Resting state EEG in young children with Tuberous Sclerosis Complex: associations with medications and seizures - PubMed (original) (raw)

Resting state EEG in young children with Tuberous Sclerosis Complex: associations with medications and seizures

Caitlin C Clements et al. J Neurodev Disord. 2025.

Abstract

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.

Keywords: Biomarker; EEG; Epilepsy; GABA agonists; Seizures; Tuberous Sclerosis Complex.

© 2025. The Author(s).

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Conflict of interest statement

Declarations. Ethical approval: Informed consent was provided by all participating families. Study procedures were approved by the Boston Children’s Hospital Institutional Review Board ( IRB P00017878 for JETS; IRB P00018377 for ISP2). Consent for publication: All participating families consented to having the results of the research published in medical books or journals. Competing interests: SJ reports a relationship with TSC Alliance that includes board membership and travel reimbursement.

Figures

Fig. 1

Fig. 1

Decomposition of absolute spectral power into periodic and aperiodic components. The absolute power spectrum can be decomposed into the periodic and aperiodic components by fitting an exponential decay curve (y = 1/f) to the absolute power spectrum to model the aperiodic component. The 1/f curve (aperiodic component) can be described with the offset value (similar to intercept) and exponent (reflects how steep or shallow the curve is, similar to slope). The modeled 1/f curve can then be subtracted from the absolute power spectrum, leaving only the periodic, oscillatory curve. This decomposition can be implemented using the SpecParam algorithm [36] (also known as FOOOF v 1.0.0 [35])

Fig. 2

Fig. 2

Seizure frequency, medication, and infantile spasms in individual TSC participants. Data reflect 49 participants with TSC in a randomized control trial of the JASPER behavioral intervention. At baseline, participants presented with heterogenous profiles of seizure frequency, GABAergic medication use, and presence of infantile spasms. The profile of each participant is depicted as a column of three shaded rectangles reflecting the presence (dark gray), absence (white), or history (light gray) of each clinical feature. For example, participant #18 outlined in red was reported at baseline to experience seizures at least monthly over the last two months; not to take a GABAergic medication; and to have a history of infantile spasms but not currently experience infantile spasms. Seizure severity scores are derived from the E-Chess [45] and incorporate the frequency of seizures, types of seizures (including infantile spasms), and number of anti-epileptic mediations (all classes)

Fig. 3

Fig. 3

TSC and Typical Development parameterized power spectra. TSC and TD groups showed significantly different resting power in several frequency ranges, denoted by an asterisk and black bar spanning the significant frequency range. In aperiodic power (middle row), the TSC group showed significantly greater broadband nonscillatory neuronal firing than the TD group in the posterior intercept, denoted by an asterisk. No group differences were observed in the slope, which reflects the excitatory-inhibitory balance

Fig. 4

Fig. 4

Parameterized frontal periodic power spectrum stratified by seizure composite and GABAergic medication use. (A) As a group, children with TSC (red, n = 49) showed significantly greater peak beta power than age- and sex- matched typically developing controls (gray, n = 49). (B) When the TSC participants were stratified by seizure severity composite, seizure severity appeared to drive the elevated peak beta power finding. The high seizure severity group (red, n = 13) showed significantly greater peak beta power than the moderate (orange, n = 23) and low (yellow, n = 12) seizure severity groups, neither of which differed significantly from typically developing controls (gray, n = 49). (C) When participants with TSC were stratified by GABAergic medication use, GABAergic medication use also appeared to drive the elevated peak beta power finding. The participants with TSC on a GABAergic medication (red dashed line, pink box plot, n = 42) showed significantly greater peak beta power than participants with TSC not on a GABAergic medication (solid red, n = 7), who were not significantly different from typically developing controls (gray, n = 49). (D) Among participants with TSC on GABAergic medication (left), those with high seizure severity (red, n = 12) showed the greatest peak beta power. Seizure severity and GABAergic medication use were independently associated with elevated peak beta power; there was no significant interaction

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