Dynamical and individualised approach of transcranial ultrasound neuromodulation effects in non-human primates.
Authors: Atkinson-Clement C, Alkhawashki M, Ross J, Gatica M, Zhang C, Sallet J, Kaiser M
Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
To characterize how low-frequency transcranial ultrasound stimulation (TUS) alters whole-brain functional connectivity over time across different targets and individuals, and whether baseline brain features can predict these changes.
Animal model / Human subject
Rhesus macaque (Macaca mulatta); strain: not specified; age: average 6.35 years; sex: male
Disease model
Healthy
MRI or image guidance method
Frameless stereotaxic neuronavigation (Rogue Research) using registration of the animal's T1-weighted MRI to the head with continuous infrared tracking of the ultrasound transducer and the head
Targeted brain region(s)
Anterior Medial Prefrontal Cortex; Supplementary Motor Area; Perigenual Anterior Cingulate Cortex
Target coordinates
amPFC (AP=24, ML=-0.7, DV=11); SMA (AP=2, ML=0.1, DV=19); pACC (AP=15, ML=0, DV=6)
Route of administration
Inhalational (isoflurane); intramuscular injection (ketamine, xylazine, midazolam, atropine); intravenous injection (meloxicam, ranitidine)
Outcomes and Safety
Summary of Outcomes
Low-frequency transcranial ultrasound stimulation produced heterogeneous, target-dependent alterations in resting-state functional connectivity with both transient and long-lasting network effects
Duration of biological effect
>2 h
Safety-related matter
The paper does not report any adverse effects or safety issues related to transcranial ultrasound stimulation; no injuries, adverse events, or safety concerns were mentioned.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Single-element ultrasound transducer H115-MR (Sonic Concept); diameter 64 mm; focal depth 51.74 mm
FUS Frequency
250 kHz
FUS Intensity
31.7 W/cm2 (ISSPA, amPFC); 24.1 W/cm2 (ISSPA, SMA); 18.8 W/cm2 (ISSPA, pACC); 9.5 W/cm2 (ISPTA, amPFC); 7.2 W/cm2 (ISPTA, SMA); 5.63 W/cm2 (ISPTA, pACC)
FUS Pressure
1.01 MPa; 0.88 MPa; 0.78 MPa
FUS Mode
pulsed
Pulse duration
30 ms
Duration of a single FUS session
40 s
Focal Characteristics
Focal depth: 51.74 mm; Focal length: None; Aperture size: 64 mm
Treatment frequency
multiple
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