Phase locking of auditory steady state responses is modulated by a predictive sensory context and linked to degree of myelination in the cerebellum

Background 40 Hz auditory steady state responses (ASSR) can be evoked by brief auditory clicks delivered at 40 Hz. While the neuropharmacology behind the generation of ASSR is well examined, the link between ASSR and microstructural properties of the brain is unclear. Further, whether the 40 Hz ASSR can be manipulated through processes involving top-down control, such as prediction, is currently unknown. Methods We recorded EEG in 50 neurotypical participants while they engaged in a 40 Hz Auditory steady state paradigm. We manipulated the predictability of tones to test the modulatory effect of prediction on 40 Hz steady state responses. Further, we acquired T1w and T2w structural MRI and used the T1/T2 ratio as a proxy to determine myelination in grey matter. Results The phase locking of the 40 Hz ASSR was indeed modulated by prediction and this modulation extended to all frequency bands, suggesting prediction violation as a phase resetting mechanism. Interestingly, we found that the prediction violation of the phase locking at 40 Hz (gamma) was associated with the degree of grey matter myelination in the right cerebellum. Discussion We demonstrate that prediction violations evoke resetting of oscillatory activity and suggest that the efficiency of this process is promoted by greater cerebellar myelin. Our findings provide a structural-functional relationship for myelin and phase locking of auditory oscillatory activity. These results introduce a setting for looking at the interaction of predictive processes and ASSR in disorders where these processes are impaired such as in psychosis. ### Competing Interest Statement HRS has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark and as senior editor (NeuroImage) and editor-in-chief (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. HRS has also received royalties as book editor from Springer Publishers, Stuttgart, Germany and Gyldendahl Publishers, Copenhagen, Denmark. All disclosures are independent of the work published here. All other authors report no financial disclosures. ### Funding Statement This work was funded by the Australian Research Council Centre of Excellence for Integrative Brain Function (ARC Centre Grant CE140100007). KML received funding from the Lundbeck foundation (R322-2019-2311) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This research was approved by the University of Queensland Human Research Ethics. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors