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Preattentional and attentional cognitive deficits as targets for treating schizophrenia

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Abstract

Background and rationale

Pharmacotherapy of schizophrenia has traditionally targeted positive psychotic symptoms. An emerging view is that developing medications that improve cognition in schizophrenia patients is a major step forward in achieving better functional outcome. The cognitive deficits that are often observed in schizophrenia can be assessed using (1) neuropsychological tests; and (2) neurophysiological tests, the topic of this article. These neurophysiological measures cover a spectrum from automatic preattentional to attention-dependent processes.

Objectives

This article focuses on cognitive deficits that appear to be promising targets for a new “third generation” of medications that may be used to treat schizophrenia and other patients with specific deficits in cognition and functioning. We discuss the possible use of the following six measures of preattentional and attention-dependent cognitive deficits: mismatch negativity, P50 event-related potential suppression, prepulse inhibition of the startle response, P300 event-related potential, continuous performance task performance, and oculomotor antisaccade performance.

Conclusions

The use of preattentional and attention-dependent measures offer unique opportunities to improve our armamentarium of pharmacologic strategies for the treatment of cognitive deficits in schizophrenia patients. This review illustrates the usefulness of these measures as targets for existing and new antipsychotic medications that will potentially (1) characterize the cognitive deficits that occur in schizophrenia patients and (2) assess medication-related improvement on these measures and the potential associated improvement in functional outcome.

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References

  • Adler LE, Pachtman E, Franks RD, Pecevich M, Waldo MC, Freedman R (1982) Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry 17:639–654

    CAS  PubMed  Google Scholar 

  • Adler LE, Hoffer LJ, Griffith J, Waldo MC, Freedman R (1992) Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry 32:607–616

    CAS  PubMed  Google Scholar 

  • Adler LE, Hoffer LD, Wiser A, Freedman R (1993) Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry 150:1856–1861

    CAS  PubMed  Google Scholar 

  • Alho K (1995) Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes. Ear Hear 16:38–51

    CAS  PubMed  Google Scholar 

  • Alho K, Woods DL, Algazi A, Knight RT, Naatanen R (1994) Lesions of frontal cortex diminish the auditory mismatch negativity. Electroencephalogr Clin Neurophysiol 91:353–362

    Article  CAS  PubMed  Google Scholar 

  • Alho K, Winkler I, Escera C, Huotilainen M, Virtanen J, Jaaskelainen IP, Pekkonen E, Ilmoniemi RJ (1998) Processing of novel sounds and frequency changes in the human auditory cortex: magnetoencephalographic recordings. Psychophysiology 35:211–224

    Article  CAS  PubMed  Google Scholar 

  • Baldeweg T, Klugman A, Gruzelier JH, Hirsch SR (2002) Impairment in frontal but not temporal components of mismatch negativity in schizophrenia. Int J Psychophysiol 43:111–122

    Article  PubMed  Google Scholar 

  • Bharath S, Gangadhar BN, Janakiramaiah N (2000) P300 in family studies of schizophrenia: review and critique. Int J Psychophysiol 38:43–54

    Article  CAS  PubMed  Google Scholar 

  • Blackwood DH, St Clair DM, Muir WJ, Duffy JC (1991) Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees. Arch Gen Psychiatry 48:899–909

    Google Scholar 

  • Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ (2001) Schizophrenia and affective disorders—cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Am J Hum Genet 69:428–433

    Article  CAS  PubMed  Google Scholar 

  • Bleuler E (1950) Dementia praecox. International Universities, Madison, Conn.

  • Bolino F, Di Michele V, Di Cicco L, Manna V, Daneluzzo E, Casacchia M (1994) Sensorimotor gating and habituation evoked by electro-cutaneous stimulation in schizophrenia. Biol Psychiatry 36:670–679

    CAS  PubMed  Google Scholar 

  • Boutros NN, Zouridakis G, Overall J (1991) Replication and extension of P50 findings in schizophrenia. Clin Electroencephalogr 22:40–45

    CAS  PubMed  Google Scholar 

  • Bowen L, Wallace CJ, Glynn SM, Nuechterlein KH, Lutzker JR, Kuehnel TG (1994) Schizophrenic individuals’ cognitive functioning and performance in interpersonal interactions and skills training procedures. J Psychiatr Res 28:289–301

    Article  CAS  PubMed  Google Scholar 

  • Braff DL (1993) Information processing and attention dysfunctions in schizophrenia. Schizophr Bull 19:233–259

    CAS  PubMed  Google Scholar 

  • Braff DL, Freedman R (2002) Endophenotypes in studies of the genetics of schizophrenia. In: Davis KL, Charney DS, Coyle JT, Nemeroff C (eds) Neuropsychopharmacology: the fifth generation of progress. Lippincott, Williams & Wilkins, Philadelphia, pp 703–716

  • Braff DL, Geyer MA (1990) Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 47:181–188

