The maturation of auditory gamma oscillations reflects the cortical excitability: An MEG study

• In Event: Poster Session 11
  In Poster Session: PS 11 Topic - Biological Processes: Neuroscience and Genetics

Abstract

Introduction
The information processing in sensory systems, including the primary auditory cortex (AC), relies on the interplay between neural excitation (E) and inhibition (I), and gamma-aminobutyric acid (GABA) inhibitory neurotransmitter plays a significant role in E-I balance regulation. The homeostatic E-I balance can be evaluated with electro- or magnetoencephalography (EEG / MEG) by recording the frequency-specific synchronization in the gamma band (30-80Hz), generated by parvalbumin-positive (PV+) inhibitory neurons (e.g., Sohal et al., 2009; Wyss et al., 2017). Moreover, animal studies with optogenetic manipulations showed that PV+ interneurons control sensory processing in AC and regulate the neural adaptation to tones (Natan et al., 2017; Blackwell & Geffen, 2017).
The mechanisms of E-I interaction are usually impaired in such neurodevelopmental disorders as autism, causing increased excitability of sensory systems (Orekhova et al., 2007; Rubenstein, Merzenich, 2003; Yizhar et al., 2011). However, it is unclear whether the cortical marker of E-I interaction (gamma oscillations) can be used as a biomarker of young children with autism, because of the known GABA maturation until early adolescence (Edgar et al., 2016).
The present study investigates the gamma synchrony in the AC. One reliable way to elicit this activity is by presenting to an amplitude-modulated sound at gamma frequency (~40Hz auditory entrainment or auditory steady-state response, ASSR). We aim to register this response in different age groups of children in the left and right Heschl’s gyri. Here, preliminary data of 8 children are presented.

Method
Eight typically developing children participated in the study (four 8-9-year-olds, four 10-11-year-olds). Non-verbal IQ was measured with the Raven’s Colored Progressive Matrices, all children were within the normal range. We used whole-head 306-channel MEG for recording neuromagnetic activity and individual MRI of each child for providing realistic head models. MEG source estimation was performed with minimum-norm imaging method and then normalized with z-score. Time-frequency analysis at the source level was performed with Morlet wavelets (central frequency = 40Hz, time resolution = 0.3 sec) for the right and left Heschl’s gyri.

Results
First, we found a clear bilateral but right-dominant induced 40Hz ASSR in the older group and the absence of this response in younger children in both hemispheres (Figure 1). This pattern for young group reflects the developmental state of GABAeric neurotransmission. Second, the results showed that unmatured GABA causes more excitability of the AC, so leading to a higher magnetic response to the auditory stimulus of the right Heschl’s gyrus in the young group comparing to the older group (Figure 2).

Conclusion
Preliminary data showed the lack of 40Hz ASSR in children younger than 10-year-old. It means that this type of gamma oscillations cannot be used as a biomarker of autism at least for those who younger than 10 years. However, we found that the absence of 40Hz ASSR / unmatured GABA caused higher response in the right Heschl’s gyrus to this type of auditory stimulus. Perhaps, event-related fields to amplitude-modulated sound at ~40Hz gamma frequency may be a more precise marker of cortical E-I balance than gamma oscillations themselves.

Authors

• Vardan Arutiunian, Seattle Children’s Research Institute
  Presenting Author

• Giorgio Arcara, IRCCS San Camillo Hospital
  Non-Presenting Author

• Olga Dragoy, HSE University
  Non-Presenting Author