Brian J Roach1, Judith M Ford2, Daniel H Mathalon3. 1. Mental Health Service, San Francisco Veterans Affairs Health Care System, University of California, San Francisco, San Francisco, California; Northern California Institute for Research and Education, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California. 2. Mental Health Service, San Francisco Veterans Affairs Health Care System, University of California, San Francisco, San Francisco, California; Department of Psychiatry, University of California, San Francisco, San Francisco, California. 3. Mental Health Service, San Francisco Veterans Affairs Health Care System, University of California, San Francisco, San Francisco, California; Department of Psychiatry, University of California, San Francisco, San Francisco, California. Electronic address: daniel.mathalon@ucsf.edu.
Abstract
BACKGROUND: In 1999, Kwon et al. reported several electroencephalographic gamma band auditory steady-state response (ASSR) abnormalities in schizophrenia, spawning approximately 100 subsequent studies. While many studies replicated the finding of reduced 40-Hz ASSR power in schizophrenia and extended this by showing that 40-Hz phase synchrony (phase-locking factor [PLF]) was also reduced, none attempted to replicate the original phase delay finding of Kwon et al. Accordingly, we measured the 40-Hz ASSR phase-locking angle (PLA) to assess phase delay and examined its differential sensitivity to schizophrenia, relative to power and PLF measures. METHODS: To obtain ASSRs, electroencephalography data were recorded from 28 patients with schizophrenia and 25 healthy control subjects listening to repeated 40-Hz 500-ms click trains. Evoked power, total power, PLF, and PLA were calculated after Morlet wavelet time-frequency decomposition of single trial data from electrode Fz. RESULTS: In patients with schizophrenia, 40-Hz PLA was significantly reduced (i.e., phase delayed) (p < .0001) and was unrelated to reductions in their 40-Hz power or PLF. PLA discriminated patients from healthy control subjects with 85% accuracy compared with 67% for power and 65% for PLF. CONCLUSIONS: Consistent with the original Kwon et al. study, 40-Hz click train-driven gamma oscillations were phase delayed in schizophrenia. Importantly, this phase delay abnormality was substantially larger than the gamma power and phase synchrony abnormalities that have been the focus of prior 40-Hz ASSR studies in schizophrenia. PLA provides a unique neurobiological measure of gamma band abnormalities in schizophrenia, likely reflecting a distinct pathophysiological mechanism from those underlying PLF and power abnormalities.
BACKGROUND: In 1999, Kwon et al. reported several electroencephalographic gamma band auditory steady-state response (ASSR) abnormalities in schizophrenia, spawning approximately 100 subsequent studies. While many studies replicated the finding of reduced 40-Hz ASSR power in schizophrenia and extended this by showing that 40-Hz phase synchrony (phase-locking factor [PLF]) was also reduced, none attempted to replicate the original phase delay finding of Kwon et al. Accordingly, we measured the 40-Hz ASSR phase-locking angle (PLA) to assess phase delay and examined its differential sensitivity to schizophrenia, relative to power and PLF measures. METHODS: To obtain ASSRs, electroencephalography data were recorded from 28 patients with schizophrenia and 25 healthy control subjects listening to repeated 40-Hz 500-ms click trains. Evoked power, total power, PLF, and PLA were calculated after Morlet wavelet time-frequency decomposition of single trial data from electrode Fz. RESULTS: In patients with schizophrenia, 40-Hz PLA was significantly reduced (i.e., phase delayed) (p < .0001) and was unrelated to reductions in their 40-Hz power or PLF. PLA discriminated patients from healthy control subjects with 85% accuracy compared with 67% for power and 65% for PLF. CONCLUSIONS: Consistent with the original Kwon et al. study, 40-Hz click train-driven gamma oscillations were phase delayed in schizophrenia. Importantly, this phase delay abnormality was substantially larger than the gamma power and phase synchrony abnormalities that have been the focus of prior 40-Hz ASSR studies in schizophrenia. PLA provides a unique neurobiological measure of gamma band abnormalities in schizophrenia, likely reflecting a distinct pathophysiological mechanism from those underlying PLF and power abnormalities.