UCLA

Individuals with schizophrenia (SZ) commonly demonstrate attentional deficits, which in turn may contribute to higher-level cognitive dysfunction and clinical symptoms associated with the disorder. In EEG studies, these deficits are reliably observed during an auditory paired-stimulus paradigm, in which two identical stimuli are presented 500 ms apart. Relative to healthy comparison participants (HC), SZ typically exhibit a smaller N100 component of the event-related brain potential (ERP) following the first stimulus, indicative of impaired allocation of attention. HC generally demonstrate a decrease in N100 amplitude in response to the second stimulus relative to the first (i.e., N100 suppression), whereas SZ reliably demonstrate less suppression, indicative of inhibitory filtering dysfunction. A separate body of research using fMRI has linked salience and inhibitory processing deficits in SZ to insufficient suppression of the default mode network (DMN) of the brain, which supports internally-based processes and self-referential processing. The salience network (SAL), a higher-order system responsible for monitoring stimulus salience, regulates DMN as needed for tasks requiring attention to external stimuli. Given the shared constructs associated with N100 responses and the connectivity between DMN and SAL, it was hypothesized that these N100 variables and neural network measures capture disorder-related dysfunction in shared mechanisms of salience and inhibitory processing and would thus be related. To evaluate these relationships in SZ (N = 52) and HC (N = 25), a multimodal approach was employed using resting-state fMRI, resting-state EEG, and EEG recorded during the paired-stimulus paradigm. Among SZ, resting state hyperconnectivity within DMN was observed using both oscillatory EEG and fMRI data, with DMN hyperconnectivity observed specifically in the EEG beta frequency band. SZ and HC generally demonstrated opposing relationships between resting state DMN connectivity and N100 variables, such that greater intra-DMN connectivity was associated with attenuated N100 amplitude and higher N100 ratio scores in SZ. SZ also demonstrated greater resting state DMN-to-SAL effective connectivity than SAL-to-DMN connectivity, whereas HC demonstrated no such asymmetry. In oscillatory EEG collected during the paired-stimulus paradigm, SZ demonstrated less evoked theta-band connectivity within DMN following presentation of the auditory stimulus. No relationships between task-based network connectivity measures and N100 variables were identified. Present findings demonstrate specific profiles of DMN dysfunction in SZ that differentially relate to attentional processes indexed by measures obtained from the N100 ERP component during the paired-stimulus paradigm. Multimodal data fusion demonstrated that EEG and fMRI assessments of DMN were related yet also captured unique aspects of network function associated with N100 phenomena in SZ. Future work can build upon this research to further clarify how alterations in these neural mechanisms contribute to disorder-related impairments and inform promising targets for individualized prevention and treatment.