Transcranial focused ultrasound remotely modulates extrastriate visual cortex by stimulating frontal eye field with subregion specificity.
Authors: Yu K, Schmitt S, Ni Y, Crane EC, Smith MA, He B
<i>Objective.</i>Low-intensity transcranial focused ultrasound (tFUS) has emerged as a powerful neuromodulation tool characterized by its deep penetration and precise spatial targeting to influence neural activity. Our study directed low-intensity tFUS stimulation onto a region of prefrontal cortex (the frontal eye field, or FEF) of a rhesus macaque to examine its impact on a remote site, the extrastriate visual cortex (area V4) through this top-down modulatory circuit that has been studied extensively with electrical microstimulation.<i>Approach.</i>To measure the impact of tFUS stimulation, we recorded local field potentials and multi-unit spiking activities from a multi-electrode array implanted in the visual cortex. To deliver tFUS stimulation, we leveraged a customized 128-element random array ultrasound transducer with precise spatial targeting.<i>Main results.</i>We observed that tFUS stimulation in FEF produced modulation of V4 neuronal activity, either through enhancement or suppression, dependent on the pulse repetition frequency of the tFUS stimulation. Electronically steering the transcranial ultrasound focus through the targeted FEF cortical region produced changes in the level of modulation, indicating that the tFUS stimulation was spatially targeted within FEF. Modulation of V4 activity was confined to specific frequency bands, and this modulation was dependent on the presence or absence of a visual stimulus during tFUS stimulation. A control study targeting the insula produced no effect, emphasizing the region-specific nature of tFUS neuromodulation.<i>Significance.</i>Our findings shed light on the capacity of tFUS to modulate specific neural pathways and provide a comprehensive understanding of its potential applications for neuromodulation within brain networks.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
To test whether low-intensity transcranial focused ultrasound (tFUS) targeted to the frontal eye field (FEF) can noninvasively modulate neuronal activity in the remote extrastriate visual cortex (area V4) of rhesus macaques and to characterize the spatial- and parameter-specific nature of that modulation.
Animal model / Human subject
Rhesus macaque (Macaca mulatta); strain: not reported; age: not reported; sex: not reported
Targeted brain region(s)
Frontal Eye Field (Fef)
Outcomes and Safety
Summary of Outcomes
Transcranial focused ultrasound (tFUS) applied to the frontal eye field produced region-specific, bidirectional remote modulation of V4 activity—100 Hz PRF (50% duty cycle; tone bursts ~5 ms) caused suppression, 200 Hz PRF (50% duty cycle) caused excitation, electronic beam steering within FEF (also tested at 2 kHz PRF with 50% DC) changed modulation strength spatially, higher duty cycles increased excitatory effects, and control stimulation of the insula produced no effect.
Duration of biological effect
43 ms
Safety-related matter
The authors state that the tFUS stimulations on the animal subject were observed as safe (see Supplementary Note 2: tFUS Safety Monitoring). They also report a control (insula) stimulation that did not produce remote V4 effects, which they use to rule out auditory side‑effects as a confound; no adverse effects are reported in the text.
Brain Region
Ultrasound Parameters
Ultrasound instrument
not reported
FUS Frequency
not reported
FUS Intensity
not reported
FUS Pressure
not reported
FUS Mode
pulsed
Pulse duration
not reported
Duration of a single FUS session
43 ms
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