Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection

Abstract

Focused ultrasound (FUS) has gained recognition as a technique for non-invasive neuromodulation with high spatial precision and the ability to both excite and inhibit neural activity. Here we demonstrate that MRI-guided FUS is capable of exciting precise targets within areas 3a/3b in the monkey brain, causing downstream activations in off-target somatosensory and associated brain regions which are simultaneously detected by functional MRI. The similarity between natural tactile stimulation-and FUS- evoked fMRI activation patterns suggests that FUS likely can excite populations of neurons and produce associated spiking activities that may be subsequently transmitted to other functionally related touch regions. The across-region differences in fMRI signal changes relative to area 3a/3b between tactile and FUS conditions also indicate that FUS modulated the tactile network differently. The significantly faster rising (>1 sec) fMRI signals elicited by direct FUS stimulation at the targeted cortical region suggest that a different neural hemodynamic coupling mechanism may be involved in generating fMRI signals. This is the first demonstration of imaging neural excitation effects of FUS with BOLD fMRI on a specific functional circuit in non-human primates.

Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

“…As a promising new technique, low-intensity tFUS can be applied in many neuromodulation applications due to its high spatial focality (compared to TMS and tCS (Polania et al, 2018)) and its non-invasive nature (Naor et al, 2016). During tFUS neuromodulation, pulsed mechanical energy is transmitted though the skull with high spatial selectivity (Legon et al, 2014), which can be steered (Haritonova et al, 2015) and utilized to elicit activation or inhibition through parameter tuning (King et al, 2013;Ye et al, 2016). Pilot studies have investigated the neural effects of ultrasound parameters, such as ultrasound fundamental frequencies (UFF), intensities (UI), durations (UD), duty cycles (UDC), pulse repetition frequencies (UPRF), etc.…”

“…Pilot studies have investigated the neural effects of ultrasound parameters, such as ultrasound fundamental frequencies (UFF), intensities (UI), durations (UD), duty cycles (UDC), pulse repetition frequencies (UPRF), etc. Besides a few human studies (Hameroff et al, 2013;Lee et al, 2016b;Legon et al, 2014), animal models, such as worms (Ibsen et al, 2015;Kubanek et al, 2018;Zhou et al, 2017), rodents (Tufail et al, 2010;Ye et al, 2016;Yu et al, 2016), rabbits , swine (Dallapiazza et al, 2018), and monkeys Folloni et al, 2019), have been utilized to investigate the effects of ultrasonic parameters and acoustic-induced effects. tFUS have been observed to induce behavioral changes, e.g.…”

“…motor responses (King et al, 2013;Mehic et al, 2014), electrophysiological responses, e.g. electromyography (EMG) (King et al, 2014;Ye et al, 2016), electroencephalography (EEG) (Darvas et al, 2016;Yu et al, 2016), local field potentials (LFPs) (Tufail et al, 2010), and multiunit activities (MUAs) (Tufail et al, 2010), with high in vivo temporal / spatial measurement fidelity, or neurovascular activities, e.g. blood-oxygenation-level-dependent (BOLD) signal Verhagen et al, 2019;Yang et al, 2018;Yoo et al, 2011), etc.…”

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

“…tFUS has demonstrated its robust neuromodulatory effects in numerous in vivo preparations of animals ranging from mice [14–18] and rats [19–23], to rabbits [24], swine [25,26], sheep [27], and even monkeys [28,29]. More recently it has been shown to be a safe and effective method for the transcranial stimulation of humans [30–36] with clinical applicability.…”

“…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.…”