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Resting state EEG in young children with Tuberous Sclerosis Complex: associations with medications and seizures
Caitlin C Clements1,2, Anne-Michelle Engelstad3,4, Carol L Wilkinson3,5
1Department of Psychology, University of Notre Dame, 340 Corbett Family Hall Notre Dame, South Bend, IN, 46556, USA. cclemen2@nd.edu.
Insights
Resting state EEG in Tuberous Sclerosis Complex (TSC) shows elevated beta power, potentially influenced by seizures and GABAergic medications. This highlights challenges in using EEG as a biomarker in neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Genetics
- Biomarker Discovery
Background:
- Tuberous Sclerosis Complex (TSC) is a genetic disorder affecting 1 in 7000 births, linked to TSC1/TSC2 gene mutations.
- TSC presents with autism, epilepsy, and intellectual disability, impacting neurodevelopment.
- Resting state EEG can reveal neural activity patterns, potentially serving as a biomarker for TSC.
Purpose of the Study:
- To compare resting state EEG features in young children with TSC against typically developing controls.
- To investigate associations between EEG features, seizure severity, and GABA agonist use in children with TSC.
Main Methods:
- Cross-sectional study comparing 49 children with TSC (12-37 months) to 49 matched controls.
- Resting state EEG data analyzed for spectral power and aperiodic/periodic components.
- Correlation analysis between EEG features, seizure severity, and GABAergic medication use.
Main Results:
- Children with TSC exhibited significantly higher beta power compared to controls.
- Elevated aperiodic offset (non-oscillatory firing) was also observed in TSC.
- Increased beta power in TSC was independently associated with higher seizure severity and GABA agonist use.
Conclusions:
- Elevated beta power in TSC may be influenced by seizures and GABAergic medications.
- Collecting seizure and medication data alongside EEG is crucial for clinical trials.
- Challenges exist in utilizing resting state EEG as a biomarker in TSC due to epilepsy and medication effects.
Background:
Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response. However, seizures and antiepileptic medications also affect resting neural oscillatory activity and could undermine the utility of resting state EEG features as biomarkers in neurodevelopmental disorders such as TSC.
Methods:
This paper compares resting state EEG features in a cross-sectional cohort of young children with TSC (n = 49, ages 12-37 months) to 49 age- and sex-matched typically developing controls. Within children with TSC, associations were examined between resting state EEG features, seizure severity composite score, and use of GABA agonists.
Results:
Compared to matched typically developing children, children with TSC showed significantly greater beta power in permutation cluster analyses. Children with TSC also showed significantly greater aperiodic offset (reflecting nonoscillatory neuronal firing) after power spectra were parameterized using SpecParam into aperiodic and periodic components. Within children with TSC, both greater seizure severity and use of GABAergic antiepileptic medication were significantly and independently associated with increased periodic peak beta power.
Conclusions:
The elevated peak beta power observed in children with TSC compared to matched typically developing controls may be driven by both seizures and GABA agonist use. It is recommended to collect seizure and medication data alongside EEG data for clinical trials. These results highlight the challenge of using resting state EEG features as biomarkers in trials with neurodevelopmental disabilities when epilepsy and anti-epileptic medication are common.
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