Modulatory effects of low-intensity retinal ultrasound stimulation on rapid and non-rapid eye movement sleep
Teng Wang, Mengran Wang, Jiawei Wang, Zhen Li, Yi Yuan
Cerebral Cortex 2024 · 10.1093/cercor/bhae143
Abstract
Depression is one of the most serious mental disorders affecting modern human life and is often caused by chronic stress. Dopamine system dysfunction is proposed to contribute to the pathophysiology of chronic stress, especially the ventral tegmental area (VTA) which mainly consists of dopaminergic neurons. Focused ultrasound stimulation (FUS) is a promising neuromodulation modality and multiple studies have demonstrated effective ultrasonic activation of cortical, subcortical, and related networks. However, the effects of FUS on the dopamine system and the potential link to chronic stress-induced depressive behaviors are relatively unknown. Here, we measured the effects of FUS targeting VTA on the improvement of depression-like behavior and evaluated the dopamine concentration in the downstream region - medial prefrontal cortex (mPFC). We found that targeting VTA FUS treatment alleviated chronic restraint stress (CRS) -induced anhedonia and despair behavior. Using an in vivo photometry approach, we analyzed the dopamine signal of mPFC and revealed a significant increase following the FUS, positively associated with the improvement of anhedonia behavior. FUS also protected the dopaminergic neurons in VTA from the damage caused by CRS exposure. Thus, these results demonstrated that targeting VTA FUS treatment significantly rescued the depressive-like behavior and declined dopamine level of mPFC induced by CRS. These beneficial effects of FUS might be due to protection in the DA neuron of VTA. Our findings suggest that FUS treatment could serve as a new therapeutic strategy for the treatment of stress-related disorders.
Abstract via europepmc.
Exposures
Exposure 1: retinal ultrasound stimulation (RUS) of healthy and Alzheimer's disease mice
Target: retina — “retina (mouse eyeball)”
Device: Olympus / Panametrics · Olympus, USA · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 50 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 900 | ✓✓✓ |
| 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 | |
| Pressure, domain unspecified (kPa) | 310 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 3.2 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.16 | ✓✓✓ |
RUS was administered once daily, with each session lasting a cumulative duration of 15 min, consistently for 7 consecutive days. The unfocused ultrasound transducer was affixed to the mouse eyeball via a conical collimator; mice that were awake were gently immobilized using specialized headgear during administration.
Flags from extraction
n_subjects— Table 1 gives per-arm group sizes (n=6 RUS, n=6 CTRL, per healthy/AD group); recorded n_subjects as the 12 animals (6 healthy + 6 AD) that actually received real RUS, excluding the amplifier-off control arms.exposures[0]— Domain (free-field vs in-situ) for the 0.31 MPa pressure / 3.2 & 0.16 W/cm2 intensities is not stated by the paper; recorded as unspecified_domain.exposures[0].timing.pulse_duration_ms— Paper labels 50 ms as 'stimulation duration' alongside frequency/PRF/duty cycle; this matches duty_cycle/PRF (5% of a 1 s period = 50 ms) so was recorded as pulse duration under the burst rule.blinding— Only sleep-stage classification is stated as done 'without any information regarding the identity of the animals'; no blinding of stimulation delivery is described.