Insights Gained from Electrophysiological Investigation of High-Risk Infants: Early Markers of ASD in Infants with Tuberous Sclerosis Complex

Background: Early identification and intervention research has traditionally relied on behavioral markers to predict outcomes and measure change across development. While valuable, this approach is limited by the restricted behavioral repertoire of infants and young children, particularly those with developmental delays. The integration of quantifiable brain-based measures in developmental research provides a means to capture subtle and covert processes, both within and across individuals, which may not be detected at the behavioral level. In this context, non-invasive brain-based measures that can be used from early in life, such as electroencephalography (EEG), hold promise as biomarkers of risk, prediction, stratification and treatment monitoring. Importantly, as EEG reflects the synchronous activation of large populations of neurons, it serves as a “bridge” between genes and behavior that holds considerable promise in mechanistic discovery in neurodevelopmental disorders.

Objectives: Here, we draw upon our prospective, longitudinal study of infants with TSC to demonstrate (1) how we have used EEG to explore whether impairments in higher-order visually mediated behaviors in TSC are grounded in alterations in low-level visual processing, (2) the ability of EEG to facilitate the deeper characterization of early development in this rare population, (3) the promise of EEG methods to guide the search for early, predictive biomarkers that uniquely sensitive to ASD and Intellectual Disability in this high-risk population.  

Methods: High-density EEG recordings were conducted with infants with TSC and typically-developing control infants at 6, 12, 18, 24 and 36 months using 128-channel HydroCel Geodesic Sensor Nets (EGI Inc.). Based on evidence from animal models of TSC for alterations in the retinogeniculate pathway, we used a visual evoked potential (VEP) paradigm to determine whether alterations in low-level visual processing in TSC may be a potential mechanism for deficits in higher-order visually mediated behaviors (as indexed on behavioral measures). We also assayed more complex visual processing in TSC by recording event-related potentials (ERPs) to faces versus objects. 

Results: To date, we have identified intact low-level visual processing in TSC (as demonstrated by remarkably intact VEPs; Varcin et al., in press) albeit with alterations in more complex visual processing emerging between 12 and 24 months. These findings suggest that atypical face processing does not appear to be a consequence of early visual processing alterations, and instead, point toward aberrations in circuits associated with the processing of more complex visual stimuli.

Conclusions: Impairments in the non-verbal, visually-mediated behaviors in TSC do not appear to be rooted in disturbances in low-level visual processing and, instead, may stem from higher-level alterations in information processing. Our EEG findings are also capturing changes in the processing of complex visual stimuli between 12 and 24 months, complementing our behavioral findings in highlighting this period as an important target for early intervention and guiding further investigation into potential mechanisms accounting for this change.