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Ultrasound Deep Brain Stimulation Modulates Body Temperature in Mice

Na Pang, Wen Meng, Yongsheng Zhong, Xiufang Liu, Zhengrong Lin, Tianxu Guo, Hui Zhou, Lin Qi, Long Meng, Lisheng Xu, Lili Niu

IEEE Transactions on Neural Systems and Rehabilitation Engineering 2022 · 10.1109/tnsre.2022.3188516

rodenthealthyautonomic physiologyhistology molecular

Abstract

Body temperature plays a critical role in rehabilitation, and numerous studies proved that the regulation of body temperature contributes to the sensorimotor recovery of patients with brain diseases such as stroke. The hypothalamus plays a key role in thermoregulation. Ultrasound deep brain stimulation (UDBS) can noninvasively modulate deep brain nuclei and have potential applications in the treatment of Parkinson's disease, Alzheimer's disease, and depression, among others. The purpose of this study was to investigate whether ultrasound stimulation of the hypothalamus could regulate body temperature in free-moving mice. Results showed that thermoregulation was related to ultrasonic parameters (pulse repetition frequency (PRF), duty cycle, total time, and acoustic pressure). UDBS of the preoptic area of the anterior hypothalamus at 500 Hz PRF could significantly reduce body temperature ( [Formula: see text] at t = 5 min, [Formula: see text] at t = 10 min, [Formula: see text] at t = 15 min). Meanwhile, UDBS of the dorsomedial hypothalamus at 10 Hz PRF triggered a significant increase in body temperature ( [Formula: see text] at t = 5 min, [Formula: see text] at t = 10 min). These results suggest that UDBS, as a noninvasive neuromodulation tool, may play a key role in the future clinical treatment of malignant hyperthermia and hypothermia.

Abstract via europepmc.

Speciesmouse (C57BL/6J)
Subjects48, 18swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlundescribed
Auditory controlnot reported
Readout timingboth
Anaesthesiaawake
Readoutsautonomic physiology, histology molecular — infrared thermal imaging of skin temperature; c-Fos immunofluorescence
Direction of effectbidirectionalUDBS of the POA reduced body temperature (up to about 0.84 C at 15 min) while UDBS of the DMH increased it (about 1.16 C at 10 min); c-Fos expression increased at both sites.
Adverse eventsnot reportedCavitation and heating judged unlikely from MI and thermocouple measurements; no adverse events discussed.

Exposures

Exposure 1: POA stimulation

Target: hypothalamus — “preoptic area of the anterior hypothalamus (POA)”
Device: other named manufacturer · Siansonic, Beijing · PZT-8 focused transducer ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)3,740✓✓✓
Pulse duration (ms)not reported⚑
Pulse repetition frequency (Hz)500✓✓✓
Duty cycle (%)10, 30, 50swept✓✓✓
Sonication duration (s)2✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatemeasurementsingle value
In-situ pressure (kPa)388, 514, 751, 981swept✓✓✓⚑
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Sonication duration 2 s and inter-stimulus interval 2 s repeated for a total time (TT) of 10-30 min, with PRF, duty cycle, total time and acoustic pressure varied across groups (Table I). Pulse duration is not stated. POA: PRF 500 Hz, DC 10/30/50%, TT 10/15/20/30 min; DMH: PRF 10 Hz or 500 Hz, DC 30/50%, TT 10 min.

Exposure 2: DMH stimulation

Target: hypothalamus — “dorsomedial hypothalamus (DMH)”
Device: other named manufacturer · Siansonic, Beijing · PZT-8 focused transducer ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)3,740✓✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)10, 500swept✓✓✓⚑
Duty cycle (%)30, 50swept✓✓✓
Sonication duration (s)2✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatemeasurementsingle value
In-situ pressure (kPa)751✓✓✓⚑
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Sonication duration 2 s and inter-stimulus interval 2 s repeated for a total time (TT) of 10-30 min, with PRF, duty cycle, total time and acoustic pressure varied across groups (Table I). Pulse duration is not stated. POA: PRF 500 Hz, DC 10/30/50%, TT 10/15/20/30 min; DMH: PRF 10 Hz or 500 Hz, DC 30/50%, TT 10 min.

Flags from extraction

  • n_subjects — Group sizes (POA 48, DMH 18, sham 5) do not sum to 90 and the immunofluorescence subgroup sizes (sham 9, POA 4, DMH 6) disagree with the c-Fos results (sham n=4 and 5); 90 recorded as stated total.
  • exposures[0].in_situ.pressure_kpa — Table I labels pressure 'AP (kPa, with skull)'; the text says negative pressure was measured by hydrophone with and without skull. Treated as in situ measurement; not stated whether peak negative or other.
  • exposures[1].timing.pulse_repetition_frequency_hz — Fig. 3B shows DMH at PRF 500 Hz (DC 30, 50%) and 10 Hz; Table I does not say which rows were DMH, so DMH parameter lists come from the Results text.
  • exposures[1].in_situ.pressure_kpa — 751 kPa for the DMH is from Fig. 4 legend and Table I; table does not label target.
  • exposures[0].timing.pulse_duration_ms — Pulse duration not stated; not computed from PRF and duty cycle.
  • anaesthesia — Isoflurane used only for collimator mounting; stimulation was in free-moving mice.
  • exposures[0].timing.sonication_duration_s — Sonication duration (SD) 2 s with 2 s ISI repeated for total time of 10-30 min.