New FAST-funded research led by Dr. Michael Sidorov points to a candidate EEG biomarker that could help show early brain responses to treatment, even before day-to-day changes are noticeable.
Quick Takeaways
What was measured: An electroencephalography (EEG) brainwave signal called peak alpha frequency (PAF) that usually increases frequency with age and can reflect how efficiently brain circuits are working.
What was found: In Angelman syndrome, a clear alpha peak showed up far less often, and when it did, PAF was slower and did not increase with age. This pattern held up across two independent analysis methods.
Why it matters now: The results support PAF as a candidate EEG biomarker that could show early brain effects of treatment before day-to-day changes are easy to see. Because EEG is routine and noninvasive, adding PAF to trials would be minimal extra steps for clinics and families. If validated across age groups, PAF could also support studies in adolescents and adults.
About the Study
Angelman syndrome affects how brain networks communicate. A new study in NeuroImage: Clinical looked at a brainwave signal called peak alpha frequency (PAF). In most children, PAF speeds up with age and reflects efficient communication across brain circuits.
The team analyzed 159 EEG recordings from 95 children with Angelman syndrome and compared them with 185 age-matched peers. A clear alpha “peak” appeared in more than 90 percent of typical EEGs but in fewer than half of Angelman EEGs. When present in Angelman syndrome, the peak was slower and did not increase with age. These results were consistent across two methods and were seen alongside the familiar elevation in slow delta activity in Angelman syndrome.
Taken together, the findings support PAF as a candidate, objective EEG measure to be tested in clinical trials. Because EEG is noninvasive and already common in care, PAF tracking could be added with minimal extra steps and interpreted with other outcome measures as part of a sensitive biomarker panel. This study focused on children ages 1-15; next steps will be to evaluate whether PAF is useful in adolescents and adults so it can support trials across the lifespan.
Why This Matters for Families
EEG is already used in clinics, is noninvasive, and is easy to repeat. If PAF reliably reflects how well brain circuits are working, it could give families and researchers an earlier indication of whether a brain-directed therapy is starting to help the brain, before speech, sleep, or motor changes are noticeable. For families, that can mean less waiting in uncertainty, clearer conversations with your care team, and studies that can learn faster and adjust sooner. That kind of early signal can help studies make faster, better decisions and, over time, lead to better treatments. PAF would be used alongside what families and clinicians see day to day; it does not change care today, but it could help the field move toward better treatments sooner. If PAF proves reliable across ages, it may also help teens and adults, where day-to-day changes can be slower to appear.
FAQ
What is a biomarker? A measurable sign in the body that can give an early signal that a disease is changing, or a treatment is having an effect.
What is an EEG and how is it done? An EEG is a safe, noninvasive test that records brain activity using small sensors on the scalp. Sedation is rarely needed.
What does this mean for my loved one living with AS today? It does not change care today. PAF is a promising research measure that could give an early read on brain response. It would be used alongside what families and clinicians already track.
Is peak alpha frequency (PAF) ready to use in clinical trials? Not yet. Scientists are validating it across clinics and with other outcomes. If it proves to be reliable, it may be added to trials.
How This Fits FAST’s Funding Strategy
This project is part of our Pillar 5: Accelerating and Preparing for Clinical Trials. Pillar 5 focuses on practical tools that make trials work well, including endpoints, biomarkers, natural history, and site readiness. Through our Angelman Biomarker and Outcome Measure Consortium (A-BOM), we invest in measures that are meaningful to families and useful for sponsors and regulators.
The PAF study was supported by a FAST grant (FT2022-003; $472,783; PI Michael Sidorov, PhD) to develop EEG biomarkers that work across ages, since many current measures are strongest in early childhood and less informative for adolescents and adults. Validating PAF across ages will allow more trials to include teens and adults.
This is trial readiness at work: funding practical tools that reduce uncertainty and help sponsors see earlier whether a therapy is affecting the brain. When we can read early brain effects, trials can make faster, smarter decisions about what to adjust, continue, or scale.
Help fund the next steps for PAF
Your gift supports cross-clinic standards, reliability testing, and adding this EEG measure to upcoming studies so families get clearer answers sooner.