Cortical grey matter volume and sensorimotor gating in schizophrenia

Veena Kumari, Dominic Fannon, Mark A Geyer, Preethi Premkumar, Elena Antonova, Andrew Simmons, Elizabeth Kuipers, Veena Kumari, Dominic Fannon, Mark A Geyer, Preethi Premkumar, Elena Antonova, Andrew Simmons, Elizabeth Kuipers

Abstract

Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable tool to study the known inability of a large proportion of individuals with schizophrenia to effectively screen out irrelevant sensory input. The cortico-striato-pallido-thalamic circuitry is thought to be responsible for modulation of PPI in experimental animals. The involvement of this circuitry in human PPI is supported by observations of deficient PPI in a number of neuropsychiatric disorders that are characterised by abnormalities at some level in this circuitry, and findings of recent functional neuroimaging studies in healthy participants. The current study sought to investigate the structural neural correlates of PPI in a sample of 42 stable male outpatients with schizophrenia. Participants underwent magnetic resonance imaging (MRI) at 1.5T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimised volumetric voxel-based morphometry implemented in SPM2 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120msec) to regional grey matter (GM) volumes. Significant positive correlations were obtained between PPI and GM volume in the dorsolateral prefrontal, middle frontal and the orbital/medial prefrontal cortices. Our findings are consistent with (a) previous suggestions of susceptibility of PPI to cognitive processes controlled in a 'top down' manner by the cortex and (b) the hypothesis that compromised neural resources in the frontal cortex contribute to reduced PPI in schizophrenia.

Figures

Fig. 1
Fig. 1
Group correlation map thresholded at p < .001 in SPM2 showing positive associations between PPI and GM volumes in the left prefrontal cortex (1a), right middle frontal cortex (1b), and the orbital/medial prefrontal cortex (1c) imposed on the SPM2 single brain. Associated scatter plots (1a–c) show the relationships between the percentage GM volume at the maxima voxel (Y-axis) in the localised region and PPI (X-axis) for each participant. Left hemisphere is shown on the left. Colours represent voxel level t-values and strength of the correlation with PPI.

