Modulating nociception networks: the impact of low-intensity focused ultrasound on thalamocortical connectivity
Arabinda Mishra, Pai-Feng Yang, Thomas J Manuel, Allen T Newton, M Anthony Phipps, Huiwen Luo, Michelle K Sigona, Allison Q Dockum, Jamie L Reed, John C Gore, William A Grissom, Charles F Caskey, Li Min Chen
Brain Communications 2024 · 10.1093/braincomms/fcaf062
Abstract
Pain engages multiple brain networks, with the thalamus serving as a critical subcortical hub. This study aims to explore the effects of low-intensity transcranial focused ultrasound-induced suppression on the organization of thalamocortical nociceptive networks. We employed MR-guided focused ultrasound, a potential non-invasive therapy, with real-time ultrasound beam localization feedback and fMRI monitoring. We first functionally identified the focused ultrasound target at the thalamic ventroposterior lateral nucleus by mapping the whole-brain blood oxygenation level-dependent responses to nociceptive heat stimulation of the hand using fMRI in each individual macaque monkey under light anaesthesia. The blood oxygenation level-dependent fMRI signals from the heat-responsive thalamic ventroposterior lateral nucleus were analysed to derive thalamocortical effective functional connectivity network using the psychophysical interaction method. Nineteen cortical regions across sensorimotor, cognitive, associative and limbic networks exhibited strong effective functional connectivity to the thalamic ventroposterior lateral during heat nociceptive processing. Focused ultrasound-induced suppression of heat activity in the thalamic ventroposterior lateral nucleus altered nociceptive responses in most of the 19 regions. Data-driven hierarchical clustering analyses of blood oxygenation level-dependent time courses across all thalamocortical region-of-interest pairs identified two effective functional connectivity subnetworks. The concurrent suppression of thalamic heat response with focused ultrasound reorganized these subnetworks and modified thalamocortical connection strength. Our findings suggest that the thalamic ventroposterior lateral nucleus has extensive and causal connections to a wide array of cortical areas during nociceptive processing. The combination of MR-guided focused ultrasound with fMRI enables precise dissection and modulation of nociceptive networks in the brain, a capability that no other device-based neuromodulation methods have achieved. This presents a promising non-invasive tool for modulating pain networks with profound clinical relevance. The robust modulation of nociceptive effective functional connectivity networks by focused ultrasound strongly supports the thalamic ventroposterior lateral as a viable target for pain management strategies.
Abstract via europepmc.
Exposures
Exposure 1: Thalamic VPL nucleus with heat stimulation (heat + FUS blocks)
Target: ventral posterolateral nucleus — “thalamic ventroposterior lateral nucleus”
Device: IGT / Imasonic · Imasonic (Besancon, France) · custom-designed, MR-compatible, 128-element transducer
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓⚑ |
| Sonication duration (s) | 0.5 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 761.8, 902.7swept | ✓?⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Trains of 650 kHz pulses, 500 ms pulse train duration, PRF 1 kHz, pulse duration 0.5 ms; the train is repeated at 0.5 Hz for 16 s, followed by 30 s rest, each condition repeated seven times; pulses ramped (50 us).
Flags from extraction
exposures[0].timing.duty_cycle_pct— 50% is the within-train duty cycle (Fig. 1E legend); the text also gives a duty cycle of 12.5% over the 16 s block (time-averaged power calculation).exposures[0].timing.sonication_duration_s— 16 s is the block length; each 500 ms train is repeated at 0.5 Hz within the block.exposures[0].in_situ.pressure_kpa— Simulation range of 761.75-902.74 kPa peak negative pressure differs from the stated target in vivo pressure of 550 kPa (free-field value derated by an assumed 39% transmission); only the simulated range is recorded.n_sessions_per_subject— Three animals had one session, one animal two sessions; recorded as a list.randomised— Only the order of heat, FUS and heat + FUS blocks within runs is stated to be a randomized sequence; no group allocation.sham_type— Heat-only blocks serve as the no-FUS comparison within the same runs; no sham sonication.