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Abnormal saccadic distractibility in patients with schizophrenia: a 99mTc-HMPAO SPET study

Published online by Cambridge University Press:  09 July 2009

T. J. Crawford*
Affiliation:
Academic Unit of Neurosciences and Departments of Psychiatry and Nuclear Medicine, Charing Cross and Westminster Medical School, London; and School of Psychiatry and Behavioural Sciences, University of Manchester
B. K. Puri
Affiliation:
Academic Unit of Neurosciences and Departments of Psychiatry and Nuclear Medicine, Charing Cross and Westminster Medical School, London; and School of Psychiatry and Behavioural Sciences, University of Manchester
K. S. Nijran
Affiliation:
Academic Unit of Neurosciences and Departments of Psychiatry and Nuclear Medicine, Charing Cross and Westminster Medical School, London; and School of Psychiatry and Behavioural Sciences, University of Manchester
B. Jones
Affiliation:
Academic Unit of Neurosciences and Departments of Psychiatry and Nuclear Medicine, Charing Cross and Westminster Medical School, London; and School of Psychiatry and Behavioural Sciences, University of Manchester
C. Kennard
Affiliation:
Academic Unit of Neurosciences and Departments of Psychiatry and Nuclear Medicine, Charing Cross and Westminster Medical School, London; and School of Psychiatry and Behavioural Sciences, University of Manchester
S. W. Lewis
Affiliation:
Academic Unit of Neurosciences and Departments of Psychiatry and Nuclear Medicine, Charing Cross and Westminster Medical School, London; and School of Psychiatry and Behavioural Sciences, University of Manchester
*
1Address for correspondence: Dr T. J. Crawford, Academic Neurosciences. Charing Cross and Westminster Medical School, Fulham Palace Road. London W6 8RF.

Synopsis

Recent research has shown that some patients with schizophrenia have a severe impairment in the suppression of reflexive saccadic eye movements in the ANTI-saccade task. This saccadic distractibility has previously been found in patients with lesions of dorsolateral prefrontal cortex, implicating an abnormality of prefrontal cortex. The objective of the present study was to determine the contribution of these and other areas to the ANTI-saccadic abnormality in schizophrenia by functional neuroimaging. Using 99mtechnetium-HMPAO high resolution multidetector single-photon emission tomography, regional cerebral blood flow (rCBF) during performance of the ANTI-saccade eye-movement task was compared, by statistical parametric mapping, in ten male schizophrenic patients on stable antipsychotic medication who had a high distractibility error rate on the task, and eight similar patients who had normal distractibility error rates. Compared with the normal error group, the patients with high error rates showed significantly decreased rCBF bilaterally, in the anterior cingulate, insula, and in left striatum. These same patients also had increased perseverative errors on the Wisconsin Card Sort Test.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 1996

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References

REFERENCES

Albin, R. L., Young, A. B. & Penney, J. B. (1989). The functional anatomy of basal ganglia disorders. Trends in Neurosciences 12, 366375.Google Scholar
Alexander, G. E., Delong, M. R. & Strick, P. L. (1986). Parallel organisation of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neurosciences 9, 357381.Google Scholar
Anderson, T. J., Jenkins, I. H., Brooks, D. J., Hawken, M. B., Frackowiak, R. S. J. & Kennard, C. (1994). Cortical control of saccades and fixation in man: a positron emission tomographic study. Brain 117, 10731084.Google Scholar
Andreasen, N. C. (1984 a). Schedule for the Assessment of Negative Symptoms (SANS). University of Iowa: Iowa City.Google Scholar
