Atypical cortical connectivity in autism spectrum disorder (ASD) as measured by magnetoencephalography (MEG)

Thesis by publication.Bibliography: pages 168-183.Chapter 1. General introduction -- Chapter 2. The detection of phase amplitude coupling during sensory processing -- Chapter 3. Dysregulated oscillatory connectivity in the visual system in autism spectrum disorder -- Chapter 4. Reduced auditory steady state responses in autism spectrum disorder -- Chapter 5. Testing predictive coding theories of autism spectrum disorder using the auditory oddball paradigm - an MEG study -- Chapter 6. The neural basis of perspective-taking in neurotypical and autistic populations -- Chapter 7. General discussion -- References -- Appendices.Autism Spectrum Disorder (ASD) is a neurodevelopmental condition, characterised by impairments in social interaction and communication, the presence of repetitive behaviours, and multisensory hyper- and hypo-sensitives. This thesis utilised magnetoencephalography, in combination with robust analysis techniques, to investigate the neural basis of ASD. Based on previous research, it was hypothesised that cortical activity in ASD would be associated with disruptions to oscillatory synchronisation during sensory processing, as well as during high-level perspective-taking. More specifically, a novel framework was introduced, based on local gamma-band dysregulation, global hypoconnectivity and deficient predictive-coding. To test this framework, data were collected from adolescents diagnosed with ASD and age-matched controls.Using a visual grating stimulus, it was found that in primary visual cortex, ASD participants had reduced coupling between the phase of alpha oscillations and the amplitude of gamma oscillations (i.e. phase amplitude coupling), suggesting dysregulated visual gamma in ASD. These findings were based on a robust analysis pipeline outlined in Chapter 2. Next, directed connectivity in the visual system was quantified using Granger causality. Compared with controls, ASD participants showed reductions in feedback connectivity, mediated by alpha oscillations, but no differences in inter-regional feed forward connectivity, mediated by gamma oscillations. In the auditory domain, it was found that ASD participants had reduced steady-state responses at 40Hz, in terms of oscillatory power and inter-trial coherence, again suggesting dysregulated gamma. Investigating predictive-coding theories of ASD using an auditory oddball paradigm, it was found that evoked responses to the omission of an expected tone were reduced for ASD participants. Finally, we found reductions in theta-band oscillatory power and connectivity for ASD participants, during embodied perspective-taking. Overall, these findings fit the proposed framework, and demonstrate that cortical activity in ASD is characterised by disruptions to oscillatory synchronisation, at the local and global scales, during both sensory processing and higher-level perspective-taking.Mode of access: World wide web1 online resource (192 pages) illustrations (some colour