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Ultrasound Neuromodulation and Correlation Change in the Rat Somatosensory Cortex

Sandhya Ramachandran, Xiaodan Niu, Kai Yu, Bin He

2022 · 10.1101/2022.03.18.484914

rodenthealthyinvasive electrophysiology

Abstract

Transcranial focused ultrasound (tFUS) is a neuromodulation technique which has been the focus of increasing interest for noninvasive brain stimulation with high spatial specificity. Its ability to excite and inhibit neural circuits as well as to modulate perception and behavior has been demonstrated, however, we currently lack understanding of how tFUS modulates the ways neurons interact with each other. This understanding would help explain tFUS’s mechanism of high-level neuromodulation and allow future development of therapies for neurological disorders. In this study we investigate how tFUS modulates neural interaction and response to peripheral electrical limb stimulation through intracranial multi-electrode recordings in the rat somatosensory cortex. We deliver ultrasound in a pulsed pattern to attempt to induce frequency dependent plasticity in a manner similar to that found following electrical stimulation. We show that neural firing in response to peripheral electrical stimulation is increased after ultrasound stimulation at all frequencies, showing tFUS induced excitation in individual neurons in vivo . We demonstrate tFUS frequency dependent pairwise correlation changes between neurons, with both potentiation and depression observed at different frequencies. These results extend previous research showing tFUS to be capable of inducing synaptic depression and demonstrate its ability to modulate network dynamics as a whole.

Abstract via europepmc.

Speciesrat (Wistar)
Subjects32 animals
Sessions per subject2
Randomisedyes
Blindingnot reported
Sham / controlactive control site
Auditory controlother
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology — 32-channel intracortical multi-unit recording; spike sorting; PSTH; spike time tiling coefficient correlation
Direction of effectexcitatoryFiring in response to peripheral electrical stimulation increased after ultrasound at all SRFs relative to sham; pairwise correlation decreased at 10 and 50 Hz and increased at 75, 100 and 125 Hz.
Adverse eventsnot reported

Exposures

Exposure 1: S1HL tFUS at five SRFs

Target: primary somatosensory cortex — “S1HL region of the rat brain”
Device: Blatek · Blatek Industries, Inc., USA · AT31529 ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)0.2✓✓✓
Pulse repetition frequency (Hz)3,000✓✓✓
Duty cycle (%)60pulse duration × PRF gives 60%✓✓✓⚑
Sonication duration (s)300✓✓✓
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 estimatenot 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

Nested pulsing: 200 us tone bursts at PRF 3 kHz (burst duty cycle 60%) gated at a sonication repetition frequency (SRF) of 10, 50, 75, 100 or 125 Hz at 60% duty cycle (total duty cycle 36%), delivered for five minutes between peripheral electrical stimulation epochs.

Flags from extraction

  • exposures[0].free_field.pressure_kpa — No pressure or intensity is reported; the text only notes the paradigm did not reach 131 kPa.
  • n_sessions_per_subject — Each animal received two ultrasound sessions and one sham session in random order; 2 counts ultrasound sessions only.
  • auditory_control — Sham sonication to a different brain region equidistant from auditory cortex was used to account for indirect auditory effects; not a listed vocabulary term.
  • exposures[0].timing.duty_cycle_pct — Total duty cycle 36% (burst duty cycle 60% x 60%); 0.2 ms burst times 3 kHz PRF is consistent with the 60% burst duty cycle.
  • n_subjects — Thirty-two animals stated in words; some sessions excluded for quality.