Optically-generated focused ultrasound for noninvasive brain stimulation with ultrahigh precision

Abstract

High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited precision at the millimeter level. Here, we report optically-generated focused ultrasound (OFUS) for non-invasive brain stimulation with ultrahigh precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83 µm, which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound (tFUS). Here, we show effective OFUS neurostimulation in vitro with a single ultrasound cycle. We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo. An acoustic energy of 0.6 mJ/cm 2 , four orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision non-invasively.

Abstract via europepmc.

Flags from extraction

• n_subjects — The paper reports per-figure sample sizes (dishes, cultures, and small numbers of mice, e.g. n=3 for c-Fos quantification) but never a single total count of animals/cultures used across the study.
• exposures[0].timing.pulse_duration_ms — Derived from Table 1's stated duration of 0.09x10^-6 s (converted to ms), which the table attributes to a single optoacoustic cycle at 15 MHz.
• exposures[0].in_situ.pressure_kpa — reported_as is coded as mean_or_range_across_subjects because the value is a mean+/-SD across N=46 trials from 11 cultures, not a single fixed measurement.
• exposures[1].timing.pulse_duration_ms — The c-Fos protocol nests a fixed 10 Hz single-optoacoustic-cycle laser repetition inside a stated 33% duty-cycle on/off envelope (2 s on, 4 s off); it is ambiguous which timescale corresponds to schema pulse_duration vs sonication_duration, so both are left not_reported and described in protocol_description (burst-rule ambiguity).
• exposures[1].in_situ.pressure_kpa — Paper also reports an estimated transcranial peak-to-peak pressure of 6.0 MPa (a different pressure metric) for the same exposure; the peak-negative-pressure value (2.7 MPa) is recorded here since it is the more standard convention, but both are in the source quote.
• auditory_control — No explicit auditory-masking/deafening method was used; the paper instead used a spatial control (somatosensory cortex stimulation, no EMG response) and spatial confinement of c-Fos signal to argue against an auditory/bone-conduction confound.