Neuromodulation with single-element transcranial focused ultrasound in human thalamus

Abstract

Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical tissue in humans. tFUS confers high spatial resolutions with deep focal lengths and as such, has the potential to noninvasively modulate neural targets deep to the cortex in humans. We test the ability of single-element tFUS to noninvasively modulate unilateral thalamus in humans. Participants (N = 40) underwent either tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that contains the ventro-posterior lateral (VPL) nucleus of thalamus. Somatosensory evoked potentials (SEPs) were recorded from scalp electrodes contralateral to median nerve stimulation. Activity of the unilateral sensory thalamus was indexed by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity by subsequent inflexions of the SEP and through time/frequency analysis. Participants also under went tactile behavioral assessment during either the tFUS or sham condition in a separate experiment. A detailed acoustic model using computed tomography (CT) and magnetic resonance imaging (MRI) is also presented to assess the effect of individual skull morphology for single-element deep brain neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham. There is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities. These results were accompanied by alpha and beta power attenuation as well as time-locked gamma power inhibition. Furthermore, participants performed significantly worse than chance on a discrimination task during tFUS stimulation.

Keywords: human; neuromodulation; somatosensory; thalamus; transcranial; ultrasound.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1

Targeting and application of tFUS. (a) Anatomical MRI showing overlaid targeted somatosensory volume in pseudocolor at green cross hairs taken from Behrens et al. (2003). Bottom right shows the typical center of transducer placement (green point) on individual subject scalp rendering from MRI anatomical image. (b) Schematic of the ultrasound pulsing strategy. ISI = interstimulus interval; PRF = pulse repetition frequency; Af = acoustic frequency. (c) Schematic of the position of the 5 electrodes on the scalp referenced in space to electrode CZ at vertex. Electrodes were spaced from CZ at 2 cm increments. Bottom represents the timing of transcranial focused ultrasound (tFUS) application relative to median nerve stimulation (MN stim). EEG represents continuous electroencephalographic recording from the 5 scalp electrodes

Figure 2

Ultrasound beam characteristics. (a) Normalized 3D pseudocolor empirical plot of ultrasound beam recorded in free water. Maximum Isppa in free water was 14.56 W/cm2 with an MI of 0.89 and 7.03 W/cm2 measured through a sectioned human temporal bone. (b) Normalized pseudocolor empirical plot of XY lateral resolution (taken at Z maximum) of ultrasound in free water. (c) X, Y, and Z normalized line plots of pressure profiles normalized to peak pressure. Dashed lines and red numbers indicate −3 dB pressure attenuation in respective axes

Figure 3

Group average somatosensory evoked potentials. (a) Group mean (n = 20) peak‐to‐peak amplitude of the N20‐P14 SEP for 5 channel recordings. * denotes p < .01. Bars represent ± SEM. (b) Group average (n = 20) somatosensory evoked potential (SEP) traces recorded from 5 scalp EEG channels. Vertical grey bars denote time windows that met statistical significance (p < .05 corrected)

Figure 4

Group average frequency spectra. (a) Group mean (n = 20) FFT frequency spectra for EEG time window 10–300 ms post MN stimulation. Vertical grey bars denote time widows that met statistical significance (p < .05 corrected). (b) Group mean pseudocolor (n = 20) Morlet wavelet time–frequency spectra in decibels (dB) relative to a prestimulus baseline. Top row is Sham stimulation and middle row is ultrasound (tFUS) stimulation. Gold and maroon boxes (bottom row) are statistical maps of time–frequency data; gold areas met statistical significance (p < .05 corrected)

Figure 5

Group average behavioral results. (a) Group average (n = 20) two point discrimination behavior for tFUS condition (black and grey) and sham condition (light and dark blue). Light bars (grey and light blue) for each condition denotes % of trials where subjects verbally responded they felt one pin, and dark bars (black and dark blue) denote % of trials where subjects reported feeling two pins. Catch trials with only one pin is denoted with 0 on x‐axis. (b) Collapsed data from 1.6 and 1.9 mm separations as percent correct as compared to chance (50%). * denotes significantly (p < .05) different from chance

Figure 6

Acoustic modeling of ultrasound wave propagation. Normalized pseudocolor pressure distribution in a single subject acoustic model of ultrasound wave propagation using CT scan to account for the effect of skull morphology. Image shows MRI with CT overlay. Transducer is placed at the top of the transverse image (left) and on the left of the coronal image