Abstract
Positron emission tomography (PET) and the deoxyglucose method were used to measure cerebral metabolism in 14 normals and 13 schizophrenics at rest and during performance of simple and complex finger-movement sequences. The normals, but not the schizophrenics, showed significant metabolic activation in mesial frontal and contralateral sensorimotor and premotor regions during the complex movement. The relative metabolism of schizophrenics was significantly lower than normal in frontal regions and higher than normal in thalamus and basal ganglia underall scanning conditions. The results suggest that schizophrenics may have a brain dysfunction which limits their capacity to produce a focal metabolic response to stimulation in several functionally distinct brain regions.
Similar content being viewed by others
References
American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders (DSM-III-R), 3rd edn, revised. American Psychiatric Association, Washington DC
Bartlett EJ, Brodie JD, Wolf AP, Christman DR, Laska E, Meissner M (1988) Reproducibility of cerebral glucose metabolic measurements in resting human subjects. J Cereb Blood Flow Metab 8:502–512
Bartlett E, Brodie JD, Simkowitz P, Dewey SL, Rusinek H, Wolf AP, Fowler JS, Volkow ND, Smith G, Wolkin A, Cancro R (1994) Effects of a haloperidol challenge on regional cerebral glucose utilization in normal human subjects. Am J Psychiatry 151:681–686
Baxter LR, Phelps ME, Mazziotta JC, Schwartz JM, Gerner RH, Selin CE, Sumida RM (1985) Cerebral metabolic rates for glucose in mood disorders. Arch Gen Psychiatry 42:441–447
Baxter LB, Schwartz JM, Phelps ME, Mazziotta JC, Guze BH, Selin CE, Gerner RH, Sumida RM (1989) Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch Gen Psychiatry 46:243–250
Bleuler E (1950) Dementia Praecox or the group of schizophrenias. New York International Press, New York
Bogerts B, Meertz E, Schonfeldt-Bausch R (1985) Basal ganglia and limbic system pathology in schizophrenia: a morphometric study of brain volume and shrinkage. Arch Gen Psychiatry 42: 784–791
Bogerts B, Ashtari M, Degreef G, Alvir JMJ, Bilder MR, Lieberman JA (1990) Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia. Psychiatry Res 35:1–13
Brown R, Colter N, Corsellis JA et al. (1986) Postmortem evidence of structural brain changes in schizophrenia: differences in brain weight, temporal horn area and parahippocampal gyrus compared with affective disorder. Arch Gen Psychiatry 43: 36–42
Buchsbaum MS, Haier RJ (1987) Functional and anatomical brain imaging: impact on schizophrenia research. Schizophr Bull 13:115–132
Buchsbaum MS, DeLisi LE, Holcomb HH, Cappelletti J, King AC, Johnson J, Hazlett E, Dowling-Zimmerman S, Post RM, Morihisa J, Carpenter W, Cohen R, Pickar D, Weinberger DR, Margolin R, Kessler RM (1984) Antero-posterior gradients in cerebral glucose use in schizophrenia and affective disorders. Arch Gen Psychiatry 41:1159–1166
Buchsbaum MS, Wu J, DeLisi LE, Holcomb H, Kessler R, Johnson J, King AC, Hazlett E, Langston K, Post RM (1986) Frontal cortex and basal ganglia metabolic rates assessed by positron emission tomography with [18F]2-deoxyglucose in affective illness. J Affective Disord 10:137–152
Buchsbaum MS, Nuechterlein KH, Haier RJ, Wu J, Sicotte N, Hazlett E, Asarnow R, Potkin S, Guich SM (1990) Glucose metabolic rates in normals and schizophrenics during the continuous performance test assessed by positron emission tomography. Br J Psychiatry 156:216–227
Buchsbaum MS, Potkin SG, Siegel BV, Lohr J, Katz M, Gottschalk LA, Gulasekaram B, Marshall JF, Lottenberg S, Teng CY, Abel L, Plon L, Bunney W Jr (1992) Striatal metabolic rate and clinical response to neuroleptics in schizophrenia. Arch Gen Psychiatry 49:966–974
Cohen RM, Semple WE, Gross M, Nordahl TE, DeLisi LE, Holcomb HH, King AC, Morihisa JM, Pickar D (1987) Dysfunction in a prefrontal substrate of sustained attention in schizophrenia. Life Sci 40:2031–2039
Cohen RM, Semple WE, Gross M, Nordahl TE (1988) From symptom to illness: delineating the pathophysiology of schizophrenia with PET. Schizophr Bull 14:169–176
Colombo C, Abbruzzese M, Livian S, Scotti G, Locatelli M, Bonfanti A, Scarone S (1993) Memory functions and temporal-limbic morphology in schizophrenia. Psychiatry Res 50:45–56
Creese I, Burt DR, Snyder SH (1984) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 225:728–731
