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.

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease—A New Navigated Focal Brain Therapy

“…[7] Here we demonstrate, that the target for the new TPS technique can be spatially distinct, highly focal, and is not restricted to superficial layers of the brain. [7] Here we demonstrate, that the target for the new TPS technique can be spatially distinct, highly focal, and is not restricted to superficial layers of the brain.…”

Sonogenetics for noninvasive and cellular-level neuromodulation in rodent brain

“…Existing FUS neuromodulation techniques use ultrasound pulses with low intensity to produce mechanical effects for neural and behavioral modulation with a negligible temperature increase 4 . Numerous studies have confirmed that FUS can noninvasively modulate neural activity and brain function in animal models 5,6 and humans 1,3 .…”

“…Technologies for noninvasive modulation of mammalian brain activity with spatiotemporal precision and cell-type specificity have long been desired for experimental investigation of intact neural systems. Compared with electric, magnetic, optical, and chemical stimuli that have been used by existing neuromodulation technologies, focused ultrasound (FUS) offers unique advantages as it can noninvasively deliver ultrasound energy through the intact human scalp and skull deep into the brain and focus at cortical areas 1,2 as well as deep brain areas 3 with high spatial selectivity. Existing FUS neuromodulation techniques use ultrasound pulses with low intensity to produce mechanical effects for neural and behavioral modulation with a negligible temperature increase 4 .…”

Safety of transcranial focused ultrasound for human neuromodulation

“…Transcranial focused ultrasound (tFUS) is a new and promising non-surgical low-energy technique that uses mechanical energy to modulate neuronal activity with high spatial resolution and adjustable depth of focus. tFUS has been used safely and effectively for cortical neuromodulation in mouse [1][2][3][4], rat [5,6], rabbit [7], sheep [8], pig [9] and monkey [10,11] models, and has also been demonstrated to be an effective method of transient cortical and sub-cortical neuromodulation in humans [12,13]. In humans, tFUS has been applied to the temporal cortex [14], primary somatosensory cortex (S1) [12,15], secondary somatosensory cortex (S2) [16], primary motor cortex [17,18] , primary visual cortex [19] and thalamus [13,20] .…”

“…tFUS has been used safely and effectively for cortical neuromodulation in mouse [1][2][3][4], rat [5,6], rabbit [7], sheep [8], pig [9] and monkey [10,11] models, and has also been demonstrated to be an effective method of transient cortical and sub-cortical neuromodulation in humans [12,13]. In humans, tFUS has been applied to the temporal cortex [14], primary somatosensory cortex (S1) [12,15], secondary somatosensory cortex (S2) [16], primary motor cortex [17,18] , primary visual cortex [19] and thalamus [13,20] . tFUS has been shown to affect the amplitude of evoked potentials [7,12,15], the power, phase and frequency of the electroencephalogram (EEG) [12,21]; the blood oxygen level dependent (BOLD) magnetic resonance imaging signal [7,17], as well as tactile [12,15] and reaction time [18] behaviour.…”