ERP Assessments in Rare Pediatric Conditions

Context‍

Event-related potentials (ERPs), recorded using scalp electrophysiology (EEG), offer a non-invasive, high-temporal-resolution method for assessing the cognitive and socio-emotional development in rare pediatric CNS disorders, where objective biomarkers to assess treatment response are often lacking¹.

By capturing neural responses to sensory, cognitive, and motor stimuli, ERPs enable the quantification of dysfunctions in information processing, even in pre-verbal or minimally communicative patients. Specific ERP components, such as mismatch negativity (MMN) for auditory processing and P300 for cognitive function, can serve as biomarkers of disease progression and treatment response. Their sensitivity to subtle neural changes makes ERPs valuable endpoints for clinical trials, facilitating early detection and evaluation of therapeutic efficacy in pediatric CNS patients.

‍Challenge‍

Ensuring high-quality ERP endpoints for assessing treatment efficacy in rare pediatric CNS disorders, both with and without developmental delays, requires developmentally and age-appropriate acquisition protocols, paradigm selection, hardware setups, and task designs to overcome technical and operational challenges.

Solution‍

To address these, Clouds of Care puts forward a study design with the appropriate ERP components for the clinical hypothesis, such as P300, MMN, Auditory Brainstem Response (ABR), N170, and Error-Related Negativity (ERN).

To ensure consistent acquisition across patients, Clouds of Care leverages the EEG hardware of curated Digital Health Technology (DHT) partners with fit-for-purpose equipment and electrode setup in this context of use, balancing EEG application time and invasiveness, all whilst optimizing signal quality. Related ERP procedures are compiled in a comprehensive ERP charter, with participating EEG technicians given training to ensure proficiency in the ERP procedures.

To ensure the highest degree of ERP interpretation, preprocessing and automated ERP extraction are applied in combination with verification by an expert reader, enabling a higher degree of accuracy in treatment efficacy assessment.

Impact‍

By accommodating the unique circumstances and challenges of measuring ERPs in pediatric subjects, we unlock a direct and non-invasive method to reveal critical aspects of processing, attention, and cognition. Such a development- and age-appropriate ERP approach can enhance our understanding of rare pediatric CNS disorders and ultimately speed up the clinical development and delivery of new treatment options for pediatric patients.

Beyond rare pediatric CNS disorders, ERPs have also been used as objective endpoints in adult conditions such as Alzheimer's Disease² and Major Depressive Disorder³, further demonstrating their broad applicability in CNS clinical development.

Made possible by our curated DHT partner:

Sources:

1. Webb et al. 2022, “The Autism Biomarker Consortium for Clinical Trials: Initial Evaluation of a Battery of Candidate EEG biomarkers”; Tye et al. 2022, “Understanding the Nature of Face Processing in Early Autism: A Prospective Study”; Berchio et al. 2022, “Cognitive assessment using ERP in child and adolescent pshyiatry: Difficulties and opportunities”, Wiersema et al. 2005, “ERP correlates of impaired error monitoring in children with ADHD”.
2. Tsolaki et al. 2017, “Brain source localization of MMN and P300 ERPs in mild cognitive impairment and Alzheimer's disease: a high-density EEG approach.”; Vaitkevičius et al. 2015, “Distinctive Effect of Donepezil Treatment on P300 and N200 Subcomponents of Auditory Event-Related Evoked Potentials in Alzheimer Disease Patients”.
3. Fotti et al. 2010, “Reduced electrocortical response from threatening faces in major depressive disorder”; Bruder et al. 2012, “20 Event-Related Brain Potentials in Depression: Clinical, Cognitive, and Neurophysiological implications”.