Influence of inter-stimulus interval on 40-Hz auditory steady-state response in patients with schizophrenia

Decreased 40-Hz auditory steady-state response (ASSR) is believed to reflect abnormal gamma oscillation in patients with schizophrenia (SZ). However, previous studies have reported conflicting results due to variations in inter-stimulus interval (ISI) used. In this study, we aimed to investigate the influence of varying ISI on the 40-Hz ASSR, particularly for patients with SZ and healthy controls (HCs). Twenty-four SZ patients (aged 40.8 ± 13.9 years, male: n = 11) and 21 HCs (aged 33.3 ± 11.3 years, male: n = 8) were recruited. For every participant, 40-Hz ASSRs were acquired for three different stimulus types: 500, 2000, and 3500 ms of ISIs. Two conventional ASSR measures (total power and inter-trial coherence, ITC) were calculated. Several additional ASSR measures were also analyzed: (i) ISI-dependent power; (ii) power onset slope; (iii) power centroid latency; (iv) ISI-dependent ITC; (v) ITC onset slope (500, 2000, 3500 ms); (vi) ITC centroid latency (500, 2000, 3500 ms). As ISI increased, total power and ITC increased in patients with SZ but decreased in HCs. In addition, patients with SZ showed higher ISI-dependent ITC, which was positively correlated with the psychotic symptom severity. The abnormal ITC onset slope and centroid latency for the ISI-500 ms condition were associated with cognitive speed decline in patients with SZ. Our study confirmed that the 40-Hz ASSR could be severely influenced by ISI. Furthermore, our results showed that the additional ASSR measures (ISI-dependent ITC, ITC onset slope, ITC centroid latency) could represent psychotic symptom severity or impairment in cognitive function in patients with SZ.