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Transcranial focused ultrasound to the thalamus alters anesthesia time in rats

Seung-Schik Yoo, Hyungmin Kim, Byoung-Kyong Min, Eric Franck, Shinsuk Park

NeuroReport 2011, 22, 783-787 · 10.1097/wnr.0b013e32834b2957

rodenthealthybehaviourautonomic physiology

Abstract

A pulsed application of focused ultrasound (FUS) to the regional brain tissue alters the state of tissue excitability and thus provides the means for noninvasive functional neuromodulation. We report that the application of transcranial FUS to the thalamus of anesthetized rats reduced the time to emergence of voluntary movement from intraperitoneal ketamine/xylazine anesthesia. Low-intensity FUS was applied to the thalamus of anesthetized animals. The times required for the animals to show distinct physiological/behavioral changes were measured and compared with those times required in a control session without sonication. The sonication significantly reduced the time to show pinch response and voluntary movement. The modulatory effects of FUS on anesthesia suggest potential therapeutic applications for disorders of consciousness such as minimally consciousness states.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects13 animals
Sessions per subject1
Randomisedyes
Blindingnone
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsbehaviour, autonomic physiologyTime to increased respiratory rate, rapid/irregular respiration, whisker movement, eye-blink response to air puff, hind-paw pinch response, and initiation of voluntary movement following ketamine/xylazine anesthesia; rectal temperature and respiratory rate
Direction of effectexcitatoryFUS to the thalamus (at Isppa=6 W/cm2, Ispta=300 mW/cm2) significantly reduced time to hind-paw pinch response (~55 vs ~67 min) and to voluntary movement (69.8+/-9 vs 88.2+/-12.9 min) compared to a no-sonication control session, indicating faster emergence from anesthesia; the paper notes that in prior studies a lower intensity (Isppa=3.3 W/cm2) with the same pulse parameters had instead produced suppressive effects on cortical excitability.
Adverse eventsnone observedThe acoustic intensity and MI used were sufficiently below FDA diagnostic imaging limits (MI=1.9, Ispta=720 mW/cm2), and all animals showed normal behavior and weight gain (~50%) after sonication.

Exposures

Exposure 1: Pulsed FUS to thalamus (anesthesia emergence experiment)

Target: thalamus — “thalamus
Device: custom-built · Sonomo, Korea

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)650✓✓
Pulse duration (ms)0.5✓✓
Pulse repetition frequency (Hz)100✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 5%
Sonication duration (s)1,200✓✓
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 estimatederatingsingle value
In-situ pressure (kPa)490✓✓
In-situ Isppa (W/cm²)6✓✓
In-situ Ispta (W/cm²)0.3✓✓
Protocol, in the paper’s words

For sonication parameters, tone burst duration of 0.5 ms and pulse repetition frequency of 100 Hz were used. Sonication began 40 min after the onset of anesthesia and was maintained for 20 min.

Flags from extraction

  • n_subjects17 rats were enrolled total (2 used only for a pilot timing survey); of the remaining 15, 2 were excluded (atypical hyperventilation n=1, incomplete anesthetic induction n=1). Statistical tests report df=12, consistent with n=13 analysed; n_subjects set to 13 (the analysed cohort) rather than 17 (total enrolled).
  • exposures[0].in_situ.isppa_w_cm2The text describes 6 W/cm2 Isppa (490 kPa, MI 0.61) as the parameters of an earlier 'preliminary test on three animals'; it is not stated in an entirely unambiguous single sentence that this is exactly the same protocol used for the main n=13 anesthesia-emergence cohort, though the surrounding text and use of the same tone-burst duration/PRF strongly implies it.
  • direction_of_effectClassified as 'excitatory' because sonication accelerated emergence/arousal from anesthesia, but the paper explicitly discusses that a lower intensity with identical pulse timing previously produced a suppressive effect on cortical excitability in other studies -- direction is parameter (intensity) dependent.
  • blindingSet to 'none' based on the Discussion statement about 'the use of less subjective and nonblinded assessment of the anesthetic states', implying the physiological/behavioural scoring was not blinded.

Notes: Study design is a within-animal crossover (FUS vs. no-sonication control session, order randomised and counter-balanced). The higher-intensity protocol (Isppa=6 W/cm2) used in the reported main comparison was first identified in an unreported preliminary 3-animal test; a previously published lower-intensity protocol (Isppa=3.3 W/cm2, same 0.5 ms/100 Hz timing) is mentioned for context but was not itself tested in this paper's main dataset.