Bidirectional Neuronal Control of Epileptiform Activity by Repetitive Transcranial Focused Ultrasound Stimulations
Taewon Choi, Minseok Koo, Jaesoon Joo, Taekyung Kim, Young‐Min Shon, Jinhyoung Park
Advanced Science 2024 · 10.1002/advs.202302404
Abstract
Repetitive stimulation procedures are used in neuromodulation techniques to induce persistent excitatory or inhibitory brain activity. The directivity of modulation is empirically regulated by modifying the stimulation length, interval, and strength. However, bidirectional neuronal modulations using ultrasound stimulations are rarely reported. This study presents bidirectional control of epileptiform activities with repetitive transcranial-focused ultrasound stimulations in a rat model of drug-induced acute epilepsy. It is found that repeated transmission of elongated (40 s), ultra-low pressure (0.25 MPa) ultrasound can fully suppress epileptic activities in electro-encephalography and cerebral blood volume measurements, while the change in bursting intervals from 40 to 20 s worsens epileptic activities even with the same burst length. Furthermore, the suppression induced by 40 s long bursts is transformed to excitatory states by a subsequent transmission. Bidirectional modulation of epileptic seizures with repeated ultrasound stimulation is achieved by regulating the changes in glutamate and γ-Aminobutyric acid levels, as confirmed by measurements of expressed c-Fos and GAD65 and multitemporal analysis of neurotransmitters in the interstitial fluid obtained via microdialysis.
Abstract via europepmc.
Exposures
Exposure 1: rtFUS to right anterior thalamic nucleus (TXH_0.25_30, TXL_40_40, TXL_10_50, TXL_20_40, TXL_40_20, TX_HYBRID)
Target: anterior thalamic nucleus — “right anterior thalamic nucleus (ATN)”
Device: custom-built · Del Piezo Specialties LLC (PZT element supplier) · 690 kHz single-element ring transducer (PZT DL-47), 10/31 mm inner/outer diameter ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 690 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.25, 10, 20, 40swept | ✓✓✓⚑ |
| 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) | 250, 1,000swept | ✓✓✓⚑ |
Two families of repeated sonication: TXL, six repetitions of a 0.25 MPa burst of 10, 20 or 40 s with 50, 40, 40 or 20 s intervals; and TXH, eleven repetitions of a 1 MPa, 0.25 s burst with 30 s intervals (50% duty cycle, 100 Hz PRF, 5 ms bursts of 3450 cycles). TX_HYBRID is TXL_40_40 then TXH_0.25_30 after a 3 min rest.
Flags from extraction
n_subjects— Fifty-nine rats stated for the experiments; microdialysis used twenty additional rats per the Methods, so overlap is unclear.exposures[0].unspecified_domain.pressure_kpa— 0.25 MPa and 1 MPa given without stating water or in-brain.exposures[0].timing.waveform— TXH is stated as 50% duty at 100 Hz PRF (pulsed); TXL is called a 'consecutive burst train' with no internal gating stated.exposures[0].timing.pulse_duration_ms— 5 ms, duty cycle 50% and PRF 100 Hz are stated for the TXH sequence only; not applicable as stated to TXL.exposures[0].timing.sonication_duration_s— List of burst lengths across sequences: 0.25 s (TXH), 10, 20, 40 s (TXL).exposures[0].device.family— Transducer is described as fabricated, with a PZT element from Del Piezo Specialties; recorded as custom_built.