Activation of primate frontal eye fields with a CMUT phased array system

Mitchell R. Riley, Brent M. Roeder, Wolf Zinke, Michael P. Weisend, Derek M. Eidum, Gianmarco F. Pinton, Ali O. Biliroglu, Feisal Y. Yamaner, Omer Oralkan, Robert E. Hampson, Patrick M. Connolly

Journal of Neuroscience Methods 2024, 402, 110009 · 10.1016/j.jneumeth.2023.110009

nonhuman primatehealthyinvasive electrophysiologybehaviour

Abstract

Background There are pushes toward non-invasive stimulation of neural tissues to prevent issues that arise from invasive brain recordings and stimulation. Transcranial Focused Ultrasound (TFUS) has been examined as a way to stimulate non-invasively, but previous studies have limitations in the application of TFUS. As a result, refinement is needed to improve stimulation results. New method We utilized a custom-built capacitive micromachined ultrasonic transducer (CMUT) that would send ultrasonic waves through skin and skull to targets located in the Frontal Eye Fields (FEF) region triangulated from co-registered MRI and CT scans while a non-human primate subject was performing a discrimination behavioral task. Results We observed that the stimulation immediately caused changes in the local field potential (LFP) signal that continued until stimulation ended, at which point there was higher voltage upon the cue for the animal to saccade. This co-incided with increases in activity in the alpha band during stimulation. The activity rebounded mid-way through our electrode-shank, indicating a specific point of stimulation along the shank. We observed different LFP signals for different stimulation targets, indicating the ability to"steer" the stimulation through the transducer. We also observed a bias in first saccades towards the opposite direction. Conclusions In conclusion, we provide a new approach for non-invasive stimulation during performance of a behavioral task. With the ability to steer stimulation patterns and target using a large amount of transducers, the ability to provide non-invasive stimulation will be greatly improved for future clinical and research applications.

Abstract via europepmc.

Speciesrhesus macaque (Macaca mulatta)

Subjects1 animals

Sessions per subjectnot reported

Randomisedyes

Blindingnot reported

Sham / controlnone

Auditory controlnot reported

Readout timingonline

Anaesthesianot reported

Readoutsinvasive electrophysiology, behaviour — Local field potential (LFP) recordings from a multishank electrode; saccade direction and latency in a two-alternative visual discrimination task

Direction of effectexcitatoryTFUS stimulation of FEF produced an immediate rise in LFP activity that continued until stimulation ended, a rise in alpha-band power, and biased first saccades toward the opposite (contralateral) direction, consistent with excitatory activation similar to electrical microstimulation.

Adverse eventsnot reported

Exposures

Exposure 1: Frontal eye field (FEF) TFUS stimulation (targets FEF 4, FEF 10, FEF 7)

Target: frontal eye field — “Frontal Eye Fields (FEF)”
Device: custom-built

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	2,800	✓✓✓
Pulse duration (ms)	not reported	⚑
Pulse repetition frequency (Hz)	1,500, 1,600swept	✓✓✓
Duty cycle (%)	40	✓✓✓
Sonication duration (s)	0.2	✓✓✓

Pressure and intensity, by domain
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

Protocol, in the paper’s words

TFUS was delivered as a single 200 ms burst per trial to one of three FEF target locations (FEF 4, FEF 10, FEF 7), each stimulated independently, using simulation-derived per-element timing to compensate for skull aberrations. Stimulation was applied pseudorandomly to 2/3 of all tested trials, beginning 133 ms prior to the saccade cue onset and continuing through the saccade preparation stage of the task. Driving frequency, PRF, stimulation onset time, and duty cycle were varied substantially across the testing period to explore the parameter space; the values reported here (2.8 MHz, 1500-1600 Hz PRF, 40% duty cycle, 200 ms) correspond to the parameters used for the results shown.

Flags from extraction

exposures[0].free_field.pressure_kpa — The pressure at the ultrasound focus is shown only in Fig. 1B (left); no numeric value is given in the main text.
exposures[0].timing.pulse_duration_ms — Individual pulse-on duration within the 200 ms burst is not stated directly; computing it from duty cycle (40%) and PRF (1500-1600 Hz) would require arithmetic not explicitly performed by the paper.
anaesthesia — The animal performed a visual discrimination behavioral task during stimulation, implying an awake state, but the paper never explicitly states 'awake' or describes anaesthesia status.
n_subjects — Results are from a single animal; authors note 'caution is warranted due to only testing in one subject.'