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Neurodegeneration

Does C9orf72 already change parietal EEG before ALS symptoms?

Dukic S, van Veenhuijzen K, Westeneng HJ, et al. · Human brain mapping · 2025

Open access · cc by · source: Europe PMC

In 87 asymptomatic relatives of C9orf72 ALS patients, carriers and non-carriers scored the same on a Go/NoGo attention task, but carriers showed stronger N2 negativity localized to precuneus and superior parietal cortex.

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Study at a glance

Design
Case-control — Asymptomatic C9orf72 expansion carriers vs related non-carriers; high-density EEG during SART Go/NoGo, linear mixed models with pedigree
N
N=87 · 87 asymptomatic family members (37 C9+, 50 C9−) after excluding 12 of 99 recruited relatives
Population
Adult asymptomatic relatives of patients with familial C9orf72 ALS (UMC Utrecht, 2020–2024)
Outcome
Sensor- and source-space EEG (N2/P3 and response-locked) plus six SART behavioral measures

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Key findings

No group difference on six SART metrics. During N2, C9+ carriers had a larger negative potential at central sensors; source analysis localized this to bilateral precuneus and superior parietal regions, with response-locked data implicating the same posterior network.

Methodology

Recorded 128-channel BioSemi EEG at 512 Hz during SART in 37 C9+ and 50 C9− family members, analyzing stimulus-locked N2 (180–350 ms) and P3 (300–600 ms) plus response-locked ±100 ms windows with pedigree-aware linear mixed models.

Limitations

Cross-sectional EEG cannot prove these parietal changes predict conversion to ALS/FTD, and groups were not age-matched until sensitivity analyses; it is not a treatment or diagnostic-accuracy trial.

How this study connects

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