Differential effects of amplitude-modulated transcranial focused ultrasound on excitatory and inhibitory neurons
Duc T. Nguyen, Destiny Berisha, Elisa Konofagou, Jacek P. Dmochowski
2020 · 10.1101/2020.11.26.400580
Abstract
Although stimulation with ultrasound has been shown to modulate brain activity at multiple scales, it remains unclear whether transcranial focused ultrasound stimulation (tFUS) exerts its influence on specific cell types. Here we propose a novel form of tFUS where a continuous waveform is amplitude modulated (AM) at a slow rate (i.e., 40 Hz) targeting the temporal range of electrophysiological activity: AM-tFUS. We stimulated the rat hippocampus while recording multi-unit activity (MUA) followed by classification of spike waveforms into putative excitatory pyramidal cells and inhibitory interneurons. At low acoustic intensity, AM-tFUS selectively reduced firing rates of inhibitory interneurons. On the other hand, higher intensity AM-tFUS increased firing of putative excitatory neurons with no effect on inhibitory firing. Interestingly, firing rate was unchanged during AM-tFUS at intermediate intensity. Consistent with the observed changes in firing rate, power in the theta band (3-10 Hz) of the local field potential (LFP) decreased at low-intensity, was unchanged at intermediate intensity, and increased at higher intensity. Temperature increases at the AM-tFUS target were limited to 0.2°C. Our findings indicate that inhibitory interneurons exhibit greater sensitivity to ultrasound, and that cell-type specific neuromodulation may be achieved by calibrating the intensity of AM-tFUS.
Abstract via europepmc.
Exposures
Exposure 1: AM-tFUS to right hippocampus (low, intermediate, high intensity)
Target: hippocampus — “right hippocampus”
Device: Ultran · Ultran · KS25-2 immersion transducer ✓
| Waveform | other patterned | |
|---|---|---|
| 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 | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 1.6, 3.2, 6.4swept | ✓✓✓ |
Continuous 2.0 MHz carrier amplitude modulated at 40 Hz (100% AM depth), three-minute sonications, recorded two minutes before and five minutes after; low, intermediate and high intensity delivered in fixed order with 20 min to 1 h between; sham before active at each intensity.
Flags from extraction
exposures[0].unspecified_domain.ispta_w_cm2— Ispta was set from calibration in water with a model skull between transducer and hydrophone (skull gives 2/3 of free-field pressure); continuous-wave values 2.5, 5.0 and 10.0 W/cm2 traversing the skull were reduced for the AM waveform to 1.6, 3.2 and 6.4 W/cm2. Domain not stated in those words, so placed in unspecified_domain.exposures[0].timing— Amplitude-modulated continuous carrier, not a pulse train; no PRF or pulse duration.n_subjects— 28 rats: electrophysiology n=20, thermometry n=8 (separate follow-up experiment).randomised— Order of intensities fixed for all animals and sham always preceded active.n_sessions_per_subject— Each rat received three intensities, each in sham and active configurations, in one preparation; number of sessions not stated.doi— bioRxiv preprint version.