Phase Locking of 40 Hz Auditory Steady State Responses Is Modulated by Sensory Predictability and Linked to Cerebellar Myelination

Abstract

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. We recorded EEG in 50 neurotypical participants while they engaged in a 40 Hz auditory steady-state paradigm. We manipulated the predictability of the stimuli to test the modulatory effect of prediction on 40 Hz steady-state responses. Further, we acquired T1w and T2w structural MRI on the same individuals and used the T1/T2 ratio as a proxy to determine myelination content in gray matter. The phase locking of the 40 Hz ASSR was indeed modulated by prediction, suggesting that prediction violation directly affects phase locking to the 40 Hz ASSR. We found that the prediction violation of the phase locking at 40 Hz (gamma) was associated with the degree of gray matter myelination in the right cerebellum, such that greater myelin led to less desynchronization induced by prediction violations. We demonstrate that prediction violations modulate steady-state activity at 40 Hz 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 framework for investigating the interaction of predictive processes and ASSR in disorders where these processes are impaired, such as in psychosis.

FIGURE 1

Click trains with a frequency of 40 Hz were arranged in a classical oddball paradigm where the deviant changed tone duration to either be longer than the standard (long block) or shorter than the standard (short block). The MMN_short responses were derived by contrasting the standard tone in the long block with the deviant tone in the short block to ensure comparison of stimuli with the same duration. Likewise, the MMN_long responses were derived by contrasting the standard tone in the short block with the deviant stimuli in the long block. Epochs were extracted from 250 ms pre‐stimulus to 1000 ms post‐stimulus onset.

FIGURE 2

Time‐frequency responses at channel Cz averaged across participants (for the long block, similar findings in the short block, see sup Figure 2). Dotted lines indicate onset and offset of auditory stimuli. (A) Full frequency spectrum covering 2–60 Hz. (B) Zoomed in at 15‐60 Hz to highlight the successful evoking of 40 Hz.

FIGURE 3

Power (bottom) and phase‐locking factor (top) extracted from channel Cz in the period of stimulation averaged across the long and short blocks. Blue indicates standard and green is deviant. The connecting gray line indicates the relationship between the standard and deviant for each individual participant. ** is p < 0.01, *** is p < 0.001, corrected for multiple comparison.

FIGURE 4

(A) Association between myelin content and phase‐locking for the gamma band (between the standard and deviant). Peak of the association was found in MNI coordinates [53 −57 −34]. Cluster forming threshold was set to p = 0.001 uncorrected, and results here only show the cluster that survived correction at the cluster level at p < 0.05. (B) T1w/T2w intensity values extracted from the cluster in the cerebellum increase with the phase‐locking factor of the difference wave (between the standards and deviants).