2025 HDBuzz Prize: Calm Before the Storm: Early Clues of Huntington’s Disease Found in Brainwaves

We know that HD affects how we move, think, and feel but these symptoms don’t appear overnight. Tiny hidden changes in the brain can begin years before a diagnosis. One way that scientists can detect these early shifts is by measuring brainwaves. This is a painless, non-invasive way to see how the brain is working during rest or while performing simple tasks. 

A recent study used this approach to see whether people who carry the HD gene, both before and after symptoms start, show differences in how their brains respond to unexpected noises. The result of this study suggests that even in the “silent” pre-manifest stage of HD (HD-ISS stage 0), the brain’s automatic reactions are already changing. This could open the door to new ways of tracking HD’s earliest effects. 

Eavesdropping On The Brain’s Electrical Chatter 

You might remember Sherlock Holmes saying, “The world is full of obvious things which nobody by any chance ever observes.”  When it comes to HD, that seems to be especially true. While we often notice the louder, more obvious, symptoms of HD like movement difficulties, mood changes or thinking problems, the brain can “whisper” clues for years beforehand. The challenge for researchers is learning how to listen. 

Our brains are constantly alive with tiny bursts of electricity zipping along and between neurons. Even when we’re resting or not paying attention, this electrical chatter never stops. Imagine a stadium full of fans. From far away, you can’t hear individual conversations, but you can tell when the crowd gasps at a near goal, bursts into cheers, or suddenly falls silent. That’s how brainwaves work, rhythmic electric signals made by networks of brain cells talking to one another.  

To “hear” these brainwaves, researchers use a very fancily named tool called electroencephalography, or EEG, for short. It’s painless, requires no needles, and simply involves placing small sensors on the scalp. EEG doesn’t read our thoughts (sorry, no mind reading here!), but it does detect patterns and timing of brain activity. A bit like noticing when the crowd shifts from calm murmuring to roaring cheers.  

The Brain’s Surprise Detector 

In this study, researchers were particularly interested in a certain brainwave signal called mismatch negativity (MMN). Think of MMN as your brain’s “surprise detector.” Even if you aren’t paying attention, your brain automatically notices when something changes around you. 

Picture yourself on a long train journey, listening to the steady click-clack of the train on the tracks. If one clack sounds different, louder, or higher pitched, your brain reacts instantly, even if you’re daydreaming. That small, automatic reaction is what MMN represents. 

To test this, researchers invited people with the HD gene (both with and without symptoms) as well as volunteers without the gene. While wearing an EEG cap, participants listened to a series of steady beeps, with the occasional odd “bleep” slipped in. EEG measured how strongly and consistently each person’s brain reacted to the odd sounds.  

What the Study Found: Cracking Open The Brain’s Whispering

When the results were compared, one pattern stood out. People with symptoms of HD had smaller MMN signals, especially at the front of the brain. This suggests their automatic “something’s different” response was weaker. 

People who carried the gene but had no symptoms yet did not show a reduction in MMN signal size. But their brainwave timing told an interesting story. The researchers looked at something called theta phase coherence, a fancy way to measure precisely how the brain’s rhythm lined up each time a surprise sound occurred. 

In people without symptoms but who carry the HD gene, their theta phase coherence was higher than in both people with symptoms and those without the HD gene. This is interesting for us as this finding suggests that perhaps the brain is trying to overcompensate, like a drummer keeping an unusually strict beat to hold the rest of the band together. These brainwave changes may be the brain’s way of coping, helping it keep things working in the early stages of the disease.

Why Does This matter?

Think of your brain like an orchestra. In healthy brains, the instruments (neurons) keep perfect time, adjusting smoothly to new notes (unexpected sounds). In early HD, the orchestra might still sound fine to an outside listener, but behind the scenes, the conductor is working overtime to keep everyone in sync, maybe even counting every beat twice. 

This extra timing consistency in people with the HD gene but without symptoms, could be that overworked conductor. The brain finding clever ways to compensate before symptoms emerge. In people with symptoms, that compensation may no longer be enough, leading to weaker responses.

What This Doesn’t Tell Us (Yet)

Like all early-stage research, this study has limits. It involved a relatively small number of participants (25 people with HD symptoms and 14 people carrying the HD gene without symptoms) , so larger studies will be needed to confirm these patterns. In this study, brainwave changes didn’t directly match the results of the other HD symptoms tests the team used, such as thinking, mood or movement assessments typically used in HD research. That doesn’t mean the signals aren’t important, it just means researchers still need to figure out how, or if, these brainwave changes connect to the real challenges people with HD face in their daily lives, like thinking clearly, managing mood, or moving easily.

A Quiet but Promising signal

One of the best parts of this type of research is how easy it is on participants, no tricky tasks, no needles, just sitting back with headphones on while the EEG listens to your brain’s reactions.  In the future, this type of test might even be possible at home.  Because it’s so simple, it could be repeated regularly, making it a valuable way to track changes over time.  A big thank you goes to the amazing participants who made this research possible.

In HD, where the disease can quietly cause damage for years before symptoms appear, that’s a big deal. The sooner we can detect these changes, the earlier we can respond. For now, this research is a promising step, not a finished tool. But it shows that the brain’s whispers are there if we know how to listen. And just like Sherlock Holme said, the clues are often in plain sight, or in this case, plain sound, waiting for someone to observe them. 

Summary

• Brainwave changes can appear in people with the HD gene before symptoms show.
• EEG detects the brain’s automatic “surprise responses” in a painless, simple test.
• Early-stage gene carriers show compensating brain activity, while symptomatic HD shows weaker signals.
• EEG could become a home-friendly tool to track HD long before obvious symptoms appear.

Learn More 

To find out more please see the original research article, “Auditory mismatch negativity in pre-manifest and manifest Huntington’s disease” (open access).

Meet the 2025 HDBuzz Writing Competition Winner

Eva Woods is a PhD student at Trinity College Dublin, Ireland. Eva completed her BSc in Biological and Biomedical Sciences at Maynooth University, where she worked with the Department of Electronic Engineering on a final-year project investigating EEG-based Brain-Computer Interfaces. Following this, she progressed directly into her PhD at Trinity. A key focus of Eva’s research is identifying early changes in the brain in people who carry the Huntington’s disease gene but have not yet shown symptoms. Her work combines brain imaging (MRI) with techniques such as electroencephalography (EEG), which records tiny electrical signals from the brain, and transcranial magnetic stimulation (TMS), which uses magnetic pulses to safely stimulate brain activity. Through this research, she aims to improve understanding of early disease mechanisms and contribute to the search for new biomarkers of disease progression. Eva is also passionate about science literacy and engaging Huntington’s disease families in Ireland with research. Each year, she hosts “TCD’s Huntington’s Disease Research Day”, which brings together researchers, clinicians, advocates, and families from across the country. The event is designed to be welcoming and accessible, with talks delivered in clear, easy-to-understand language and plenty of space for families to ask questions and engage with speakers in a supportive environment.

This year, the HDBuzz Prize is brought to you by the Hereditary Disease Foundation (HDF), who are sponsoring this year’s competition.