References

    1. Andreasen N.C., O'leary D.S., Flaum M., Nopoulos P., Watkins G.L., Boles Ponto L.L., Hichwa R.D. Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naive patients. Lancet. 1997;349:1730–1734.
    1. Antonova E., Sharma T., Morris R., Kumari V. The relationship between brain structure and neurocognition in schizophrenia: a selective review. Schizophrenia Research. 2004;70:117–145.
    1. Ashburner J., Friston K.J. Nonlinear spatial normalization using basis functions. Human Brain Mapping. 1999;7:254–266.
    1. Ashburner J., Friston K.J. Voxel-based morphometry – the methods. NeuroImage. 2000;11:805–821.
    1. Banich M.T., Milham M.P., Atchley R.A., Cohen N.J., Webb A., Wszalek T., Kramer A.F., Liang Z., Barad V., Gullett D., Shah C., Brown C. Prefrontal regions play a predominant role in imposing an attentional ‘set’: evidence from fMRI. Cognitive Brain Research. 2000;10:1–9.
    1. Banich M.T., Milham M.P., Atchley R., Cohen N.J., Webb A., Wszalek T., Kramer A.F., Liang Z.P., Wright A., Shenker J., Magin R. fMRI studies of Stroop tasks reveal unique roles of anterior and posterior brain systems in attentional selection. Journal of Cognitive Neuroscience. 2000;12:988–1000.
    1. Blumenthal T.D. Short lead interval startle modification. In: Dawson M.E., Schell A.M., Böhmelt A.H., editors. Startle Modification: Implications for Neuroscience, Cognitive Science and Clinical Science. Cambridge University Press; Cambridge: 1999. pp. 51–71.
    1. Bitsios P., Giakoumaki S.G. Relationship of prepulse inhibition of the startle reflex to attentional and executive mechanisms in man. International Journal of Psychophysiology. 2005;55:229–241.
    1. Bitsios P., Giakoumaki S.G., Theou K., Frangou S. Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males. Neuropsychologia. 2006;44:2494–2499.
    1. Blasi G., Goldberg T.E., Weickert T., Das S., Kohn P., Zoltick B., Bertolino A., Callicott J.H., Weinberger D.R., Mattay V.S. Brain regions underlying response inhibition and interference monitoring and suppression. European Journal of Neuroscience. 2006;23:1658–1664.
    1. Braff D.L. Information processing and attention dysfunctions in schizophrenia. Schizophrenia Bulletin. 1993;19:233–259.
    1. Braff D.L., Geyer M.A., Swerdlow N.R. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology. 2001;156:234–258.
    1. Braff D.L., Light G.A., Ellwanger J., Sprock J., Swerdlow N.R. Female schizophrenia patients have prepulse inhibition deficits. Biological Psychiatry. 2005;57:817–820.
    1. Braff D.L., Stone C., Callaway E., Geyer M., Glick I., Bali L. Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology. 1978;15:339–343.
    1. Bunge S.A., Ochsner K.N., Desmond J.E., Glover G.H., Gabrieli J.D. Prefrontal regions involved in keeping information in and out of mind. Brain. 2001;124:2074–2086.
    1. Butler R.W., Jenkins M.A., Geyer M.A., Braff D.L. Wisconsin card sorting deficits and diminished sensorimotor gating in a discrete subgroup of schizophrenic patients. In: Tamminga C.A., Schulz S.C., editors. vol. 1. Raven Press; New York: 1991. pp. 163–168. (Schizophrenia Research: Advances in Neuropsychiatry and Psychopharmacology).
    1. Dawson M.E., Schell A.M., Swerdlow N.E., Filion D.L. Cognitive, clinical, and neurophysiological implications of startle modification. In: Lang P.J., Simons R.F., Balaban M., editors. Attention and Orienting: Sensory and Motivational Processes. Lawrence Erlbaum Associates; Mahwah, NJ: 1997. pp. 257–279.
    1. Ettinger U., Kumari V., Chitnis X.A., Corr P.J., Sumich A.L., Rabe-Hesketh S., Crawford T.J., Sharma T. Relationship between brain structure and saccadic eye movements in healthy humans. Neuroscience Letters. 2002;328:225–228.
    1. Ettinger U., Kumari V., Chitnis X.A., Corr P.J., Crawford T.J., Fannon D.G., O'ceallaigh S., Sumich A.L., Doku V.C., Sharma T. Volumetric neural correlates of antisaccade eye movements in first-episode psychosis. American Journal of Psychiatry. 2004;161:1918–1921.
    1. Ettinger U., Antonova E., Crawford T.J., Mitterschiffthaler M., Sharma T., Kumari V. Structural neural correlates of prosaccade and antisaccade eye movements in healthy humans. NeuroImage. 2005;24:487–494.
