Efficacy of chronic ultrasound neurostimulation on behaviors and distributed brain metabolism in depressive-like mice
Marc Legrand, Laurent Galineau, Anthony Novell, Barbara Planchez, Bruno Brizard, Samuel Leman, Clovis Tauber, Jean-Michel Escoffre, Antoine Lefèvre, Philippe Gosset, Wissam El-Hage, Patrick Emond, Catherine Belzung, Ayache Bouakaz
2019 · 10.1101/813006
Abstract
Major depression is one of the main factors contributing to the Global Burden of Disease. Current treatment strategies ( e.g., antidepressants and neurostimulation techniques) of major depression show some limitations including inaccuracy and invasiveness. Ultrasound neurostimulation (USNS) has been recently introduced as a physical non-invasive method for brain tissue stimulation and has gained increasing interest. In this study, we sought to evaluate the efficacy of transcranial USNS in an unpredictable chronic mild stress (UCMS) mouse model. The results show that transcranial USNS of the infralimbic cortex reduced anxiety-related behaviors as well as some, but not all, depression-related parameters. [ 18 F]-FDG microPET imaging and brain metabolomic analyses showed that USNS triggered the activation of targeted brain region in addition to brain areas at a distance from the targeted zone, alleviating anxiety and depression-related behaviors induced by the UCMS regimen. Transcranial ultrasound neurostimulation show therapeutic potential in some aspects of major depression.
Abstract via europepmc.
Exposures
Exposure 1: single-pulse USNS of primary motor cortex M1 for parameter optimization
Target: primary motor cortex — “left primary motor cortex M1”
Device: IGT / Imasonic · Imasonic ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.16 | ✓✓✓ |
| Free-field pressure (kPa) | 50, 500swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | derating | |
| In-situ pressure (kPa) | not reported | ⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Single-pulse USNS (160-ms tone bursts) was delivered over left M1 at peak negative pressures stepped from 50 to 500 kPa in 50-kPa increments. In a first subset (n=20), 10 pulses 10 s apart were delivered per pressure step via a threshold-hunting algorithm (electrode-free motor response scoring). In a second subset (n=10, EMG), pressures from 350-500 kPa were tested; 400 kPa (160-msec pulse) gave the best combination of motor success, MEP amplitude, reliability and focality and was adopted for subsequent infralimbic-cortex USNS.
Exposure 2: acute and chronic repeated USNS of the infralimbic cortex (IL)
Target: subgenual anterior cingulate cortex — “infralimbic cortex (IL), the sgACC equivalent in rodents”
Device: IGT / Imasonic · Imasonic ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.16 | ✓✓✓ |
| Free-field pressure (kPa) | 400 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | derating | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Acute USNS was a 10-min session of 60 pulses (each pulse 400 kPa, 160-msec) repeated at a rate of 0.1 Hz over the infralimbic cortex under 1% isoflurane. For chronic USNS, one such session was applied every day for 5 consecutive days (day 29-33), totalling 300 stimuli over 60 min; a Sham group received the same procedure with the transducer deactivated.
Flags from extraction
n_subjects— Paper gives group sizes for separate sub-experiments (M1 parameter-finding: 20 electrode-free + 10 EMG; acute USNS: 4; chronic USNS: 15) rather than one exposed total; listed rather than summed.n_sessions_per_subject— Varies by sub-experiment: single session for M1 parameter-finding and acute USNS, 5 daily sessions for chronic USNS.exposures[0].in_situ.pressure_kpa— Paper states a skull attenuation coefficient (6.32±2.18% at 500 kHz) used to derate pressure inside the brain but does not give the resulting derated kPa value for specific stimulation levels.exposures[1].target.terms— Paper equates the infralimbic cortex (IL) with the rodent sgACC counterpart; target term chosen on that explicit equivalence rather than the vmPFC/prelimbic hierarchy.