Hypothesis\n\nPsilocybin’s acute 5‑HT2A agonism increases cortical entropy, which can selectively dissolve the hyper‑synchronized, low‑frequency microstate patterns that underlie functional rigidity in aging brains, thereby restoring a balance between prediction and surprise without requiring new structural growth.\n\n## Background\n\nAging is associated with reduced modularity and increased between‑network integration that persists despite modest structural loss【1】(https://onlinelibrary.wiley.com/doi/10.1111/psyp.14159). This functional rigidity appears as compensatory hypersynchrony in delta/theta bands and inefficient microstate transitions【2】(https://pmc.ncbi.nlm.nih.gov/articles/PMC12667136/). Importantly, age drives connectivity decline beyond what atrophy predicts【3】(https://pmc.ncbi.nlm.nih.gov/articles/PMC8916110/), indicating a network‑level inflexibility. Nonlinear transitions around ages 43 and 67 suggest critical windows where rigidity may be most labile【5】(https://www.pnas.org/doi/10.1073/pnas.2416433122).\n\n## Mechanistic Insight\n\nWe propose that the entropic surge produced by psilocybin does not merely add noise; it preferentially destabilizes the most stable, high‑occupancy microstates that dominate in rigid brains. By flattening the energy landscape of these microstates, the drug reduces the attractor strength of entrenched predictive models, allowing the brain to sample alternative configurations. This process is distinct from BDNF‑mediated spine growth because it operates on millisecond‑second timescales of network dynamics rather than days‑weeks of structural remodeling.\n\n## Testable Predictions\n\n1. In adults aged 50‑75, a single moderate dose of psilocybin will decrease the occupancy percentage of the dominant EEG microstate (typically microstate B) and increase microstate transition entropy within 2 h post‑dose, measured with high‑density EEG.\n2. The same session will increase functional modularity (quantified by Louvain community detection) and decrease between‑network functional connectivity in the default‑mode and frontoparietal networks, effects that persist for at least 24 h.\n3. These electrophysiological shifts will correlate with improved performance on a surprise‑sensitivity task (e.g., oddball discrimination) but not with changes in serum BDNF levels, indicating a functional rather than structural mechanism.\n4. Older participants with baseline microstate rigidity scores above the 75th percentile will show the largest entropy gains, while those with already flexible networks will exhibit minimal change, establishing a floor‑ceiling effect.\n\n## Experimental Design\n\nA double‑blind, placebo‑controlled crossover trial with 60 participants (30 aged 50‑60, 30 aged 61‑75). Each receives psilocybin (20 mg/70 kg) and placebo separated by two weeks. Resting‑state EEG (5 min eyes closed) and simultaneous fMRI are acquired at baseline, 30 min, 2 h, and 24 h post‑dose. Microstate analysis follows the microstate‑toolbox pipeline; functional connectivity is computed using weighted phase lag index. Behavioral surprise sensitivity is assessed via an auditory oddball with variable inter‑stimulus intervals.\n\n## Potential Outcomes\n\nIf psilocybin reduces microstate dominance and boosts modularity as predicted, the data will support the idea that functional rigidity is a reversible, entropy‑sensitive state rather than irreversible decay. Failure to observe these changes would challenge the entropic reset hypothesis and suggest that age‑related network inflexibility requires structural interventions.