Effects of sonication parameters on transcranial focused ultrasound brain stimulation in an ovine model

Abstract

Low-intensity focused ultrasound (FUS) has significant potential as a non-invasive brain stimulation modality and novel technique for functional brain mapping, particularly with its advantage of greater spatial selectivity and depth penetration compared to existing non-invasive brain stimulation techniques. As previous studies, primarily carried out in small animals, have demonstrated that sonication parameters affect the stimulation efficiency, further investigation in large animals is necessary to translate this technique into clinical practice. In the present study, we examined the effects of sonication parameters on the transient modification of excitability of cortical and thalamic areas in an ovine model. Guided by anatomical and functional neuroimaging data specific to each animal, 250 kHz FUS was transcranially applied to the primary sensorimotor area associated with the right hind limb and its thalamic projection in sheep (n = 10) across multiple sessions using various combinations of sonication parameters. The degree of effect from FUS was assessed through electrophysiological responses, through analysis of electromyogram and electroencephalographic somatosensory evoked potentials for evaluation of excitatory and suppressive effects, respectively. We found that the modulatory effects were transient and reversible, with specific sonication parameters outperforming others in modulating regional brain activity. Magnetic resonance imaging and histological analysis conducted at different time points after the final sonication session, as well as behavioral observations, showed that repeated exposure to FUS did not damage the underlying brain tissue. Our results suggest that FUS-mediated, non-invasive, region-specific bimodal neuromodulation can be safely achieved in an ovine model, indicating its potential for translation into human studies.

Abstract via europepmc.

Flags from extraction

• exposures[2] — Per the 'one exposure per target x frequency' rule, the thalamus exposure combines two very different protocols that share only the target (thalamus) and frequency (250 kHz): a short (200 ms/60-140 ms), high-duty-cycle (30-100%) excitatory protocol (EP1-EP30) and a long (2 min), low-duty-cycle (3-5%) suppressive protocol (SP1-SP8). The resulting list-valued timing/intensity fields span both protocols and should not be read as paired combinations; see protocol_description and exp_m1/exp_s1 for the disaggregated values.
• exposures[2].target — The paper treats a single spatial coordinate in the thalamus as the sonication target because the proximity of VL (motor) and VPL (sensory) nuclei was below the spatial accuracy of sonication/registration; both target ids (ventral_lateral_nucleus, ventral_posterolateral_nucleus) are listed since the intended targets for excitatory vs suppressive sessions differed (VL vs VPL) even though a single physical coordinate was used.
• *.free_field — The paper reports only 'in situ' (derated) Isppa/Ispta/MI values in Tables 1-2; the pre-derating (free-field, degassed-water) intensities are not given as numbers in the text, only the attenuation percentages (16.3% coupling gel, 69.4% skull) used to derive the in-situ values, so free_field fields are left not_reported.
• n_sessions_per_subject — 66 total sonication sessions were conducted across 10 sheep with 'up to four' sessions per animal and variable numbers of animals per parameter set (see Tables 1-2); not reduced to a single number per subject.
• sham_type — For the suppressive (SEP) experiments, an active control condition was used: 'we also delivered sonication to the S1 and thalamic area in the right hemisphere' (functionally non-target, contralateral-pathway hemisphere) using SP3/SP7 parameters, classified as active_control_site. No sham/control condition is described for the excitatory (EMG) experiments.
• auditory_control — Discussion notes that audible buzzing sound was sometimes produced by the coupling hydrogel during excitatory (but not suppressive) sonication, raising a possible auditory confound, but no explicit auditory masking or control procedure is reported.
• exposures[2] (thalamus) — Source quotes for this combined exposure are keyed primarily to the excitatory Table 1 (EP1-EP30) HTML row content; the suppressive Table 2 (SP1-SP8) content, quoted separately under exposures[1], additionally contributes the duty_cycle_pct=[3,5], pulse_repetition_frequency_hz=[30,50,60,100] and sonication_duration_s=120 s values in this exposure's lists but is not re-keyed here because only one source quote is stored per field path.