Duara R, Gross-Glenn K, Barker WW, Apicella A, Loewenstein D, Boothe T (1986) Behavioral activation and the variability of cerebral glucose metabolic measurements. J Cereb Blood Flow Metab 83:1140–1144
Evarts EV (1981) Functional studies of the motor cortex. In: Schmitt FO, Worden FG, Alderman G, Dennis SG (eds) The organization of the cerebral cortex. MIT Press, Cambridge, Mass
Falkai P, Bogerts B, Rozumek M (1988) Limbic pathology in schizophrenia: the entorhinal regions—a morphometric study. Biol Psychiatry 24:515–521
Fox PT, Raichle ME, Mintun MA, Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462–463
Ghez C (1985) Cortical control of voluntary movement. In: Kandel ER, Schwartz JH (eds) Principles of neural science, 2nd edn. Elsevier, New York, pp 487–500
Ginsberg MD, Dietrich WD, Busto R (1987) Coupled forebrain increases of local cerebral glucose utilization and blood flow during physiological stimulation of a somatosensory pathway in the rat: demonstration by double-label autoradiography. Neurology 37:11–19
Ginsberg MD, Chang JY, Kelley RE, Yoshii F, Barker WW, Ingenito G, Boothe TE (1988) Increases in both cerebral glucose utilization and blood flow during execution of a somatosensory task. Ann Neurol 23:152–160
Goldberg G (1985) Structure and function of the supplementary motor area: review and hypothesis. Behav Brain Sci 8:567–616
Gur RE, Resnick SM, Alavi A, Gur RC, Caroff S, Dann D, Silver FL, Saykin AJ, Chawluck JB, Kushner M, Reivich M (1987) Regional brain function in schizophrenia: I. A positron emission study. Arch Gen Psychiatry 44:119–125
Guenther W, Moser E, Mueller-Spahn F, Vefele K, Buell U, Hippius H (1986) Pathological cerebral blood flow during motor function in schizophrenic and endogenous depressed patients. Biol Psychiatry 21:889–899
Guenther W, Petsch R, Steinberg R, Moser E, Streck P, Heller H, Kurtz G, Hippius H (1991) Brain dysfunction during motor activation and corpus callosum alterations in schizophrenia measured by cerebral blood flow and magnetic resonance imaging. Biol Psychiatry 29:535–555
Guenther W, Alper K, Bartlett E, Barouche F, Wolf A, Dewey S, Henn F, Riedel R, Klages U, Brodie J, John R (1993) Simultaneous electroencephalogram mapping and positron emission tomography in chronic schizophrenia: preliminary results in neuroleptic treated patients. In: Maurer K (ed) Imaging of the brain and related fields. Springer, Berlin Heidelberg New York, pp 325–333
Guy W (1976) ECDEU assessment manual for psychopharmacology, revised DHEW Pub. No. (ADM) 76-338. National Institute of Mental Health, Rockville, MD
Huang S-C, Phelps ME, Hoffman EJ, Sideris K, Selin CJ, Kuhl DE (1980) Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol 238:E69-E82
Jakob H, Beckmann H (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 65:303–326
Kirch DG, Weinberger DR (1986) Anatomical neuropathology in schizophrenia: post-mortem findings. In: Nasrallah HA, Weinberger DR (eds) The neurology of schizophrenia. Handbook of schizophrenia, vol 1. Elsevier, Amsterdam, pp 325–348
Kishimoto H, Kuwahara H, Ohno S, Takazu O, Hama Y, Sato C, Ishii T, Nomura Y, Fujita H, Miyauchi T, Matsushita M, Yokoi S, Iio M (1987) Three subtypes of chronic schizophrenia identified using11C-glucose positron emission tomography. Psychiatry Res 21:285–292
Kraepelin E (1971) Dementia praecox and paraphrenia. RE Krieger, New York
MacGregor RR, Fowler JS, Wolf A, Shive CY, Lade RE, Wan CN (1978) A synthesis of 2-deoxy-D-(1-11C)glucose for regional metabolism studies. J Nucl Med 22:800–803
Matsui T, Hirano H (1978) An atlas of the human brain for computerized tomography, Igaku-Shoin, Tokyo
Metz JT, Johnson MD, Pliskin NH, Luchins DJ (1994) Maintenance of training effects on the Wisconsin card sorting test by patients with schizophrenia or affective disorders. Am J Psychiatry 151:120–122
Nasrallah HA, Olson SC, McCalley-Whitters M et al. (1986) Cerebral ventricular enlargement in schizophrenia. Arch Gen Psychiatry 43:157–159
Oldfield RD (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113
Overall JE, Gorham DR (1988) Introduction: the brief psychiatric rating scale: recent developments in ascertainment and scaling. Psychopharmacology Bull 24:97–99
Pakkenberg B (1987) Post-mortem study of chronic schizophrenic brains. Br J Psychiatry 151:744–752
Pakkenberg B (1992) Stereological quantitation of human brains from normal and schizophrenic individuals. Acta Neurol Scand 137 (Suppl):20–33
