Stimulus train duration but not attention moderates γ-band entrainment abnormalities in schizophrenia

Abstract

Electroencephalographic (EEG) studies of auditory steady-state responses (aSSRs) non-invasively probe gamma-band (40-Hz) oscillatory capacity in sensory cortex with high signal-to-noise ratio. Consistent reports of reduced 40-Hz aSSRs in persons with schizophrenia (SZ) indicate its potential as an efficient biomarker for the disease, but studies have been limited to passive or indirect listening contexts with stereotypically short (500ms) stimulus trains. An inability to modulate sensorineural processing in accord with behavioral goals or within the sensory environmental context may represent a fundamental deficit in SZ, but whether and how this deficit relates to reduced aSSRs is unknown. We systematically varied stimulus duration and attentional contexts to further mature the 40-Hz aSSR as biomarker for future translational or mechanistic studies. Eighteen SZ and 18 healthy subjects (H) were presented binaural pure-tones with or without sinusoidal amplitude modulation at 40-Hz. Stimulus duration (500-ms or 1500-ms) and attention (via a button press task) were varied across 4 separate blocks. Evoked potentials recorded with dense-array EEGs were analyzed in the time-frequency domain. SZ displayed reduced 40-Hz aSSRs to typical stimulation parameters, replicating previous findings. In H, aSSRs were reduced when stimuli were presented in longer trains and were slightly enhanced by attention. Only the former modulation was impaired in SZ and correlated with sensory discrimination performance. Thus, gamma-band aSSRs are modulated by both attentional and stimulus duration contexts, but only modulations related to physical stimulus properties are abnormal in SZ, supporting its status as a biomarker of psychotic perceptual disturbance involving non-attentional sensori-cortical circuits.

40 Hz Auditory Steady-State Responses Predict Transition to Psychosis in Clinical-High-Risk Participants: A MEG Study

“…In terms of the location of 40-Hz-ASSR impairments, we found reductions in both RROL and RTHA in CHR-P participants, while deficits in the FEP-group were confined to the RTHA. These findings contrast with previous observations in ScZ that have localized 40-Hz-ASSR deficits to primary auditory cortex (Heschl's gyrus) and/or the superior temporal cortex (29,30). Accordingly, our data highlight that impairments in the 40-Hz-ASSR during emerging psychosis may involve higher auditory areas as well as contributions from thalamic sources while impairments in primary auditory regions may emerge during later illness stages.…”

Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents

“…This added complexity makes P300 less valuable for a pure assessment of contextual modulation of sensory processing (Picton, 1992;Näätänen, 1995;Ethridge et al, 2015). This is especially important given that people with SZ often have both attentional and pre-attentive processing deficits (Rabinowicz et al, 2000;Schechter et al, 2006;Elshaikh et al, 2015;Hamm et al, 2015;Javitt and Freedman, 2015), and, thus, a marker of pre-attentive context processing like the MMN is advantageous for animal experimentation where attention may be difficult to obtain or gauge.…”

Neural network dynamics underlying gamma synchronization deficits in schizophrenia

“…[20][21][22] Schizophrenia patients have selectively reduced synchrony to auditory-based 40-Hz stimulation, but normal responses to other rates of stimulation. 3,18,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] This gamma band auditory-steady response (ASSR) has received significant attention as a potential translatable biomarker advancing procognitive treatment development in schizophrenia and other brain disorders, such as bipolar disorder, autism spectrum disorder and 22q11.2 deletion syndrome. 26,35,[37][38][39][40][41][42][43][44] Despite this interest, there is limited information in schizophrenia patients about how different brain regions coordinate, interact and produce ASSR deficits through the stimulus entrainment period.…”