    CAS  PubMed  Google Scholar 

  • Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15:339–343

    CAS  PubMed  Google Scholar 

  • Braff DL, Grillon C, Geyer MA (1992) Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49:206–215

    CAS  PubMed  Google Scholar 

  • Braff DL, Swerdlow NR, Geyer MA (1999) Symptom correlates of prepulse inhibition deficits in male schizophrenic patients. Am J Psychiatry 156:596–602

    CAS  PubMed  Google Scholar 

  • Braff DL, Geyer MA, Light GA, Sprock J, Perry W, Cadenhead KS, Swerdlow NR (2001a) Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophr Res 49:171–178

    CAS  PubMed  Google Scholar 

  • Braff DL, Geyer MA, Swerdlow NR (2001b) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 156:234–258

    CAS  PubMed  Google Scholar 

  • Buchsbaum MS, Nuechterlein KH, Haier RJ, Wu J, Sicotte N, Hazlett E, Asarnow R, Potkin S, Guich S (1990) Glucose metabolic rate in normals and schizophrenics during the Continuous Performance Test assessed by positron emission tomography. Br J Psychiatry 156:216–227

    CAS  PubMed  Google Scholar 

  • Butler RW, Jenkins M, Geyer MA, Braff DL (1991) Wisconsin card sorting deficits and diminished sensory motor gating in a discrete subgroup of schizophrenia patients. In: Tamminga CA, Schulz SC (eds) Advances in neuropsychiatry and psychopharmacology, vol 1, schizophrenia research. Raven, New York

  • Cadenhead KS, Geyer MA, Braff DL (1993) Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder. Am J Psychiatry 150:1862–1867

    CAS  PubMed  Google Scholar 

  • Cadenhead KS, Light GA, Geyer MA, Braff DL (2000a) Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder. Am J Psychiatry 157:55–59

    Article  CAS  PubMed  Google Scholar 

  • Cadenhead KS, Swerdlow NR, Shafer KM, Diaz M, Braff DL (2000b) Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits. Am J Psychiatry 157:1660–1668

    CAS  PubMed  Google Scholar 

  • Cadenhead KS, Light GA, Geyer MA, McDowell JE, Braff DL (2002) Neurobiological measures of schizotypal personality disorder: defining an inhibitory endophenotype? Am J Psychiatry 159:869–871

    Article  PubMed  Google Scholar 

  • Callaway E, Naghdi S (1982) An information processing model for schizophrenia. Arch Gen Psychiatry 39:339–347

    CAS  PubMed  Google Scholar 

  • Carter RJ, Lione LA, Humby T, Mangiarini L, Mahal A, Bates GP, Dunnett SB, Morton AJ (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington’s disease mutation. J Neurosci 19:3248–3257

    CAS  PubMed  Google Scholar 

  • Ceponiene R, Cheour M, Naatanen R (1998) Interstimulus interval and auditory event-related potentials in children: evidence for multiple generators. Electroencephalogr Clin Neurophysiol 108:345–354

    Article  CAS  PubMed  Google Scholar 

  • Clementz BA, Reid SA, McDowell JE, Cadenhead KS (1995) Abnormality of smooth pursuit eye movement initiation: specificity to the schizophrenia spectrum? Psychophysiology 32:130–134

    CAS  PubMed  Google Scholar 

  • Clementz BA, Geyer MA, Braff DL (1997) P50 suppression among schizophrenia and normal comparison subjects: a methodological analysis. Biol Psychiatry 41:1035–1044

    Article  CAS  PubMed  Google Scholar 

  • Clementz BA, Geyer MA, Braff DL (1998) Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. Am J Psychiatry 155:1691–1694

    CAS  PubMed  Google Scholar 

  • Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Earlbaum, Mahwah, N.J.

  • Cornblatt BA, Keilp JG (1994) Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophr Bull 20:31–46

    CAS  PubMed  Google Scholar 

  • Cornblatt BA, Risch NJ, Faris G, Friedman D, Erlenmeyer-Kimling L (1988) The Continuous Performance Test, identical pairs version (CPT-IP): I. New findings about sustained attention in normal families. Psychiatry Res 26:223–238

    Google Scholar 

  • Cornblatt BA, Lenzenweger MF, Erlenmeyer-Kimling L (1989) The continuous performance test, identical pairs version: II. Contrasting attentional profiles in schizophrenic and depressed patients. Psychiatry Res 29:65–85

    Google Scholar 

  • Cornblatt B, Obuchowski M, Roberts S, Pollack S, Erlenmeyer-Kimling L (1999) Cognitive and behavioral precursors of schizophrenia. Dev Psychopathol 11:487–508

    Article  CAS  PubMed  Google Scholar 

  • Crawford TJ, Haeger B, Kennard C, Reveley MA, Henderson L (1995) Saccadic abnormalities in psychotic patients. I. Neuroleptic-free psychotic patients. Psychol Med 25:461–471

