40-Hz Auditory Steady-State Responses in Schizophrenia: Toward a Mechanistic Biomarker for Circuit Dysfunctions and Early Detection and Diagnosis

Grent-‘t-Jong, Tineke; Brickwedde, Marion; Metzner, Christoph; Uhlhaas, Peter J.

doi:10.1016/j.biopsych.2023.03.026

Cited by 18 publications

(6 citation statements)

References 111 publications

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“…Stimulus-evoked, phase-locked responses and response amplification (i.e., resonance) through intrinsic cortical circuit interactions differentially shape the transient and sustained components of cortical power responses (Donner and Siegel, 2011), with early transient response components reflecting predominantly the stimulus-evoked activity and late sustained components reflecting intrinsic circuitry (Ross, Picton and Pantev, 2002;Tada et al, 2021;Grent-'t-Jong et al, 2023). Here, we found that the lorazepam effect was evident in both the early and sustained parts of the total spectral power response at 40 Hz (Fig.…”

Section: Discussionmentioning

confidence: 58%

“…The auditory steady state response (ASSR), an oscillatory brain response to a periodically modulated auditory stimulus, has recently gained attention as a candidate neurophysiological biomarker of schizophrenia (Grent-'t-Jong et al, 2023). The ASSR can be measured noninvasively via electroencephalography (EEG) or magnetoencephalography (MEG) (Tan, Gross and Uhlhaas, 2015;Thune, Recasens and Uhlhaas, 2016).…”

Section: Introductionmentioning

confidence: 99%

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40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by GABAergic Neuronal Inhibition

Toso,

Wermuth,

Arazi

et al. 2023

Preprint

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The 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, non-invasive physiological biomarker for schizophrenia and related disorders. Because the 40Hz oscillation is injected into the brain by means of the sensory input, ASSR responses measured in the cortex may, in principle, just result from the passive propagation of stimulus oscillations across the auditory pathways, without any intracortical generation or amplification. Alternatively, the ASSR responses may involve cortical circuit interactions that amplify the stimulus-evoked oscillation, which would imply it as mechanistic signature of cortical circuit dysfunctions. Here, we tested whether the 40 Hz ASSR in human auditory cortex depends on two key synaptic components of neuronal interactions within cortical circuits: excitation via N-methyl-aspartate glutamate (NMDA) receptors and inhibition via gamma-amino-butyric acid (GABA) receptors. We combined magnetoencephalography MEG recordings with placebo-controlled, low-dose pharmacological interventions in the same healthy human participants. All participants exhibited a robust 40 Hz ASSR in auditory cortices (stronger on the right) under placebo. The GABAA receptor-agonist lorazepam increased the amplitude of this ASSR, while no effect was detectable under the NMDA-blocker memantine. Our findings indicate that the 40 Hz ASSR in auditory cortex involves synaptic (and likely intracortical) inhibition via the GABA-A receptor, thus highlighting its utility as a mechanistic signature of cortical circuit dysfunctions involving GABAergic inhibition.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by GABAergic Neuronal Inhibition

Toso,

Wermuth,

Arazi

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…In addition, studies focusing on the auditory steady-state response (ASSR) caused by rhythmic compound tone stimuli have found that compared to other frequency tone stimuli, rhythmic tone stimuli at 40-Hz can induce stronger gamma band neural oscillatory responses in individuals ( Cortes-Briones, 2021 ; Pastor et al., 2002 ; Voicikas et al., 2016 ). Related studies have found significant ASSR deficits in patients with schizophrenia, revealing possible abnormal synchronous activity of auditory cortical neurons in patients ( Grent-‘t-Jong, Brickwedde, Metzner & Uhlhaas, 2023 ; O'Donnell et al., 2013 ; Thuné, Recasens & Uhlhaas, 2016 ). Some studies have also found that first-episode schizophrenia patients, first-episode emotional disorders patients, and PRS individuals all have ASSR deficits ( Grent-’t-Jong et al., 2021 ; Spencer, Salisbury, Shenton & McCarley, 2008 ; Tada et al., 2016 ), and ASSR induced by 40-Hz rhythmic tone stimulation can more effectively predict the clinical outcomes of PRS ( Cortes-Briones, 2021 ; Grent-’t-Jong et al., 2021 ).…”

Section: Introductionmentioning

confidence: 89%

The specificity of the auditory P300 responses and its association with clinical outcomes in youth with psychosis risk syndrome

Hou,

Qiu,

Xia

et al. 2024

International Journal of Clinical and Health Psychology

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“…An important objective of current translational research is the identification of biomarkers of the neural circuit dysfunctions underlying schizophrenia and related disorders, such as autism spectrum disorders. The auditory steady-state response (ASSR), an oscillatory brain response to a periodically modulated auditory stimulus, has recently gained attention as a candidate neurophysiological biomarker of schizophrenia ( Grent-'t-Jong et al, 2023 ). The ASSR can be measured noninvasively via electroencephalography (EEG) or magnetoencephalography (MEG; Tan et al, 2015 ; Thune et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by Gabaergic Neuronal Inhibition

Toso,

Wermuth,

Arazi

et al. 2024

J. Neurosci.

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The 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, non-invasive physiological biomarker for schizophrenia and related neuropsychiatric disorders. The 40 Hz ASSR might be amplified by synaptic interactions in cortical circuits, which are, in turn, disturbed in neuropsychiatric disorders. Here, we tested whether the 40 Hz ASSR in human auditory cortex depends on two key synaptic components of neuronal interactions within cortical circuits: excitation via N-methyl-aspartate glutamate (NMDA) receptors and inhibition via gamma-amino-butyric acid (GABA) receptors. We combined magnetoencephalography (MEG) recordings with placebo-controlled, low-dose pharmacological interventions in the same healthy human participants (13 males, 7 females). All participants exhibited a robust 40 Hz ASSR in auditory cortices, especially in the right hemisphere, under placebo. The GABAAreceptor-agonist lorazepam increased the amplitude of the 40 Hz ASSR, while no effect was detectable under the NMDA-blocker memantine. Our findings indicate that the 40 Hz ASSR in auditory cortex involves synaptic (and likely intracortical) inhibition via the GABA-A receptor, thus highlighting its utility as a mechanistic signature of cortical circuit dysfunctions involving GABAergic inhibition.Significance statementThe 40 Hz auditory steady-state response is a candidate non-invasive biomarker for schizophrenia and related neuropsychiatric disorders. Yet, the understanding of the synaptic basis of this neurophysiological signature in humans has remained incomplete. We combined magnetoencephalography (MEG) recordings with placebo-controlled pharmacological interventions in healthy human subjects to test the modulation of the 40 Hz ASSR in auditory cortex by two synaptic components that have been implicated in the generation of neuronal oscillations in cortical microcircuits: glutamate N-methyl-aspartate glutamate (NMDA) receptors and gamma-amino-butyric acid (GABA) -A receptors. Boosting GABAergic transmission, but not blocking NMDA-receptors, increased the amplitude of this ASSR. Thus, GABAergic inhibition modulates 40 Hz steady-state responses in auditory cortex.

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40-Hz Auditory Steady-State Responses in Schizophrenia: Toward a Mechanistic Biomarker for Circuit Dysfunctions and Early Detection and Diagnosis

Cited by 18 publications

References 111 publications

40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by GABAergic Neuronal Inhibition

40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by GABAergic Neuronal Inhibition

The specificity of the auditory P300 responses and its association with clinical outcomes in youth with psychosis risk syndrome

40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by Gabaergic Neuronal Inhibition

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