Microscopic deconstruction of cortical circuit stimulation by transcranial ultrasound
Théo Lemaire, Yi Yuan, Celia Gellman, Amy M. LeMessurier, Sarah R. Haiken Dray, Justin P. Little, Robert C. Froemke, Shy Shoham
2024 · 10.1101/2024.10.10.617091
Abstract
Transcranial Ultrasound Stimulation (TUS) can noninvasively and reversibly perturb neuronal activity, but the mechanisms by which ultrasound engages brain circuits to induce functional effects remain unclear. To elucidate these interactions, we applied TUS to the cortex of awake mice and concurrently monitored local neural activity at the acoustic focus with two-photon calcium imaging. We show that TUS evokes highly focal responses in three canonical neuronal populations, with cell-type-specific dose dependencies. Through independent parametric variations, we demonstrate that evoked responses collectively scale with the time-average intensity of the stimulus. Finally, using computational unmixing we propose a physiologically realistic cortical circuit model that predicts TUS-evoked responses as a result of both direct effects and local network interactions. Our results provide a first direct evidence of TUS’s focal effects on cortical activity and shed light on the complex circuit mechanisms underlying these effects, paving the way for TUS’s deployment in clinical settings.
Abstract via europepmc.
Exposures
Exposure 1: Focused TUS to primary visual cortex (V1), 2.1 MHz, pressure and duty-cycle sweeps
Target: primary visual cortex — “primary visual cortex (V1)”
Device: custom-built · Beijing C.C.W. Ultrasonic Science & Technology, China (PZT-4 ceramic ring element, custom-assembled transducer) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 2,100 | ✓✓✓ |
| Pulse duration (ms) | not reported | ⚑ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5, 80swept | ✓✓✓ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| 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) | 0, 800swept | ✓?⚑ |
| Ispta, domain unspecified (W/cm²) | 0, 15.8swept | ✓? |
TUS delivered as 200 ms pulse trains (internal PRF 100 Hz) through a coaxial annular transducer aligned with the 2-photon objective; independent sweeps of peak pressure amplitude (0-0.8 MPa at fixed 50% duty cycle) and duty cycle (5-80% at fixed 0.8 MPa) were performed. For each condition, 16 consecutive stimuli were presented with a 25-28 s inter-trial interval; no more than 15 conditions were explored per session (imaging time <2 hours).
Flags from extraction
n_subjects— Different sub-experiments (dose-response sweeps, offset control, buzzing control, A1/deafening control) report different, partially overlapping animal counts (e.g. SST n=6, Thy1 n=10, PV n=7, offset n=3, buzzing n=4); no single total number of animals used in the study is stated.exposures[0].timing.pulse_duration_ms— Paper gives duty cycle (5-80%) and PRF (100 Hz) but never states an explicit pulse duration in ms; computing it from duty cycle/PRF would be arithmetic not stated by the paper, so left not_reported per the burst rule.exposures[0].unspecified_domain.pressure_kpa— Peak pressure amplitude (0-0.8 MPa) is given without specifying whether it is a free-field or in-situ/at-target value; placed in unspecified_domain.exposures[0]— A second target (primary auditory cortex, A1) was also stimulated with the same transducer/frequency as a confound-control experiment (deafened animal, n=1); this was not modelled as a separate exposure because it served as a mechanistic control rather than a primary parametric target.