Preattentive Sensory Processing as Indexed by the MMN and P3a Brain Responses is Associated with Cognitive and Psychosocial Functioning in Healthy Adults

Light, Gregory A.; Swerdlow, Neal R.; Braff, David L.

doi:10.1162/jocn.2007.19.10.1624

Cited by 155 publications

(145 citation statements)

References 66 publications

(68 reference statements)

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“…MMN is considerably attenuated in amplitude (effect size d ∼1.00) in schizophrenia (12)(13)(14), and can be easily and reliably assessed even in the absence of attention or behavioral tasks, a major advantage in patient assessments. In addition, MMN has well-established relationships to cognition (15,16) and psychosocial functioning in both healthy volunteers and schizophrenia patients (17,18). The substantial 1-y stability of MMN (interclass correlation coefficients ∼0.90) also lends support for its use as an endophenotype in genomic investigations, as well as a reliable biomarker in clinical outcome studies (19).…”

Section: Translational Models Of Schizophreniarelated Cognitive Deficitsmentioning

confidence: 96%

“…There is therefore a need to identify predictive biomarkers of response to this daily, resource-intensive intervention. Considering that MMN is regarded as a robust, reliable, and sensitive index of central auditory system plasticity (30) with important relationships to cognition and psychosocial functioning (15)(16)(17)(18), could it also serve as a biomarker that predicts or corresponds to changes following TCT? Studies are underway to investigate this application, with a notable precedent showing that MMN predicts response to an intensive psychosocial skills training intervention (31).…”

Section: Using Biomarkers To Predict Track And/or Inform Treatmentsmentioning

confidence: 99%

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Mismatch negativity is a breakthrough biomarker for understanding and treating psychotic disorders

Light

Näätänen

2013

Proc. Natl. Acad. Sci. U.S.A.

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117

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Section: Translational Models Of Schizophreniarelated Cognitive Deficitsmentioning

confidence: 96%

Section: Using Biomarkers To Predict Track And/or Inform Treatmentsmentioning

confidence: 99%

Mismatch negativity is a breakthrough biomarker for understanding and treating psychotic disorders

Light

Näätänen

2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

117

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“…Increases in both PPI and MMN have been associated with enhanced neurocognition, function, and treatment responsivity Light et al, 2007;Swerdlow et al, 2006a). There may also be a rational basis for suggesting therapeutic value of memantine under conditions requiring improved frontal function.…”

Section: Introductionmentioning

confidence: 99%

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Swerdlow

Bhakta

Chou

et al. 2015

Neuropsychopharmacol

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Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects. Baseline PPI was measured in HS and patients with a diagnosis of schizophrenia or schizoaffective disorder, depressed type. Subjects (total n = 84) were then tested twice, in a double-blind crossover design, comparing either: (1) placebo vs 10 mg of memantine or (2) placebo vs 20 mg memantine. Tests included measures of acoustic startle magnitude and habituation, PPI, MMN, autonomic indices, and subjective self-rating scales. Memantine (20 mg) significantly enhanced PPI in CPD subjects, and enhanced MMN across subject groups. These effects on PPI were age dependent and most evident in older CPD patients, whereas those on MMN were most evident in younger subjects. The lower dose (10 mg) either had no detectable effect or tended to degrade these measures. The NMDA antagonist, memantine, has dose-dependent effects on preconscious, automatic measures of sensorimotor gating and auditory sensory processing that are associated with enhanced cognition and function in CPD patients. Ongoing studies will determine whether these memantine-induced changes predict acute pro-cognitive or otherwise clinically beneficial effects in CPD patients.

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“…11 The positive going P3a component is putatively reported to reflect frontocentral orienting processes 12,13 elicited following the detection of the deviant stimuli. 14 Friedman and colleagues 13 describe the neurophysiological "handover" from MMN to P3a, where the former is a preattentive index of deviance detection and the latter reflects the involuntary capture of attention. There is accumulating evidence, however, suggesting that these biomarkers may not be specific to schizophrenia; rather, they reflect a common or overlapping pathophysiology in psychotic (and possibly other psychiatric) disorders.…”

Section: Introductionmentioning

confidence: 99%

Neurophysiological biomarkers support bipolar-spectrum disorders within psychosis cluster

Kaur

Battisti

Lagopoulos

et al. 2012

J Psychiatry Neurosci

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IntroductionA current topic of controversy in psychiatry is whether or not bipolar-spectrum disorders should be considered as part of the psychosis cluster in the upcoming DSM-V. Currently, bipolarspectrum disorders are classified as mood disorders in line with the Kraeplinian dichotomy; however, recent literature suggests that there may be more overlap in the underlying neurobiology in these major psychiatric illnesses than once thought.1 It is not unusual for patients with similar pheno typic presentation and common symptomatology to receive a diagnosis of either a bipolar-spectrum or a schizophrenia-spectrum disorder, particularly in the early stages of illness. Thus, investigation of the underlying neurobiology of these 2 major psychi atric groups is crucial to our understanding of their pathophysiological overlap. Shared genetic vulnerabilities in individuals with bipolar disorder and schizophrenia have been documented and describe how some symptoms overlap and how some are unique. [2][3][4][5] In support of the shared genetic basis of these disorders, there is evidence that first-degree relatives of probands with bipolar disorder or schizophrenia are at increased risk for either disorder, irrespective of the phenotype present in their relative. Background: Mismatch negativity (MMN) and P3a are event-related potentials that index deviance detection and the orienting response, respectively. We have previously shown that the MMN/P3a complex is impaired in patients with schizophrenia and affective spectrum psychoses, which suggests that it may index a common pathophysiology and argues against the purported specificity in schizo phrenia. Further research is warranted to determine whether patients with bipolar-spectrum disorders show similar impairments in these biomarkers. Methods: We assessed patients aged 15-30 years with early schizophrenia-spectrum disorders (schizophrenia, schizoaffective disorder, schizophreniform disorder), early bipolar-spectrum disorders (bipolar I or II, with and without psychotic features) and healthy, matched controls. We acquired MMN/P3a amplitudes during a 2-tone, auditory paradigm with 8% duration deviants. Clinical, psychosocial and neuro psychological assessments were also undertaken. Results: We included 20 patients with schizophrenia-spectrum disorders, 20 with bipolar-spectrum disorders and 20 controls in our study. Both patient groups showed significantly reduced frontocentral MMN and central P3a amplitudes. The schizophrenia-spectrum group had additional impairments in left temporal MMN and frontal P3a. Both patient groups performed worse than controls across psychosocial and clinical measures; however, only the schizophrenia-spectrum group performed significantly worse than controls for cognitive measures. Correlational analyses between patient groups revealed associations between frontocentral or left temporal MMN and psychiatric symptomatology or quality of life measures. Limitations: Limitations to our study include the modest sample size and the lack of control with r...

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Preattentive Sensory Processing as Indexed by the MMN and P3a Brain Responses is Associated with Cognitive and Psychosocial Functioning in Healthy Adults

Cited by 155 publications

References 66 publications

Mismatch negativity is a breakthrough biomarker for understanding and treating psychotic disorders

Mismatch negativity is a breakthrough biomarker for understanding and treating psychotic disorders

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Neurophysiological biomarkers support bipolar-spectrum disorders within psychosis cluster

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