Auditory steady-state EEG response across the schizo-bipolar spectrum

Parker, David A.; Hamm, Jordan P.; McDowell, Jennifer E.; Keedy, Sarah K.; Gershon, Elliot S.; Ivleva, Elena I.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Tamminga, Carol A.; Sweeney, John A.; Clementz, Brett A.

doi:10.1016/j.schres.2019.04.014

Cited by 44 publications

(28 citation statements)

References 45 publications

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“…ASSR is reduced in schizophrenia (for meta-analysis see [ 54 ]), bipolar disorders [ 55 , 56 , 57 , 58 ], and autism spectrum disorders (ASD) [ 59 , 60 ], which are the disorders with implicated GABAergic dysfunctions and altered NMDA signaling. The 40-Hz ASSR deficit occurs in non-psychotic first-degree relatives of patients with schizophrenia [ 61 ] and ASD [ 59 ], which is consistent with an effect of familial or genetic risk factors.…”

Section: Introductionmentioning

confidence: 99%

40-Hz Auditory Steady-State Response (ASSR) as a Biomarker of Genetic Defects in the SHANK3 Gene: A Case Report of 15-Year-Old Girl with a Rare Partial SHANK3 Duplication

Neklyudova

Portnova

Rebreikina

et al. 2021

IJMS

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SHANK3 encodes a scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+ inhibitory neurons—the key players in the generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response (ASSR). However, 40-Hz ASSR was not studied in relation to SHANK3 functioning. Here, we present a 15-year-old girl (SH01) with previously unreported duplication of the first seven exons of the SHANK3 gene (22q13.33). SH01’s electroencephalogram (EEG) during 40-Hz click trains of 500 ms duration binaurally presented with inter-trial intervals of 500–800 ms were compared with those from typically developing children (n = 32). SH01 was diagnosed with mild mental retardation and learning disabilities (F70.88), dysgraphia, dyslexia, and smaller vocabulary than typically developing (TD) peers. Her clinical phenotype resembled the phenotype of previously described patients with 22q13.33 microduplications (≈30 reported so far). SH01 had mild autistic symptoms but below the threshold for ASD diagnosis and microcephaly. No seizures or MRI abnormalities were reported. While SH01 had relatively preserved auditory event-related potential (ERP) with slightly attenuated P1, her 40-Hz ASSR was totally absent significantly deviating from TD’s ASSR. The absence of 40-Hz ASSR in patients with microduplication, which affected the SHANK3 gene, indicates deficient temporal resolution of the auditory system, which might underlie language problems and represent a neurophysiological biomarker of SHANK3 abnormalities.

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Section: Introductionmentioning

confidence: 99%

40-Hz Auditory Steady-State Response (ASSR) as a Biomarker of Genetic Defects in the SHANK3 Gene: A Case Report of 15-Year-Old Girl with a Rare Partial SHANK3 Duplication

Neklyudova

Portnova

Rebreikina

et al. 2021

IJMS

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“…In Sz, the majority of studies have shown a reduction of ASSR power (e.g., (Hong et al, 2004;Kwon et al, 1999;Light et al, 2006;Reilly et al, 2018;Spencer et al, 2009;Thune et al, 2016), although increases are also reported (Hamm et al, 2012;Kim et al, 2019). Deficits are observed as well across the psychosis spectrum (Parker et al, 2019). Although the reductions have often been attributed to reduced NMDAR dysfunction on PV interneurons themselves, alternative formulations suggest that the high firing rate of PV interneurons is critically dependent upon rapid Ca 2+ influx through Ca 2+ -permeable AMPA receptors, and that the slower kinetics of Ca 2+ entry through NMDAR may impede rather than support 40 Hz response (Goldberg et al, 2003;Gonzalez-Burgos and Lewis, 2012).…”

Section: Discussionmentioning

confidence: 99%

Translational neurophysiological biomarkers of N-methyl-D-aspartate receptor dysfunction in serine racemase knockout mice

