Sleep affects low-gamma range effective cortical connectivity for 40-Hz auditory steady-state responses

Abstract

The 40-Hz auditory steady-state response (40-Hz ASSR) is a sensitive marker of changes in arousal level, which has been reported to decrease during slow-wave sleep. However, sleep-related changes in directional connectivity during 40-Hz ASSR across cortical networks remain underexplored. In this study, we examined how wakefulness, NREM (N1, N2, N3) and REM sleep affect the direction and extent of neural signal propagation. EEG data during periodic 40-Hz auditory stimulation were collected during an overnight study from 29 normal-hearing human subjects (including 16 females). A source analysis was implemented to locate cortical activity, and effective connectivity was assessed with the Directed Transfer Function (DTF) in the low-gamma band (37-43 Hz). We focused on the connections between auditory cortical regions, prefrontal and temporo-parietal associative cortices. We hypothesized that: 1) feedback connections from associative to primary auditory areas will be the most affected by the arousal state changes; 2) associative reciprocal connectivity between prefrontal and temporo-parietal regions will display gradual connectivity reduction with increasing NREM sleep depth, with partial restoration during REM sleep. Our results showed that feedforward rather than feedback connectivity was most strongly disrupted during sleep, particularly in NREM N2 and N3 stages, contradicting our first hypothesis. The second hypothesis was supported: reciprocal connectivity between prefrontal and parietal associative cortices significantly decreased with sleep depth. Overall, our findings suggest that reduced cortical propagation of 40-Hz ASSR related neuronal signals during sleep primarily reflects a breakdown in bottom-up signal transmission, and a parallel weakening of reciprocal prefrontal-parietal coupling.