    1. Filion D.L., Dawson M.E., Schell A.M. The psychological significance of human startle eyeblink modification: a review. Biological Psychology. 1998;47:1–43.
    1. Filion D.L., Poje A.B. Selective and nonselective attention effects on prepulse inhibition of startle: a comparison of task and no-task protocols. Biological Psychology. 2003;64:283–296.
    1. First M.B., Spitzer R.L., Gibbon M., Williams J.B.W. New York State Psychiatric Institute, Biometrics Research; New York: 1995. Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-P), Version 2.
    1. Gaser C., Schlaug G. Brain structures differ between musicians and non-musicians. Journal of Neuroscience. 2003;23:9240–9245.
    1. Garver D.L., Holcomb J.A., Christensen J.D. Cerebral cortical gray expansion associated with two second generation antipsychotics. Biological Psychiatry. 2005;58:62–66.
    1. Geyer M.A., Swerdlow N.R., Mansbach R.S., Braff D.L. Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Research Bulletin. 1990;25:485–498.
    1. Geyer M.A., Krebs-Thomson K., Braff D.L., Swerdlow N.R. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology. 2001;156:117–154.
    1. Giakoumaki S.G., Bitsios P., Frangou S. The level of prepulse inhibition in healthy individuals may index cortical modulation of early information processing. Brain Research. 2006;1078:168–170.
    1. Good C.D., Johnsrude I.S., Ashburner J., Henson R.N., Friston K.J., Frackowiak R.S. A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage. 2001;14:21–36.
    1. Graham F.K. The more or less startling effects of weak prestimuli. Psychophysiology. 1975;12:238–248.
    1. Hazeltine E., Bunge S.A., Scanlon M.D., Gabrieli J.D. Material-dependent and material-independent selection processes in the frontal and parietal lobes: an event-related fMRI investigation of response competition. Neuropsychologia. 2003;41:1208–1217.
    1. Hazlett E.A., Buchsbaum M.S. Sensorimotor gating deficits and hypofrontality in schizophrenia. Frontiers in Bioscience. 2001;6:D1069–D1072.
    1. Hazlett E.A., Buchsbaum M.S., Haznedar M.M., Singer M.B., Germans M.K., Schnur D.B., Jimenez E.A., Buchsbaum B.R., Troyer B.T. Prefrontal cortex glucose metabolism and startle eyeblink modification abnormalities in unmedicated schizophrenia patients. Psychophysiology. 1998;35:186–198.
    1. Jennings P.D., Schell A.M., Filion D.L., Dawson M.E. Tracking early and late stages of information processing: contributions of startle eyeblink reflex modification. Psychophysiology. 1996;33:148–155.
    1. Karper L.P., Freeman G.K., Grillon C., Morgan CA Charney D.S., III, Krystal J.H. Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis. Journal of Neuropsychiatry and Clinical Neurosciences. 1996;8:60–66.
    1. Kay S.R., Fishbein A., Olper L.A. The positive and negative syndrome scale. Schizophrenia Bulletin. 1987;13:261–276.
    1. Kumari V., Antonova E., Geyer M.A., Ffytche D., Williams S.C., Sharma T. A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics. International Journal of Neuropsychopharmacology. 2007;10:463–477.
    1. Kumari V., Antonova E., Zachariah E., Galea A., Aasen I., Ettinger U., Mitterschiffthaler M.T., Sharma T. Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans. NeuroImage. 2005;26:1052–1058.
    1. Kumari V., Gray J.A., Geyer M.A., Ffytche D., Mitterschiffthaler M.T., Vythelingum G.N., Williams S.C.R., Simmons A., Sharma T. Neural correlates of prepulse inhibition in normal and schizophrenic subjects: a functional MRI Study. Psychiatry Research: Neuroimaging. 2003;122:99–113.
    1. Kumari V., Ettinger U. Prepulse inhibition deficits in schizophrenia: static or amenable to treatment? In: Lang M.V., editor. Progress in Schizophrenia Research. Nova Publishers; New York: 2005.
    1. Kumari V., Sharma T. Effects of typical and typical antipsychotics on prepulse inhibition in schizophrenia: a critical evaluation of current evidence and directions for future research. Psychopharmacology. 2002;162:97–101.
    1. Kumari V., Soni W., Sharma T. Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia. Human Psychopharmacology. 2001;16:321–326.
