Navigating Opportunities and Challenges in Large-Scale Longitudinal Electroencephalography Studies

To the Editor:

We appreciate Bartholow’s (1) thoughtful commentary on our work examining the association between adolescent alcohol use and electrophysiological markers of error processing in a large adolescent sample (n = 1525) drawn from a population-based cohort (2). We acknowledge that our findings require careful interpretation, as we discussed extensively in the limitations section of our original article. Nevertheless, we would like to address 2 specific conceptual and methodological points raised in the commentary.

Regarding the Error-Related Negativity as an Index of Cognitive Control

Bartholow notes limited evidence linking error-related negativity (ERN) amplitude with between-person differences in cognitive control and indicates that behavioral indices are lacking in our study. While we acknowledge this perspective, numerous theoretical frameworks conceptualize error processing as a component of cognitive control (3,4). As we already indicated in our article, cognitive control represents a broader concept than error processing alone. We do not claim that error processing is synonymous with cognitive control. Having said this, the ERN is a generally accepted marker of error processing, and we emphasize that the present study was not designed to investigate the fundamental nature of the ERN. Rather, this investigation served as an epidemiological examination of biomarkers for alcohol use problems in adolescence. Therefore, our primary conclusion remains well-supported: “These findings show an important link between prevalent alcohol use behaviors and altered electrophysiological markers of error processing.” The theoretical interpretation of these findings naturally remains open for discussion, and future studies, including additional analyses of reaction time data or the NoGo-P3, may provide further clarity on the involvement of other neural and/or behavioral mechanisms of cognitive control.

Regarding Methodological Considerations

Bartholow expresses concern that requiring only 5 error trials may compromise measurement reliability. We addressed this concern in 2 ways. We explicitly acknowledged this limitation in our original article: “Another important limitation is the short EEG measurement duration, which necessitated a relatively low minimum error threshold to retain enough participants and minimize selection bias, but still resulted in substantial exclusions, potentially introducing selection bias.” In a detailed psychometric article [currently under review, but publicly available (5)], we carefully examined the trade-offs involved in setting this threshold. Specifically, there exists an inherent tension between excluding participants with fewer than 5 error trials to increase reliability and maintaining adequate sample representativeness to ensure generalizability and minimize sampling bias.

Critically, error trials are not randomly distributed across participants. Individuals with stronger cognitive control and error processing capacity make fewer errors. Implementing more stringent exclusion criteria would disproportionately exclude individuals with better-functioning error-monitoring systems, thereby introducing systematic selection bias. Based on our psychometric analyses, we determined that a 5-trial threshold achieves an appropriate balance between reliability and representativeness (5).

Second, to empirically test the robustness of our findings, we reanalyzed the data using a minimum threshold of 10 error trials. All associations maintained the same direction, and the main findings were replicated; earlier drinking remained associated with smaller ERN amplitude, and binge drinking remained associated with larger error positivity amplitude. As expected, given the reduced statistical power from the smaller sample (n = 673/582/525 participants depending on the specific analysis: initiation, age of initiation, or recent use), some secondary findings no longer reached statistical significance. Nevertheless, our primary results remain consistent across this alternative threshold.

Bartholow also suggests that longer tasks with more trials would be preferable. We fully agree that increased trial numbers would enhance measurement reliability. However, large population-based epidemiological studies require careful consideration of practical feasibility constraints. Our participants complete a full day of comprehensive assessments, making task duration a critical consideration. Extending task length would likely increase participant fatigue and, more importantly, decrease the willingness to participate in future waves, a particularly consequential concern for longitudinal studies spanning more than 25 years, such as ours.

Concluding Remarks

If electrophysiological research is to advance toward large-scale epidemiological application, an opportunity we believe remains significantly underutilized (6), researchers must thoughtfully navigate these methodological trade-offs rather than dismiss them. We hope our response clarifies the rationale behind our methodological decisions and demonstrates that our core findings are robust to alternative analytic approaches. We welcome continued dialogue on optimizing the balance between psychometric rigor and epidemiological validity in developmental neuroscience research.