Cortical hemodynamic responses induced by low-intensity transcranial ultrasound stimulation of mouse cortex
Yi Yuan, Zhijie Wang, Mengyang Liu, Shy Shoham
NeuroImage 2020, 211, 116597 · 10.1016/j.neuroimage.2020.116597
Abstract
Ultrasound-mediated neuromodulation is emerging as a key technology for targeted noninvasive brain stimulation, but key insights into its effects and dose-response characteristics are still missing. The purpose of this study is to systematically evaluate the effect of low-intensity transcranial ultrasound stimulation (TUS) on complementary aspects of cerebral hemodynamic. We simultaneously record the EMG signal, local field potential (LFP) and cortical blood flow (CBF) using electrophysiological recording and laser speckle contrast imaging under ultrasound stimulation to simultaneously monitor motor responses, neural activities and hemodynamic changes during the application of low-intensity TUS in mouse motor cortex, using excitation pulses which caused whisker and tail movement. Our experimental results demonstrate interdependent TUS-induced motor, neural activity and hemodynamic responses that peak approximately 0.55s, 1.05s and 2.5s after TUS onset, respectively, and show a linear coupling relationship between their respective varying response amplitudes to repeated stimuli. We also found monotonic dose-response parametric relations of the CBF peak value increase as a function of stimulation intensity and duration, while stimulus duty-cycle had only a weak effect on peak responses. These findings demonstrate that TUS induces a change in cortical hemodynamics and LSCI provide a high temporal resolution view of these changes.
Abstract via europepmc.
Exposures
Exposure 1: TUS of mouse motor cortex, multi-parameter sweep
Target: motor cortex — “motor cortex”
Device: Olympus / Panametrics · Olympus, USA · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 10, 20, 30, 40swept | ✓✓✓ |
| Sonication duration (s) | 0.05, 0.1, 0.2, 0.3, 0.4swept | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Isppa, domain unspecified (W/cm²) | 0.2, 0.4, 0.8, 1.1swept | ✓✓✓⚑ |
Three groups were used in our experiments: Group 1, six mice for the tail motor response, neural activity and CBF response experiments. Group 2, nine mice for the whisker motor response and deoxyhemoglobin metabolism. Group 3, eleven mice for CBF response vs multi-parameters. Group 4, three mice for evaluating the thermal effects for CBF response. An f=500 kHz US frequency, 1 kHz PRF pulse train was used across all experiments. For group 1 and group 2, the SD and DC were 400 ms and 40%, respectively. For the group 3, additional combinations of ultrasound parameters were used, including Isppa, DC and SD as shown in Table 1. A CCD camera records for 25s; ultrasound was delivered to brain tissue followed by a baseline of 5s; sixteen trials were averaged to improve signal-to-noise ratio.
Flags from extraction
exposures[0].unspecified_domain.isppa_w_cm2— Field distribution (kPa) was measured by needle hydrophone after passing through the coupling cone/skull path, but the paper does not explicitly state whether the reported Isppa sweep values are free-field or in-situ; domain left unspecified.sham_type— No sham/control ultrasound arm is described for the main dose-response experiments; only a separate deep-anaesthesia control was used to probe thermal confounds.