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Diagnostic ultrasound enhances, then reduces, exogenously induced brain activity of mice.

Authors: Tan H, Griggs DJ, Chen L, Culevski KA, Floerchinger K, Phutirat A, Koh G, Schimek N, Mourad PD

Transcranially delivered diagnostic ultrasound (tDUS) applied to the human brain can modulate those brains such that they became more receptive to external stimulation relative to sham ultrasound exposure. Here, we sought to directly measure the effect of tDUS on mouse brain activity subjected to an external stimulation-a blinking light. Using electrocorticography, we observed a substantial increase in median brain activity due to tDUS plus a blinking light relative to baseline and relative to sham tDUS plus a blinking light. Subsequent brain activity decreased after cessation of tDUS but with continuation of the blinking light, though it remained above that demonstrated by mice exposed to only a blinking light. In a separate experiment, we showed that tDUS alone, without a blinking light, had no observable effect on median brain activity, but upon its cessation, brain activity decreased. These results demonstrate that <i>simultaneous</i> exposure to tDUS and blinking light can increase the receptivity of the visual cortex of mice exposed to that light, and that <i>prior</i> exposure to tDUS can reduce subsequent brain activity. In each case, these results are consistent with published data. Our results on mice echo published human results but do not directly explain them, since their test subjects received less intense diagnostic ultrasound than did our mice. Given the near ubiquity of diagnostic ultrasound systems, further progress along this line of research could one day lead to the widespread use of <i>diagnostic</i> ultrasound to intentionally modulate human brain function during exogenous stimulation.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To determine whether transcranially delivered diagnostic ultrasound (tDUS) enhances mouse visual cortex responsiveness to an external blinking light stimulus.
Animal model / Human subject Mouse, C56BL/6, (Mus musculus); strain not reported; age not reported; sex not reported
Targeted brain region(s) Visual Cortex
Target coordinates AP: -3.5 mm, ML: +-2.2 mm, DV: 1.0 mm. Somastosensory cortex: AP: -0.2 mm, ML: +- 2.5 mm, DV = 2.0 mm

Outcomes and Safety

Summary of Outcomes Simultaneous transcranial diagnostic ultrasound (tDUS) plus a blinking light increased visual-cortex brain activity in mice versus light or sham, tDUS alone produced no immediate evoked activity, and prior tDUS exposure led to a subsequent reduction in responsiveness.
Safety-related matter The paper reports that tDUS can produce reductions or suppression of brain activity after cessation (their mice and prior studies showed effects lasting ~10 min to up to an hour) and that tDUS made mice less receptive to subsequent sensory stimulation. It also warns that mice received substantially higher ultrasound intensities than humans, so dose/mitigation is required before extrapolating to human safety.

Brain Region

Ultrasound Parameters

Ultrasound instrument Sonosite MicroMaxx with P21x5-1 scan head
Duration of a single FUS session 10 min
Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency single session

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