Prepulse inhibition and P50 suppression: Commonalities and dissociations

Patients with schizophrenia exhibit reduced levels of both prepulse inhibition of the startle reflex (PPI) and condition-test suppression of the P50 event-related potential. This study investigated the extent to which PPI and P50 suppression, which exhibit similar parametric sensitivities, are intrinsically auditory phenomena or can be induced cross-modally, and reflect common or distinct neural mechanisms of inhibition. PPI, N100, and P50 were assessed in 20 healthy male volunteers, using auditory test probes and both visual and auditory lead stimuli, separated by 100- or 500-ms interstimulus intervals (ISIs). PPI was found in the auditory-lead condition across the complete group, and with visual-lead stimuli in approximately half of the subjects. Intra-modal auditory PPI was significantly higher with the 100-ms ISI than with the 500-ms ISI. P50 suppression was found only with the 500-ms ISI, with no difference between the auditory and visual conditions. Source analyses revealed that suppression was associated with frontal cortical activity. N100 suppression was found only in the auditory condition, with no difference between 100- and 500-ms ISIs. Although both phenomena are considered to provide operational measures of gating, PPI and P50 suppression are differentially sensitive to ISI and therefore reflect partly different neural mechanisms. They are not intrinsically auditory phenomena, and both appear to involve frontal cortical activity. In contrast, N100 suppression is most likely based on refractory mechanisms intrinsic to the auditory system.

[1]  Christian Grillon,et al.  Gating and habituation of the startle reflex in schizophrenic patients. , 1992 .

[2]  M S Buchsbaum,et al.  Prefrontal cortex glucose metabolism and startle eyeblink modification abnormalities in unmedicated schizophrenia patients. , 1998, Psychophysiology.

[3]  F. Graham,et al.  Presidential Address, 1974. The more or less startling effects of weak prestimulation. , 1975, Psychophysiology.

[4]  Michael F. Green,et al.  Prepulse facilitation and prepulse inhibition in schizophrenia patients and their unaffected siblings , 2004, Biological Psychiatry.

[5]  M. Koch,et al.  The neurobiology of startle , 1999, Progress in Neurobiology.

[6]  J. Lamberti,et al.  Concurrent assessment of acoustic startle and auditory P50 evoked potential measures of sensory inhibition , 1993, Biological Psychiatry.

[7]  M. Geyer,et al.  Multiple site evaluation of P50 suppression among schizophrenia and normal comparison subjects , 1998, Schizophrenia Research.

[8]  R Freedman,et al.  Schizophrenia, sensory gating, and nicotinic receptors. , 1998, Schizophrenia bulletin.

[9]  W. Perlstein,et al.  Prepulse effects as a function of cortical projection system , 2001, Biological Psychology.

[10]  N. Swerdlow,et al.  The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications , 1992, Journal of psychopharmacology.

[11]  G. Mulder,et al.  Event-Related Brain Research (EEG suppl. 42) , 1991 .

[12]  J. Kenemans,et al.  Removal of the ocular artifact from the EEG: a comparison of time and frequency domain methods with simulated and real data. , 1991, Psychophysiology.

[13]  M. Geyer,et al.  Neurobiological measures of schizotypal personality disorder: defining an inhibitory endophenotype? , 2002, The American journal of psychiatry.

[14]  N. Swerdlow,et al.  Startle response models of sensorimotor gating and habituation deficits in schizophrenia , 1990, Brain Research Bulletin.

[15]  C. Rennie,et al.  Decrement of the N1 auditory event-related potential with stimulus repetition: habituation vs. refractoriness. , 1998, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[16]  P. Venables,et al.  INPUT DYSFUNCTION IN SCHIZOPHRENIA. , 1964, Progress in experimental personality research.

[17]  A. Mcghie,et al.  Disorders of attention and perception in early schizophrenia. , 1961, The British journal of medical psychology.

[18]  M. Davis,et al.  Prepulse inhibition of the acoustic startle reflex using visual and auditory prepulses: disruption by apomorphine , 1995, Psychopharmacology.

[19]  H. Jasper,et al.  Epilepsy and the Functional Anatomy of the Frontal Lobe , 1995 .

