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Transcranial ultrasound neuromodulation induces neuronal correlation change in the rat somatosensory cortex

Sandhya Ramachandran, Xiaodan Niu, Kai Yu, Bin He

Journal of Neural Engineering 2022 · 10.1088/1741-2552/ac889f

rodenthealthyinvasive electrophysiology

Abstract

Objective. 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 elucidate tFUS's mechanism of systemic neuromodulation and allow future development of therapies for treating neurological disorders. Approach. 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 induce frequency dependent plasticity in a manner similar to what is found following electrical stimulation. Main Results. We show that neural firing in response to peripheral electrical stimulation is increased after ultrasound stimulation at all frequencies, showing tFUS induced changes in excitability of individual neurons in vivo . We demonstrate tFUS sonication repetition frequency dependent pairwise correlation changes between neurons, with both increases and decreases observed at different frequencies. Significance. 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)
Subjects30 animals
Sessions per subject2
Randomisedyes
Blindingnot reported
Sham / controlactive control site, inactive transducer
Auditory controlmatched device sound
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology — 32-channel intracortical multi-unit recording; spike time tiling coefficient (STTC) of neuron-pair correlation; peripheral electrical hind-limb stimulation response
Direction of effectexcitatoryFiring in response to peripheral electrical stimulation increased after ultrasound at all five SRFs; pairwise correlation decreased at 10 and 50 Hz SRF and increased at 75, 100 and 125 Hz.
Adverse eventsnot reported

Exposures

Exposure 1: pulsed tFUS at five SRFs (10-125 Hz), S1HL

Target: primary somatosensory cortex — “somatosensory hind limb (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 estimatemeasurementsingle value
In-situ pressure (kPa)114✓✓✓⚑
In-situ Isppa (W/cm²)0.417✓✓✓⚑
In-situ Ispta (W/cm²)0.25✓✓✓⚑
Protocol, in the paper’s words

500 kHz tone bursts of 200 us at a 3 kHz PRF (burst duty cycle 60%) delivered in blocks at a sonication repetition frequency (SRF) of 10, 50, 75, 100 or 125 Hz (60% duty cycle at the SRF level, total duty cycle 36%) for 5 min, between 30 min before and 60 min after peripheral electrical stimulation every 5 s.

Flags from extraction

  • exposures[0].in_situ.pressure_kpa — Measured by hydrophone behind an excised rat skull in degassed water; text calls it pressure amplitude while the Fig. 1 legend says peak-to-peak. Recorded under in_situ as a through-skull measurement.
  • exposures[0].in_situ.isppa_w_cm2 — Paper says the intensities were 'estimated'; converted from 417 mW/cm2 to W/cm2. Method labelled measurement because the pressure was hydrophone-measured through skull.
  • exposures[0].in_situ.ispta_w_cm2 — Converted from 250 mW/cm2 to W/cm2; described as estimated.
  • exposures[0].timing.duty_cycle_pct — Paper gives burst duty cycle 60%, SRF-level duty cycle 60% and total 36%; the total (36) is recorded.
  • exposures[0].timing.pulse_repetition_frequency_hz — Nested protocol: 3 kHz PRF of 200 us bursts inside SRF blocks of 10-125 Hz; the 3 kHz PRF is recorded and SRF is in protocol_description.
  • n_sessions_per_subject — Each animal had two ultrasound sessions and a sham session (3 sessions in total including sham).
  • sham_type — Sham was the collimator moved 3-4 mm laterally still aimed at the anterior skull; three animals also had five baseline sessions without ultrasound.
  • exposures[0].fundamental_frequency_khz — Source text reads 'of0.5 MHz' (missing space); 500 kHz also stated elsewhere.