Neuronal responses to focused ultrasound are gated by pre-stimulation brain rhythms
Duc T. Nguyen, Destiny E. Berisha, Elisa E. Konofagou, Jacek P. Dmochowski
Brain Stimulation 2022 · 10.1016/j.brs.2022.01.002
Abstract
Background Owing to its high spatial resolution and penetration depth, transcranial focused ultrasound stimulation (tFUS) is one of the most promising approaches to non-invasive neuromodulation. Identifying the impact of endogenous neural activity on neuromodulation outcome is critical to harnessing the potential of tFUS. Objective Here we sought to identify the relationship between pre-stimulation neural activity and the neuronal response to tFUS. Methods We applied 3 min of continuous-wave tFUS to the hippocampal region of the rat while recording local field potentials (LFP) and multi-unit activity (MUA) from the target. We also tested the application of tFUS but with an air gap separating the transducer and the skull, as well as active stimulation of the contralateral olfactory bulb. Results We observed a modest but significant increase in firing rate during hippocampal tFUS, but not during stimulation of the olfactory bulb or when an air gap was present. Importantly, the observed firing rate increase was significantly modulated by the power of baseline oscillations in the LFP, with low levels of delta (1-3 Hz) and high levels of theta (4-10 Hz) and gamma (30-250 Hz) power producing significantly larger firing rate increases. Firing rate increases were also amplified by a factor of 7× when stimulation was applied during periods of frequent sharp-wave ripple (SWR) activity. Conclusion Our findings suggest that baseline brain rhythms may effectively "gate" the response to tFUS.
Abstract via europepmc.
Exposures
Exposure 1: FUS HPC, 2.0 MHz (Ultran)
Target: hippocampus — “the right hippocampal region”
Device: Ultran · The Ultran Group · Ultran KS25-2 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 2,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 180 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 14, 28swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 0.013, 0.052swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | not reported |
Continuous-wave tFUS for 3 min (180 s) at 13 or 52 mW/cm2; electrophysiology recorded 2 min before, during the 3-min stimulation and 5 min after; at least 1 h between conditions.
Exposure 2: FUS HPC, 2.5 MHz (Sonic Concepts)
Target: hippocampus — “the right hippocampal region”
Device: Sonic Concepts · Sonic Concepts · SU-132 (driven by TPO-201) ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 2,500 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 180 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 14, 28swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | 0.013, 0.052swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Continuous-wave tFUS for 3 min (180 s) at 13 or 52 mW/cm2; electrophysiology recorded 2 min before, during the 3-min stimulation and 5 min after; at least 1 h between conditions.
Exposure 3: FUS OLF, 2.0 MHz (Ultran)
Target: other — “the left olfactory bulb”
Device: Ultran · The Ultran Group · Ultran KS25-2 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 2,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 180 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 14, 28swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | 0.013, 0.052swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Continuous-wave tFUS for 3 min (180 s) at 13 or 52 mW/cm2; electrophysiology recorded 2 min before, during the 3-min stimulation and 5 min after; at least 1 h between conditions.
Exposure 4: FUS OLF, 2.5 MHz (Sonic Concepts)
Target: other — “the left olfactory bulb”
Device: Sonic Concepts · Sonic Concepts · SU-132 (driven by TPO-201) ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 2,500 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 180 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 14, 28swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | 0.013, 0.052swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Continuous-wave tFUS for 3 min (180 s) at 13 or 52 mW/cm2; electrophysiology recorded 2 min before, during the 3-min stimulation and 5 min after; at least 1 h between conditions.
Flags from extraction
exposures[0].in_situ.isppa_w_cm2— Paper gives 'acoustic intensity' (13 and 52 mW/cm2) without naming Isppa or Ispta; CW so equal, recorded as isppa. Values are with a model rat skull in a water tank; no free-field values are given.exposures[0].in_situ.pressure_kpa— Pressures 14 and 28 kPa given at a 2 MHz center frequency; measured with a model skull (hydrophone), applied here to both transducers as the paper states them.exposures[0].timing.sonication_duration_s— 3 min CW stated; recorded as 180 s.exposures— Two transducers (2.0 MHz Ultran, 2.5 MHz Sonic Concepts) used with identical protocols; results not split by frequency in the text, so four exposures (2 targets x 2 frequencies) share the same intensities.exposures[2].target.terms— Contralateral olfactory bulb has no matching target id; 'other' used.sham_type— FUS AIR: 1 cm air gap between transducer and skull; olfactory stimulation acts as off-target active control.