Imaging of Neurovascular Activity during Motor Responses Evoked by Displacement-guided Focused Ultrasound (DgFUS) Neuromodulation in Mice
Elisa Konofagou, Seongyeon Kim, Daniella Jimenez, Jonas Bendig, Moshe Willner, Gillian Ciaccio, Sergio Jimenez-Gambin, Nancy Kwon, Saachi Munot, Erica McCune, Samuel Blackman
2026 · 10.21203/rs.3.rs-9173358/v1
Abstract
Focused ultrasound (FUS) shows great promise for precise and non-invasive neuromodulation, with applications from basic neuroscience investigation to the treatment of neurological disorders. Yet, mechanistic monitoring of FUS is challenging and a causal link between FUS-induced displacement and both neurovascular and behavioral responses evoked by FUS in mice remains poorly understood. Here we harness displacement-guided focused ultrasound (DgFUS) to induce target-specific and non-auditory motor responses in anesthetized mice, and functional ultrasound (fUS) to image neurovascular activity during the evoked responses. We show that DgFUS elicits ipsilateral neurovascular responses, in which the primary (i.e. focal-onset) activation localizes with brain displacement, followed by mild contralateral responses. We demonstrate that switching the target hemisphere of DgFUS within the thalamus results in lateralized hindlimb responses concurrent with lateralized neurovascular activation. We show strong correlation between displacement and both cerebral blood volume (CBV) and electromyography (EMG) measurement (Disp. vs. CBV: Spearman r = 0.9091, p
Abstract via europepmc.
Exposures
Exposure 1: 4 MHz DgFUS of thalamus and somatosensory cortex (cranial window, motor responses)
Target: thalamus, somatosensory cortex — “somatosensory cortex and thalamus”
Device: Sonic Concepts · Sonic Concepts · H-215 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 4,000 | ✓✓✓ |
| Pulse duration (ms) | 80 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 8% | |
| Sonication duration (s) | 10 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 1,690, 2,540, 3,390swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Continuous FUS pulses with a pulse duration of 80 ms (320k cycles, 4 MHz) and a sonication duration of 10 s at a pulse repetition frequency of 1 Hz; pressure 0 (sham) to 3.39 MPa, all stated as derated. FUS was manually scanned over the cranial window until motor activation was seen.
Exposure 2: Transcranial fUS-guided FUS of bilateral hippocampus (FUS-N)
Target: hippocampus — “bilateral hippocampus”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | 150 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 15% | |
| Sonication duration (s) | 120 | ✓✓✓ |
| 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) | 1,900 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
FUS was applied for 2 minutes (1 Hz PRF, 1.9 MPa pressure, and 150 ms pulse duration) with a total of 120 FUS pulses delivered per bilateral target. Transducer and frequency are not stated for this arm.
Flags from extraction
exposures[0].in_situ.pressure_kpa— Paper states all pressures were derated but not the derating method or whether to tissue; recorded as in_situ derating. Pressure levels 1.69, 2.54, 3.39 MPa read from the latency sentence; 1.54 MPa also named as threshold; intensity only in a figure table.exposures[0].timing.pulse_duration_ms— Paper calls the 80 ms pulse continuous (320k cycles at 4 MHz) repeated at 1 Hz for 10 s; recorded as pulsed. Duty cycle not stated.exposures[1].fundamental_frequency_khz— Frequency and transducer for the hippocampal FUS-N arm are not stated in the text.exposures[1].unspecified_domain.pressure_kpa— Domain of the 1.9 MPa not stated.n_subjects— 22 is the stated total of mice and includes FUS-BBBO (5) and sham (4) animals and one histology and one temperature animal; the FUS-BBBO arm (microbubbles) is not recorded as an exposure.auditory_control— No masking; the paper argues non-auditory origin from latency, lateralisation and a 0.5 mm off-target control, classified here as control_experiment.sham_type— Sham (0 MPa) in motor experiments and sham mice in the behavioural arm; mechanism not described.