Focused Ultrasound Neuromodulation of Salience Network Hubs Selectively Enhances Anxiety-Relevant Autonomic Habituation in Humans

Anxiety involves heightened vigilance and sustained anticipatory responding that may reflect impaired sensory habituation. Disrupted sensory filtering may bias monitoring toward threat, promoting persistent autonomic and defensive responses. We examined associations between state and trait anxiety and acoustic startle habituation across somatic (EMG), cortical (EEG), and autonomic (electrodermal response; EDR) measures, and tested whether modulation of the right anterior insula (AI) or anterior mid-cingulate cortex (aMCC) with low-intensity focused ultrasound (LIFU) alters these dynamics. Forty healthy participants (median STAI-T = 39.5; range 25–68) completed three sessions (AI, aMCC, sham) during which EMG, EEG, and EDR were recorded during 12 acoustic startle trials before and after LIFU. Habituation slopes were computed separately for early (Trials 2–6) and late (Trials 7–12) phases and analyzed with linear mixed-effects models controlling for baseline magnitude and anxiety covariates. Before LIFU, higher trait anxiety predicted weaker EMG habituation (ρ ≈ 0.3), whereas state anxiety was unrelated to habituation in any modality. Early slopes were steeper than late slopes across measures, indicating reduced adaptation over repeated trials. LIFU to AI or aMCC did not alter EMG or EEG habituation but enhanced early-phase EDR habituation relative to sham, indicating transient autonomic facilitation. EMG and EEG habituation were correlated (ρ ≈ 0.4–0.5, p < 0.01), independent of anxiety, whereas EDR habituation varied independently. Coordinated cortical-somatic habituation may represent an anxiety-relevant biomarker, while AI and aMCC neuromodulation selectively facilitates autonomic adaptation.