Low-intensity transcranial ultrasound stimulation improves memory in vascular dementia by enhancing neuronal activity and promoting spine formation
Jiamin Pei, Cong Zhang, Xiao Zhang, Zhe Zhao, Xiangjian Zhang, Yi Yuan
NeuroImage 2024 · 10.1016/j.neuroimage.2024.120584
Abstract
Memory is closely associated with neuronal activity and dendritic spine formation. Low-intensity transcranial ultrasound stimulation (TUS) improves the memory of individuals with vascular dementia (VD). However, it is unclear whether neuronal activity and dendritic spine formation under ultrasound stimulation are involved in memory improvement in VD. In this study, we found that seven days of TUS improved memory in VD model while simultaneously increasing pyramidal neuron activity, promoting dendritic spine formation, and reducing dendritic spine elimination. These effects lasted for 7 days but disappeared on 14 d after TUS. Neuronal activity and dendritic spine formation strongly corresponded to improvements in memory behavior over time. In addition, we also found that the memory, neuronal activity and dendritic spine of VD mice cannot be restored again by TUS of 7 days after 28 d. Collectively, these findings suggest that TUS increases neuronal activity and promotes dendritic spine formation and is thus important for improving memory in patients with VD.
Abstract via europepmc.
Exposures
Exposure 1: TUS of the barrel cortex in VD mice
Target: primary somatosensory cortex — “barrel cortex (BC)”
Device: Olympus / Panametrics · Olympus, USA · V301-SU focused ultrasound probe ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 50 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 1,500 | ✓✓✓⚑ |
| 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) | 200 | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 1.33 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.066 | ✓✓✓ |
50,000-cycle pulses at 1 MHz (5% duty cycle, 1 Hz PRF); stimulation daily for 7 consecutive days as three blocks of 25 min separated by 5 min breaks.
Exposure 2: TUS of the visual cortex in VD mice (control site)
Target: primary visual cortex — “visual cortex”
Device: Olympus / Panametrics · Olympus, USA · V301-SU focused ultrasound probe ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 50 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 1,500 | ✓✓✓ |
| 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) | 200 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 1.33 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.066 | ✓✓✓ |
50,000-cycle pulses at 1 MHz (5% duty cycle, 1 Hz PRF); stimulation daily for 7 consecutive days as three blocks of 25 min separated by 5 min breaks.
Flags from extraction
n_subjects— 50 mice enrolled in five groups of 10 (sham, VD, VD+TUS barrel and visual cortex, VD+trapezoidal); includes groups that received no ultrasound, and exposed total is not stated.n_sessions_per_subject— Seven consecutive days; each day had three 25 min blocks.exposures[0].timing.pulse_duration_ms— Pulse duration not stated as such; paper gives 50,000 cycles at 1 MHz and 'stimulation time = 50 ms', which with 5% DC at 1 Hz PRF matches a 50 ms pulse (resolved by arithmetic).exposures[0].timing.sonication_duration_s— 'a total of three groups of 25 min' read as three 25 min blocks of repeated pulses; may alternatively mean 25 min in total.exposures[0].unspecified_domain.pressure_kpa— 0.2 MPa given without stating water or in-brain; sound field was simulated in COMSOL but no in-brain values reported.exposures[1].target— Visual cortex TUS (control site) described only in the limitations section, with the same parameters; results in a supplementary figure.auditory_control— Trapezoidal-pulse VD+TUS group used to test for auditory effects, recorded as ramped_pulses.sham_type— Sham and VD groups received no ultrasound; visual cortex TUS served as an active control site.anaesthesia— Mice awake during imaging; state during sonication not stated.readouts— Local field potential recording reported in the limitations section (supplementary figure).