Impaired Auditory 40-Hz Steady-State Responses Noted in Schizophrenia

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40-Hz ASSR spectral power and phase-locking deficits could be useful probes for assessing circuit dysfunctions in the disorder.
40-Hz ASSR spectral power and phase-locking deficits could be useful probes for assessing circuit dysfunctions in the disorder.

Individuals with schizophrenia have consistent impairments in 40-Hz auditory steady-state response (ASSR), according to a new meta-analysis published in JAMA Psychiatry.1

A team of researchers affiliated with the University of Glasgow, Scotland, analyzed 20 studies that compared 590 healthy controls to 606 patients with schizophrenia.

The studies used electroencephalographic (EEG) and magnetoencephalographic (MEG) recordings to measure steady-state responses, which the researchers define as “evoked oscillatory responses that are entrained to the frequency and phase of temporally modulated stimuli.” AASRs, which show a peak frequency at around 40-Hz, reflect the synchronization of endogenous oscillations and the propensity of neurons to oscillate at a particular gamma-band “resonant” frequency induced by external periodic stimulation, the authors explained. The 40-Hz ASSR has been a candidate mechanism underlying the fast temporal integration and resolution of auditory inputs. 

The connection between 40-Hz ASSR and schizophrenia is attributable to the relationship between gamma-band (30- to 200-Hz) oscillations and schizophrenia-associated cognitive deficits.. These oscillations are hypothesized to establish communication between distributed neuronal ensembles. It is possible that disturbances in these neurons can underlie the cognitive and perceptual disturbances in patients with schizophrenia.  For this reason, it may be possible that the 40-Hz ASSR could constitute a potential biomarker for schizophrenia. However, studies of this phenomenon have utilized diverse patient groups — primarily those with chronic schizophrenia — and few have examined first episode psychosis, at risk populations, early onset schizophrenia, and first-degree relatives. The researchers undertook the meta-analysis to draw conclusions about the role of 40-Hz ASSR across different patient samples and study designs.

The researchers identified 17 studies that reported significant reductions in 40-Hz ASSR spectral power and/or phase locking in patients with schizophrenia, as compared with healthy controls. Effect sizes from spectral power and phase-locking measures did not differ significantly. Stimulus characteristics and analysis methods were not associated with findings of 40-Hz ASSR impairment in schizophrenia, according to the study.

The researchers commented that the 40-Hz ASSR spectral power and phase-locking deficits are “robust in schizophrenia,” which suggests that “these measures could be useful probes for assessing circuit dysfunctions in the disorder.” The added that their findings “should motivate large-scale studies of the longitudinal expression in patients and at-risk populations to further validate the 40-Hz ASSR as a potential biomarker…to shed light on the neurobiology of circuit dysfunctions in patients with schizophrenia.”


1. Thuné H, Recasens M, Uhlhaas PJ. The 40-Hz Auditory Steady-State Response in Patients With Schizophrenia. JAMA Psych. 2016;73(11):1145-1153.

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