23. Biomarker Discovery in ASD: Visual Evoked Potentials as a Biomarker of Phelan-McDermid Syndrome

Siper, Paige M.; George-Jones, Julia; Lurie, Stacey; Rowe, Mikaela; Durkin, Allison; Weissman, Jordana; Meyering, Kristin; Rouhandeh, Audrey; Buxbaum, Joseph D.; Kolevzon, Alexander

doi:10.1016/j.biopsych.2018.02.040

Cited by 3 publications

(6 citation statements)

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“…Thus, there might be some common deficits in the early stage of auditory processing in the auditory cortex in patients with abnormalities related to the SHANK3 gene. The decrease in the early component of visual ERP to checkerboard stimuli, which was registered within the same latency range, 50-75 ms post-stimulus, was also reported in PMS [86,87], pointing to the fact that neurophysiological abnormalities occur in PMS at the early stages of sensory processing regardless of the modality of stimulation. Whether such deficits also spread to the visual system in our patient was not studied.…”

Section: Discussionsupporting

confidence: 60%

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: Discussionsupporting

confidence: 60%

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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“…Here, group differences occurred at high frequencies (≥30 Hz), and an early peak (P 60 ‐N 75 ) correlated with these frequency bands. The current findings of smaller P 60 ‐N 75 and N 75 ‐P 100 amplitudes in autistic children are consistent with the previous work of Siper et al (2016) and (2018). Measures of high‐frequency (possibly excitatory) activity may be among the most useful in classifying autistic individuals (Siper et al, 2016).…”

Section: Discussionsupporting

confidence: 93%

“…The tVEP to a contrast‐reversing checkerboard has been posited as a promising biomarker candidate (McPartland et al, 2020; Siper et al, 2018), and the frequency analysis techniques employed in the current study strengthen the value of tVEPs. It should be noted, however, that to be effective as a biomarker, these tests may need to be combined in a prediction equation with additional validated measures as the specificity found here based on ROC curve analysis and Youden's index is low.…”

Section: Discussionmentioning

confidence: 58%

“…Dickinson et al (2018) collected steady‐state VEPs to differentially‐modulated radial patterns and concluded that lateral inhibitory processes are largely intact in autistic individuals. Siper et al (2016, 2018) collected tVEPs to a contrast‐reversing checkerboard pattern and suggested that excitatory activity in visual cortex is attenuated in ASD. Other studies have also suggested that high variability in neural responses may be associated with ASD (Al‐Jawahiri et al, 2019; Dinstein et al, 2012; Edgar et al, 2015; Haigh et al, 2015; Milne, 2011; Weinger et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Objective frequency analysis of transient visual evoked potentials in autistic children

et al. 2021

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Visual evoked potentials (VEPs) provide a means to examine neural mechanisms in autism with high temporal resolution. Conventional VEP analysis relies on subjective inspection of a few points (peaks and troughs) in the time‐domain waveform. The current study applied power spectral analysis and magnitude‐squared coherence (MSC) statistics (frequency‐domain measures) to VEPs recorded during 1‐minute runs and with a recently developed short‐duration technique that allow for objective examination of the responses (Zemon & Gordon, European Journal of Neuroscience, 2018, 48, 1765–1788) from nonautistic and autistic children. Results indicate that, for both groups, early time‐domain measures (P60, N75, P100) are highly correlated with middle‐ and high‐frequency (14–28 and 30–48 Hz, respectively) mechanisms, and late measures are highly correlated with a low‐frequency (6–12 Hz) mechanism. One frequency‐domain measure (power in the middle‐frequency band) is capable of predicting the key amplitude measure (N75‐P100) with high accuracy. MSC and power measures were combined to yield separate measures of signal and noise strength to evaluate alternate hypotheses in autism. Linear mixed‐effects modeling demonstrated selective differences in early time‐domain and middle‐to‐high frequency‐domain measures in autistic children as compared to nonautistic children given both recording techniques, implicating weaker excitatory input to the cortex. Receiver‐operating‐characteristic curve analysis showed predictive diagnostic accuracy for middle‐ and high‐frequency bands based on MSC. These findings support the value of frequency analysis measures (power spectral analysis and MSC) in the objective examination of neural differences in autism. Lay Summary Visual evoked potentials (VEPs) are used to assess neural mechanisms. Typically, VEPs are analyzed by subjective examination of time‐series waveforms; but here objective techniques were applied to quantify VEP frequency components to investigate neural differences between autistic and nonautistic children. The objective measures demonstrate group differences in brain function that point to weaker excitatory input to the cortex in autism.

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“…Thus, there might be some common deficits in the early stage of auditory processing in the auditory cortex in patients with abnormalities related to SHANK3 gene. The decrease in the early component of visual ERP to checkerboard stimuli, registered within the same latency range, 50-75 ms post-stimulus were also reported in PMS [74,75], pointing to the fact that neurophysiological abnormalities occurs in PMS at the early stages of sensory processing regardless of the modality of stimulation. We should also point out that attenuation of P1 in response to auditory stimuli was also reported in patients with idiopathic autism [76][77][78], linking these behavioral and neurophysiological abnormalities.…”

Section: Discussionsupporting

confidence: 60%

40-Hz Auditory Steady State Response (ASSR) as a Biomarker of Abnormalities in SHANK3 Gene: a Case-Report of 15-years Old Girl with Rare Microduplication in 22q13.33

Ak¹,

Gv²,

Ab³

et al. 2020

Preprint

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SHANK3 encodes scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+inhibitory neurons – the key players in generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response(ASSR). Here we describe a clinical and neurophysiological phenotype of a 15-years old girl (SH01) with microduplication of 16389 bp in 22q13.33, affecting the SHANK3 gene in comparison to typically developing children (n=32). EEG were recorded during the binaurally presentation of 40-Hz clicks’ trains lasting for 500 ms with inter-trial intervals 500-800 ms. SH01 was diagnosed with mild mental retardation and learning disabilities(F70.88) and had problems with reading and writing, as well as smaller vocabulary than TD peers. Her clinical phenotype generally resembled the phenotype of previously described patients with 22q13.33 microduplication. SH01 had mild autistic symptoms but below the threshold for ASD diagnosis. 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. Absence of 40-Hz ASSR in patient with microduplication, affected SHANK3 gene, indicates deficient temporal resolution of the auditory system, that might underlie language problems, and represent neurophysiological biomarker of SHANK3 abnormalities.

show abstract

23. Biomarker Discovery in ASD: Visual Evoked Potentials as a Biomarker of Phelan-McDermid Syndrome

Cited by 3 publications

References 0 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

Objective frequency analysis of transient visual evoked potentials in autistic children

40-Hz Auditory Steady State Response (ASSR) as a Biomarker of Abnormalities in SHANK3 Gene: a Case-Report of 15-years Old Girl with Rare Microduplication in 22q13.33

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