Background Transcranial focused ultrasound (FUS) has emerged as a new brain stimulation modality. The range of sonication parameters for successful brain stimulation warrants further investigation. Objective The objective of this study was to examine the range of FUS sonication parameters that minimize the acoustic intensity/energy deposition while successfully stimulating the motor brain area in Sprague-Dawley rats. Methods We transcranially administered FUS to the somatomotor area of the rat brain and measured the acoustic intensity that caused excitatory effects with respect to different pulsing parameters (tone-burst duration, pulse-repetition frequency, duty cycle, and sonication duration) at 350 and 650 kHz of fundamental frequency. Results We observed that motor responses were elicited at minimum threshold acoustic intensities (4.9–5.6 W/cm2 in spatial-peak pulse-average intensity; 2.5–2.8 W/cm2 in spatial-peak temporal-average intensity) in a limited range of sonication parameters, i.e. 1–5 ms of tone-burst duration, 50% of duty cycle, and 300 ms of sonication duration, at 350 kHz fundamental frequency. We also found that the pulsed sonication elicited motor responses at lower acoustic intensities than its equivalent continuous sonication. Conclusion Our results suggest that the pulsed application of FUS selectively stimulates specific brain areas-of-interest at an acoustic intensity that is compatible with regulatory safety limits on biological tissue, thus allowing for potential applications in neurotherapeutics.
We investigated the use of pulsed low-intensity focused ultrasound (FUS) to suppress the visual neural response induced by light stimulation in rodents. FUS was administered transcranially to the rat visual cortex using different acoustic intensities and pulsing duty cycles. The visual evoked potentials (VEP) generated by an external strobe light stimulation were measured three times before, once during, and five times after the sonication. The VEP magnitude was suppressed during the sonication using a 5% duty cycle (pulse-repetition frequency of 100 Hz) and spatial-peak pulse-average acoustic intensity of 3 W/cm2; however, this suppressive effect was not present when a lower acoustic intensity and duty cycle were used. The application of a higher intensity and duty cycle resulted in a slight elevation of VEP magnitude, which suggested excitatory neuromodulation. Our findings demonstrate that the application of pulsed FUS to the region-specific brain area not only suppresses its excitability, but also can enhance the excitability depending on the acoustic intensity and rate of energy deposition. This bimodal feature of FUS-mediated neuromodulation, which has been predicted by numerical models on neural membrane capacitance change by the external acoustic pressure waves, suggests its versatility for neurotherapeutic applications.
This study investigates the spatial profile and the temporal latency of the brain stimulation induced by the transcranial application of pulsed focused ultrasound (FUS). The site of neuromodulation was detected by using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) immediately after FUS sonication on the unilateral thalamic area of the Spague-Dawley rats. The latency of the stimulation was estimated by measuring the time taken from the onset of the stimulation of the appropriate brain motor area to the corresponding tail motor response. The brain area showing elevated glucose uptake from the PET image was much smaller (56±10% in diameter, 24±6% in length) than the size of the acoustic focus, which is conventionally defined by the full-width at half-maximum (FWHM) of the acoustic intensity field. The spatial dimension of the FUS-mediated neuromodulatory area was more localized, approximated to be full-width at 90%-maximum of the acoustic intensity field. In addition, the time delay of motor responses elicited by the FUS sonication was 171±63 (s.d.) ms from the onset of sonication. When compared to latencies of other non-ultrasonic neurostimulation techniques, the longer time delay associated with FUS-mediated motor responses is suggestive of the non-electrical modes of neuromodulation, making it a distinctive brain stimulation method.
BackgroundAn ovine model can cast great insight in translational neuroscientific research due to its large brain volume and distinct regional neuroanatomical structures. The present study examined the applicability of brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to sheep using a clinical MR scanner (3 tesla) with a head coil. The blood-oxygenation-level-dependent (BOLD) fMRI was performed on anesthetized sheep during the block-based presentation of external tactile and visual stimuli using gradient echo-planar-imaging (EPI) sequence.ResultsThe individual as well as group-based data processing subsequently showed activation in the eloquent sensorimotor and visual areas. DTI was acquired using 26 differential magnetic gradient directions to derive directional fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values from the brain. White matter tractography was also applied to reveal the macrostructure of the corticospinal tracts and optic radiations.ConclusionsUtilization of fMRI and DTI along with anatomical MRI in the sheep brain could shed light on a broader use of an ovine model in the field of translational neuroscientific research targeting the brain.
Transcranial focused ultrasound (FUS) has emerged as a noninvasive neuromodulatory modality with exquisite depth penetration and spatial selectivity. Liquids, such as degassed water or mineral oil, are used as acoustic coupling media between the ultrasound‐generating transducer and the brain; however, they require a separate container that limits the spatial orientation of the transducers with respect to the sonication target. Nonliquid, gel‐like materials that do not require a housing container have been sought after as coupling media to overcome such limitations. Polyvinyl alcohol (PVA), when dissolved in water and undergone freeze–thaw cycle(s), forms a flexible hydrogel having a high level of acoustic transmission. To examine the feasibility of the PVA cryogel as the coupling material for transcranial FUS, the mechanical properties (in terms of its Young's modulus) and acoustic attenuation of the PVA cryogel were examined using different concentrations and number of freeze–thaw cycles. The cryogel with 6 or 7% (w/v) concentrations and two freeze–thaw cycles showed minimum pressure attenuation (on the order of 1%) across the different ultrasound frequencies (250–650 kHz). The cryogel was molded to fit around a single‐element FUS transducer and was applied to a head phantom, showing the flexibility in orienting the sonication paths at different angles and depths. The use of the cryogel did not alter the location and shape of acoustic focal profile compared to the one measured in the degassed water. The present work suggests that PVA cryogel may be used as an alternative acoustic coupling medium for low‐intensity FUS applications.
This functional magnetic resonance imaging (fMRI) study investigated the secondary somatosensory area (SII) in humans, especially regarding the presence of distinctive spatial arrangements of neural subunits responding to different types of tactile stimuli. Ten healthy volunteers received four different sensory stimuli on the palmar side of the right hand—vibrotactile, pressure, warmth, and coolness. Based on group‐level analysis of the fMRI data, all four of the somatosensory stimuli resulted in activations in the bilateral SII and insula as well as the SI contralateral to the stimulation. The spatial distribution of neural activations corresponding to each stimulus, as examined by cortical inflation technique, revealed significant overlaps, but also showed the differences in terms of its overall topology. The local maxima of the activation within the SII, corresponding to these stimuli, manifested distinctive spatial location. These results suggest that differential networks of the SII subregions are involved in the processing of the different nature of the tactile stimuli, while sharing common regions in the parietal operculum.
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