    CAS  PubMed  Google Scholar 

  • Cullum CM, Harris JG, Waldo MC, Smernoff E, Madison A, Nagamoto HT, Griffith J, Adler LE, Freedman R (1993) Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia. Schizophr Res 10:131–141

    Article  CAS  PubMed  Google Scholar 

  • Deouell LY, Bentin S, Giard MH (1998) Mismatch negativity in dichotic listening: evidence for interhemispheric differences and multiple generators. Psychophysiology 35:355–365

    CAS  PubMed  Google Scholar 

  • Fabiani M, Karis D, Donchin E (1986) P300 and recall in an incidental memory paradigm. Psychophysiology 23:298–308

    CAS  PubMed  Google Scholar 

  • Fischer C, Morlet D, Bouchet P, Luaute J, Jourdan C, Salord F (1999) Mismatch negativity and late auditory evoked potentials in comatose patients. Clin Neurophysiol 110:1601–1610

    Article  CAS  PubMed  Google Scholar 

  • Fischer C, Morlet D, Giard M (2000) Mismatch negativity and N100 in comatose patients. Audiol Neurootol 5:192–197

    Article  CAS  PubMed  Google Scholar 

  • Franks RD, Adler LE, Waldo MC, Alpert J, Freedman R (1983) Neurophysiological studies of sensory gating in mania: comparison with schizophrenia. Biol Psychiatry 18:989–1005

    CAS  PubMed  Google Scholar 

  • Freedman R, Adler LE, Waldo MC, Pachtman E, Franks RD (1983) Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients. Biol Psychiatry 18:537–551

    CAS  PubMed  Google Scholar 

  • Freedman R, Adler LE, Gerhardt GA, Waldo M, Baker N, Rose GM, Drebing C, Nagamoto H, Bickford-Wimer P, Franks R (1987) Neurobiological studies of sensory gating in schizophrenia. Schizophr Bull 13:669–678

    CAS  PubMed  Google Scholar 

  • Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, Polymeropoulos M, Holik J, Hopkins J, Hoff M, Rosenthal J, Waldo MC, Reimherr F, Wender P, Yaw J, Young DA, Breese CR, Adams C, Patterson D, Adler LE, Kruglyak L, Leonard S, Byerley W (1997) Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 94:587–592

    CAS  PubMed  Google Scholar 

  • Friedman D, Vaughan HG Jr, Erlenmeyer-Kimling L (1982) Cognitive brain potentials in children at risk for schizophrenia: preliminary findings. Schizophr Bull 8:514–531

    CAS  PubMed  Google Scholar 

  • Frodl-Bauch T, Kathmann N, Moller HJ, Hegerl U (1997) Dipole localization and test–retest reliability of frequency and duration mismatch negativity generator processes. Brain Topogr 10:3–8

    Article  CAS  PubMed  Google Scholar 

  • Fukushima J, Morita N, Fukushima K, Chiba T, Tanaka S, Yamashita I (1990) Voluntary control of saccadic eye movements in patients with schizophrenic and affective disorders. J Psychiatr Res 24:9–24

    Google Scholar 

  • Gene-Cos N, Ring HA, Pottinger RC, Barrett G (1999) Possible roles for mismatch negativity in neuropsychiatry. Neuropsychiatry Neuropsychol Behav Neurol 12:17–27

    CAS  PubMed  Google Scholar 

  • Geyer MA, Braff DL, Swerdlow NR (1999) Startle-response measures of information processing in animals: relevance to schizophrenia, Chap. 8. In: Whalen MHaRE (ed) Animal models of human emotion and cognition. APA, Washingtion D.C., pp 103–116

  • Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156:117–154

    CAS  PubMed  Google Scholar 

  • Giard MH, Perrin F, Pernier J, Bouchet P (1990) Brain generators implicated in the processing of auditory stimulus deviance: a topographic event-related potential study. Psychophysiology 27:627–640

    CAS  PubMed  Google Scholar 

  • Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153:321–330

    CAS  PubMed  Google Scholar 

  • Green JF, King DJ (1998) The effects of chlorpromazine and lorazepam on abnormal antisaccade and no-saccade distractibility. Biol Psychiatry 44:709–715

    CAS  Google Scholar 

  • Green MF, Braff DL (2001) Translating the basic and clinical cognitive neuroscience of schizophrenia to drug development and clinical trials of antipsychotic medications. Biol Psychiatry 49:374–384

    Article  CAS  PubMed  Google Scholar 

  • Green MF, Kern RS, Braff DL, Mintz J (2000) Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophr Bull 26:119–136

    CAS  PubMed  Google Scholar 

  • Grillon C, Ameli R, Courchesne E, Braff DL (1991) Effects of task relevance and attention on P3 in schizophrenic patients. Schizophr Res 4:11–21

    CAS  PubMed  Google Scholar 

  • Heidrich A, Strik WK (1997) Auditory P300 topography and neuropsychological test performance: evidence for left hemispheric dysfunction in schizophrenia. Biol Psychiatry 41:327–335

