99mTc-ECD SPECT at rest and activation in young patients with schizophrenia

Anna Nocuń 1 , Justyna Pawęzka 2 , Beata Chrapko 1 , Kinga Szymona 2 , Agata Smoleń 3 , and Hanna Karakuła 2
  • 1 Department of Nuclear Medicine, Medical University of Lublin, 20-954, Lublin, Poland
  • 2 Department of Psychiatry, Medical University of Lublin, 20-954, Lublin, Poland
  • 3 Department of Mathematics and Biostatistics, Medical University of Lublin, 20-954, Lublin, Poland


The aim of the study was to localize brain parts involved in executive functions in patients with schizophrenia by means of 99mTc-ECD single photon emission computed tomography (SPECT) with 3-dimensional automatic software. We examined 12 men with schizophrenia (mean age 29±3.9 years). Brain perfusion SPECT was performed at rest and during Wisconsin Card Sorting Test (WCST). Two types of quantitative SPECT analysis were applied; voxel-based and volume of interest (VOI)-based. With voxel-based approach, rest and activation SPECT were compared. VOI-based analysis allowed for correlation of regional cerebral blood flow (rCBF) in 20 VOIs with WCST scores. In voxel-based analysis, the patterns of rCBF decrease and increase after activation varied between patients, with combinations of different brain regions involved. In VOI-based approach, the only statistically significant difference between activation and rest was rCBF decrease in the left basal ganglia (p=0.028). The thalami and right temporal cortex correlated with the greatest number of WCST scores, followed by left occipital cortex and left cerebellum. In conclusion, our results suggest that patterns of WCST activation and deactivation vary between patients with schizophrenia. Among the network of involved brain structures, right temporal cortex and thalami appear to play the major role.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • [1] Royall D.R., Lauterbach E.C., Cummings J.L., Reeve A., Rummans T.A., Kaufer D.I., et al., Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association, J. Neuropsychiatry Clin. Neurosci., 2002, 14, 377–405 http://dx.doi.org/10.1176/appi.neuropsych.14.4.377

  • [2] Volz H.P., Gaser C., Häger F., Rzanny R., Mentzel H.J., Kreitschmann-Andermahr I., et al., Brain activation during cognitive stimulation with the Wisconsin Card Sorting Test—a functional MRI study on healthy volunteers and schizophrenics, Psychiatry Res., 1997, 75, 145–157 http://dx.doi.org/10.1016/S0925-4927(97)00053-X

  • [3] Parellada E., Catafau A.M., Bernardo M., Lomeña F., Catarineu S., González-Monclús E., The resting and activation issue of hypofrontality: a single photon emission computed tomography study in neurolepticnaive and neuroleptic-free schizophrenic female patients, Biol. Psychiatry, 1998, 44, 787–790 http://dx.doi.org/10.1016/S0006-3223(98)00057-2

  • [4] González-Hernández J.A., Pita-Alcorta C., Cedeño I., Bosch-Bayard J., Galán-Garcia L., Scherbaum W.A., et al., Wisconsin Card Sorting Test synchronizes the prefrontal, temporal and posterior association cortex in different frequency ranges and extensions, Hum. Brain. Mapp., 2002, 17, 37–47 http://dx.doi.org/10.1002/hbm.10051

  • [5] Barcelo F., Escera C., Corral M.J., Periáñez J.A., Task switching and novelty processing activate a common neural network for cognitive control, J. Cogn. Neurosci., 2006, 8, 1734–1748 http://dx.doi.org/10.1162/jocn.2006.18.10.1734

  • [6] Ciçek M., Nalçaci E., Interhemispheric asymmetry of EEG alpha activity at rest and during the Wisconsin Card Sorting Test: relations with performance, Biol. Psychol., 2001, 58, 75–88 http://dx.doi.org/10.1016/S0301-0511(01)00103-X

