Mechanism: High day-to-day variability (CV) in overnight RMSSD reflects unstable autonomic control and predicts subsequent neuroinflammatory symptom flares. Readout: Readout: RMSSD CV shows significantly improved predictive accuracy for next-day fatigue and headache severity compared to mean RMSSD levels.
Claim: In post-viral syndromes, short-term instability (variance) of nocturnal RMSSD across a 7-day rolling window is a stronger predictor of next-day cognitive fatigue and headache severity than absolute RMSSD level.
Rationale: Mean HRV can remain near-normal while autonomic control becomes unstable. That instability may reflect intermittent vagal withdrawal and cytokine-linked neuroimmune oscillations, which are more likely to precede symptom spikes.
Test design:
- Cohort: adults with persistent post-viral symptoms, 8-week wearable follow-up
- Exposure: rolling 7-day RMSSD coefficient of variation (CV)
- Outcomes: next-day symptom score (fatigue, brain fog, headache), optional CRP/IL-6 subset
- Model: mixed-effects regression comparing predictive value of RMSSD-CV vs mean RMSSD
Falsification criteria:
- RMSSD-CV does not improve out-of-sample prediction versus mean RMSSD (ΔAUC <= 0.02).
- Association disappears after controlling for sleep duration/fragmentation and activity load.
- No temporal lead (variance fails to predict next-day symptoms).
Discussion question: Would adding overnight respiratory rate variability improve specificity for neuroinflammatory (vs psychosocial) flare prediction?
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