Manipulation of Subcortical and Deep Cortical Activity in the Primate Brain Using Transcranial Focused Ultrasound Stimulation.
Authors: Folloni D, Verhagen L, Mars RB, Fouragnan E, Constans C, Aubry JF, Rushworth MFS, Sallet J
The causal role of an area within a neural network can be determined by interfering with its activity and measuring the impact. Many current reversible manipulation techniques have limitations preventing their application, particularly in deep areas of the primate brain. Here, we demonstrate that a focused transcranial ultrasound stimulation (TUS) protocol impacts activity even in deep brain areas: a subcortical brain structure, the amygdala (experiment 1), and a deep cortical region, the anterior cingulate cortex (ACC, experiment 2), in macaques. TUS neuromodulatory effects were measured by examining relationships between activity in each area and the rest of the brain using functional magnetic resonance imaging (fMRI). In control conditions without sonication, activity in a given area is related to activity in interconnected regions, but such relationships are reduced after sonication, specifically for the targeted areas. Dissociable and focal effects on neural activity could not be explained by auditory confounds.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
To test whether focused transcranial ultrasound stimulation can causally and focally modulate neural activity in deep primate brain regions (amygdala and ACC) and to evaluate the duration and specificity of these effects using fMRI.
Animal model / Human subject
Macaque (non-human primate; species None), strain: None, age: None, sex: None
Disease model
Healthy
Targeted brain region(s)
Amygdala And Anterior Cingulate Cortex (Acc)
Outcomes and Safety
Summary of Outcomes
Focused transcranial ultrasound stimulation (TUS) targeted to macaque amygdala or ACC produced focal, region-specific and long-lasting (>1 h) reductions in BOLD functional coupling between the stimulated site and its connected network, demonstrating effective neuromodulation of deep subcortical and deep cortical areas without auditory confounds. Successful stimulation parameters were: 250 kHz carrier frequency, 30-ms bursts every 100 ms (10 Hz pulse envelope), single 40-s offline train delivered with a single‑element transducer and a region‑specific coupling cone filled with degassed water.
Duration of biological effect
More than 1 hour
Safety-related matter
No adverse tissue effects were observed: structural MRI shortly after TUS showed no transient edema and a referenced histological study (Verhagen et al., 2019) reported no permanent tissue damage; recordings began ~30 min post‑TUS to avoid auditory/somatosensory confounds. However, the authors caution that sonication can sometimes impact the meninges and that further safety evaluation is needed for multiple sessions, longer durations, higher intensities, and prior to routine human use.
Brain Region
Ultrasound Parameters
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
single
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