[20]  D L Braff,et al.  Sensory gating deficits in schizophrenia: new results. , 1992, The American journal of psychiatry.

[21]  M. Scherg.  Fundamentals if dipole source potential analysis , 1990 .

[22]  R. Knight,et al.  Human prefrontal lesions increase distractibility to irrelevant sensory inputs , 1995, Neuroreport.

[23]  Robert Freedman,et al.  Sensory gating in schizophrenics and normal controls: Effects of changing stimulation interval , 1989, Biological Psychiatry.

[24]  M. Davis,et al.  A primary acoustic startle circuit: lesion and stimulation studies , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  H. Hoffman,et al.  Reflex modification in the domain of startle: II. The anomalous history of a robust and ubiquitous phenomenon. , 1983, Psychological bulletin.

[26]  P. Ward,et al.  Replication of a P50 auditory gating deficit in Australian patients with schizophrenia , 1996, Psychiatry Research.

[27]  M Scherg,et al.  Is frontal lobe involved in the generation of auditory evoked P50? , 2001, Neuroreport.

[28]  T. Sharma,et al.  Sex differences in prepulse inhibition deficits in chronic schizophrenia , 2004, Schizophrenia Research.

[29]  D L Braff,et al.  Sensorimotor gating and schizophrenia. Human and animal model studies. , 1990, Archives of general psychiatry.

[30]  B. Rossi,et al.  Modulation of electrically elicited blink reflex components by visual and acoustic prestimuli in man. , 1995, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[31]  J. Ford,et al.  Failures of automatic and strategic processing in schizophrenia: comparisons of event-related brain potential and startle blink modification , 1999, Schizophrenia Research.

[32]  J. Endicott,et al.  A diagnostic interview: the schedule for affective disorders and schizophrenia. , 1978, Archives of general psychiatry.

[33]  E. Hazlett,et al.  Attention, startle eyeblink modification, and psychosis proneness. , 1995 .

[34]  G. Romani,et al.  Auditory evoked magnetic fields and electric potentials , 1990 .

[35]  H. Davis,et al.  The slow response of the human cortex to auditory stimuli: recovery process. , 1966, Electroencephalography and clinical neurophysiology.

[36]  Robert Freedman,et al.  Gating of auditory response in schizophrenics and normal controls Effects of recording site and stimulation interval on the P50 wave , 1991, Schizophrenia Research.

[37]  R Freedman,et al.  Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. , 1982, Biological psychiatry.

[38]  M. Geyer,et al.  Prestimulus effects on human startle reflex in normals and schizophrenics. , 1978, Psychophysiology.

[39]  Brett A. Clementz,et al.  P50 Suppression among schizophrenia and normal comparison subjects: A methodological analysis , 1997, Biological Psychiatry.

[40]  R. Knight,et al.  Role of human prefrontal cortex in attention control. , 1995, Advances in neurology.

[41]  B. Maher,et al.  Progress in experimental personality research , 1964 .

[42]  Robert Freedman,et al.  Elementary neuronal dysfunctions in schizophrenia , 1991, Schizophrenia Research.

[43]  M. Geyer,et al.  Strain-specific effects of amphetamine on prepulse inhibition and patterns of locomotor behavior in mice. , 2001, The Journal of pharmacology and experimental therapeutics.

[44]  Robert Freedman,et al.  Gating of auditory P50 in schizophrenics: Unique effects of clozapine , 1996, Biological Psychiatry.

[45]  J. Ison,et al.  Effects of single and repeated exposure to apomorphine on the acoustic startle reflex and its inhibition by a visual prepulse , 1995, Psychopharmacology.

[46]  Robert Freedman,et al.  Auditory sensory gating in hippocampal neurons: A model system in the rat , 1990, Biological Psychiatry.

[47]  Bob Oranje,et al.  P50 suppression and prepulse inhibition of the startle reflex in humans: a correlational study , 1999, Biological Psychiatry.

[48]  N C Andreasen,et al.  The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. , 1992, Archives of general psychiatry.

[49]  T W Picton,et al.  Separation and identification of event-related potential components by brain electric source analysis. , 1991, Electroencephalography and clinical neurophysiology. Supplement.