Pulsed Ultrasound Differentially Stimulates Somatosensory Circuits in Humans as Indicated by EEG and fMRI
Wynn Legon, Abby Rowlands, Alexander Opitz, Tomokazu F. Sato, William J. Tyler
PLoS ONE 2012 · 10.1371/journal.pone.0051177
Abstract
Peripheral somatosensory circuits are known to respond to diverse stimulus modalities. The energy modalities capable of eliciting somatosensory responses traditionally belong to mechanical, thermal, electromagnetic, and photonic domains. Ultrasound (US) applied to the periphery has also been reported to evoke diverse somatosensations. These observations however have been based primarily on subjective reports and lack neurophysiological descriptions. To investigate the effects of peripherally applied US on human somatosensory brain circuit activity we recorded evoked potentials using electroencephalography and conducted functional magnetic resonance imaging of blood oxygen level-dependent (BOLD) responses to fingertip stimulation with pulsed US. We found a pulsed US waveform designed to elicit a mild vibration sensation reliably triggered evoked potentials having distinct waveform morphologies including a large double-peaked vertex potential. Fingertip stimulation with this pulsed US waveform also led to the appearance of BOLD signals in brain regions responsible for somatosensory discrimination including the primary somatosensory cortex and parietal operculum, as well as brain regions involved in hierarchical somatosensory processing, such as the insula, anterior middle cingulate cortex, and supramarginal gyrus. By changing the energy profile of the pulsed US stimulus waveform we observed pulsed US can differentially activate somatosensory circuits and alter subjective reports that are concomitant with changes in evoked potential morphology and BOLD response patterns. Based on these observations we conclude pulsed US can functionally stimulate different somatosensory fibers and receptors, which may permit new approaches to the study and diagnosis of peripheral nerve injury, dysfunction, and disease.
Abstract via europepmc.
Exposures
Exposure 1: Peripheral ultrasonic neurostimulation (PUNS) of the index fingertip: mechanical (PUNS-M) and thermal (PUNS-T) waveforms
Target: digital nerve — “volar surface of the index finger (fingertip)”
Device: Ultran · Ultran Group · custom 0.35 MHz MR-compatible gas matrix piezocomposite transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 2, 10swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 70, 100swept | ✓✓✓ |
| Duty cycle (%) | not reported | ⚑ |
| Sonication duration (s) | 0.5, 1swept | ✓✓✓ |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 11.8, 54.8swept | ✓?⚑ |
Two PUNS waveforms were delivered to the volar surface of the index finger through an acoustic-gel reservoir on the transducer face. PUNS-M (mild vibration sensation): PD=2 msec, PRF=70 Hz, np=35, stimulus duration 0.5 s, ISPTA=11.8 W/cm2. PUNS-T (thermal/warming sensation): PD=10 msec, PRF=100 Hz, np=100, stimulus duration 1.0 s, ISPTA=54.8 W/cm2. During EEG recording, stimuli were delivered every 12 s (+ up to 2 s random jitter) in alternating 50-event blocks to the right and left index fingers, three blocks per finger (150 stimulations per finger, ~1 h 15 min total). During fMRI, stimuli were delivered every sixth TR (12 s), 75 stimuli per finger in separate ~15-min runs.
Flags from extraction
exposures[0]— PUNS-M and PUNS-T share the same target (fingertip) and fundamental frequency (0.35 MHz) and differ only in timing/intensity parameters, so per the one-exposure-per-target-x-frequency rule they are combined into a single exposure with list-valued timing/intensity fields rather than split into two exposures.exposures[0].target— The paper describes stimulation of 'the volar surface of the index finger' rather than a named nerve; mapped to the closest vocabulary term, digital_nerve (finger nerve).exposures[0].unspecified_domain.ispta_w_cm2— The paper does not state whether the hydrophone-measured ISPTA values are free-field or account for any tissue path to the finger; recorded as unspecified_domain.exposures[0].timing.duty_cycle_pct— Not stated as a percentage. Note PUNS-T's stated PD (10 msec) equals its own period (1/PRF = 1/100 Hz = 10 msec), implying an unusually high (near 100%) duty cycle despite being described as 'pulsed'; not computed or filled per the no-arithmetic rule.auditory_control— Earplugs to dampen auditory stimulation are described only for the conventional vibrotactile control condition ('All subjects were outfitted with earplugs...'), not for the PUNS (ultrasound) stimulation conditions; recorded as not_reported for the ultrasound exposure.readout_timing— EEG/fMRI responses are time-locked to stimulus onset (online), while VAS intensity/thermal ratings were collected as a separate subjective report; coded as both.