Modulation of Cerebellar Cortical Plasticity Using Low-Intensity Focused Ultrasound for Poststroke Sensorimotor Function Recovery
Hongchae Baek, Ki Joo Pahk, Min-Ju Kim, Inchan Youn, Hyungmin Kim
Neurorehabilitation and Neural Repair 2018, 32, 777-787 · 10.1177/1545968318790022
Abstract
Background Stroke affects widespread brain regions through interhemispheric connections by influencing bilateral motor activity. Several noninvasive brain stimulation techniques have proved their capacity to compensate the functional loss by manipulating the neural activity of alternative pathways. Over the past few decades, brain stimulation therapies have been tailored within the theoretical framework of modulation of cortical excitability to enhance adaptive plasticity after stroke. Objective However, considering the vast difference between animal and human cerebral cortical structures, it is important to approach specific neuronal target starting from the higher order brain structure for human translation. The present study focuses on stimulating the lateral cerebellar nucleus (LCN), which sends major cerebellar output to extensive cortical regions. Methods In this study, in vivo stroke mouse LCN was exposed to low-intensity focused ultrasound (LIFU). After the LIFU exposure, animals underwent 4 weeks of rehabilitative training. Results During the cerebellar LIFU session, motor-evoked potentials (MEPs) were generated in both forelimbs accompanying excitatory sonication parameter. LCN stimulation group on day 1 after stroke significantly enhanced sensorimotor recovery compared with the group without stimulation. The recovery has maintained for a 4-week period in 2 behavior tests. Furthermore, we observed a significantly decreased level of brain edema and tissue swelling in the affected hemisphere 3 days after the stroke. Conclusions This study provides the first evidence showing that LIFU-induced cerebellar modulation could be an important strategy for poststroke recovery. A longer follow-up study is, however, necessary in order to fully confirm the effects of LIFU on poststroke recovery.
Abstract via europepmc.
Exposures
Exposure 1: Cerebellar LCN sonication (stroke + LIFU group)
Target: deep cerebellar nuclei — “lateral cerebellar nucleus (LCN)”
Device: Ultran · The Ultran Group · GPS350-D25 FL25 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 2.54 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 1.25 | ✓✓✓ |
The animals in the stroke + LIFU group were subjected to 2 successive 20-minute long LIFU stimulations separated by 20-minute rest intervals 1 day after the stroke, whereas LIFU stimulation was not applied to the stroke group. Repetitive sonication of LCN over the first 20-minute LIFU session generated 600 consecutive MEP responses in sync with the cerebellar stimulation every 2 seconds, with a 2-second interstimulus interval (ISI).
Flags from extraction
n_subjects— Different LIFU-exposed sub-cohorts are reported for different tests (balance beam n=12, adhesive removal n=10, edema n=5, histology n=3 additional healthy mice); no single total is stated.n_sessions_per_subject— Paper describes 2 successive 20-minute LIFU stimulations separated by a 20-minute rest interval, given once 1 day after stroke; unclear whether this counts as 1 or 2 'sessions'.exposures[0].unspecified_domain.isppa_w_cm2— Domain (free-field vs in-situ/brain) of the reported Isppa/Ispta values is not stated by the paper; transducer characterization (FWHM) was done in water but the exposure intensity value itself is not explicitly assigned to a domain.blinding— Only the adhesive removal test is described as a 'blind test'; blinding for other outcome measures is not explicitly stated.