The Effect of Low-Intensity Transcranial Ultrasound Stimulation on Neural Oscillation and Hemodynamics in the Mouse Visual Cortex Depends on Anesthesia Level and Ultrasound Intensity.

OBJECTIVE: Low-intensity transcranial ultrasound stimulation (TUS) can induce motor responses, neural oscillation and hemodynamic responses. Early studies demonstrated that the motor responses evoked by TUS critically depend on anesthesia levels and ultrasound intensity. However, the neural mechanism of how anesthesia levels and ultrasound intensity influence on brain responses during TUS has never been explored yet. To investigate this question, we applied different anesthesia levels and ultrasound intensities on the visual cortex of mouse and observed neural oscillation change and hemodynamic responses during TUS. METHODS: low-intensity ultrasound was delivered to mouse visual cortex under different anesthesia levels, and simultaneous recordings for local field potentials (LFPs) and hemodynamic responses were carried out to measure and analyze the changes quantitatively. RESULTS: (i) The change of mean amplitude and mean relative power of sharp wave-ripple (SPW-R) in LFPs induced by TUS decreased as the anesthesia level increased (from awake to 1.5% isoflurane). (ii) The hemodynamic response level induced by TUS decreased as the anesthesia level increased (from awake to1.5% isoflurane). (iii) The coupling strength between neural activities and hemodynamic responses was dependent on anesthesia level. (iv) The neural activities and hemodynamic responses increase as a function of ultrasound intensity. CONCLUSION: These results support that the neural activities and hemodynamic response of the mouse visual cortex induced by TUS are related to the anesthesia level and ultrasound intensity. SIGNIFICANCE: This finding suggests that careful maintenance of anesthesia level and ultrasound intensity is required to acquire accurate LFP and hemodynamic data from samples with TUS.

The Effect of Low-Intensity Transcranial Ultrasound Stimulation on Behavior in a Mouse Model of Parkinson's Disease Induced by MPTP.

This study investigated the effects of low-intensity transcranial ultrasound stimulation (TUS) on behavior in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD mouse model was induced by consecutive injecting the mice with MPTP for 7 days. When the animal model is completed, we performed behavioral tests including the wire hanging test, open field test and forced swimming test on day 1, 2, 3, 4, 7, 14 during 2 weeks. Simultaneously, the ultrasound was used to stimulate the brain tissue of the mice daily for these 2 weeks. The data were analyzed to examine treatment effects. When the PD+TUS and PD+Sham groups were compared, the behavior of the PD+TUS mice was better on the fourth day after TUS (*p<0.05) and had further improved on the fourteenth day of TUS (**p<0.01). These results demonstrate that TUS can improve behavior in mice with MPTP-induced PD. The treatment effect gradually improved as the TUS duration increased.

Transcranial Ultrasound Stimulation Directly Influences the Cortical Excitability of the Motor Cortex in Parkinsonian Mice.

BACKGROUND: Low-intensity transcranial ultrasound stimulation is a new noninvasive brain modulation method with high spatial resolution and high penetration depth. However, until now, it was unclear whether transcranial ultrasound stimulation has a significant effect on PD. OBJECTIVES: In order to evaluate the effect of transcranial ultrasound stimulation on PD. METHODS: We used transcranial ultrasound stimulation to modulate parkinsonian-related activity in mice administered MPTP and recorded local field potentials in the motor cortex before and after ultrasound stimulation. We analyzed neuronal oscillatory activity known to be relevant to the pathophysiology of PD. RESULTS: After ultrasound stimulation, mean power intensity in the beta band (13-30 Hz) significantly decreased, and the phase-amplitude coupling strength between the beta and high gamma (55-100 Hz) bands and between the beta and ripple (100-200 Hz) bands also became significantly weaker. CONCLUSIONS: This study demonstrates that ultrasonic neuromodulation can significantly decrease parkinsonian-related activity in mice administered MPTP. © 2019 International Parkinson and Movement Disorder Society.