    Article  CAS  PubMed  Google Scholar 

  • Ito M, Kanno M, Mori Y, Niwa S (1997) Attention deficits assessed by Continuous Performance Test and Span of Apprehension Test in Japanese schizophrenic patients. Schizophr Res 23:205–211

    Article  CAS  PubMed  Google Scholar 

  • Jeon YW, Polich J (2003) Meta-analysis of P300 and schizophrenia: patients, paradigms, and practical implications. Psychophysiology 40:684–701

    Article  PubMed  Google Scholar 

  • Jessen F, Fries T, Kucharski C, Nishimura T, Hoenig K, Maier W, Falkai P, Heun R (2001) Amplitude reduction of the mismatch negativity in first-degree relatives of patients with schizophrenia. Neurosci Lett 309:185–188

    Article  CAS  PubMed  Google Scholar 

  • Johnson R Jr, Pfefferbaum A, Kopell BS (1985) P300 and long-term memory: latency predicts recognition performance. Psychophysiology 22:497–507

    PubMed  Google Scholar 

  • Judd LL, McAdams L, Budnick B, Braff DL (1992) Sensory gating deficits in schizophrenia: new results. Am J Psychiatry 149:488–493

    CAS  PubMed  Google Scholar 

  • Kane NM, Curry SH, Rowlands CA, Manara AR, Lewis T, Moss T, Cummins BH, Butler SR (1996) Event-related potentials—neurophysiological tools for predicting emergence and early outcome from traumatic coma. Intensive Care Med 22:39–46

    CAS  PubMed  Google Scholar 

  • Karper LP, Freeman GK, Grillon C, Morgan CA III, Charney DS, Krystal JH (1996) Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis. J Neuropsychiatr Clin Neurosci 8:60–66

    CAS  PubMed  Google Scholar 

  • Kasai K, Nakagome K, Itoh K, Koshida I, Hata A, Iwanami A, Fukuda M, Hiramatsu KI, Kato N (1999) Multiple generators in the auditory automatic discrimination process in humans. Neuroreport 10:2267–2271

    CAS  PubMed  Google Scholar 

  • Kathmann N, Frodl-Bauch T, Hegerl U (1999) Stability of the mismatch negativity under different stimulus and attention conditions. Clin Neurophysiol 110:317–323

    Article  CAS  PubMed  Google Scholar 

  • Kim MS, Kang SS, Youn T, Kang DH, Kim JJ, Kwon JS (2003) Neuropsychological correlates of P300 abnormalities in patients with schizophrenia and obsessive-compulsive disorder. Psychiatry Res 123:109–123

    Google Scholar 

  • Kraepelin E (1971) Dementia praecox and paraphrenia. R.E. Krieger, Huntington, N.Y.

  • Kramer AF, Strayer DL (1988) Assessing the development of automatic processing: an application of dual-task and event-related brain potential methodologies. Biol Psychol 26:231–267

    Google Scholar 

  • Kujala T, Kallio J, Tervaniemi M, Naatanen R (2001) The mismatch negativity as an index of temporal processing in audition. Clin Neurophysiol 112:1712–1719

    Article  CAS  PubMed  Google Scholar 

  • Kumari V, Gray JA, Geyer MA, ffytche D, Soni W, Mitterschiffthaler MT, Vythelingum GN, Simmons A, Williams SC, Sharma T (2003) Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects. Psychiatry Res 122:99–113

    Article  PubMed  Google Scholar 

  • Light GA, Braff DL (1998) The “incredible shrinking” P50 event-related potential. Biol Psychiatry 43:918–920

    Article  CAS  PubMed  Google Scholar 

  • Light GA, Braff DL (2003) Sensory gating deficits in schizophrenia: can we parse the effects of medication, nicotine use, and changes in clinical status? Clin Neurosci Res 3:47–54

    Article  CAS  Google Scholar 

  • Light GA, Braff DL (in submission) Mismatch negativity deficits are associated with poor functioning in schizophrenia patients. Re-submitted to Arch Gen Psych

  • Lipska BK, Swerdlow NR, Geyer MA, Jaskiw GE, Braff DL, Weinberger DR (1995) Neonatal excitotoxic hippocampal damage in rats causes post-pubertal changes in prepulse inhibition of startle and its disruption by apomorphine. Psychopharmacology 122:35–43

    CAS  PubMed  Google Scholar 

  • Lohr JB, Braff DL (2003) The value of referring to recently introduced antipsychotics as “second generation.” Am J Psychiatry 160:1371–1372

    Google Scholar 

  • McDowell JE, Clementz BA (1997) The effect of fixation condition manipulations on antisaccade performance in schizophrenia: studies of diagnostic specificity. Exp Brain Res 115:333–344

