Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI

Abstract

Background: Transcranial focused ultrasound (tFUS) is a new non-invasive neuromodulation technique that uses mechanical energy to modulate neuronal excitability with high spatial precision. tFUS has been shown to be capable of modulating EEG brain activity in humans that is spatially restricted, and here, we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD fMRI signals from individual finger representations in the human primary motor cortex (M1) and connected cortical motor regions. Participants (N = 5) performed a cued finger tapping task in a 7T MRI scanner with their thumb, index, and middle fingers to produce a BOLD signal for individual M1 finger representations during either tFUS or sham neuromodulation to the thumb representation.Results: Results demonstrated a statistically significant increase in activation volume of the M1 thumb representation for the tFUS condition as compared to sham. No differences in percent BOLD changes were found. This effect was spatially confined as the index and middle finger M1 finger representations did not show similar significant changes in either percent change or activation volume. No effects were seen during tFUS to M1 in the supplementary motor area (SMA) or the dorsal premotor cortex (PMd). Conclusions:Single element tFUS can be paired with high field MRI that does not induce significant artifact. tFUS increases activation volumes of the targeted finger representation that is spatially restricted within M1 but does not extend to functionally connected motor regions.

Safety of transcranial focused ultrasound for human neuromodulation

“…In addition to our group, Yoo's lab has performed human ultrasound neuromodulation studies and completed thorough safety analysis including similar telephone follow-up as well as neurological assessment pre and post experiment including anatomical MRI and reported zero events from their three studies [15,16,19]. In the published literature (N = 233) [12][13][14][15][16][17][18][19]41,49] and including the experiments in this study, a total of 260 individuals have participated in human ultrasound neuromodulation experiments to date with no reported serious adverse events and the data from this report is the first to report on minor transient events associated with the tFUS intervention. Caution is always advised when imparting energy into the brain and further research is recommended examining the effect of total number of stimulations and the interstimulus interval and the potential interaction of these parameters with intensity and duty cycle.…”

“…All experiments were conducted in neurologically healthy volunteer participants to test the effect of tFUS on either cortical or sub-cortical [18] neuronal excitability and/or effect on specific behaviours. The environment of the experiments differed as one experiment (Experiment 4) [41] was conducted in a 7T MRI scanner at the Center for Magnetic Resonance Research at the University of Minnesota (https://www.cmrr.umn.edu) and experiment 6 and 7 also involved transcranial magnetic stimulation (TMS) either concurrent with tFUS [18] or as a pre/post measure of motor cortical excitability. For all experiments (except fMRI experiment), participants were seated in a dentist-type chair and asked to either perform a simple task or sit passively for the duration of the experimental protocol.…”

Neuronal responses to focused ultrasound are gated by pre-stimulation brain rhythms

“…Historically employed to image soft tissue, low-intensity focused ultrasound has more recently been shown to modulate brain activity (1; 2; 3; 4) in models spanning cell cultures (5; 6; 7), rodents (8; 9; 10; 11; 12; 13; 14; 15), primates (16; 17; 18; 19; 20), and humans (21; 22; 23; 24; 25; 26; 27; 28; 29; 30). Ultrasound overcomes the critical limitations of conventional (electromagnetic) non-invasive brain stimulation: it can be focused through the skull with millimeter precision (31) and penetrate deep brain regions (21).…”