Clarifying directional dependence among measures of early auditory processing and cognition in schizophrenia: leveraging Gaussian graphical models and Bayesian networks.

BACKGROUND: Research using latent variable models demonstrates that pre-attentive measures of early auditory processing (EAP) and cognition may initiate a cascading effect on daily functioning in schizophrenia. However, such models fail to account for relationships among individual measures of cognition and EAP, thereby limiting their utility. Hence, EAP and cognition may function as complementary and interacting measures of brain function rather than independent stages of information processing. Here, we apply a data-driven approach to identifying directional relationships among neurophysiologic and cognitive variables. METHODS: Using data from the Consortium on the Genetics of Schizophrenia 2, we estimated Gaussian Graphical Models and Bayesian networks to examine undirected and directed connections between measures of EAP, including mismatch negativity and P3a, and cognition in 663 outpatients with schizophrenia and 630 control participants. RESULTS: Chain structures emerged among EAP and attention/vigilance measures in schizophrenia and control groups. Concerning differences between the groups, object memory was an influential variable in schizophrenia upon which other cognitive domains depended, and working memory was an influential variable in controls. CONCLUSIONS: Measures of EAP and attention/vigilance are conditionally independent of other cognitive domains that were used in this study. Findings also revealed additional causal assumptions among measures of cognition that could help guide statistical control and ultimately help identify early-stage targets or surrogate endpoints in schizophrenia.

Novel N100 area reliably captures aberrant sensory processing and is associated with neurocognition in early psychosis.

BACKGROUND: Despite findings from translational and genetic studies in the event-related potential (ERP) literature, the validity and reliability of P50 suppression as a schizophrenia spectrum endophenotype has been questioned. Here, we aimed to examine sensory registration and gating measures derived from P50 and N100 amplitude, as well as N100 area-a novel approach proposed herein-in early psychosis versus health. METHODS: Individuals at clinical high risk for psychosis (CHR; n = 77), first-episode psychosis (FE; n = 52), and healthy controls (HC; n = 65) were assessed in a paired-click auditory ERP paradigm. Eight CHR converted to psychosis (CHRC) and 39 did not (CHR-NC) by 24 months, while 30 CHR were lost to follow-. Group differences, test-retest reliability, and associations with neurocognitive function were assessed in nine ERP measures. RESULTS: Significant differences were observed in N100 S1 amplitude, S1 area, and area difference between HC and FE, as well as in N100 S1 area between HC and CHR, among the total population. Furthermore, significant differences were found in N100 S1 area between HC and CHR-NC (Cliff's delta, Δ = 0.32), as well as in N100 area difference between HC and CHR-C (Δ = 0.55). Both N100 S1 area and area difference demonstrated moderate to acceptable reliability (intraclass correlation coefficients: 0.61-0.78). Processing speed negatively correlated with both N100 S1 area and area difference, while executive function negatively correlated with N100 S1 area alone in CHR and FE. CONCLUSION: Among the ERP measures studied, N100 area measures may serve as a reliable biomarker of aberrant sensory processing and neurocognition in early psychosis.