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Development of a wireless ultrasonic brain stimulation system for concurrent bilateral neuromodulation in freely moving rodents

Evgenii Kim, Jeungeun Kum, Seung Hyun Lee, Hyungmin Kim

Frontiers in Neuroscience 2022 · 10.3389/fnins.2022.1011699

rodenthealthyeeg meg

Abstract

Bilateral brain stimulation is an important modality used to investigate brain circuits and treat neurological conditions. Recently, low-intensity pulsed ultrasound (LIPUS) received significant attention as a novel non-invasive neurostimulation technique with high spatial specificity. Despite the growing interest, the typical ultrasound brain stimulation study, especially for small animals, is limited to a single target of sonication. The constraint is associated with the complexity and the cost of the hardware system required to achieve multi-regional sonication. This work presented the development of a low-cost LIPUS system with a pair of single-element ultrasound transducers to address the above problem. The system was built with a multicore processor with an RF amplifier circuit. In addition, LIPUS device was incorporated with a wireless module (bluetooth low energy) and powered by a single 3.7 V battery. As a result, we achieved an ultrasound transmission with a central frequency of 380 kHz and a peak-to-peak pressure of 480 kPa from each ultrasound transducer. The developed system was further applied to anesthetized rats to investigate the difference between uni- and bilateral stimulation. A significant difference in cortical power density extracted from electroencephalogram signals was observed between uni- and bilateral LIPUS stimulation. The developed device provides an affordable solution to investigate the effects of LIPUS on functional interhemispheric connection.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects9 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutseeg meg — EEG power spectral density by band
Direction of effectmixed or unclearAll four conditions changed EEG band power versus baseline; uni- and bilateral stimulation differed significantly in some bands, with no clear single direction.
Adverse eventsnot reported

Exposures

Exposure 1: Uni- and bilateral LIPUS of motor cortex

Target: primary motor cortex — “right and left primary motor cortex”
Device: custom-built · In-house built (PZT from Steiner & Martins Inc.) · SMD07T02R412WL (PZT element) ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)380✓✓✓
Pulse duration (ms)not reported⚑
Pulse repetition frequency (Hz)1,000, 100swept✓✓✓
Duty cycle (%)50, 5swept✓✓✓
Sonication duration (s)0.3✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)481✓✓✓⚑
Free-field Isppa (W/cm²)2.3✓✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Sonication duration 300 ms, inter-stimulus interval 2 s, 200 trials per condition; conditions 1 kHz PRF with 50% DC or 100 Hz PRF with 5% DC applied unilaterally to the right M1 or bilaterally in combination.

Consistency checks: intensity pressure inconsistent free field.

Flags from extraction

  • exposures[0].free_field.pressure_kpa — Value is peak-to-peak pressure (481 kPa) measured in free water; a 10% loss through the rat skull is stated but not applied.
  • exposures[0].timing.pulse_duration_ms — Pulse duration not stated; DC and PRF stated for two protocols; left not_reported.
  • exposures[0].timing.protocol_description — Four conditions: unilateral 1 kHz/50%, unilateral 100 Hz/5%, bilateral mixed, bilateral 1 kHz/50%; both motor cortices are one target at the same frequency so a single exposure with listed PRF and DC.
  • exposures[0].device.family — Transducers built in-house from Steiner & Martins PZT-4 elements.