    CAS  PubMed  Google Scholar 

  • McDowell JE, Myles-Worsley M, Coon H, Byerley W, Clementz BA (1999) Measuring liability for schizophrenia using optimized antisaccade stimulus parameters. Psychophysiology 36:138–141

    Article  CAS  PubMed  Google Scholar 

  • Michie PT (2001) What has MMN revealed about the auditory system in schizophrenia? Int J Psychophysiol 42:177–194

    Article  CAS  PubMed  Google Scholar 

  • Michie PT, Innes-Brown H, Todd J, Jablensky AV (2002) Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders. Biol Psychiatry 52:749–758

    Article  PubMed  Google Scholar 

  • Morlet D, Bouchet P, Fischer C (2000) Mismatch negativity and N100 monitoring: potential clinical value and methodological advances. Audiol Neurootol 5:198–206

    Article  CAS  PubMed  Google Scholar 

  • Muller BW, Juptner M, Jentzen W, Muller SP (2002) Cortical activation to auditory mismatch elicited by frequency deviant and complex novel sounds: a PET study. Neuroimage 17:231–239

    Article  CAS  PubMed  Google Scholar 

  • Naatanen R (1992) Attention and brain function. Lawrence Erlbaum, Mahwah, N.J.

  • Naatanen R (2003) Mismatch negativity: clinical research and possible applications. Int J Psychophysiol 48:179–188

    Article  PubMed  Google Scholar 

  • Naatanen R, Alho K (1995) Generators of electrical and magnetic mismatch responses in humans. Brain Topogr 7:315–320

    CAS  PubMed  Google Scholar 

  • Naatanen R, Paavilainen P, Alho K, Reinikainen K, Sams M (1989) Do event-related potentials reveal the mechanism of the auditory sensory memory in the human brain? Neurosci Lett 98:217–221

    PubMed  Google Scholar 

  • Nagamoto HT, Adler LE, Waldo MC, Griffith J, Freedman R (1991) Gating of auditory response in schizophrenics and normal controls. Effects of recording site and stimulation interval on the P50 wave. Schizophr Res 4:31–40

    Article  CAS  PubMed  Google Scholar 

  • Nuechterlein KH (1991) Vigilance in schizophrenia and related disorders. In: Steinhauer S, Zubin J, Gruzelier JH (eds) Handbook of schizophrenia, neuropsychology, psychophysiology and information processing. Elsevier, Amsterdam, pp 397–433

  • Nuechterlein KH, Parasuraman R, Jiang Q (1983) Visual sustained attention: image degradation produces rapid sensitivity decrement over time. Science 220:327–329

    CAS  PubMed  Google Scholar 

  • Nuechterlein KH, Dawson ME, Gitlin M, Ventura J, Goldstein MJ, Snyder KS, Yee CM, Mintz J (1992) Developmental processes in schizophrenic disorders: longitudinal studies of vulnerability and stress. Schizophr Bull 18:387–425

    CAS  PubMed  Google Scholar 

  • Nuechterlein KH, Asarnow RF, Subotnik KL, Fogelson DL, Ventura J, Torquato R, Dawson ME (1998) Neurocognitive vulnerability factors for schizophrenia: convergence across genetic risk studies and longitudinal trait/state studies. In: Lenzenweger MF, Dworkin RH (eds) Origins and development of schizophrenia: advances in experimental psychopathology. American Psychological Association, Washington D.C., pp 299–327

  • Oades RD, Zerbin D, Dittmann-Balcar A, Eggers C (1996) Auditory event-related potential (ERP) and difference-wave topography in schizophrenic patients with/without active hallucinations and delusions: a comparison with young obsessive-compulsive disorder (OCD) and healthy subjects. Int J Psychophysiol 22:185–214

    Article  CAS  PubMed  Google Scholar 

  • Oades RD, Dittmann-Balcar A, Zerbin D, Grzella I (1997) Impaired attention-dependent augmentation of MMN in non-paranoid vs paranoid schizophrenic patients: a comparison with obsessive-compulsive disorder and healthy subjects. Biol Psychiatry 41:1196–1210

    Article  CAS  PubMed  Google Scholar 

  • Orzack MH, Kornetsky C (1966) Attention dysfunction in chronic schizophrenia. Arch Gen Psychiatry 14:323–326

    CAS  PubMed  Google Scholar 

  • Pakkenberg B (1990) Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 47:1023–1028

    CAS  PubMed  Google Scholar 

  • Pallanti S, Quercioli L, Pazzagli A (1999) Basic symptoms and P300 abnormalities in young schizophrenic patients. Comp Psychiatry 40:363–371

    CAS  PubMed  Google Scholar 

  • Palmer BW, Heaton RK, Paulsen JS, Kuck J, Braff D, Harris MJ, Zisook S, Jeste DV (1997) Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology 11:437–446