  • [7] Lie C.H., Specht K., Marshall J.C., Fink G.R., Using fMRI to decompose the neural processes underlying the Wisconsin Card Sorting Test, Neuroimage, 2006, 30, 1038–1049 http://dx.doi.org/10.1016/j.neuroimage.2005.10.031

  • [8] Konishi S., Hayashi T., Uchida I., Kikyo H., Takahashi E., Miyashita Y., Hemispheric asymmetry in human lateral prefrontal cortex during cognitive set shifting, Proc. Natl. Acad. Sci. U S A, 2002, 99, 7803–7808 http://dx.doi.org/10.1073/pnas.122644899

  • [9] Rogers R.D., Andrews T.C., Grasby P.M., Brooks D.J., Robbins T.W., Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans, J. Cogn. Neurosci., 2000, 12, 142–162 http://dx.doi.org/10.1162/089892900561931

  • [10] Monchi O., Petrides M., Petre V., Worsley K., Dagher A., Wisconsin Card Sorting revisited: distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging, J. Neurosci., 2001, 21, 7733–7741

  • [11] Tien A.Y., Schlaepfer T.E., Orr W., Pearlson G.D., SPECT brain blood flow changes with continuous ligand infusion during previously learned WCST performance, Psychiatry Res., 1998, 82, 47–52 http://dx.doi.org/10.1016/S0925-4927(98)00003-1

  • [12] Catafau A.M., Parellada E., Lomeña F.J., Bernardo M., Pavía J., Ros D., et al., Prefrontal and temporal blood flow in schizophrenia: resting and activation technetium-99m-HMPAO SPECT patterns in young neuroleptic-naive patients with acute disease, J. Nucl. Med., 1994, 35, 35–941

  • [13] Ortuño F., Moreno-Iñiguez M., Millán M., Soutullo C.A., Bonelli R.M., Cortical blood flow during rest and Wisconsin Card Sorting Test performance in schizophrenia, Wien. Med. Wochenschr., 2006, 156, 179–184 http://dx.doi.org/10.1007/s10354-005-0248-3

  • [14] Moreno-Iñiguez M., Ortuño F., Bonelli R.M., Millán M., Soutullo C.A., Cervera-Enguiz S., Perseverative error in schizophrenia: correlation with cortical blood flow by SPECT, Actas Esp. Psiquiatr., 2007, 35, 20–28

  • [15] Liu Z., Tam W.C., Xie Y., Zhao J., The relationship between regional cerebral blood flow and the Wisconsin Card Sorting Test in negative schizophrenia, Psychiatry Clin. Neurosci., 2002, 56, 3–7 http://dx.doi.org/10.1046/j.1440-1819.2002.00924.x

  • [16] Zhao J., He X., Liu Z., Yang D., The effects of clozapine on cognitive function and regional cerebral blood flow in the negative symptom profile schizophrenia, Int. J. Psychiatry Med., 2006, 36, 171–181 http://dx.doi.org/10.2190/1AA0-UW9Q-1CNK-3E2N

  • [17] Kapucu O.L., Nobili F., Varrone A., Booij J., Vander Borght T., Någren K., et al., EANM procedure guideline for brain perfusion SPECT using (99m) Tc-labelled radiopharmaceuticals, version 2, Eur. J. Nucl. Med. Mol. Imaging, 2009, 36, 2093–2102 http://dx.doi.org/10.1007/s00259-009-1266-y

  • [18] Andreasen N.C., Scale for the Assessment of Negative Symptoms (SANS). Iowa City, University of Iowa, 1982

  • [19] Andreasen N.C., Scale for the Assessment of Positive Symptoms (SAPS). Iowa City, University of Iowa, 1984

  • [20] Gracia Marco R., Aguilar Garcia-Iturrospe E.J., Fernandez Lopez L., Cejas Mendez M.R., Herreros Rodriguez O., Diaz Ramirez A., et al., Hypofrontality in schizophrenia: influence of normalization methods, Prog. Neuropsychopharmacol. Biol. Psychiatry, 1997, 21, 1239–56 http://dx.doi.org/10.1016/S0278-5846(97)00161-9

