Transcranial ultrasound stimulation at the peak-phase of theta-cycles in the hippocampus improve memory performance
Zhenyu Xie, Shuxun Dong, Yiyao Zhang, Yi Yuan
NeuroImage 2023, 283, 120423 · 10.1016/j.neuroimage.2023.120423
Abstract
The present study aimed to investigate the effectiveness of closed-loop transcranial ultrasound stimulation (closed-loop TUS) as a non-invasive, high temporal-spatial resolution method for modulating brain function to enhance memory. For this purpose, we applied closed-loop TUS to the CA1 region of the rat hippocampus for 7 consecutive days at different phases of theta cycles. Following the intervention, we evaluated memory performance through behavioral testing and recorded the neural activity. Our results indicated that closed-loop TUS applied at the peak phase of theta cycles significantly improves the memory performance in rats, as evidenced by behavioral testing. Furthermore, we observed that closed-loop TUS modifies the power and cross-frequency coupling strength of local field potentials (LFPs) during memory task, as well as modulates neuronal activity patterns and synaptic transmission, depending on phase of stimulation relative to theta rhythm. We demonstrated that closed-loop TUS can modulate neural activity and memory performance in a phase-dependent manner. Specifically, we observed that effectiveness of closed-loop TUS in regulating neural activity and memory is dependent on the timing of stimulation in relation to different theta phase. The findings implied that closed-loop TUS may have the capability to alter neural activity and memory performance in a phase-sensitive manner, and suggested that the efficacy of closed-loop TUS in modifying neural activity and memory was contingent on timing of stimulation with respect to the theta rhythm. Moreover, the improvement in memory performance after closed-loop TUS was found to be persistent.
Abstract via europepmc.
Exposures
Exposure 1: Closed-loop phase-locked TUS to hippocampal CA1 (peak, trough, or random phase of theta cycle)
Target: CA1 — “CA1 region of the rat hippocampus”
Device: not reported
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.05 | ✓✓✓ |
| 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) | 510 | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 8.66 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.43 | ✓✓✓ |
Closed-loop, phase-locked 50 ms ultrasound tone bursts (0.5 MHz) were triggered at the peak, trough, or (in the random group) at 5 fixed times within each 1 s window based on real-time detection of hippocampal theta phase, with a 1 s stimulation refractory period, for a total stimulation time of 15 min/day for 7 consecutive days; sham stimulation group received no phase-locked triggering (mechanism not described). Rats were anesthetized during stimulation and awake during the Y-maze memory test.
Flags from extraction
exposures[0].timing.waveform— The figure legend (Fig. 1D) additionally defines 'CPP: number of cycles per pulse' and 'PEF: pulse repetition frequency' terms, implying possible internal pulsing within the 50 ms burst, but no PRF or duty-cycle values are given in the text, so the 50 ms tone burst was treated as a single continuous burst per the 'single uninterrupted burst' rule.exposures[0].unspecified_domain.pressure_kpa— Pressure (0.51 MPa) and intensities (Isppa 8.66 W/cm2, Ispta 0.43 W/cm2) are given without stating whether they are free-field or in-situ/derated values.n_subjects— Only the three ultrasound-exposed group sizes (peak, trough, random stimulation, n=5 each) are counted; the sham stimulation group (also n=5) is assumed not to have received real ultrasound, but the sham mechanism is not described.sham_type— The mechanism of the 'sham stimulation' group (e.g., inactive transducer vs. no output) is not described in the text.