    CAS  PubMed  Google Scholar 

  • Palmer BW, Heaton RK, Gladsjo JA, Evans JD, Patterson TL, Golshan S, Jeste DV (2002) Heterogeneity in functional status among older outpatients with schizophrenia: employment history, living situation, and driving. Schizophr Res 55:205–215

    Article  PubMed  Google Scholar 

  • Park HJ, Kwon JS, Youn T, Pae JS, Kim JJ, Kim MS, Ha KS (2002) Statistical parametric mapping of LORETA using high density EEG and individual MRI: application to mismatch negativities in schizophrenia. Hum Brain Map 17:168–178

    Article  PubMed  Google Scholar 

  • Pekkonen E, Rinne T, Naatanen R (1995) Variability and replicability of the mismatch negativity. Electroencephalogr Clin Neurophysiol 96:546–554

    Article  CAS  PubMed  Google Scholar 

  • Penney JB Jr, Young AB (1983) Speculations on the functional anatomy of basal ganglia disorders. Annu Rev Neurosci 6:73–94

    PubMed  Google Scholar 

  • Perry W, Braff DL (1994) Information-processing deficits and thought disorder in schizophrenia. Am J Psychiatry 151:363–367

    CAS  PubMed  Google Scholar 

  • Perry W, Geyer MA, Braff DL (1999) Sensorimotor gating and thought disturbance measured in close temporal proximity in schizophrenic patients. Arch Gen Psychiatry 56:277–281

    CAS  PubMed  Google Scholar 

  • Polich J, Herbst KL (2000) P300 as a clinical assay: rationale, evaluation, and findings. Int J Psychophysiol 38:3–19

    Article  CAS  PubMed  Google Scholar 

  • Polich J, Comerchero MD (2003) P3a from visual stimuli: typicality, task, and topography. Brain Topogr 15:141–152

    Article  PubMed  Google Scholar 

  • Ross RG, Olincy A, Harris JG, Radant A, Adler LE, Freedman R (1998) Anticipatory saccades during smooth pursuit eye movements and familial transmission of schizophrenia. Biol Psychiatry 44:690–697

    Article  CAS  PubMed  Google Scholar 

  • Ross RG, Olincy A, Harris JG, Radant A, Hawkins M, Adler LE, Freedman R (1999) Evidence for bilineal inheritance of physiological indicators of risk in childhood-onset schizophrenia. Am J Med Genet 88:188–199

    Article  CAS  PubMed  Google Scholar 

  • Rosvold HE, Mirsky A, Sarason I, Bransome ED Jr, Beck LH (1956) A continuous performance test of brain damage. J Consult Psychol 20:343–350

    PubMed  Google Scholar 

  • Roth WT, Cannon EH (1972) Some features of the auditory evoked response in schizophrenics. Arch Gen Psychiatry 27:466–471

    CAS  PubMed  Google Scholar 

  • Rutschmann J, Cornblatt B, Erlenmeyer-Kimling L (1977) Sustained attention in children at risk for schizophrenia. Report on a continuous performance test. Arch Gen Psychiatry 34:571–575

    CAS  PubMed  Google Scholar 

  • Rutschmann J, Cornblatt B, Erlenmeyer-Kimling L (1986) Sustained attention in children at risk for schizophrenia: findings with two visual continuous performance tests in a new sample. J Abnorm Child Psychol 14:365–385

    CAS  PubMed  Google Scholar 

  • Sabri M, Campbell KB (2002) The effects of digital filtering on mismatch negativity in wakefulness and slow-wave sleep. J Sleep Res 11:123–127

    Article  PubMed  Google Scholar 

  • Saccuzzo DP, Braff DL (1980) Associative cognitive dysfunction in schizophrenia and old age. J Nerv Ment Dis 168:41–45

    CAS  PubMed  Google Scholar 

  • Saitoh O, Niwa S, Hiramatsu K, Kameyama T, Rymar K, Itoh K (1984) Abnormalities in late positive components of event-related potentials may reflect a genetic predisposition to schizophrenia. Biol Psychiatry 19:293–303

    CAS  PubMed  Google Scholar 

  • Sato Y, Yabe H, Todd J, Michie P, Shinozaki N, Sutoh T, Hiruma T, Nashida T, Matsuoka T, Kaneko S (2003) Impairment in activation of a frontal attention-switch mechanism in schizophrenic patients. Biol Psychol 62:49–63

    Article  PubMed  Google Scholar 

  • Schairer KS, Gould HJ, Pousson MA (2001) Source generators of mismatch negativity to multiple deviant stimulus types. Brain Topogr 14:117–130

    Article  CAS  PubMed  Google Scholar 

  • Schall U, Catts SV, Karayanidis F, Ward PB (1999) Auditory event-related potential indices of fronto-temporal information processing in schizophrenia syndromes: valid outcome prediction of clozapine therapy in a three-year follow-up. Int J Neuropsychopharmacol 2:83–93

