Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex

Wonhye Lee, Hyungmin Kim, Yujin Jung, In-Uk Song, Yong An Chung, Seung-Schik Yoo, Wonhye Lee, Hyungmin Kim, Yujin Jung, In-Uk Song, Yong An Chung, Seung-Schik Yoo

Abstract

Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.

Figures

Figure 1. Schematics of the image-guided FUS…
Figure 1. Schematics of the image-guided FUS sonication setup and parameters.
(a) The acoustic focus of the FUS transducer was positioned on the targeted brain area using the spatial information (coordinates and orientations in space) provided by the optical trackers that are attached to the FUS transducer and the forehead. Each tracker contained four infrared-reflective markers to be detected by a motion tracking camera. (b) Representations of the planned target (the red dot) and path (in yellow) of the sonication overlaid on the anatomical MRI. The entry point on the scalp (green circle) on the left somatosensory cortex and real-time display of the focal location (green crosshairs) and the path of the sonication (angled green line) are also shown. (c) The functional MRI (t-value map, upper panel) and cranial CT (lower panel) data on the same location, which can be selected by the operator to monitor the location of the focus and incident angle of the sonication path relative to the skull. (d) The spatial profile of the acoustic intensity at the sonication focus generated by the 250 kHz FUS transducer in the longitudinal (50 × 150 mm2 rectangular area, 1 mm step) and the transversal (inset, 30 × 30 mm2 square area, 1 mm step) planes of the sonication. The arrow indicates the direction of the sonication. A cigar-shaped (47 mm in length and 7 mm in diameter) acoustic focus based on the full-width at half-maximum (FWHM) of the acoustic intensity is depicted by the dashed line. Scale bar, 10 mm. (e) The schematics of the acoustic parameters used to generate the pulsed FUS for the transcranial brain stimulation to elicit the excitation in the somatosensory cortex. The batches of sinusoidal acoustic pressure waves at 250 kHz, each 300 ms in sonication duration, were given every 3 s. Each batch consisted of a 1 ms burst of sonication pulses (i.e., tone-burst-duration) operating at a pulse repetition frequency of 500 Hz (i.e. duty cycle of 50%). This figure was drawn by W.L., H.K. and S.-S.Y.
Figure 2. Illustration depicting the locations of…
Figure 2. Illustration depicting the locations of tactile sensations experienced by the subjects under FUS stimulation.
The regions of sensations felt from the left and right hands, including the wrist, as represented by the semi-transparent purple layers, were merged onto the palmar (left) and dorsal (right) view of the right hand (‘h1' through ‘h12'). The number of occurrences for a set of distinctive locations of sensation are represented by a color scale (1–6). The locations of other reported sensations (i.e. arm, forearm, armpit, elbow, wrist, buttock, and foot) were labeled at the bottom of each panel. Subject ‘h5' did not report any sensations (noted as ‘NR').
Figure 3. Electroencephalographic (EEG) evoked potential elicited…
Figure 3. Electroencephalographic (EEG) evoked potential elicited by image-guided transcranial FUS to the hand primary somatosensory cortex.
The grand average (n = 6, the subjects ‘h13' through ‘h18') evoked potentials of the EEG electrode sites C3 (a) and P3 (b) were shown in the case of median nerve stimulation (100 trials, SEP, black line) and transcranial FUS stimulation (100 trials, red line, noted as ‘FUS'). The FUS was given at the initial period of 300 ms (thick solid black bar). Positive (noted with prefix P) and negative (noted with prefix N) peaks of the SEP are annotated across the two electrode sites. Gray vertical bars indicate the time-segments that showed significant differences (paired t-test, two-tailed, P < 0.05) in amplitudes between the SEP and the FUS-mediated evoked potentials. The inset shows the EEG signals measured at the same electrode sites from the baseline (i.e. no stimulation) and sham FUS conditions.
Figure 4. Simulated acoustic intensity profiles overlaid…
Figure 4. Simulated acoustic intensity profiles overlaid on the region of the hand primary somatosensory cortex.
The acoustic intensity profiles projected on (a) a 3D rendering and (b) a coronal section of the volumetric MRI data (from ‘h1'). The value, 1.07, indicates the maximum Isppa value (in W/cm2) at the focus. Scale bar, 1 cm. (c) The simulation results displayed on the axial view of each individual's anatomical MRI (‘h1' through ‘h12'; white arrows indicate the subject's central sulci; CS). The location of the intended FUS focus is marked with ‘+'. The numbers under each simulated focus indicate the maximum acoustic intensities (Isppa in W/cm2).

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