Electroencephalographic Markers of Atypical Development in Infants with Tuberous Sclerosis Complex
Objectives: We aimed to identify potential neural markers associated with the development of ASD in TSC. Specifically, we examined whether developmental trajectories of electroencephalographic (EEG) power (as a marker of neural synchrony) and coherence (as a measure of connectivity) distinguish infants with TSC/ASD from infants with TSC/noASD from very early in development.
Methods: These data were collected as part of a multisite, prospective study of infants with TSC (n=40) and typically developing (TD) infants (n=32) across the first three years of life. Baseline EEG was recorded from infants at 9, 12, 18, 24 and 36 months using a high-density system (EGI Inc.). ASD diagnosis at 24 and 36 months was determined using the Autism Diagnostic Observation Schedule and clinical best estimate. We assessed developmental functioning using the Mullen Scales of Early Learning and we collected clinical information regarding epilepsy and medication status across development.
Results: Mixed-effects models revealed differences in developmental trajectories of both EEG alpha power and alpha phase coherence between (i) TSC and TD infants, and (ii) TSC/ASD and TSC/noASD. TSC infants had reduced whole-brain alpha power across early development (from 9-36mo) compared to TD infants (p<.001). From 12 months, alpha power trajectories differentiated TSC/ASD infants from TSC/noASD, with TSC/ASD infants showing the lowest levels of whole-brain alpha power (p<.01). We also identified significant differences in alpha phase coherence across early development between TSC/ASD and TSC/noASD infants from 12 months (t(24)=2.07, p<.05). These differences were identified despite overall comparable rates of seizures and medication exposure between the TSC/ASD and TSC/noASD groups.
Conclusions: We identified differences in brain function between infants with TSC/ASD and TSC/noASD from 12 months of age, well before the age at which an ASD diagnosis may be established in this population. Our findings suggest that EEG may show promise in identifying patterns of brain function that may precede or underlie the development of ASD in TSC. In particular, group differences in alpha trajectories are suggestive of alterations in white matter development in TSC/ASD. These findings highlight the need for further prospective studies mapping early brain function in TSC from within the first year of life, to identify whether differences in developmental trajectories may precede even the earliest emerging behavioral signs of ASD.