Andreasen, N. C. (1984 b). Schedule for the Assessment of Positive Symptoms (SAPS) University of Iowa: Iowa City.Google Scholar
Annett, M. (1970). Classification of hand preference by association analysis. British Journal of Psychology 61, 303321.Google Scholar
Bailey, D. L, Jones, T., Friston, K. J, Colebatch, J. G. & Frackowiak, R. S. J. (1991). Physical validation of statistical parametric analysis. Journal of Cerebral Blood Flow 11, S150.Google Scholar
Bronstein, A. M. & Kennard, C. (1985). Predictive ocular motor control in Parkinson's disease. Brain 108, 925940.Google Scholar
Bruce, C. J. & Goldberg, M. E. (1985). Primate frontal eye fields. I. Single neurones discharging before saccades. Journal of Neurophysiology 53, 603635.Google Scholar
Bruce, C. J., Goldberg, M. E., Bushnell, M. C. & Stanton, G. B. (1985). Primate frontal eye fields. II. Physiological and anatomical correlates of electrically evoked eye movements. Journal of Neurophysiology 54, 714734CrossRefGoogle Scholar
Carpenter, R. H. S. (1988). Movement of the Eyes. Pion: LondonGoogle Scholar
Chollet, F., Dipiero, V., Wise, R. J. S., Brooks, D. J., Dolan, R. J. & Frackowiak, R. S. J. (1991). The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. Annals of Neurology 29, 6371.Google Scholar
Clementz, B. A. & Sweeney, J. A. (1990). Is eye movement dysfunction a biological marker for schizophrenia? A methodological review. Psychological Bulletin 108, 7792.CrossRefGoogle Scholar
Cohen, R. M., Semple, W. E., Gross, M., Nordahl, T. E., De Lisi, L. E., Holcomb, H. H., King, A. C., Morihisa, J. M. & Pickar, D. (1987). Dysfunction in a prefrontal substrate of sustained attention in schizophrenia. Life Sciences 20, 20312039.Google Scholar
Cohen, R. M., Semple, W. E., Gross, M. & Nordahl, T. E. (1988). From syndrome to illness: delineating the pathology of schizophrenia with PET. Schizophrenia Bulletin 14, 169176Google Scholar
Colebatch, J. G., DeiberM. P, Passingham, R. E. M. P, Passingham, R. E., Friston, K. J. & Frackowiak, R. S. J. (1991). Regional cerebral blood flow during voluntary arm and hand movements in human subjects. Journal of Neurophysiology 65, 13921401.Google Scholar
Crawford, T. J., Henderson, L. & Kennard, C. (1989 a). Abnormalities of nonvisually-guided eye movements in Parkinson's disease. Brain 112, 15731586.Google Scholar
Crawford, T. J., Goodrich, S., Henderson, L. & Kennard, C. (1989 b). Predictive responses in Parkinson's disease: manual keypresses and saccadic eye movements to regular stimulus events. Journal of Neurology, Neurosurgery and Psychiatry 52, 10331042.Google Scholar
Crawford, T. J., Haegar, B., Kennard, C., Reveley, M. A. & Henderson, L. (1995 a). Saccadic abnormalities in psychotic patients. I. Neuroleptic-free psychotic patients. Psychological Medicine 25, 461471.Google Scholar
Crawford, T. J., Haegar, B., Kennard, C., Reveley, M. A. & Henderson, L. (1995 b). Saccadic abnormalities in psychotic patients. II. The role of neuroleptic treatment. Psychological Medicine 25, 473483.Google Scholar
Degos, J. D., Fonseca, N. da, Gray, F. & Cesaro, P. (1993). Severe frontal syndrome associated with infarcts of the left anterior cingulate gyrus and the head of the right caudate nucleus. A clinico-pathological case. Brain 116, 15411548.Google Scholar
Deiber, M. P., Passingham, R. E., Colebatch, J. G., Friston, K. J., Nixon, P. D. & Frackowiak, R. S. J. (1991). Cortical areas and the selection of movement: a study with positron emission tomography. Experimental Brain Research 84, 393402.Google Scholar
Diefendorf, A. R. & Dodge, R. (1908). An experimental study of the ocular reactions of the insane from photographic records. Brain 31, 451489.Google Scholar
Folstein, M. F., Folstein, S. E. & McHugh, P. R. (1975). ‘Mini-mental state.’ A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.Google Scholar
