Antidepressant-Like Effect of Low-Intensity Transcranial Ultrasound Stimulation
Daqu Zhang, Hangdao Li, Junfeng Sun, Weiwei Hu, Wen Jin, Shengtian Li, Shanbao Tong
IEEE Transactions on Biomedical Engineering 2019, 66, 411-420 · 10.1109/tbme.2018.2845689
Abstract
Objective Transcranial ultrasound stimulation (TUS) is a noninvasive neuromodulation technique with good spatial resolution and deep penetration. This study aims to investigate whether TUS has antidepressant-like effect to depressed rats. Methods Rats were divided into five groups, including two groups (ST-Ctr and ST-Res) for evaluating the short-term impact of restraint stress and three groups (LT-Ctr-ShamTUS, LT-Res-ShamTUS and LT-Res-TUS) for studying the long-term effects of restraint and TUS stimulation. The TUS-treated rats were subjected to 15 min TUS stimulation to the prelimbic cortex every day for 2 weeks after the restraint. Then, depressive symptoms related behavioral outcomes were estimated in ST-Ctr and ST-Res groups (1 week after restraint), as well as in the other three groups (3 weeks after restraint). Results The 48-h-restraint stress could lead to long lasting reduction of exploratory behavior (1 and 3 weeks after restraint) and protracted anhedonia (only observed 3 weeks after restraint). TUS application successfully reversed the core depressive phenotype, anhedonia, indicated by significantly higher sucrose preference index in LT-Res-TUS group [Formula: see text] than LT-Res-ShamTUS group [Formula: see text]. Furthermore, the brain derived neurotrophic factor expression in left hippocampus was significantly promoted in LT-Res-TUS group [Formula: see text] compared to LT-Res-ShamTUS group [Formula: see text]. In addition, the histologic results of hematoxylin and eosin staining showed no TUS-induced brain tissue injury. Conclusion These results demonstrated that low intensity TUS had antidepressant-like effect. Significance TUS has been speculated to have therapeutic effect in depression. This study provide evidence for the antidepressant-like effects of TUS in rats for the first time.
Abstract via europepmc.
Exposures
Exposure 1: Transcranial ultrasound stimulation (TUS) of left prelimbic cortex
Target: prefrontal cortex — “prelimbic cortex (PLC, homologous to human PFC)”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.4 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,500 | ✓✓✓ |
| Duty cycle (%) | 60pulse duration × PRF gives 60% | ✓✓✓ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| Free-field pressure (kPa) | 380 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 7.59 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 4.55 | ✓✓✓ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 3 | ✓✓✓⚑ |
Rats were treated with TUS 15 min/day for 2 weeks, with an interval of 3 s adopted between two stimulation trials to avoid thermal accumulation. Sham-TUS animals underwent the identical anaesthesia, fixation and gel-coupling procedure with the transducer powered off.
Flags from extraction
n_subjects— n_subjects reflects the enrolled LT-Res-TUS group size (N=17); analysed sample sizes differ across outcomes (e.g. n=16 for behavioural tests, n=5 for BDNF western blot, n=3 for histology).n_sessions_per_subject— Paper states TUS was given '15 min every day for 2 weeks' but never states an explicit number of sessions; not computed from the duration description.exposures[0].in_situ.ispta_w_cm2— In-brain ISPTA (~3 W/cm2) is a theoretical estimate obtained by derating the free-field value using a calculated 33% skull/tissue attenuation, not a direct measurement.