Focused ultrasound brain stimulation to anesthetized rats induces long‐term changes in somatosensory evoked potentials

Seung‐Schik Yoo, Kyungho Yoon, Phillip Croce, Amanda Cammalleri, Ryan W. Margolin, Wonhye Lee

International Journal of Imaging Systems and Technology 2018, 28, 106-112 · 10.1002/ima.22262

rodenthealthyeeg meg

Abstract

Low-intensity transcranial focused ultrasound (FUS) has emerged as a non-invasive brain stimulation modality that can reach deep brain areas with high spatial specificity. Previous studies have identified transient effects of FUS on the brain excitability and accompanying physiological responses. Yet the presence of long-lasting effects of FUS, which extend on the order of half an hour or more, has not been probed. We transcranially applied FUS to the somatosensory areas of the anesthetized rats for 10 min at a low duty cycle (5%) and intensity, far below the level that could alter the tissue temperature. Concurrently, we measured electroencephalographic (EEG) somatosensory evoked potentials (SEP) induced by the unilateral electrical stimulation of the hind limb before and after the sonication. Compared to the control sham condition that did not involve sonication, differential SEP features were evident and persisted beyond 35 min after the administration of FUS. The presence of this non-transient neuromodulatory effect may provide early evidence that FUS-mediated brain stimulation has the potential to induce neuroplasticity.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)

Subjects11 animals

Sessions per subject1

Randomisedyes

Blindingnot reported

Sham / controlinactive transducer

Auditory controlnot reported

Readout timingoffline

Anaesthesiaanaesthetised

Readoutseeg meg — Somatosensory evoked potentials (SEP) via needle EEG electrodes, evoked by electrical stimulation of the hind limb

Direction of effectmixed or unclearFUS produced SEP waveforms that differed from sham (additional/shifted peaks) persisting beyond 35 min post-sonication, but the authors could not determine whether the change reflected potentiation or depression of excitability.

Adverse eventsnot reportedTheoretical bioheat modelling estimated a temperature rise of 0.093 degrees C at the FUS focus, judged negligible; thermocouple measurement at the focus during a separate 10 min session at room temperature showed no measurable temperature change.

Exposures

Exposure 1: Wearable transcranial FUS to somatosensory area (hind limb representation)

Target: primary somatosensory cortex — “somatosensory area (of the left hind limb)”
Device: custom-built

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	650	✓✓✓
Pulse duration (ms)	0.5	✓✓✓
Pulse repetition frequency (Hz)	100	✓✓✓
Duty cycle (%)	5pulse duration × PRF gives 5%	✓✓✓
Sonication duration (s)	600	✓✓✓

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
Isppa, domain unspecified (W/cm²)	4.2	✓✓✓
Ispta, domain unspecified (W/cm²)	0.21	✓✓✓

Protocol, in the paper’s words

FUS was given with 100 Hz pulse repetition frequency, 0.5 ms tone burst duration (5% duty cycle) at 4.2 W/cm2 Isppa (210 mW/cm2 Ispta), applied transcranially for 10 min. SEP was measured twice before sonication (Base 1 at -5 min, Base 2 at -2 min) and five times after (Post 1-5 at 5, 10, 15, 25, and 35 min post-sonication); sham sessions used the identical setup without sonication, on a different day, with FUS/sham order randomized and balanced across animals.

Flags from extraction

exposures[0].unspecified_domain — Paper does not state whether the reported Isppa/Ispta values are free-field or in-situ/derated; placed in unspecified_domain.