Low-intensity focused ultrasound to human amygdala reveals a causal role in ambiguous emotion processing and alters local and network activity

Abstract

The amygdala shows abnormal metabolism in depression, a disorder marked by altered emotion, motivation, and learning. Yet its causal role in these processes remains unclear because non-invasive, reversible perturbation in humans has not been possible. We used transcranial focused ultrasound stimulation (TUS) to modulate basolateral amygdala (BLA) activity. In separate sessions, healthy volunteers received offline TUS to bilateral BLA, mid-insula, or sham before completing a novel emotional learning task validated online. 7T-resting-state connectivity and metabolite measures confirmed target engagement: BLA-TUS reduced the BLA's connectivity fingerprint and lowered its excitation/inhibition balance. Behaviorally, BLA-TUS increased approach tendencies toward neutral, emotionally ambiguous faces in a stimulation-volume-dependent manner and slowed responses to neutral and happy faces. These effects were functionally and regionally specific and suggest a causal role for the amygdala in resolving emotional ambiguity. Our findings inform studies of mood disorders, where difficulty resolving ambiguity may contribute to emotional and learning biases.

Abstract via europepmc.

Flags from extraction

• n_subjects — 36 healthy volunteers were enrolled and underwent TUS, but the final behavioural sample was n=29 (4 further excluded for task performance), and neuroimaging analyses used varying, smaller sub-samples (n=20 for BLA resting-state/behavioural analyses requiring sufficient BLA stimulation volume, n=18 for mIns MRS, n=11 for BLA MRS). Enrolled total (36) is reported here per the enrolled-vs-analysed rule.
• n_sessions_per_subject — Each participant underwent 3 TUS+MRI visits (BLA, mIns, sham, counterbalanced order) plus 1 MRI-only planning visit; each active target (BLA, mid-insula) was stimulated once. No single explicit 'n sessions' statement covers this crossover design, so the field is left not_reported rather than inferred.
• randomised — The paper states stimulation order was 'counterbalanced' across BLA/mIns/sham visits but never uses the word randomised/randomized for this within-subject ordering.
• blinding — No explicit single/double-blind label is given; participants' inability to distinguish sham from active TUS above chance (Bang Index near 0 for sham) suggests effective participant blinding, but the paper does not state who (participants, experimenters, assessors) was formally blinded.
• exposures[0].free_field.pressure_kpa — Table 1 reports free-field pressure/intensity settings generically for the overall protocol without splitting values by BLA vs mIns target; the same range is applied to both exposures here.
• exposures[1].free_field.pressure_kpa — Table 1 reports free-field pressure/intensity settings generically for the overall protocol without splitting values by BLA vs mIns target; the same range is applied to both exposures here.
• exposures[0].in_situ.isppa_w_cm2 — Recorded as the achieved mean (6.9 W/cm2); paper also reports the achieved range (2.9-9.3 W/cm2) and a separate planned target range (5-8 W/cm2), see quote.
• exposures[0].in_situ.pressure_kpa — Authors note that pressure estimates from acoustic simulations remain highly uncertain due to limited knowledge of bone acoustic properties; no single in-situ pressure (kPa) figure is given in the main text.