Hypothesis

Controlled uncertainty introduced during slow-wave sleep will reduce functional inflexibility in aging brains by forcing hippocampal-cortical networks to compete, thereby restoring adaptive plasticity without requiring structural repair.

Mechanistic Rationale

Age-related over-consolidation stems from excessive stabilization of cortical representations, which suppresses inter-network competition during memory replay [1]. This rigidity is amplified by fragmented sleep and unstable circadian rhythms that impair hippocampal-cortical transfer [2]. If we inject mild, unpredictable sensory cues (e.g., intermittent auditory tones) specifically during slow-wave epochs, we create a prediction error signal that temporarily lifts the dominance of entrenched maps. The resulting surge in neuromodulators like norepinephrine enhances synaptic tagging and promotes reconsolidation of labile traces, encouraging the cortex to update its models [3]. Importantly, this process does not rely on neurogenesis; it exploits existing plasticity mechanisms that remain intact but are gated by network confidence.

Experimental Design

• Participants: Older adults (65‑80 y) with normal cognition and age‑matched young controls.
• Intervention: Two‑week home‑based protocol. Experimental group receives rhythmic light‑tone pairs (50 ms tone, 200 lux blue light) delivered pseudorandomly during detected slow‑wave periods via a closed‑loop auditory‑tactile system. Control group receives sham stimuli matched for timing but lacking predictive uncertainty.
• Measures: Pre‑ and post‑intervention resting‑state fMRI to assess between‑network flexibility (especially default‑mode vs frontoparietal connectivity) [4]; overnight polysomnography to verify slow‑wave preservation; episodic memory task (word‑pair recall) before and after.
• Analysis: Mixed‑effects model testing group × time interaction on flexibility scores and memory performance, covarying for total sleep time and baseline volume.

Expected Outcomes

If controlled uncertainty restores flexibility, the experimental older group will show:

1. Significant increase in default‑frontoparietal segregation/reintegration metrics compared with sham [5].
2. Improved overnight memory consolidation that correlates with the magnitude of flexibility change.
3. No significant change in hippocampal volume, indicating functional rather than structural rescue. Failure to observe these changes would falsify the hypothesis, suggesting that uncertainty alone cannot overcome age‑related network rigidity without additional structural support.