Transcranial focused ultrasound stimulation of human primary visual cortex

Abstract

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

Neuromodulation with transcranial focused ultrasound

“…13,17, 22,34 The current surge of interest in it as a noninvasive neurostimulation modality has been triggered by the following relatively recent findings: 1) FUS can elicit neuromodulatory effects in the CNS by using relatively short stimuli; 59 2) short stimuli of low intensity can trigger visible movements upon motor cortex stimulation in rodents; 25–27,35,38, 56,62 and 3) the method has been safely used in primates, including humans. 9,21,32–34,60 Given the enormous potential of this neurostimulation modality in causal brain mapping and treatments of deep brain circuits, work is currently under way to provide the information necessary for effective use. In particular, researchers are beginning to elucidate how FUS stimulates neurons and which FUS parameters mediate effective excitation or inhibition.…”

“…35 For applications in humans, in which the skull presents a significant barrier to the propagating ultrasound, carrier frequencies between 250 kHz and 500 kHz have commonly been used. 32–34 In this frequency range, the focal width is on the order of several millimeters.…”

“…27,31 In this regard, interestingly, recent neuromodulation studies in large mammals including humans used stimuli that were applied for ≥ 100 msec. 9,32–34,60 …”

Numerical evaluation of the skull for human neuromodulation with transcranial focused ultrasound

“…However, despite the advantage of passing through the skull unimpeded, TMS produces electric fields in the brain with a spatial scale of centimeters [2] and with peak effects limited to the cortical surface [3], limiting the spatial and depth specificity of neural stimulation. In contrast, tFUS can offer a higher spatial resolution on the scale of millimeters, and has been used safely and effectively for cortical neuromodulation in mouse [4], rabbit [5], monkey [6], and humans [7][8][9][10]. However, unlike TMS, ultrasound does not pass unimpeded through the skull.…”

On the neuromodulatory pathways of the in vivo brain by means of transcranial focused ultrasound

“…Here we present three potential interpretations for how the brain responds to ultrasound energy deposition (Figure 1). Given the extensive electrophysiological [20,21,30,32], neurovascular [24,29,34,41], motor [14,16–18,22,23] and cognitive [32,35,36] evidences in support of tFUS-induced direct neural effects, we further examine whether the auditory pathway in the small brain volumes of rodent or mouse models dictates or impacts the observed activation patterns.…”