Balla

Ginsberg

Abbas

et al. 2020

Preprint

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Alterations in glutamatergic function are well established in schizophrenia (Sz), but new treatment development is hampered by the lack of translational pathophysiological and target engagement biomarkers as well as by the lack of animal models that recapitulate the pathophysiological features of Sz. Here, we evaluated the rodent auditory steady state response (ASSR) and long-latency auditory event-related potential (aERP) as potential translational markers. These biomarkers were assessed for their sensitivity to both the Nmethyl-D-aspartate receptor (NMDAR) antagonist phencyclidine (PCP) and to knock-out (KO) of Serine Racemase (SR), which is known to lead to Sz-like alterations in function of parvalbumin (PV)-type cortical interneurons. Both PCP and SRKO led to significant increases of ASSR, consistent with PV interneuron effects. Similar effects were observed in mice with selective NMDAR KO on PV interneurons. By contrast, PCP but not SRKO reduced the amplitude of the rodent analog of the human N1 potential. Overall, these findings support use of rodent ASSR and long-latency aERP, along with previously described measures such as mismatch negativity (MMN), as translational biomarkers, and support SRKO mice as a potential rodent model for PV interneuron dysfunction in Sz.

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“…Our data emphasize the value of the 15q13 mouse model for the exploration of pathological and therapeutic mechanisms based on functional biomarkers associated with schizophrenia. 37 .…”

Section: Discussionmentioning

confidence: 99%

Activation of group II metabotropic receptors attenuates cortical E-I imbalance in a 15q13.3 microdeletion mouse model

Funk

Schuelert

Jaeger

et al. 2020

Preprint

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Animal models reflecting human risk for schizophrenia are essential research tools for gaining further insight into the convergence of CNS pathology and clinical biomarkers. Amongst the variety of animal models that display schizophrenia-related neuronal network deficits, transgenic mice for rare and highly penetrant copy number variants (CNVs) provide a unique opportunity to study pathological correlates in models with strong construct validity. The Df(h15q13)/+ mouse model of the human 15q13.3 microdeletion CNV has been shown to mimic deficits in parvalbumin positive (PV+) interneuron and cortical network function. However, the corresponding changes in synapse density and activity within the medial prefrontal cortex (mPFC) have not been described. Using high-content immunofluorescence imaging, we have shown a reduced density of PV+ neurons and inhibitory synapses in the mPFC of Df(h15q13)/+ mice. We found that the reduced detection of PV+ synapses were accompanied by changes in spontaneous inhibitory and excitatory synaptic activity onto layer 2/3 pyramidal neurons. The aberrant cortical function was also evident in awake animals by a reduced high frequency auditory steady-state responses (ASSR), reliably monitored by EEG. Importantly, the imbalance of excitatory to inhibitory function could be attenuated on a cellular and cortical network level by activation of mGlu2/3 receptors, indicating the relevance of excessive excitatory transmission to the cortical network deficit in the Df(15q13)/+ mouse model. Our findings highlight the preclinical value of genetic risk and in particular CNV models such as the Df(15q13)/+ mice to investigate pathological network correlates of schizophrenia risk and to probe therapeutic opportunities based on clinically relevant biomarkers.

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Auditory steady-state EEG response across the schizo-bipolar spectrum

Abstract: Deviant auditory steady-state responses (aSSRs) in the gamma range (30-90 Hz) may be translational biomarkers for schizophrenia (SZ). This study tests whether aSSR deviations are (i)

Cited by 44 publications

References 45 publications

40-Hz Auditory Steady-State Response (ASSR) as a Biomarker of Genetic Defects in the SHANK3 Gene: A Case Report of 15-Year-Old Girl with a Rare Partial SHANK3 Duplication

40-Hz Auditory Steady-State Response (ASSR) as a Biomarker of Genetic Defects in the SHANK3 Gene: A Case Report of 15-Year-Old Girl with a Rare Partial SHANK3 Duplication

Translational neurophysiological biomarkers of N-methyl-D-aspartate receptor dysfunction in serine racemase knockout mice

Activation of group II metabotropic receptors attenuates cortical E-I imbalance in a 15q13.3 microdeletion mouse model

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