    Article  PubMed  Google Scholar 

  • Schreiber H, Stolz-Born G, Kornhuber HH, Born J (1992) Event-related potential correlates of impaired selective attention in children at high risk for schizophrenia. Biol Psychiatry 32:634–651

    Article  CAS  PubMed  Google Scholar 

  • Schwarzkopf SB, Lamberti JS, Smith DA (1993) Concurrent assessment of acoustic startle and auditory P50 evoked potential measures of sensory inhibition. Biol Psychiatry 33:815–828

    PubMed  Google Scholar 

  • See JE, Howe SR, Warm JS, Dember WN (1995) Meta-analysis of the sensitivity decrement in vigilance. Psychol Bull 117:230–249

    Article  Google Scholar 

  • Seidman LJ, Van Manen KJ, Turner WM, Gamser DM, Faraone SV, Goldstein JM, Tsuang MT (1998) The effects of increasing resource demand on vigilance performance in adults with schizophrenia or developmental attentional/learning disorders: a preliminary study. Schizophr Res 34:101–112

    CAS  PubMed  Google Scholar 

  • Shajahan PM, O’Carroll RE, Glabus MF, Ebmeier KP, Blackwood DH (1997) Correlation of auditory “oddball” P300 with verbal memory deficits in schizophrenia. Psychol Med 27:579–586

    Article  CAS  PubMed  Google Scholar 

  • Sharma T, Kumari V, Zachariah E, Das M, Ettinger U, Soni W (2001) Inhibition of acoustic startle response by unilateral and bilateral prestimulation in unaffected siblings of patients with schizophrenia. Biol Psychiatry 49:28S

    Article  Google Scholar 

  • Shelley AM, Ward PB, Catts SV, Michie PT, Andrews S, McConaghy N (1991) Mismatch negativity: an index of a preattentive processing deficit in schizophrenia. Biol Psychiatry 30:1059–1062

    Article  CAS  PubMed  Google Scholar 

  • Shinozaki N, Yabe H, Sato Y, Hiruma T, Sutoh T, Nashida T, Matsuoka T, Kaneko S (2002) The difference in mismatch negativity between the acute and post-acute phase of schizophrenia. Biol Psychol 59:105–119

    Article  PubMed  Google Scholar 

  • Siegel C, Waldo M, Mizner G, Adler LE, Freedman R (1984) Deficits in sensory gating in schizophrenic patients and their relatives. Evidence obtained with auditory evoked responses. Arch Gen Psychiatry 41:607–612

    CAS  PubMed  Google Scholar 

  • Siegel BV Jr, Buchsbaum MS, Bunney WE Jr, Gottschalk LA, Haier RJ, Lohr JB, Lottenberg S, Najafi A, Nuechterlein KH, Potkin SG et al. (1993) Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients. Am J Psychiatry 150:1325–1336

    PubMed  Google Scholar 

  • Siegel BV Jr, Nuechterlein KH, Abel L, Wu JC, Buchsbaum MS (1995) Glucose metabolic correlates of continuous performance test performance in adults with a history of infantile autism, schizophrenics, and controls. Schizophr Res 17:85–94

    Article  PubMed  Google Scholar 

  • Souza VB, Muir WJ, Walker MT, Glabus MF, Roxborough HM, Sharp CW, Dunan JR, Blackwood DH (1995) Auditory P300 event-related potentials and neuropsychological performance in schizophrenia and bipolar affective disorder. Biol Psychiatry 37:300–310

    Article  CAS  PubMed  Google Scholar 

  • Sutton S, Braren M, Zubin J, John ER (1965) Evoked-potential correlates of stimulus uncertainty. Science 150:1187–1188

    CAS  PubMed  Google Scholar 

  • Swerdlow NR, Geyer MA (1998) Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull 24:285–301

    CAS  PubMed  Google Scholar 

  • Swerdlow NR, Koob GF (1987) Dopamine, schizophrenia, mania, and depression: toward a unified hypothesis of cortico-stratio-pallido-thalamic function. Behav Brain Sci 10:197–245

    Google Scholar 

  • Swerdlow NR, Braff DL, Taaid N, Geyer MA (1994a) Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 51:139–154

    CAS  PubMed  Google Scholar 

  • Swerdlow NR, Zisook D, Taaid N (1994b) Seroquel (ICI 204,636) restores prepulse inhibition of acoustic startle in apomorphine-treated rats: similarities to clozapine. Psychopharmacology 114:675–678

    Google Scholar 

  • Swerdlow NR, Paulsen J, Braff DL, Butters N, Geyer MA, Swenson MR (1995) Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington’s disease. J Neurol Neurosurg Psychiatry 58:192–200

    CAS  PubMed  Google Scholar 

  • Swerdlow NR, Taaid N, Oostwegel JL, Randolph E, Geyer MA (1998a) Towards a cross-species pharmacology of sensorimotor gating: effects of amantadine, bromocriptine, pergolide and ropinirole on prepulse inhibition of acoustic startle in rats. Behav Pharmacol 9:389–396

