How MEG/EEG can help to bridge the gap between the genes and behaviour: promises in Autism Spectrum Disorders

MSUPE Center for Neurocognitive Research “MEG – Center”

Волгоградский проспект, 46Б, ауд 210

Дата: 23.03.2017
Время: 15.00

The promising approach in building the causal link between genes and behaviour is relating the genetic pathways converging on candidate cellular/molecular process to the target neurophysiological phenotype. In my talk I will review the recent progress in this field and provide an example of the successful application of this strategy in our study of children with Autism Spectrum Disorder (ASD).

MEG was used to assess 40Hz Auditory Steady-State Response (ASSR) in children with ASD and their typically-developing peers. The ASSR refers to the ability of the neural populations of auditory cortex adjust timing of neural discharges to synchronize them with the frequency of external auditory stimulation, e.g. in response to frequency of click’s trains. Recent animal studies suggested 40 Hz ASSR as a translational biomarker that closely reflects cortical NMDA receptor function (Sivarao et al., 2015; 2016). Given that the molecular-genetic pathways, converging on NMDAR functions, are implicated in ASD, several previous studies examined 40 Hz ASSR in adults (Rojas et al., 2008, 2011) and children with ASD (Wilson, 2007; Edgar et al, 2016), although with inconsistent results. In our study we undertake different approach. We segregated the subgroups of ASD children (8 out of 56 ASD children examined), who according to the results of the whole genome sequencing had intragenic exonic copy number variations (CNVs) in a gene of key scaffolding element determining postsynaptic density of NMDA receptors (SHANK3). Consistent with our hypothesis, these children had a severe reduction of ASSR resembling that in animals with hypofunctional NMDA receptors. Noteworthy, the children with SHANK3 mutations differed in this respect not only from typically-developing peers, but also from other children with ASD lacking this genetic abnormality. Thus, our finding demonstrates a link between intragenic CNVs of SHANK3 and alteration of brain response to high-frequency auditory input – neurophysiological phenotype mediated by cellular and molecular mechanisms, which depends on the genetic abnormality. This approach gives us hope to bridge the gap between results of noninvasive studies in humans and neurophysiological results obtained in animal models of ASD. As such, this step will provide an important contribution to translational research.

«Базовые функции зрительного восприятия у детей с расстройствами аутистического спектра (РАС)»: доклад Ольги Владимировны Сысоевой (МЭГ-центр) на Московском семинаре по когнитивной науке 27 октября 2016 г.
Место проведения: Психологический институт на Моховой. В дискуссии приняла участие Татьяна Александровна Строганова.

Пропуск в НИУ ВШЭ: Алисия Воробьёва [alicianunez.v@gmail.com]