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Changes in theta and gamma oscillations of the medial prefrontal cortex following hippocampal-focused ultrasound stimulation

Jiwon Baek, Younghee Seo, Bong Soo Kim, Young Cheol Na, Won Seok Chang

Neurofunction 2024 · 10.52662/nf.2023.00094

rodenthealthyinvasive electrophysiologyhistology molecular

Abstract

Objective: Neuromodulation is a rapidly growing field of treatment, encompassing implantable and noninvasive technology-based approaches. Focused ultrasound (FUS), a noninvasive method, has the potential to modulate neural activity in deep brain regions with spatial precision based on the penetrance of sound waves into the bone and soft tissue. However, neuromodulation is limited by the inability to confirm modulation in real-time. Electrophysiological technology is required to overcome this limitation. In this study, we aimed to confirm neural activity using Neuropixel electrodes during FUS sonication.Methods: Six male C57BL/6 mice were subjected to ultrasound sonication in the hippocampus. Simultaneously, local field potential (LFP) measurements were performed using Neuropixel electrodes. The experimental groups were divided into three categories: before, during, and after FUS sonication and the measured LFP data were compared between groups.Results: Theta and gamma waves were extracted from the recorded LFP data and compared between the groups. The theta and gamma oscillations changed after FUS sonication compared to before. The theta graph showed significant changes between the pre- and during-treatment groups and between the during- and post-treatment groups (theta: 4–8 Hz, F=23.91, p<0.0001). However, the gamma graph did not show significant changes in any groups (gamma: 30–50 Hz). Additionally, the expression of c-fos, a marker of neuronal activity, increased after FUS sonication.Conclusion: Although further research is needed—including longer follow-up LFP measurements after FUS sonication and the collection of more LFP data—neuromodulation with FUS can be considered usable in other neurological disease models.

Abstract via crossref.

Speciesmouse (C57BL/6)
Subjects3 animals
Sessions per subject1
Randomisednot reported
Blindingnot reported
Sham / controlundescribed
Auditory controlnot reported
Readout timingboth
Anaesthesianot reported
Readoutsinvasive electrophysiology, histology molecularNeuropixel local field potential recording (theta 4-8 Hz, gamma 30-50 Hz bands); c-fos immunohistochemistry
Direction of effectexcitatoryTheta oscillation power increased significantly during and after FUS sonication compared with before; gamma oscillations were unchanged; cortical/hippocampal c-fos expression increased after FUS.
Adverse eventsnot reported

Exposures

Exposure 1: Hippocampal FUS with mPFC LFP recording

Target: hippocampus — “right dorsal hippocampus
Device: Sonic Concepts · Sonic Concept Inc. · H-107MR

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)515✓✓
Pulse duration (ms)0.2✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)50pulse duration × PRF gives 20%, which disagrees with the stated value✓✓
Sonication duration (s)0.3✓✓
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 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

FUS parameters were 515 kHz fundamental frequency, 50% duty cycle, 1 kHz PRF, 0.2 ms tone-burst duration (TBD), 300 ms sonication duration, and 2 s inter-stimulus interval. LFP was measured 10 minutes before, 10 minutes during, and 10 minutes after FUS modulation in each group.

Flags from extraction

  • exposures[0].timing.pulse_duration_msStated duty cycle (50%) and PRF (1 kHz) imply a 0.5 ms pulse duration, but the paper states TBD = 0.2 ms (20% duty cycle at that PRF); values are recorded as stated without correction.
  • sham_typeA 'control group (without FUS modulation)' is mentioned but the mechanism (e.g., transducer present/absent, powered off) is not described.
  • n_subjectsAbstract/methods state 6 mice were sonicated, but the methods also describe 4 groups of 3 mice (control + pre/during/post-treatment), which is not fully reconcilable with n=6; recorded as explicitly stated in the abstract/methods opening sentence.