    CAS  PubMed  Google Scholar 

  • Swerdlow NR, Varty GB, Geyer MA (1998b) Discrepant findings of clozapine effects on prepulse inhibition of startle: is it the route or the rat? Neuropsychopharmacology 18:50–56

    Article  CAS  PubMed  Google Scholar 

  • Swerdlow NR, Geyer MA, Braff DL (2001) Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology 156:194–215

    CAS  PubMed  Google Scholar 

  • Tiitinen H, May P, Reinikainen K, Naatanen R (1994) Attentive novelty detection in humans is governed by pre-attentive sensory memory. Nature 372:90–92

    Article  CAS  PubMed  Google Scholar 

  • Towey JP, Tenke CE, Bruder GE, Leite P, Friedman D, Liebowitz M, Hollander E (1994) Brain event-related potential correlates of overfocused attention in obsessive-compulsive disorder. Psychophysiology 31:535–543

    CAS  PubMed  Google Scholar 

  • Turetsky BI, Cannon TD, Gur RE (2000) P300 subcomponent abnormalities in schizophrenia: III. Deficits in unaffected siblings of schizophrenic probands. Biol Psychiatry 47:380–390

    Article  CAS  PubMed  Google Scholar 

  • Twamley EW, Jeste DV, Lehman AF (2003) Vocational rehabilitation in schizophrenia and other psychotic disorders: a literature review and meta-analysis of randomized controlled trials. J Nerv Ment Dis 191:515–523

    PubMed  Google Scholar 

  • Umbricht D, Javitt D, Novak G, Bates J, Pollack S, Lieberman J, Kane J (1998) Effects of clozapine on auditory event-related potentials in schizophrenia. Biol Psychiatry 44:716–725

    CAS  PubMed  Google Scholar 

  • Umbricht D, Javitt D, Novak G, Bates J, Pollack S, Lieberman J, Kane J (1999) Effects of risperidone on auditory event-related potentials in schizophrenia. Int J Neuropsychopharmacol 2:299–304

    Article  CAS  PubMed  Google Scholar 

  • Umbricht D, Koller R, Schmid L, Skrabo A, Grubel C, Huber T, Stassen H (2003) How specific are deficits in mismatch negativity generation to schizophrenia? Biol Psychiatry 53:1120–1131

    Article  PubMed  Google Scholar 

  • Waberski TD, Kreitschmann-Andermahr I, Kawohl W, Darvas F, Ryang Y, Gobbele R, Buchner H (2001) Spatio-temporal source imaging reveals subcomponents of the human auditory mismatch negativity in the cingulum and right inferior temporal gyrus. Neurosci Lett 308:107–110

    Article  CAS  PubMed  Google Scholar 

  • Waldo MC, Adler LE, Freedman R (1988) Defects in auditory sensory gating and their apparent compensation in relatives of schizophrenics. Schizophr Res 1:19–24

    Article  CAS  PubMed  Google Scholar 

  • Waldo MC, Carey G, Myles-Worsley M, Cawthra E, Adler LE, Nagamoto HT, Wender P, Byerley W, Plaetke R, Freedman R (1991) Codistribution of a sensory gating deficit and schizophrenia in multi-affected families. Psychiatry Res 39:257–268

    Article  CAS  PubMed  Google Scholar 

  • Waldo MC, Cawthra E, Adler LE, Dubester S, Staunton M, Nagamoto H, Baker N, Madison A, Simon J, Scherzinger A et al. (1994) Auditory sensory gating, hippocampal volume, and catecholamine metabolism in schizophrenics and their siblings. Schizophr Res 12:93–106

    CAS  PubMed  Google Scholar 

  • Waldo M, Myles-Worsley M, Madison A, Byerley W, Freedman R (1995) Sensory gating deficits in parents of schizophrenics. Am J Med Genet 60:506–511

    CAS  PubMed  Google Scholar 

  • Walker E (1981) Attentional and neuromotor functions of schizophrenics, schizoaffectives, and patients with other affective disorders. Arch Gen Psychiatry 38:1355–1358

    CAS  PubMed  Google Scholar 

  • Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669

    CAS  PubMed  Google Scholar 

  • Woods DL, Knight RT, Scabini D (1993) Anatomical substrates of auditory selective attention: behavioral and electrophysiological effects of posterior association cortex lesions. Brain Res Cognit Brain Res 1:227–240

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by grants from the National Institute of Mental Health (MH042228 and MH065571), the Department of Veteran Affairs (VISN 22 Mental Illness Research, Education, and Clinical Center), and the Bowman Family Foundation partnership with the National Alliance for Research on Schizophrenia and Depression (GL).

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Braff, D.L., Light, G.A. Preattentional and attentional cognitive deficits as targets for treating schizophrenia. Psychopharmacology 174, 75–85 (2004). https://doi.org/10.1007/s00213-004-1848-0

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