First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain

Abstract

Background: With the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior.

Methods: Twelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed.

Results: Compared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area.

Conclusions: TPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.

Keywords: Brain stimulation; Diffusion tensor imaging; Functional connectivity; Sensorimotor functions; Transcranial pulse stimulation; Ultrasound.

Conflict of interest statement

The Imaging-based Functional Brain Diagnostics and Therapy Laboratory, led by RB, is supported by Storz Medical Inc.

© 2022. The Author(s).

Figures

Fig. 1

Longitudinal study design. An experimental block lasted three weeks with magnetic resonance (MR) imaging and behavioral tasks (2-point orientation discrimination [23] and coin rotation [24]) one week before and after transcranial pulse stimulation (TPS). Each subject received one block with sham and one block with verum TPS (three sessions on consecutive days) using a within-subject crossover design and one week pause between the blocks

Fig. 2

TPS pulse characterization. a Temporal-peak intensities (ITP) of a TPS pressure pulse through a human skull bone showing a highly focal transversal resolution of a few millimeters. b Fourier spectrum of a pressure pulse at TPS focus and under the skull demonstrating pressure attenuation through the skull across the frequency spectrum

Fig. 3

Focal transcranial pulse stimulation (TPS). TPS setup included a pulse generator device, a touch screen for real-time neuronavigation and an infrared camera system tracking the positions of the handpiece and the head of the participant via goggles affixed with infrared markers (left). The TPS handpiece was fixed using a tripod with a clamp focusing the ultrasound beam on the cortical primary somatosensory representation of the right hand, in the left postcentral gyrus posterior to the individual sigmoidal hook sign (marked by a turquoise circle). The TPS pulses of one session in a representative subject are displayed on the reconstructed head surface and in top, front and left orientation of the individual brain anatomy, showing the lowest (green) to highest pulse density (magenta)

Fig. 4

Diffusion tensor imaging (DTI) analysis. a For whole-brain white matter data analysis the Tract-based Spatial Statistics (TBSS) white matter skeleton (green) was used. b For the regions of interest analysis, left primary somatosensory (S1, blue) and the left primary motor (M1, orange) white matter regions, derived from the Human Sensorimotor Tracts Labels atlas, were used

Fig. 5

Resting state global efficiency of the sensorimotor network. a The sensorimotor network comprised the precentral gyrus (PreCG), postcentral gyrus (PostCG), superior parietal lobule (SPL), anterior supramarginal gyrus (aSMG), posterior supramarginal gyrus (pSMG), angular gyrus (AG), superior lateral occipital cortex (sLOC), and the parietal operculum (PO). These anatomical ROIs were defined according to the Harvard–Oxford-atlas. b In the stimulated left-hemispheric sensorimotor network, global efficiency values were significantly higher in the verum compared to the sham condition. Significant hubs within the network are represented by red spheres weighted according to the T value for the contrast between the conditions (FDR 0.05 corr.). No effects were detected in the non-stimulated right hemisphere

Fig. 6

Diffusion tensor imaging indices. Axial diffusivity (AD) values in the left primary somatosensory (S1, upper row) and left primary motor (M1, lower row) white matter regions of interest one week before (Pre) and one week after (Post) the sham and verum TPS applications. Data is depicted for individual subjects (S01-S12) and as mean over all subjects (black line). AD values significantly decreased after the verum stimulation, indicating an improved axonal status in the stimulated sensorimotor network