P300 Event-Related Potentials as Cognitive Biomarkers in Neurological and Neuropsychiatric Disorders: A Systematic Review

AI Summary

P300 is a non-invasive transdiagnostic cognitive biomarker; clinical populations show prolonged latency and reduced amplitude versus controls (pooled SMD −0.72).
P300 demonstrates diagnostic, prognostic and treatment-monitoring utility, detecting response earlier than conventional assessments; neuromodulation most robustly normalises P300.
Near-term clinical applications include consciousness assessment, dementia cognitive screening and treatment monitoring, but standardisation, multi-site validation and scalable EEG technologies are needed.

Rev Neurol. 2026 May 26;81(5):49664. doi: 10.31083/RN49664.

ABSTRACT

BACKGROUND: Neurological and neuropsychiatric disorders constitute a major global health challenge. The P300 event-related potential, an electroencephalography-derived measure of cognitive processing, has emerged as a promising biomarker for diagnosis, treatment monitoring, and outcome prediction. This systematic review examines P300’s role across neurological and neuropsychiatric disorders, evaluating how P300 latency (processing speed) and amplitude (attentional resource allocation) may reflect neurocognitive dysfunction.

METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched PubMed, Scopus, and Web of Science for randomized controlled trials and controlled studies published January 2020-August 2025. Six research domains were examined: dementia spectrum disorders (Research Question, RQ1), acquired brain injury and disorders of consciousness (RQ2), mood and anxiety disorders (RQ3), neurodevelopmental disorders (RQ4), psychotic disorders and addiction (RQ5), and chronic neurological conditions (RQ6). Risk of bias was assessed using a modified Cochrane tool. Of 125 records identified, 52 studies met the inclusion criteria.

RESULTS: P300 emerged as a promising transdiagnostic biomarker. Prolonged latency and reduced amplitude consistently characterized clinical populations versus controls (pooled standardized mean difference [SMD] = -0.72, 95% confidence interval [CI]: -0.89 to -0.55; I² = 67.3%). In dementia spectrum disorders, P300 latency distinguishes mild cognitive impairment from healthy aging. In disorders of consciousness, the emergence of the P300 waveform provided objective indices of residual cognitive capacity. In mood disorders, baseline amplitude predicted therapy outcomes. In addition, P300 correlated with craving severity. Neuromodulation (transcranial direct current stimulation [tDCS], repetitive transcranial magnetic stimulation [rTMS]) produced the most robust normalization effects across categories. P300 changes occurred within 3 days to 6 weeks of treatment, potentially enabling earlier detection of response than conventional assessments. Portable electroencephalography (EEG) systems demonstrated adequate sensitivity for clinical applications.

CONCLUSIONS: P300 shows promise as a non-invasive biomarker for cognitive dysfunction across neuropsychiatric disorders. Its diagnostic utility, treatment responsiveness, and prognostic potential support clinical translation. Near-term applications include consciousness assessment, cognitive screening in dementia, and treatment monitoring. However, standardization of protocols, multi-site validation, and scalable technologies require further development. Advancing P300 research through interdisciplinary collaboration may contribute to precision psychiatry and population-level mental health strategies.

PMID:42216459 | DOI:10.31083/RN49664

Document this CPD