Transcranial Focused Ultrasound to the Thalamus Is Associated with Reduced Extracellular GABA Levels in Rats
Po Song Yang, Hyungmin Kim, Wonhye Lee, Mark Bohlke, Shinsuk Park, Timothy J. Maher, Seung-Schik Yoo
Neuropsychobiology 2012, 65, 153-160 · 10.1159/000336001
Abstract
Objective Transcranial focused ultrasound (FUS), with its ability to non-invasively modulate the excitability of region-specific brain areas, is gaining attention as a potential neurotherapeutic modality. The aim of this study was to examine whether or not FUS administered to the brain could alter the extracellular levels of glutamate and γ-aminobutyric acid (GABA), which are representative excitatory and inhibitory amino acid neurotransmitters, respectively. Methods FUS, delivered in the form of a train of pulses, was applied to the thalamus of Sprague-Dawley rats transcranially. Glutamate and GABA were directly sampled from the frontal lobe of the rat brain via a direct microdialysis technique before, during, and after the sonication. The dialysate concentrations were determined by high-performance liquid chromatography. Results The individual levels of the neurotransmitters sampled were normalized to the baseline level for each rat. In terms of the changes in extracellular glutamate levels, there was no difference between the FUS-treated group and the unsonicated control group. However, extracellular GABA levels started to decrease upon sonication and remained reduced (approximately 20% below baseline; repeated-measures ANOVA, p Conclusion The ability to modulate region-specific brain activity, along with the present evidence of the ability to modulate neurotransmission, demonstrates the potential utility of FUS as a completely new non-invasive therapeutic modality.
Abstract via europepmc.
Exposures
Exposure 1: FUS sonication of the thalamus
Target: thalamus, ventral lateral nucleus — “thalamus (ventrolateral and ventromedial thalamic nucleus)”
Device: other named manufacturer · SensMed · Sonomo ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 5% | |
| Sonication duration (s) | 1,200 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 350 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 3.5 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.175 | ✓✓✓ |
Microdialysates were collected every 20 min in a scheme of 3 baseline intervals (B1-B3), a single sonication interval (FUS), and 5 post-sonication intervals (P1-P5); the animal was sacrificed at the end of data collection without waking from anesthesia.
Flags from extraction
n_subjects— 11 animals enrolled/exposed to FUS but one died during the experiment and one further animal was excluded for exceeding a 3 SD fluctuation threshold, leaving n=9 analysed; enrolled number (11) is reported here.n_sessions_per_subject— Not stated explicitly as 'one session'; inferred from the single continuous terminal procedure (baseline/sonication/post intervals followed by sacrifice).target.terms— Paper states the focus sonicated 'the ventrolateral and ventromedial thalamic nucleus'; ventromedial thalamic nucleus has no exact match in the target vocabulary, so only ventral_lateral_nucleus plus the parent thalamus term are given.exposures[0].in_situ.pressure_kpa— Peak negative pressure and intensities are stated already corrected for ~87% skull attenuation ('in situ'), so classified as derating rather than free-field.