  • [21] Wobrock T., Ecker U.K., Scherk H., Schneider-Axmann T., Falkai P, Gruber O., Cognitive impairment of executive function as a core symptom of schizophrenia, World J. Biol. Psychiatry, 2009, 10, 442–451 http://dx.doi.org/10.1080/15622970701849986

  • [22] Barceló F., The Madrid card sorting test (MCST): a task switching paradigm to study executive attention with event-related potentials, Brain Res. Brain Res. Protoc., 2003, 11, 27–37 http://dx.doi.org/10.1016/S1385-299X(03)00013-8

  • [23] Toone B.K., Okocha C.I., Sivakumar K., Syed G.M., Changes in regional cerebral blood flow due to cognitive activation among patients with schizophrenia, Br. J. Psychiatry, 2000, 177, 222–228 http://dx.doi.org/10.1192/bjp.177.3.222

  • [24] Ortuño F., Arbizu J., Soutullo C.A., Bonelli R.M., Is there a cortical blood flow redistribution pattern related with perseverative error in schizophrenia?, Psychiatr. Danub., 2009, 21, 283–289

  • [25] Yang Y.K., Chen C.C., Lee I.H., Chou Y.H., Chiu N.T., Jeffries K.J., et al., Association between regional cerebral blood flow and eye-tracking performance and the Wisconsin Card Sorting Test in schizophrenics: a single photon emission computed tomography study, Psychiatry Res., 2003, 123, 37–48 http://dx.doi.org/10.1016/S0925-4927(03)00021-0

  • [26] Takeda N., Terada S., Sato S., Honda H., Yoshida H., Kishimoto Y., et al., Wisconsin card sorting test and brain perfusion imaging in early dementia, Dement Geriatr. Cogn. Disord., 2010, 29, 21–27 http://dx.doi.org/10.1159/000261645

  • [27] Lacerda A.L., Dalgalarrondo P., Caetano D., Camargo E.E., Etchebehere E.C., Soares J.C., Elevated thalamic and prefrontal regional cerebral blood flow in obsessive-compulsive disorder: a SPECT study, Psychiatry Res., 2003, 123, 125–134 http://dx.doi.org/10.1016/S0925-4927(03)00061-1

  • [28] Weinberger D.R., Hippocampal injury and chronic schizophrenia, Biol. Psychiatry, 1991, 29, 509–511 http://dx.doi.org/10.1016/0006-3223(91)90278-T

  • [29] Gur R.E., Turetsky B.I., Loughead J., Snyder W., Kohler C., Elliott M., et al., Visual attention circuitry in schizophrenia investigated with oddball eventrelated functional magnetic resonance imaging, Am. J. Psychiatry, 2007, 164, 442–449 http://dx.doi.org/10.1176/appi.ajp.164.3.442

  • [30] Friston K.J., Frith C.D., Schizophrenia: a disconnection syndrome?, Clin. Neurosci., 1995, 3, 89–97

  • [31] Wolf D.H., Gur R.C., Valdez J.N., Loughead J., Elliott M.A., Gur R.E., et al., Alterations of fronto-temporal connectivity during word encoding in schizophrenia, Psychiatry Res., 2007, 154, 221–232 http://dx.doi.org/10.1016/j.pscychresns.2006.11.008

  • [32] Crossley N.A., Mechelli A., Fusar-Poli P., Broome M.R., Matthiasson P., Johns L.C., et al., Superior temporal lobe dysfunction and frontotemporal dysconnectivity in subjects at risk of psychosis and in first-episode psychosis, Hum. Brain Mapp., 2009, 30, 4129–4137 http://dx.doi.org/10.1002/hbm.20834


Journal + Issues