Fox, P. T., Fox, J. M., Raichle, M. E. & Burde, R. M. (1985). The role of the cerebral cortex in the generation of voluntary saccades: a positron emission tomographic study. Journal of Neurophysiology 54, 348369.Google Scholar
Friston, K. J., Passingham, R. E., Nutt, J. G., Heather, J. D., Sawle, G. V. & Frackowiak, R. S. J. (1989). Localisation in PET images: direct fitting of the intercommisural (AC–PC) line. Journal of Cerebral Blood Flow and Metabolism 9, 690695.Google Scholar
Friston, K. J., Frith, C. D., Liddle, P. F., Dolan, R. J., Lammertsma, A. A. & Frackowiak, R. S. J. (1990). The relationship between global and local changes in PET scans. Journal of Cerebral Blood Flow and Metabolism 10, 458466.CrossRefGoogle Scholar
Friston, K. J., Frith, C. D., Liddle, P. F. & Frackowiak, R. S. J. (1991 a). Comparing functional (PET) images: the assessment of significant change. Journal of Cerebral Blood Flow and Metabolism 11, 690699.Google Scholar
Friston, K. J., Frith, C. D., Liddle, P. F. & Frackowiak, R. S. J. (1991 b). Plastic transformation of PET images. Journal of Computer Assisted Tomography 15, 634639.Google Scholar
Frith, C. D., Friston, K., Liddle, P. F. & Frackowiak, R. S. J. (1991). Willed action and the prefrontal cortex in man: a study with PET. Proceedings of the Royal Society. London. B 244, 241246.Google Scholar
Fukushima, J., Fukishima, K., Nobuyuki, M. & Yamashita, I. (1990). Further analysis of the control of voluntary saccadic eye movements in schizophrenic patients. Biological Psychiatry 28, 943958.Google Scholar
Funahashi, S., Bruce, C. J. & Goldman-Rakic, P. S. (1989). Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. Journal of Neurophysiology 61, 331349.Google Scholar
Funahashi, S., Chafee, M. & Goldman-Rakic, P. S. (1993). Prefrontal neuronal activity in rhesus monkeys performing a delayed anti-saccade task. Nature 365, 753756.Google Scholar
Gnadt, J. W., Anderson, R. A. & Blatt, G. J. (1986). Spatial memory and planning properties of saccade related activity in the lateral intraparietal area of the macaque. Society of Neuroscience Abstracts 12, 458.Google Scholar
Guitton, D., Buchtal, H. A. & Douglas, R. M. (1985). Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal directed saccades. Experimental Brain Research 58, 455474.Google Scholar
Gurevich, B. Kh. (1961). Universal characteristics of fixation eye jerks: change in fixation as a cybernetic model of directed behaviour. Biophysics 6, 419427.Google Scholar
Hallet, P. E. & Adams, B. D. (1980). The predictability of saccadic latency in a novel voluntary oculomotor task. Vision Research 20, 329339.Google Scholar
Herscovitch, P., Markham, J. & Raichle, M. E. (1983). Brain blood flow measured with intravenous H215O. I. Theory and error analysis. Journal of Nuclear Medicine 24, 782789.Google Scholar
Hikosaka, O. & Wurtz, R. H. (1983 a). Visual and oculomotor functions of monkey substantia nigra, pars reticulata. I. Relation of visual and auditory responses to saccades. Journal of Neurophysiology 49, 12301253.Google Scholar
Hikosaka, O. & Wurtz, R. H. (1983 b). Visual and oculomotor functions of monkey substantia nigra, pars reticulata. IV. Relation of substantia nigra to superior colliculus. Journal of Neurophysiology 49, 12851301.Google Scholar
Hikosaka, O. & Wurtz, R. H. (1985). Modification of saccadic eye movements GABA-related substances. I. Effect of muscimol and bicucculine in monkey superior colliculus. Journal of Neurophysiology 53, 266291.Google Scholar
Holzman, P. S., Proctor, L. R., Levy, D. L., Yasillo, N. J., Meltzer, H. Y. & Hurt, S. W. (1974). Eye-tracking dysfunctions and schizophrenic patients and their relatives. Archives of General Psychiatry 31, 143151.Google Scholar
