Dataset Information

Mechanisms underlying the EEG biomarker in Dup15q syndrome.

ABSTRACT: Background:Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods:To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results:Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions:Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome.

SUBMITTER: Frohlich J

PROVIDER: S-EPMC6609401 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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Mechanisms underlying the EEG biomarker in Dup15q syndrome.

Frohlich Joel J Reiter Lawrence T LT Saravanapandian Vidya V DiStefano Charlotte C Huberty Scott S Hyde Carly C Chamberlain Stormy S Bearden Carrie E CE Golshani Peyman P Irimia Andrei A Olsen Richard W RW Hipp Joerg F JF Jeste Shafali S SS

Molecular autism 20190703

<h4>Background</h4>Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene <i>UBE3A</i> and three nonimprinted gamma-aminobutyric acid type-A (GABA<sub>A</sub>) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q s ...[more]

PMID: 31312421

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Project description:Over the last decade, the efforts toward unraveling the complex interplay between the brain, body, and environment have set a promising line of research that utilizes neuroscience to study human performance in natural work contexts such as aviation. Thus, a relatively new discipline called neuroergonomics is holding the promise of studying the neural mechanisms underlying human performance in pursuit of both theoretical and practical insights. In this work, we utilized a neuroergonomic approach by combining insights from ecological psychology and embodied cognition to study flight expertise. Specifically, we focused on the Mirror Neuron system as a key correlate for understanding the interaction between an individual and the environment, suggesting that it can be used to index changes in the coupling of perception-action associated with skill development. In this study, we measured the EEG mu suppression as a proxy of the Mirror Neuron system in experts (pilots) and novices while performing a distance estimation task in a landing scenario. To survey the specificity of this measure, we considered central, parietal and occipital electrode pools and analyzed alpha (8-13 Hz) and beta (18-25 Hz) rhythm bands. We hypothesized that in experts vs. novices, specific neural sensorimotor brain activity would underpin the connection between perception and action in an in-flight context. Preliminary results indicate that alpha and beta rhythm suppression was area-specific irrespective of groups, present in the central electrodes placed over the motor areas. Group analysis revealed that specifically alpha mu rhythm, but not beta, was significantly more suppressed in pilots vs. novices. Complementing these findings we found a trend in which the strength of mu suppression increased with the sense of presence experienced by the pilots. Such sensorimotor activation is in line with the idea that for a pilot, a distance judgment is intimately associated with the function of landing. This reflects the ability to use optical invariants to see the world in terms of the capabilities of the aircraft (e.g., reachability and glide angle). These preliminary findings support the role of embodied simulation mechanisms in visual perception and add important insights into a practical understanding of flight expertise, suggesting sensorimotor mechanisms as potential neuro-markers.

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Mechanisms underlying the EEG biomarker in Dup15q syndrome.

Publications

Mechanisms underlying the EEG biomarker in Dup15q syndrome.

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