    1. Kurachi M. Pathogenesis of schizophrenia: part I. Symptomatology, cognitive characteristics and brain morphology. Psychiatry and Clinical Neurosciences. 2003;57:3–8.
    1. Kurachi M. Pathogenesis of schizophrenia: part II. Temporo-frontal two-step hypothesis. Psychiatry and Clinical Neurosciences. 2003;57:9–15.
    1. Liddle P.F., Friston K.J., Frith C.D., Hirsch S.R., Jones T., Frackowiak R.S. Patterns of cerebral blood flow in schizophrenia. British Journal of Psychiatry. 1992;160:179–186.
    1. Lieberman J.A., Tollefson G.D., Charles C., Zipursky R., Sharma T., Kahn R.S., Keefe R.S., Green A.I., Gur R.E., McEvoy J., Perkins D., Hamer R.M., Gu H., Tohen M., HGDH Study Group Antipsychotic drug effects on brain morphology in first-episode psychosis. Archives of General Psychiatry. 2005;62:361–370.
    1. Maguire E.A., Gadian D.G., Johnsrude I.S., Good C.D., Ashburner J., Frackowiak R.S., Frith C.D. Navigation-related structural change in the hippocampi of taxi drivers. Proceedings of the National Academy of Sciences of the United States of America. 2000;97:4398–4403.
    1. MacDonald A.W., 3rd, Cohen J.D., Stenger V.A., Carter C.S. Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science. 2000;288:1835–1838.
    1. Meincke U., Mörth D., Voß T., Thelen B., Geyer M.A., Gouzoulis-Mayfrank E. Prepulse inhibition of the acoustically evoked startle reflex in patients with an acute schizophrenic psychosis – a longitudinal study. European Archives of Psychiatry and Clinical Neuroscience. 2004;254:415–421.
    1. Nelson H.E., Willison J. 2nd ed. NFER-Nelson; Windsor: 1991. National Adult Reading Test (NART) Test Manual.
    1. Perry W., Geyer M.A., Braff D.L. Sensorimotor gating and thought disturbance measured in close temporal proximity in schizophrenic patients. Archives of General Psychiatry. 1999;56:277–281.
    1. Perry W., Braff D.L. Information-processing deficits and thought disorder in schizophrenia. American Journal of Psychiatry. 1994;151:363–367.
    1. Peterson B.S., Kane M.J., Alexander G.M., Lacadie C., Skudlarski P., Leung H.C., May J., Gore J.C. An event-related functional MRI study comparing interference effects in the Simon and Stroop tasks. Cognitive Brain Research. 2002;13:427–440.
    1. Sanfilipo M., Lafargue T., Rusinek H., Arena L., Loneragan C., Lautin A., Rotrosen J., Wolkin A. Cognitive performance in schizophrenia: relationship to regional brain volumes and psychiatric symptoms. Psychiatry Research. 2002;116:1–23.
    1. Schell A.M., Wynn J.K., Dawson M.E., Sinaii N., Niebala C.B. Automatic and controlled attentional processes in startle eyeblink modification: effects of habituation of the prepulse. Psychophysiology. 2000;37:409–417.
    1. Shenton M.E., Dickey C.C., Frumin M., McCarley R.W. A review of MRI findings in schizophrenia. Schizophrenia Research. 2001;49:1–52.
    1. Sowell E.R., Thompson P.M., Holmes C.J., Batth R., Jernigan T.L., Toga A.W. Localizing age-related changes in brain structure between childhood and adolescence using statistical parametric mapping. NeuroImage. 1999;9:587–597.
    1. Swerdlow N.R., Light G.A., Cadenhead K.S., Sprock J., Hsieh M.H., Braff D.L. Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function. Archives of General Psychiatry. 2006;63:1325–1335.
    1. Swerdlow N.R., Geyer M.A. Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophrenia Bulletin. 1998;24:285–301.
    1. Swerdlow N.R., Geyer M.A., Braff D.L. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology. 2001;156:194–215.
    1. Wechsler D. The Psychological Corporation; New York/San Antonio, TX: 1999. Wechsler Abbreviated Scale of Intelligence.
    1. Weiss E.M., Siedentopf C., Golaszewski S., Mottaghy F.M., Hofer A., Kremser C., Felber S., Fleischhacker W.W. Brain activation patterns during a selective attention test – a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia. Psychiatry Research. 2007;154:31–40.
    1. Wood S.J., Berger G.E., Lambert M., Conus P., Velakoulis D., Stuart G.W., Desmond P., McGorry P.D., Pantelis C. Prediction of functional outcome 18 months after a first psychotic episode: a proton magnetic resonance spectroscopy study. Archives of General Psychiatry. 2006;63:969–976.

Source: PubMed

3
订阅