The corpus callosum and brain function in schizophrenia. Brit. J. Psychiat. 141, 535, Jeeves, M. A. A comparison of interhemispheric transmission times in acallosals and normals. Psychon. Sci. 16, , Kareken, D. A., Gur, R. C., Mozley, P. D. and Mozley, L. H. Cognitive functioning and neuroanatomic volume measures in schizophrenia. Neuropsychology 9, , Kinsbourne M., and Fisher, M. Latency of uncrossed and of crossed reaction in callosal agenesis. Neuropsychologia 9, , Marzi, C. A., Bisiacchi, P. and Nicoletti, R. Is interhemispheric transfer of visuomotor information asymmetric? Evidence from a meta-analysis. Neuropsychologia 29, , Milner, A. D. Chronometric analysis in neuropsychology. Neuropsychologia 24, , Milner, A. D. Simple reaction times to lateralized visual stimuli in a case of callosal agenesis. Neuropsychologia 20, , Milner, A. D. and Lines, C. R.. Interhemispheric pathways in simple reaction time to lateralized light flash. Neuropsychologia 20, , Milner, A. D. and Rugg, M. D. Interhemispheric transmission times. In Developments in clinical and experimental neuropsychology, J. R. Crawford, and D. M. Parker (Editors) pp Plenum Press, New York, Mozley, P. D., Gur, R. E., Resnick, S. M. and Shtasel, D. L. Magnetic resonance imaging in schizophrenia: Relationship with clinical measures. Schizophr.-Res. 12, , Poffenberger, A. T. Reaction time to retinal stimulation with special reference to the time lost in conduction through nervous centers. Archs Psychol. 23, 1 73, Roberts, G. W. Schizophrenia: A neuropathological perspective. Brit. J. Psychiat. 158, 8 17, Roemer, R. A. and Shagass, C. Replication of an evoked potential study of lateralized hemispheric dysfunction in schizophrenics. Biol. Psychiat. 28, , Rossi, A., Serio, A., Stratta, P. and Petruzzi, C. Planum temporale asymmetry and thought disorder in schizophrenia. Schizophr.-Res. 12, 1 7, Shagass, C. et-al. Failure to replicate evoked potential observations suggesting corpus callosum dysfunction in schizophrenia. Brit. J. Psychiat. 142, , Shaw, J. C. The Corpus Callosum and Brain Function in Schizophrenia. Correspondence. Brit. J. Psychiat. 140, 429, Shaw, J. C., Colter, N. and Resek, G. EEG coherence, lateral preference and schizophrenia. Psychol. Med. 13, , Swanson, J. M. and Kinsbourne, M. S-R compatibility and interhemispheric transfer time. Paper presented at American Psychological Association meeting. Washington Swanson, J., Ledlow, A. and Kinsbourne, M. Lateral asymmetries revealed by simple reaction time. In Asymmetrical function of the brain, M. Kinsbourne (Editor), pp Cambridge University Press, New York:, Tomer, R. Neuroleptic effects on interhemispheric and intrahemispheric performance of tactile discrimination tasks by schizophrenic patients. Psychiat. Res. 32, , Tomer, R. and Flor-Henry, P. Neuroleptics reverse attention asymmetries in schizophrenic patients. Biol. Psychiat. 25, , 1989.

13 CUD in schizophrenia Wallace, R. J. S-R compatibility and the idea of a response code. J. Exp. Psychol. 58, , Williams, J., Farmer, A. E., Ackenheil, M., Kaufmann, C. A., McGuffin, P. and The OPCRIT Reliability Research Group. A multicentre inter-rater reliability study using the OPCRIT computerized diagnostic system. Psychol. Med. 26, Woodruff, P. W. R., McManus, I. C. and David, A. S. Meta-analysis of corpus callosum size in schizophrenia. J. Neurol. Neurosurg. Psychiat. 58, , 1995.

14 Table 1. Mean reaction times in the four visual field and hand combinations, and crosseduncrossed differences (CUDs) in the three experimental groups in ms Patients with schizophrenia (N = 22) Patients with anxiety neurosis (N = 58) Non-psychiatric control group (N = 61) LVF / Left hand LVF / Right hand RVF / Left hand RVF / Right hand Grand mean Mean crossed Mean uncrossed Crossed - uncrossed difference (CUD)

15 CUD in schizophrenia 15 Table 2. Lateral differences between reaction times of subjects in the three experimental groups in ms. Patients with schizophrenia (N = 22) Patients with anxiety neurosis (N = 58) Non-psychiatric control group (N = 61) Left hand Right hand Left visual field Right visual field

16 CUD in schizophrenia 16 Table 3. Mean reaction times of men and women. Men Women Patients with schizophrenia (N=11) Patients with anxiety neurosis (N=11) Non-psychiatric control group (N=37) (N=11) (N=47) (N=24)