Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo
Jonathan A N Fisher, Iryna Gumenchuk
Journal of Neural Engineering 2018 · 10.1088/1741-2552/aaaee1
Abstract
Objective The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Among many, one of the most exciting applications is the use of FUS to rehabilitate or augment human sensory capabilities. While there is compelling empirical evidence demonstrating this capability, basic questions regarding the spatiotemporal extent of the modulatory effects remain. Our objective was to assess the basic, yet often overlooked hypothesis that FUS in fact alters sensory-evoked neural activity within the region of the cerebral cortex at the beam's focus. Approach To address this knowledge gap, we developed an approach to optically interrogate patterns of neural activity in the cortex directly at the acoustic focus, in vivo. Implementing simultaneous wide-field optical imaging and FUS stimulation in mice, our experiments probed somatosensory-evoked electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic mice expressing GCaMP6f, monitored associated Ca 2+ responses. Main results Our results demonstrate that low-intensity FUS alters both the kinetics and spatial patterns of neural activity in primary somatosensory cortex at the acoustic focus. When preceded by 1 s of pulsed ultrasound at intensities below 1 W cm -2 (I sppa ), the onset of sensory-evoked cortical responses occurred 3.0 ± 0.7 ms earlier and altered the surface spatial morphology of Ca 2+ responses. Significance These findings support the heretofore unconfirmed assumption that FUS-induced sensory modulation reflects, at least in part, altered reactivity in primary sensory cortex at the site of sonication. The findings are significant given the interest in using FUS to target and alter spatial aspects of sensory receptive fields on the cerebral cortex.
Abstract via europepmc.
Exposures
Exposure 1: FUS to mouse forelimb S1, 510 kHz
Target: primary somatosensory cortex — “forelimb's representation on primary somatosensory cortex”
Device: Sonic Concepts · Sonic Concepts · custom 16-element ring array (modified H-205B), TPO-106 driver ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 510 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | ⚑ |
| Sonication duration (s) | 1 | ✓✓✓ |
| 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) | 170 | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 0.69, 3.5swept | ✓✓✓ |
A 1 s burst of pulsed FUS (500 us pulses at 510 kHz, 1 kHz repetition rate) ending 200 ms before electrical forelimb stimulation and optical recording of 0.5 s; trials separated by 30 s. Pressure of 0.17 MPa given for the 0.69 W/cm2 condition.
Flags from extraction
n_subjects— Group sizes vary by experiment (n=7 and n=4 VSD, n=6 Ca2+, n=2 Evans blue) and no total is given; not_reported.exposures[0].unspecified_domain.pressure_kpa— 0.17 MPa 'peak pressure at the focus' characterised with a hydrophone by the manufacturer; medium not stated, so kept unspecified.exposures[0].timing.duty_cycle_pct— Not stated; 500 us pulses at 1 kHz given.exposures[0].device.family— Custom ring array described as a modified Sonic Concepts H-205B with a Sonic Concepts TPO-106 driver; family assigned by transducer maker.