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Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection

Pai-Feng Yang, M. Anthony Phipps, Allen T. Newton, Vandiver Chaplin, John C. Gore, Charles F. Caskey, Li Min Chen

Scientific Reports 2018, 8 · 10.1038/s41598-018-26287-7

nonhuman primatehealthyfmriother mri

Abstract

Focused ultrasound (FUS) has gained recognition as a technique for non-invasive neuromodulation with high spatial precision and the ability to both excite and inhibit neural activity. Here we demonstrate that MRI-guided FUS is capable of exciting precise targets within areas 3a/3b in the monkey brain, causing downstream activations in off-target somatosensory and associated brain regions which are simultaneously detected by functional MRI. The similarity between natural tactile stimulation-and FUS- evoked fMRI activation patterns suggests that FUS likely can excite populations of neurons and produce associated spiking activities that may be subsequently transmitted to other functionally related touch regions. The across-region differences in fMRI signal changes relative to area 3a/3b between tactile and FUS conditions also indicate that FUS modulated the tactile network differently. The significantly faster rising (>1 sec) fMRI signals elicited by direct FUS stimulation at the targeted cortical region suggest that a different neural hemodynamic coupling mechanism may be involved in generating fMRI signals. This is the first demonstration of imaging neural excitation effects of FUS with BOLD fMRI on a specific functional circuit in non-human primates.

Abstract via europepmc.

Speciescynomolgus macaque (Macaca fascicularis)
Subjects2 animals
Sessions per subject3
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutsfmri, other mriBOLD fMRI at 7T; MR thermometry (proton resonance frequency shift)
Direction of effectexcitatoryFUS blocks elicited BOLD activation increases (interpreted as neural excitation) at the targeted area 3a/3b and in downstream touch-network regions, with responses generally stronger and faster-rising than those evoked by tactile stimulation.
Adverse eventsnot reportedMR thermometry showed a zero-mean temperature change (0.00 +/- 0.15 C) in the sonicated brain ROI during ultrasound blocks, with a maximum increase of 0.5 C across all blocks, consistent with bioheat estimates at the power used.

Exposures

Exposure 1: FUS to areas 3a/3b (S1) targeted via prior tactile fMRI mapping

Target: primary somatosensory cortex — “areas 3a/3b, primary somatosensory cortex (S1)
Device: Sonic Concepts · Sonic Concepts · H115

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)250✓✓
Pulse duration (ms)0.252✓✓
Pulse repetition frequency (Hz)2,000✓✓
Duty cycle (%)50pulse duration × PRF gives 50.4%✓✓
Sonication duration (s)0.3✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)935✓✓
Free-field Isppa (W/cm²)29.5✓✓
Free-field Ispta (W/cm²)1.34✓✓
In-situ estimatederatingsingle value
In-situ pressure (kPa)543✓✓
In-situ Isppa (W/cm²)9.9✓✓
In-situ Ispta (W/cm²)0.452✓✓
Protocol, in the paper’s words

FUS pulses were delivered in a block-based scheme identical to the tactile stimuli, in seven 30 sec FUS on/off cycles. During an “on” block, a 250 kHz, 300 msec pulse was emitted at 0.333 Hz (i.e. one 300 ms pulse every 3 s), with the procedure resulting in 10 FUS bursts per “on” block; each 300 msec pulse itself consisted of 63-cycle bursts repeated at 2 kHz (50% duty cycle).

Flags from extraction

  • exposures[0].timing.pulse_duration_msNot stated directly in ms; computed from '63-cycle bursts' at the 250 kHz fundamental frequency (63/250 kHz = 0.252 ms), consistent with the stated 2 kHz PRF and 50% duty cycle (0.5/2000 Hz = 0.25 ms).
  • exposures[0].timing.protocol_descriptionThe paper calls the 300 ms train a 'pulse' and its 63-cycle sub-elements 'bursts', the reverse of this archive's usual burst/pulse terminology; recorded per the paper's own wording.
  • auditory_controlPaper does not discuss auditory confounds or controls for the audible click of FUS pulsing.