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

The 40-Hz auditory steady-state response (40-Hz ASSR) is a sensitive marker of changes in arousal level, and declines during slow-wave sleep. However, sleep-related changes in directional connectivity underlying 40-Hz ASSR remain insufficiently characterized. We examined how wakefulness, NREM (N1, N2, N3) and REM sleep modulate the direction and extent of cortical signal propagation. EEG was recorded during overnight 40-Hz auditory stimulation in 29 normal-hearing human subjects (including 16 females). A source reconstruction identified cortical generators, and effective connectivity was quantified using the Directed Transfer Function (DTF) in the low-gamma band (37-43 Hz). Analyses focused on the connections between primary auditory cortical regions, prefrontal and temporo-parietal regions. We hypothesized that (1) feedback connections from associative to primary auditory cortex would be preferentially impaired by reduced arousal, and (2) associative connectivity between prefrontal and temporo-parietal cortices would decline progressively across NREM sleep, with partial restoration during REM sleep. Results showed that during sleep (NREM N2 and N3, as well as REM sleep), both feedforward and feedback connectivity were comparably reduced. At sleep onset (NREM N1), feedforward disruptions were already robust but spatially restricted, whereas feedback reductions were initially weaker and increased progressively across N2, N3, and REM sleep, contradicting the first hypothesis. The second hypothesis was confirmed: reciprocal associative prefrontal-parietal connectivity decreased significantly with increasing sleep depth. Overall, 40-Hz ASSR signal propagation during sleep is characterized by a widespread breakdown of intracortical effective connectivity emerging at sleep onset and becoming fully expressed in deeper sleep stages.