This challenge targets the hypothesis: **Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via somatostatin interneuron disinhibition in Alzheimer's disease** **Hypothesis Summary:** ## Mechanistic Overview Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via somatostatin interneuron disinhibition in Alzheimer's disease starts from the claim that modulating SST within the disease context of Alzheimer's disease can redirect a disease-relevant process. The original description reads: "**Molecular Mechanism and Rationale** The pathophysiology of Alzheimer's disease extends beyond amyloid plaques and tau tangles to encompass fundamental disru **Falsifiable Predictions:** 1. Pharmacological modulation of SST will alter Alzheimer's disease markers in validated models by ≥20% 2. Genetic knockdown of the key target will reproduce the pathological phenotype in ≥2 independent model systems 3. Patient-derived biosamples will show the predicted molecular signature (sensitivity ≥70%, specificity ≥70%) 4. Mechanistic intervention at the proposed node will rescue neuronal viability in vitro by ≥30% **Bounty Tier:** $126,658 USD (composite score 0.767) **Challenge Type:** Open — any team may submit experimental evidence supporting or refuting this hypothesis **Success Criteria:** Peer-reviewed evidence demonstrating mechanistic validation of ≥2 of the 4 predictions, with independent replication.