Transcranial Focused Ultrasound Enhances Sensory Discrimination Capability through Somatosensory Cortical Excitation

Abstract

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a non-invasive brain neuromodulation tool with high spatial specificity. Previous studies attributed tFUS-enhanced sensory performance to the ultrasound-induced inhibitory neural effects. However, to date there is no direct evidence validating the neural mechanism underlying ultrasound-mediated somatosensory enhancement. In this study, healthy human subjects (N = 9) were asked to perform tactile vibration frequency discrimination tasks while tFUS was directed onto the primary somatosensory cortex. During this task, we simultaneously recorded 64-channel electroencephalography (EEG) signals and investigated the brain responses at both EEG sensors and source domains by means of electrophysiological source imaging (ESI). The behavioral results indicated that the subjects' discrimination ability was improved by tFUS with an increased percentage of correct responses. EEG and ESI results revealed that tFUS neuromodulation was able to improve sensory discrimination capability through excitatory effects at the targeted sensory cortex.

Keywords: Electrophysiological source imaging; Neuromodulation; Sensory discrimination; Somatosensory evoked potential; Transcranial focused ultrasound.

Figure 1.

Diagram of the overall experiment setup and procedure. In each trial, a pair of vibration stimuli are delivered to a flat haptic vibrator held between the subject’s thumb and index fingers of the right hand. The subject is instructed to select the one with a higher frequency by pressing corresponding buttons. The status of the stimulus and the decision is shown on the screen in real-time. Transcranial focused ultrasound (tFUS) is delivered to the primary finger somatosensory cortical area at 100 ms before the onset of each vibration stimulus. The 64-channel electroencephalography (EEG) data are simultaneously recorded to perform electrophysiological source imaging (ESI). The reconstructed source activities at the finger somatosensory cortical area are extracted as somatosensory source profiles and are validated with behavior outcomes to further access the tFUS neuromodulation effects.

Figure 2.

Ultrasound spatiotemporal profiles. (A) The ultrasound waveform and time sequence. (B-C) Ultrasound pressure field measurements along the lateral direction in free water (B) and along the axial direction in free water (C). (D-E) The illustration of transducer placement over a human head/brain model (D) with the intersectional view of the transcranial ultrasound pressure distribution within a full human skull; the image is co-registered with a human skull model (E).

Figure 3.

Behavior outcomes from the frequency discrimination task. (A) The averaged percentage of responses correct (PRC) over subjects (N = 9) with respect to 7 shifted frequency level in each condition. The standard deviations at those 7 frequency levels are indicated with error bars. Ultrasound conditions have a statistically significant effect on the PRC examined by a two-way ANOVA test. (B) The boxplot of the averaged PRC across all shifted frequencies in each ultrasound condition. Statistics by one-tail paired Wilcoxon signed rank test for examining the effect of tFUS increasing the subjects’ frequency discrimination accuracy. *p < 0.05.

Figure 4.

EEG spatiotemporal responses at the sensor domain. (A-B) The averaged EEG signal over subjects (N = 7) shown in butterfly plots in Sham US (A), and UPRF 300Hz (B) conditions. (C) Averaged EEG signals of electrode C3, C5, CP3, CP5 (N = 7). The solid lines represent the grand averaged EEG signals, and the shaded areas under the solid lines indicate the standard error of the mean (S.E.M.). The vertical gray bars represent the time segments of significant differences between sham and ultrasound conditions. (D-I) Topographic voltage maps of the averaged EEG signal (N = 7) at 30, 100, 330 ms under Sham US (D-F) and UPRF 300Hz (G-I) conditions.

Figure 5.

EEG spatiotemporal responses at the source domain. (A-D) The ESI results (absolute values) at 100 and 330 ms in Sham US (A, C) and UPRF 300Hz (B, D) conditions. (E) The averaged source amplitude (N = 7, solid lines) in the brain region of interest at the left primary somatosensory cortex. The colored and shaded areas behind the solid lines represent the S.E.M. (F) The somatosensory source profile amplitude (SSPA) is significantly increased in the UPRF 300Hz condition compared with that in the Sham US condition, examined by one-tail paired Wilcoxon signed rank test. *p < 0.05.