Jarritt, P. H. & Ell, P. J. (1984). Gamma Camera Emission Tomography: Quality Control and Clinical Applications. Current Medical Literature: London.Google Scholar
Jenkins, I. H., Passingham, R. E., Frackowiak, R. S. J. & Brooks, D. J. (1994). The effect of movement rate on cerebral activation: a study with positron emission tomography. Movement Disorders 9, suppl. 1, p. 486.Google Scholar
Kennard, C., Crawford, T. J. & Henderson, L. (1994). A pathophysiological approach to eye movement abnormalities in neurological and psychiatric disease. Journal of Neurology, Neurosurgery and Psychiatry 57, 881885.Google Scholar
Krawieka, M., Goldberg, D. & Vaughan, M. (1977). A standardized psychiatric assessment for rating chronic psychotic patients. Acta Psychiatrica Scandinavica 55, 299308.Google Scholar
Kunzle, H. (1978). An autoradiographic analysis of the efferent connections from premotor and adjacent prefrontal regions (area 6 and 9) in Macaca fascicularis. Brain Behaviour Evolution 15, 185234.Google Scholar
Kunzle, H. & Akert, K. (1977). Efferent connections of area 8 (frontal eye field) in Macaca fascicularis. A reinvestigation using the autoradiographic technique. Journal of Comparative Neurology 173, 147164.Google Scholar
Laplane, D., Degos, J. D., Baulac, M. & Gray, F. (1981). Bilateral infarction of the anterior cingulate gyri and the fornices. Report of a case. Journal of Neurological Sciences 51, 300.Google Scholar
Lasker, A. G., Zee, D. S., Hain, T. C., Folstein, S. E. & Singer, H. S. (1987). Saccades in Huntington's disease: initiation defects and distractibility. Neurology 37, 364370.Google Scholar
Lassen, N. A., Anderson, R. A., Friberg, H. & Paulson, O. B. (1988). The retention of 99m-Tc HMPAO in the human brain after intracarotid bolus injection: a kinetic analysis. Journal of Cerebral Blood Flow and Metabolism 8, 513522.Google Scholar
Lewis, S. W., Ford, R. A., Syed, G. M., Reveley, A. M. & Toone, B. K. (1992). A controlled study of 99m Tc-HMPAO single-photon emission imaging in chronic schizophrenia. Psychological Medicine 22, 2735.Google Scholar
Lueck, C. J., Tanyeri, S., Crawford, T. J., Henderson, L. & Kennard, C. (1990). Antisaccades and remembered saccades in Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry 53, 284288.Google Scholar
Mesulam, M. M. & Mufson, E. J. (1987). The insula of Reil in man and monkey. Architectonics, connectivity and function. In Cerebral Cortex 4 (ed. Jones, E. J. and Peters, A.), pp. 179226. Plenum Press: New York.Google Scholar
Nakashima, Y., Momose, T., Sano, I., Katayama, S., Nakajima, T., Niwa, S. & Matsushita, M. (1994). Cortical control of saccade in normal and schizophrenic subjects: a PET study using a task-evoked rCBF paradigm. Schizophrenia Research 12, 259264.Google Scholar
Nelson, H. & O'Connell, A. (1978). Dementia: the estimation of premorbid intelligence using the new Adult Reading Test. Cortex 14, 234244.Google Scholar
O'Driscoll, G. A., Alpert, N. M., Matthyse, S., Levy, D. & Holzman, P. S. (1994). The neural substrates of antisaccade performance implicate oculomotor circuit dysfunction in schizophrenia. Schizophrenia Research 11, 149.Google Scholar
O'Sullivan, E. P., Jenkins, I. H., Henderson, L., Kennard, C. & Brooks, D. J. (1995). The functional anatomy of remembered saccades: a PET study. Neuroreport 1995 (in the press).Google Scholar
Park, S. & Holzman, P. S. (1992). Schizophrenics show spatial working memory deficits. Archives of General Psychiatry 49, 975982.Google Scholar
Park, S. & Holzman, P. S. (1993). Association of working memory deficit and eye tracking dysfunction in schizophrenia. Schizophrenia Research 11, 5561.Google Scholar
Paus, T., Kalina, M., Patockova, L., Angerova, Y., Cerny, R., Mecir, P., Bauer, J. & Krabec, P. (1991). Medical v. lateral frontal lobe lesions and differential impairment of central-gaze fixation maintenance in man. Brain 114, 20512067.Google Scholar
