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Focused Ultrasound Modifications of Neural Circuit Activity in a Mammalian Brain

Michael R. Bachtold, Patricia C. Rinaldi, Joie P. Jones, Frederick Reines, LeRoy R. Price

Ultrasound in Medicine & Biology 1998, 24, 557-565 · 10.1016/s0301-5629(98)00014-3

ex vivo tissuehealthyinvasive electrophysiology

Abstract

The application of focused, pulsed ultrasound was studied as a method of modifying the activity of a local neural circuit of the mammalian brain. An in vitro hippocampal preparation was used to facilitate delivery, dosimetry and assessment of mechanisms of ultrasound effects. Extracellular evoked potentials were recorded from cell and dendritic layers of the rat hippocampal dentate gyrus. Focused pulses of ultrasound with center frequency of 500 kHz and repetition rate of 200 kHz were studied and found both to enhance and to depress electrically evoked field potentials. The fiber volley and cell population potentials were depressed, whereas the dendritic potential was enhanced. Results suggest a simultaneous mechanical and thermal mechanism of ultrasound in modifying evoked field potentials of dentate local circuits.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects4, 6, 6, 6, 6swept preparations
Sessions per subjectnot applicable
Randomisednot applicable
Blindingnot applicable
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesianot applicable
Readoutsinvasive electrophysiology — Extracellular field potentials (fiber volley, dendritic potential, orthodromic and antidromic population spikes) in dentate gyrus; tissue temperature by thermocouple
Direction of effectbidirectionalFiber volley and orthodromic population spike were depressed, the dendritic field potential was enhanced and the antidromic spike was little changed during 5-min exposures.
Adverse eventsnot applicableCavitation was judged unlikely: no bubbles seen under the microscope and most responses recovered; tissue temperature rose 1.4 C on average.

Exposures

Exposure 1: 500 kHz pulsed focused ultrasound, rat hippocampal slice dentate gyrus

Target: dentate gyrus — “dentate gyrus region of the hippocampal slice”
Device: other named manufacturer · Staveley Sensors, Inc. · Harisonic 18-0016-P ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)not reported⚑
Pulse repetition frequency (Hz)200,000✓✓✓⚑
Duty cycle (%)not reported
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)40, 110swept✓✓✓⚑
In-situ estimatenot applicable
In-situ pressure (kPa)not applicable
In-situ Isppa (W/cm²)not applicable
In-situ Ispta (W/cm²)not applicable
Protocol, in the paper’s words

The transducer was driven by 100-ns-wide square spikes at a pulse repetition rate of 200 kHz, giving acoustic pulses only a few cycles long; voltage was ramped to the operating level within 5 s. Slices were exposed for 5 min, allowed to recover 5-10 min, then exposed for another 5 min.

Flags from extraction

  • exposures[0].free_field.ispta_w_cm2 — ISPTA estimated at low voltage by reciprocity calibration and calibrated hydrophone with transducer in a water tank, then extrapolated to the operating voltage; stated as a range with conservative systematic-error allowance.
  • exposures[0].timing.pulse_duration_ms — Acoustic pulse described only as 'a few cycles in duration'; no numeric value, so not recorded. The 100 ns figure is the electrical drive spike.
  • exposures[0].timing.pulse_repetition_frequency_hz — PRF of 200 kHz is stated in the text (selected to fire the next pulse immediately after ring-down).
  • n_subjects — Number of rats not stated; 4 to 6 slices per experimental set and 6 slices for temperature work, overlap between sets unknown.
  • exposures[0].timing.protocol_description — Protocol does not fit the four timing numbers: very short pulses at 200 kHz PRF with no stated pulse duration or duty cycle.