Focused ultrasound neuromodulation of cortical and subcortical brain structures using 1.9 MHz

Abstract

Purpose Ultrasound neuromodulation is a promising noninvasive technique for controlling neural activity. Previous small animal studies suffered from low targeting specificity because of the low ultrasound frequencies ( Methods FUS sonications were carried out at 1.9 MHz with 50% duty cycle, pulse repetition frequency of 1 kHz, and duration of 1 s. The robustness of the FUS neuromodulation was assessed first in sensorimotor cortex, where elicited motor activities were observed and recorded on videos and electromyography. Deeper brain regions were then targeted where pupillary dilation served as an indicative of successful modulation of subcortical brain structures. Results Contralateral and ipsilateral movements of the hind limbs were repeatedly observed when the FUS was targeted at the sensorimotor cortex. Induced trunk and tail movements were also observed at different coordinates inside the sensorimotor cortex. At deeper targeted-structures, FUS induced eyeball movements (superior colliculus) and pupillary dilation (pretectal nucleus, locus coeruleus, and hippocampus). Histological analysis revealed no tissue damage associated with the FUS sonications. Conclusions The motor movements and pupillary dilation observed in this study demonstrate the capability of FUS to modulate cortical and subcortical brain structures without inducing any damage. The variety of responses observed here demonstrates the capability of FUS to perform functional brain mapping.

Abstract via europepmc.

Flags from extraction

• n_subjects — Paper gives separate group sizes for motor-response mapping (3 mice), pupil-dilation experiments ('n = 3') and histology safety (5 mice) but never a total distinct animal count, and it is not stated whether these are overlapping or separate cohorts.
• exposures[*].timing.pulse_duration_ms — Only duty cycle (50%) and PRF (1 kHz) are stated; individual pulse duration is not given as a number in the text, so it is left not_reported rather than computed (0.5 ms) from duty/PRF.
• exposures[*].in_situ.pressure_kpa — The paper states 'the reported pressures were derated for skull attenuation, calibrated using ex vivo skulls in a water tank' only in the paragraph describing the 1.9/3.0 MPa histology safety test; it is assumed (not certain) that this derating applies to all pressures reported throughout the paper, since only one transducer calibration/derating procedure is described.
• exposures[1].target — The paper hypothesises that sonication intended for the superior colliculus may also have reached the adjacent pretectal nucleus (~0.5 mm away); pretectal_area is included as a secondary target term on this basis.
• exposures[3].target — The paper separately hypothesises that sonication intended for the hippocampus (AP=+2mm, ML=±2mm) may also reach the pretectal nucleus in the dorsal-ventral direction; pretectal_area is included as a secondary target term on this basis.
• blinding — Only the histological evaluation is stated to be performed blinded to sonication location/parameters; EMG, video and pupillometry readouts are not stated as blinded.
• n_sessions_per_subject — Recorded as 1 (one experimental session per animal), but within that session multiple spots/pressure levels were tested per animal via a spatial grid, and the opposite hemisphere was sometimes sonicated a second time to test lateralization.