Phelps ME, Huang S-C, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with [18F]-2-fluoro-2-d-deoxyglucose: validation of method. Ann Neurol 6:371–388
Pycock CJ, Kerwin RW, Carter CJ (1980) Effects of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats. Nature 286:74–77
Reivich M, Alavi A, Wolf A, Greenberg JH, Fowler J, Christman D, MacGregor R, Jones SC, London J, Shiue C, Yonekura Y (1982) Use of 2-deoxy-D-[11C]glucose for the determination of local cerebral glucose metabolism in humans: variation within and between subjects. J Cereb Blood Flow Metab 2:307–319
Reivich M, Alavi A, Wolf A, Fowler J, Russell J, Arnett C, MacGregor RR, Shiue CY, Atkins H, Anand A, Dann R, Greenberg JH (1985) Glucose metabolic rate kinetic model parameter determination in humans: the lumped constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J Cereb Blood Flow Metab 5:179–192
Roland PE, Larsen B, Lassen NA, Shinhoj E (1980) Supplementary motor area and other cortical areas in organization of voluntary movements in man. J Neurophysiol 43:118–136
Roland PE, Meyer E, Shibasaki T, Yamamoto YL, Thompson CJ (1982) Regional cerebral blood flow changes in cortex and basal ganglia during voluntary movements in normal human volunteers. J Neurophysiol 48:467–480
Schiebel AB, Kovelman JA (1981) Disorientation of the hippocampal pyramidal cell and its processes in the schizophrenia patient. Biol Psychiatry 16:101–102
Schlyer DJ, Volkow ND, Fowler JS, Wolf AP, Shiue CY, Dewey SL, Bendriem B, Logan J, Raulli R, Hitzeman R, Brodie J, Alavi AA, McGregor RR (1992) Regional distribution and kinetics of haloperidol binding in human brain: a PET study with18FHaloperidol. Synapse 11:10–19
Seidman LJ, Yurgelun-Todd D, Kremen WS, Woods BT, Goldstein JM, Faraone SV, Tsuang MT (1994) Relationship of prefrontal and temporal lobe MRI measures to neuropsychological performance in chronic schizophrenia. Biol Psychiatry 35: 225–246
Siegel BV, Buchsbaum MS, Bunney W Jr, Gottschalk LA, Haier RJ, Lohr JB, Lottenberg S, Najafi A, Nuechterlein KH, Potkin SG, Wu JC (1993) Cortico-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients. Am J Psychiatry 150:1325–1336
Sokoloff L, Reivich M, Kennedy C, Des Rosiers CS, Patlak CS, Pettigrew KD, Sakurada O, Sinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916
Suddath RL, Casanova MF, Goldberg TE, Daniel DG, Kelsoe JR Jr, Weinberger DR (1989) Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. Am J Psychiatry 146:464–472
Suddath RL, Christison GW, Torrey EF, Casanova MF, Weinberger DR (1990) Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med 322:789–794
Szechtman H, Nahmias C, Garnett S, Firnau G, Brown GM, Kaplan RD, Cleghorn JM (1988) Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia. Arch Gen Psychiatry 45:523–532
Takeuchi K, Takigawa M, Fukuzako H, Hokazono Y, Hirakawa K, Fukuzako T, Ueyama K, Fujimoto T, Matsumoto K (1994) Correlation of third ventricular enlargement and EEG slow wave activity in schizophrenic patients. Psychiatry Res 55:1–11
Volkow ND, Brodie JD, Wolf AP, Gomez-Mont F, Cancro R, Van Gelder P, Russell JAG, Overall J (1986) Brain organization in schizophrenia. J Cereb Blood Flow Metab 6:441–446
Weinberger DR, Berman KF (1988) Speculation on the meaning of cerebral metabolic hypofrontality in schizophrenia. Schizophr Bull 14:157–168
Weinberger DR, Berman KF, Zec RF (1986) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia: I. Regional cerebral blood flow (rCBF) evidence. Arch Gen Psychiatry 43:114–125
Weinberger DR, Berman KF, Illowsky BP (1988) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia, III: a new cohort and evidence for a monoaminergic mechanism. Arch Gen Psychiatry 45:609–615
Wilkinson L (1988) Systat: the system for statistics. Systat, Inc., Evanston, IL
Wolkin A, Jaeger J, Brodie JD, Wolf AP, Fowler J, Rotrosen J, Gomez-Mont F, Cancro R (1985) Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography. Am J Psychiatry 142:564–571
Wolkin A, Sanfilipo M, Wolf AP, Angrist B, Brodie JD, Rotrosen J (1992) Negative symptoms and hypofrontality in chronic schizophrenia. Arch Gen Psychiatry 49:959–965
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Guenther, W., Brodie, J.D., Bartlett, E.J. et al. Diminished cerebral metabolic response to motor stimulation in schizophrenics: a PET study. Eur Arch Psychiatry Clin Nuerosci 244, 115–125 (1994). https://doi.org/10.1007/BF02191884
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02191884