Low-intensity transcranial ultrasound stimulation improves memory behavior in an ADHD rat model by modulating cortical functional network connectivity
Mengran Wang, Zhenyu Xie, Teng Wang, Shuxun Dong, Zhenfang Ma, Xiangjian Zhang, Xin Li, Yi Yuan
NeuroImage 2024 · 10.1016/j.neuroimage.2024.120841
Abstract
Working memory in attention deficit hyperactivity disorder (ADHD) is closely related to cortical functional network connectivity (CFNC), such as abnormal connections between the frontal, temporal, occipital cortices and with other brain regions. Low-intensity transcranial ultrasound stimulation (TUS) has the advantages of non-invasiveness, high spatial resolution, and high penetration depth and can improve ADHD memory behavior. However, how it modulates CFNC in ADHD and the CFNC mechanism that improves working memory behavior in ADHD remain unclear. In this study, we observed working memory impairment in ADHD rats, establishing a corresponding relationship between changes in CFNCs and the behavioral state during the working memory task. Specifically, we noted abnormalities in the information transmission and processing capabilities of CFNC in ADHD rats while performing working memory tasks. These abnormalities manifested in the network integration ability of specific areas, as well as the information flow and functional differentiation of CFNC. Furthermore, our findings indicate that TUS effectively enhances the working memory ability of ADHD rats by modulating information transmission, processing, and integration capabilities, along with adjusting the information flow and functional differentiation of CFNC. Additionally, we explain the CFNC mechanism through which TUS improves working memory in ADHD. In summary, these findings suggest that CFNCs are important in working memory behaviors in ADHD.
Abstract via europepmc.
Exposures
Exposure 1: TUS to right prefrontal cortex for 7 days
Target: dorsolateral prefrontal cortex — “The stimulation position was in the prefrontal cortex (1.25 mm right, -4.5 mm from bregma), while the specific area that ultrasound can mainly affect was the dorsolateral prefrontal cortex (DLPFC)”
Device: Olympus / Panametrics · Olympus · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 50 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 900 | ✓✓✓⚑ |
| 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) | 360 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 4.3 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.216 | ✓✓✓ |
FF 500 kHz, PRF 1 Hz, DC 5% and stimulation duration (SD) 50 ms; total duration of each stimulation 15 min, once daily for 7 days.
Flags from extraction
n_subjects— 16 SD, 16 SHR and 16 WKY rats were used, split into control and TUS groups of 8; plus an SHR-SHAM group of N = 8 whose origin is not explained. Group sizes of the three TUS groups given; total exposed not stated.exposures[0].timing.pulse_duration_ms— Paper states stimulation duration 50 ms with PRF 1 Hz and DC 5%; 50 ms is taken as the pulse length by the burst rule (DC/PRF = 50 ms).exposures[0].timing.sonication_duration_s— 15 min is the total duration of each stimulation session of 1 Hz pulses; it is not one uninterrupted train.exposures[0].unspecified_domain.isppa_w_cm2— Intensity unit printed as 'w/cm-2' (garbled); Ispta stated as 215.8 mW/cm-2 and converted to 0.2158 W/cm2; domain not stated.anaesthesia— Anaesthesia state during TUS not stated; isoflurane used for surgery only; behaviour in freely moving rats.auditory_control— Separate experiment with trapezoidal (smoothed) pulses reported in Fig. S6 to test auditory effects.exposures[0].timing.waveform— Sham: power amplifier turned off in SHR-SHAM group.