Paus, T., Petrides, M., Evan, A. C. & Meyer, E. (1993). Role of the human anterior cingulate cortex in the control of oculomotor, manual, and speech responses: a positron emission tomography study. Journal of Neurophysiology 70, 453469.Google Scholar
Petit, L., Orssau, C.Tzourio, N.Salamon, G.,Mazoyer, B. & Berthoz, A. (1993). PET study of the voluntary saccadic eye movements in humans: basal ganglia-thalamocortical system and cingulate cortex involvement. Journal of Neurophysiology 69, 10091017.Google Scholar
Pierrot-Deseilligny, C. H., Rivaud, S., Gaymaud, B. & Agid, Y. (1991). Cortical control of reflexive visually-guided saccades. Brain 114, 14731485.Google Scholar
Posner, M. I., Petersen, S. E., Fox, P. T. & Raichle, M. E. (1988). Localization of cognitive operations in the human brain. Science 240, 16271631.Google Scholar
Raichle, M. E., Martin, W. R. W., Herscovitch, P., Mintun, M. A. & Markham, J. (1983). Brain blood flow measured with intravenous H215O. II. Implementation and validation. Journal of Nuclear Medicine 24, 790798.Google Scholar
Rosse, R. B., Schwartz, B. L., Kim, S. Y. & Deutsch, S. I. (1993). Correlation between antisaccades and Wisconsin card sorting test performance in schizophrenia. American Journal of Psychiatry 150, 333335.Google Scholar
Sabatini, U., Chollet, F., Rascol, O., Celsis, P., Rascol, A., Lenzi, L. & Marc-Vergnes, J. P. (1993). Effect of side and rate of stimulation on cerebral blood flow changes in motor areas during finger movement in humans. Journal of Cerebral Blood Flow and Metabolism 13, 639645.CrossRefGoogle Scholar
Schwartz, M. L. & Goldman-Rakic, P. S. (1982). Single neurons have axon collaterals to ipsilateral and contralateral cortex in fetal and adult primates. Nature 299, 154156.Google Scholar
Selemon, L. D. & Goldman-Rakic, P. S. (1988). Common cortical and subcortical targets of the dorsolateral prefrontal and posterior parietal cortices in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behaviour. Journal of Neuroscience 8, 40494068.Google Scholar
Showers, M. J. C. & Lauer, E. W. (1961). Somatovisceral motor patterns in the insula. Journal of Comparative Neurology 117, 107116.Google Scholar
Stanton, G. B., Goldberg, M. E. & Bruce, C. J. (1988 a). Frontal eye field efferents in the macaque monkey. II. Topography of terminal fields in midbrain and pons. Journal of Comparative Neurology 271, 493506.Google Scholar
Stanton, G. B., Goldberg, M. E. & Bruce, C. J. (1988 b). Frontal eye field efferents in the macaque monkey. I. Subcortical pathways and topography of striatal and thalamic terminal fields. Journal of Comparative Neurology 271, 473492.Google Scholar
Sugar, O., Chusid, J. G. & French, J. D. (1948). A second motor cortex in the monkey (Macaca mulatta). Journal of Neuropathology and Experimental Neurology 7, 182189.Google Scholar
Talairach, J. & Tournoux, P. (1988). Co-planar Stereotaxic Atlas of the Human Brain. Thieme: Stuttgart.Google Scholar
Thaker, G. K., Nguyen, J. A. & Tamminga, C. A. (1989). Increased saccadic distractibility in tardive dyskinesia: functional evidence for subcortical GABA dysfunction. Biological Psychiatry 25, 4559.Google Scholar
Weinberger, D. R., Berman, K. F. & Zec, R. F. (1986). Physiologic function of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Archives of General Psychiatry 43, 114124Google Scholar
Yeterian, E. H. & Van Hoesen, F. W. (1978). Cortico-striate projections in the rhesus monkey: the organization of certain Cortico-caudate connections. Brain Research 139, 4363.Google Scholar
Zee, D. S. (1984). Ocular motor control: the cerebral control of saccadic eye movements. In Neuro-Ophthalmology 3 (ed. Lessell, S. and van Dalen, J. T. W.), pp. 141156. Elsevier: Amsterdam.Google Scholar