UCLA

Cognitive symptoms of schizophrenia can be substantially improved with cognitive training (CT) interventions, such that durable cognitive gains emerge along with strengthening of relevant neural circuits. However, treatment response is often variable, and optimizing CT efficacy likely requires a deeper understanding of the pathophysiological processes associated with cognitive impairment in schizophrenia. Early auditory processing impairments, involving stimulus registration and sensory gating, are well established in schizophrenia. Further, these auditory impairments have demonstrated relationships with cognitive symptoms and may be indirectly strengthened through CT, though a range of internal and external factors may also influence these effects. Across three studies, the present dissertation examined auditory processing impairments and their potential predictors and consequences in adults experiencing a first episode of schizophrenia. Participants with schizophrenia and healthy comparison participants completed EEG recordings during a paired-stimulus procedure, along with clinical and neurocognitive assessments. Patients were evaluated before and after participation in a CT intervention. Event-related brain potentials (ERPs) derived from EEG data were used to characterize auditory processing in both cross-sectional and longitudinal analyses. Findings from Study 1 supported a combined model of sensory gating impairment in schizophrenia, reflecting both poorer registration of initial stimuli and less suppression of repeated stimuli. However, no systematic changes in auditory ERPs were observed following CT. Studies 2 and 3 examined potential sources of group- and individual-level variability in auditory and cognitive trajectories by testing the moderating effects of internal (auditory hallucinations) and external (noise pollution) factors. Study 2 demonstrated that sensory gating impairments were more pronounced in patients experiencing recent and persistent auditory hallucinations. Study 3 found evidence of larger between-group differences in sensory gating among participants exposed to high levels of environmental noise. Neither of the two factors accounted for significant variance in auditory or cognitive change trajectories, however. Although findings across the three studies were somewhat mixed, they collectively provide preliminary support for an integrated model of auditory dysfunction in schizophrenia and offer direction for future research aimed at identifying moderators of intervention response trajectories.