Ultrasound Deep Brain Stimulation Regulates Food Intake and Body Weight in Mice
Wen Meng, Zhengrong Lin, Tianyuan Bian, Xiaoyan Chen, Long Meng, Tifei Yuan, Lili Niu, Hairong Zheng
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2024 · 10.1109/tnsre.2024.3351312
Abstract
Given the widespread occurrence of obesity, new strategies are urgently needed to prevent, halt and reverse this condition. We proposed a noninvasive neurostimulation tool, ultrasound deep brain stimulation (UDBS), which can specifically modulate the hypothalamus and effectively regulate food intake and body weight in mice. Fifteen-min UDBS of hypothalamus decreased 41.4% food intake within 2 hours. Prolonged 1-hour UDBS significantly decreased daily food intake lasting 4 days. UDBS also effectively restrained body weight gain in leptin-receptor knockout mice (Sham: 96.19%, UDBS: 58.61%). High-fat diet (HFD) mice treated with 4-week UDBS (15 min / 2 days) reduced 28.70% of the body weight compared to the Sham group. Meanwhile, UDBS significantly modulated glucose-lipid metabolism and decreased the body fat. The potential mechanism is that ultrasound actives pro-opiomelanocortin (POMC) neurons in the hypothalamus for reduction of food intake and body weight. These results provide a noninvasive tool for controlling food intake, enabling systematic treatment of obesity.
Abstract via europepmc.
Exposures
Exposure 1: ARC (hypothalamus), 3.8 MHz
Target: arcuate nucleus — “hypothalamus, especially the arcuate nucleus”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,800 | ✓✓✓ |
| Pulse duration (ms) | 1, 0.067swept | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 500, 1,500swept | ✓✓✓ |
| Duty cycle (%) | 50, 10swept | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| 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) | 586 | ✓✓✓⚑ |
Two parameter sets in the acute experiment: PRF 500 Hz, DC 50%, TBD 1 ms; and PRF 1.5 kHz, DC 10%, TBD 0.067 ms; sonication duration 1 s, inter-stimulus interval 2 s (5 s in the HFD and transgenic experiments, PRF 500 Hz set only). Acute sessions 15 min; subacute 1 h/day for 2 days; db/db mice 15 min/day for 10 days then 33 days of 15 min/day; HFD mice 15 min every 2 days, 14 times.
Exposure 2: V1 control site, 3.8 MHz
Target: primary visual cortex — “visual cortex (V1)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,800 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓⚑ |
| Sonication duration (s) | 1 | ✓✓✓ |
| 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) | 586 | ✓✓✓ |
V1 control: TBD 1 ms and PRF 500 Hz (the 50% duty cycle set), 15 min, same sonication duration, interval and pressure as the acute ARC experiment; only this set was tested at V1.
Flags from extraction
exposures[0].unspecified_domain.pressure_kpa— 586 kPa is called 'acoustic pressure'; a hydrophone measured inside the skull and the paper reports 54% skull attenuation at 3.8 MHz, but does not say whether 586 kPa is free-field or in the brain.n_subjects— Group sizes differ per experiment (acute ARC 8, V1 7, subacute 8, db/db 13 per group, HFD 9) and animal reuse is unclear; only the acute groups are listed.exposures[1].timing.duty_cycle_pct— The paper states TBD 1 ms and PRF 500 Hz for V1; the 50% duty cycle is taken from the acute parameter set that applied to V1.exposures[0].timing.pulse_duration_ms— Burst rule: TBD 1 ms with PRF 500 Hz and DC 50% is consistent (1 ms x 500 Hz = 50%); TBD is the pulse.sham_type— Sham: ultrasound output abolished (inactive transducer); V1 stimulation acts as an active control site.