Disrupting nociceptive information processing flow through transcranial focused ultrasound neuromodulation of thalamic nuclei
Arabinda Mishra, Pai-Feng Yang, Thomas J. Manuel, Allen T. Newton, M. Anthony Phipps, Huiwen Luo, Michelle K. Sigona, Jamie L. Reed, John C. Gore, William A. Grissom, Charles F. Caskey, Li Min Chen
Brain Stimulation 2023, 16, 1430-1444 · 10.1016/j.brs.2023.09.013
Abstract
Background MRI-guided transcranial focused ultrasound (MRgFUS) as a next-generation neuromodulation tool can precisely target and stimulate deep brain regions with high spatial selectivity. Combined with MR-ARFI (acoustic radiation force imaging) and using fMRI BOLD signal as functional readouts, our previous studies have shown that low-intensity FUS can excite or suppress neural activity in the somatosensory cortex. Objective To investigate whether low-intensity FUS can suppress nociceptive heat stimulation-induced responses in thalamic nuclei during hand stimulation, and to determine how this suppression influences the information processing flow within nociception networks. Findings BOLD fMRI activations evoked by 47.5 °C heat stimulation of hand were detected in 24 cortical regions, which belong to sensory, affective, and cognitive nociceptive networks. Concurrent delivery of low-intensity FUS pulses (650 kHz, 550 kPa) to the predefined heat nociceptive stimulus-responsive thalamic centromedial_parafascicular (CM_para), mediodorsal (MD), ventral_lateral (VL_ and ventral_lateral_posteroventral (VLpv) nuclei suppressed their heat responses. Off-target cortical areas exhibited reduced, enhanced, or no significant fMRI signal changes, depending on the specific areas. Differentiable thalamocortical information flow during the processing of nociceptive heat input was observed, as indicated by the time to reach 10% or 30% of the heat-evoked BOLD signal peak. Suppression of thalamic heat responses significantly altered nociceptive processing flow and direction between the thalamus and cortical areas. Modulation of contralateral versus ipsilateral areas by unilateral thalamic activity differed. Signals detected in high-order cortical areas, such as dorsal frontal (DFC) and ventrolateral prefrontal (vlPFC) cortices, exhibited faster response latencies than sensory areas. Conclusions The concurrent delivery of FUS suppressed nociceptive heat response in thalamic nuclei and disrupted the nociceptive network. This study offers new insights into the causal functional connections within the thalamocortical networks and demonstrates the modulatory effects of low-intensity FUS on nociceptive information processing.
Abstract via europepmc.
Exposures
Exposure 1: Concurrent FUS suppression of thalamic VPL and surrounding nuclei during nociceptive heat stimulation
Target: ventral posterolateral nucleus, ventral posteromedial nucleus, mediodorsal nucleus, ventral lateral nucleus, centromedian nucleus — “thalamic VPL and surrounding nuclei (centromedial_parafascicular, mediodorsal, ventral_lateral, ventral_lateral_posteroventral, ventroposterior_medial_and_lateral)”
Device: IGT / Imasonic · Imasonic
| 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 | deratingsingle value | |
| In-situ pressure (kPa) | 550 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
The FUS stimulation blocks consisted of trains of 650 kHz pulses, 500 ms pulse train duration, PRF of 1 kHz, and pulse duration of 0.5 ms; this 500-ms pulse train was repeated at a slow PRF of 0.5 Hz for 16 s, matching the 16-s interleaved heat/heat+FUS stimulus blocks. Individual pulses were ramped up and down (50 us ramp) to reduce auditory-range spectral content. Each of the three stimulus conditions (FUS only, heat only, heat + FUS) was presented in interleaved 16-s blocks in randomized sequence, repeated seven times. A separate high-pressure MR-ARFI calibration pulse (650 kHz, 8.5 ms, max in vivo pressure 3.5 MPa, duty cycle 0.85%) was used only for beam/target localization, not as a neuromodulation exposure.
Flags from extraction
exposures[0].timing.waveform— Classified as 'other_patterned' because the protocol nests fast pulses (1 kHz, 50% duty, 0.5 ms) inside 500-ms trains that are themselves repeated at a slow 0.5 Hz rate for 16 s; this triple-level structure does not map cleanly onto a single waveform category.n_sessions_per_subject— Paper states 4 monkeys underwent 5 total MRI/FUS sessions (not evenly divisible per animal), so a per-subject session count cannot be determined and is left not_reported.conditions— Coded as chronic_pain because the study models nociceptive/pain processing circuits in healthy monkeys as a pain-management research model, not because the animals had a diagnosed pain condition.exposures[0].timing.duty_cycle_pct— Not explicitly stated by the paper; pulse duration (0.5 ms) and PRF (1 kHz) are both given but duty cycle itself is not named, so it is left not_reported rather than computed.