Identification of neural circuits underlying P300 abnormalities in schizophrenia

O’Donnell, Brian F.; McCarley, Robert W.; Potts, Geoffrey F.; Salisbury, Dean F.; Nestor, Paul G.; Hirayasu, Yoshio; Niznikiewicz, Margaret; Barnard, John; Shen, Zi Jen; Weinstein, David M.; Bookstein, Fred L.; Shenton, Martha E.

doi:10.1017/s0048577299971688

Cited by 82 publications

(42 citation statements)

References 74 publications

(118 reference statements)

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“…We speculate that abnormalities in this interconnected network may result in both physiological and clinical (thought disorder) disturbances. We have elsewhere extensively reviewed abnormalities in schizophrenia of the P300 ERP, an ERP that has been postulated to index processing and assimilation of infrequently occurring new information (see Salisbury et al 1999;McCarley et al 1997;O'Donnell et al 1999). Our laboratory was alerted to possible temporal lobe abnormalities by a left temporal scalp region topographic deficit of the auditory P300.…”

Section: Comment On Anatomical Substrate In Schizophrenia For Disturbmentioning

confidence: 99%

Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects

McCarley

Niznikiewicz

Salisbury

et al. 1999

European Archives of Psychiatry and Clinical Neurosciences

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Seeking to unite psychological and biological approaches, this paper links cognitive and cellular hypotheses and data about thought and language abnormalities in schizophrenia. The common thread, it is proposed, is a dysregulated suppression of associations (at the behavioral and functional neural systems level), paralleled by abnormalities of inhibition at the cellular and molecular level, and by an abnormal anatomical substrate (reduced MRI gray matter volume) in areas subserving language.At the level of behavioral experiments and connectionist modeling, data suggest an abnormal semantic network connectivity (strength of associations) in schizophrenia, but not an abnormality of network size (number of associates). This connectivity abnormality is likely to be a preferential processing of the dominant (strongest) association, with the neglect of preceding contextual information.At the level of functional neural systems, the N400 event-related potential amplitude is used to index the extent of "search" for a semantic match to a word. In a short stimulus-onset-asynchrony condition, both schizophrenic and schizotypal personality disorder subjects showed, compared with controls, a reduced N400 amplitude to the target words that were related to cues, e.g. cat-dog, a result compatible with behavioral data. Other N400 data strongly and directly suggest that schizophrenics do not efficiently utilize context. At the level of anatomical system substrates, considerable MRI data indicate abnormalities in the temporal lobe structures that subserve language and verbal associations. Gray matter volume is reduced in the posterior portion of the dominant superior temporal gyrus in both chronic and first episode schizophrenics (but not in manic-depressive psychosis), with the magnitude of reduction correlating with the degree of thought disorder.At the level of in vitro cellular and molecular analysis, NMDA receptors on inhibitory neurons are much more sensitive to blockade than are excitatory projections. A resulting failure of recurrent inhibition may account for the psychotomimetic effects of such NMDA receptor blockers as ketamine and phencyclidine, and may also be present in schizophrenia, where an endogenous NMDA receptor blocker, NAAG, is increased, and where other abnormalities of recurrent inhibition may be present. A biophysical simulation of this circuit abnormality in a model of learned pattern recognition produced, because of the reduction in recurrent inhibition, aberrant spread of excitation, resulting in confusion of normally distinguishable patterns. We suggest the neural circuit failure of inhibition and consequent aberrant spread of activation may be the substrate for an inability to use context, with the behavioral and functional consequences just described. Furthermore, there is the possibility that the unbalanced excitation might lead to progressive, neurodegenerative changes in gray matter, marked by progressive volume reduction.

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Section: Comment On Anatomical Substrate In Schizophrenia For Disturbmentioning

confidence: 99%

Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects

McCarley

Niznikiewicz

Salisbury

et al. 1999

European Archives of Psychiatry and Clinical Neurosciences

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“…Although the P300 component is usually thought to reflect memory updating and the allocation of attentional resources, this component can also offer insight into language processing Jeon and Polich, 2003). Decreased P300 amplitude was associated with reduced grey matter volume in the superior temporal gyrus (STG), an area related to language comprehension, in chronic and first-episode schizophrenia patients and also with STG activation in children genetically at-risk for psychosis (McCarley et al, 1993(McCarley et al, , 2002O'Donnell et al, 1999;Rajarethinam et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Language processing abnormalities in adolescents with psychotic-like experiences: An event related potential study

Murphy

Blanchard

Rawdon

et al. 2012

Schizophrenia Research

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Language impairments are a well established finding in patients with schizophrenia and in individuals at-risk for psychosis. A growing body of research has revealed shared risk factors between individuals with psychotic-like experiences (PLEs) from the general population and patients with schizophrenia. In particular, adolescents with PLEs have been shown to be at an increased risk for later psychosis. However, to date there has been little information published on electrophysiological correlates of language comprehension in this at-risk group. A 64 channel EEG recorded electrical activity while 37 (16 At-Risk; 21 Controls) participants completed the British Picture Vocabulary Scale (BPVS-II) receptive vocabulary task. The P300 component was examined as a function of language comprehension. The at-risk group were impaired behaviourally on receptive language and were characterised by a reduction in P300 amplitude relative to the control group. The results of this study reveal electrophysiological evidence for receptive language deficits in adolescents with PLEs, suggesting that the earliest neurobiological changes underlying psychosis may be apparent in the adolescent period.

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“…Regarding clinical characteristics, Olichney and colleagues (1998) found auditory P300 amplitude reductions in early onset schizophrenics (see also O'Donnell et al, 1999), while late onset schizophrenics had P300 amplitudes in the normal range. Furthermore, an increase in amplitude of the visual, but not the auditory P300 amplitudes accompanied clinical improvement (Duncan, Morihisa, Fawcett, & Kirch, 1987) at least in subgroups of patients (Krieger, Tegeler, Schweizer, Bertling, & Kalveram, 1989).…”

Section: Introductionmentioning

confidence: 99%

Event-Related Potential Correlates of Acquisition and Retrieval of Verbal Associations in Schizophrenics and Controls

Baving

Rockstroh

Rössner

et al. 2000

Journal of Psychophysiology

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Reduced amplitudes of event-related potentials (ERP) have often been reported for schizophrenic patients. Positive ERPs were examined in 16 schizophrenic patients and 16 controls in a visual paired-associate learning task, in which successful learning of word pairs was evidenced by recognition of "old" versus "new" word pairs. Patients performed significantly poorer than controls. During acquisition the to-be-associated word pairs evoked a P2 and positive Slow Wave (SW) of similar amplitude in both groups. Although the recognition of items as "old" induced larger positive ERPs in controls, ERPs did not vary with recognition in patients. The presentation of the word pairs (50% old, 50% new combinations) evoked a pronounced posterior positive SW in patients but an anterior negative SW in controls. This pattern is identical to the one obtained from a previous paired-associate learning task with cue-recall and suggests that schizophrenic patients are capable of producing large amplitude positive waves under conditions different from those typical for P300 evocation in normals. The larger positive SW may indicate increased effort to compensate for deficient acquisition or association formation.

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Identification of neural circuits underlying P300 abnormalities in schizophrenia

Cited by 82 publications

References 74 publications

Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects

Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects

Language processing abnormalities in adolescents with psychotic-like experiences: An event related potential study

Event-Related Potential Correlates of Acquisition and Retrieval of Verbal Associations in Schizophrenics and Controls

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