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Modification by focused ultrasound pulses of electrically evoked responses from an in vitro hippocampal preparation

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

Brain Research 1991, 558, 36-42 · 10.1016/0006-8993(91)90711-4

ex vivo tissuehealthyinvasive electrophysiology

Abstract

The application of short pulses of focused ultrasound was studied as a method of modifying electrically evoked responses in the mammalian brain. The in vitro hippocampal preparation was employed to facilitate delivery and dosimetry of ultrasound, and assessment of mechanisms of ultrasound effects. Cellular and dendritic field potential responses evoked by electrical stimulation of the Schaffer/Commissural afferents were examined before, during and after exposure of a portion of the CA1 region to focused ultrasound pulses for periods ranging from 2 to 15 min. Focused ultrasound with a repetition rate of 150 kHz was delivered in pulses comparable in duration to an electrical pulse that could initiate activity in the nervous system. The pulses had a center frequency of 750 kHz, durations of about 6 microseconds, and spatial-peak-temporal-averaged intensities of about 80 W/cm2. These parameters are markedly different from those employed in conventional diagnostic ultrasound. Temperatures in the bath and tissue were monitored. Extracellular field potentials reflecting the presynaptic fiber volley, dendritic response and cellular discharge were significantly reduced by exposure to ultrasound. Recovery occurred to varying degrees, and in one experiment was complete. Average temperature changes observed were less than 1 degree C. The present study demonstrates that the electrically evoked response in mammalian brain can be altered by ultrasound in a non-thermal, non-cavitational mode, and that such effects are potentially reversible.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects6, 6, 1, 9swept preparations
Sessions per subjectnot applicable
Randomisednot applicable
Blindingnot applicable
Sham / controlnone
Auditory controlnot reported
Readout timingboth
Anaesthesianot applicable
Readoutsinvasive electrophysiologyExtracellular field potentials (presynaptic fiber volley, population dendritic potential, population spike) evoked by electrical stimulation of Schaffer/Commissural afferents, recorded in the CA1 region of the hippocampal slice
Direction of effectinhibitoryFocused ultrasound pulses significantly reduced the presynaptic fiber volley (mean -21%) and population dendritic potential (mean -46%) amplitudes, and reduced the population spike (-15%) in a single experiment; recovery after ultrasound cessation was partial or complete in most experiments followed.
Adverse eventsnot applicable

Exposures

Exposure 1: Focused ultrasound pulses to the CA1 region of the in vitro hippocampal slice

Target: CA1 — “CA1 region
Device: other named manufacturer · Harisonics Corp.

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)750✓✓
Pulse duration (ms)0.006✓✓
Pulse repetition frequency (Hz)150,000✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 90%
Sonication duration (s)120, 900swept✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)82✓✓
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

A 750 kHz focused transducer delivered repeated ~6 microsecond acoustic pulses (generated from 100 ns electrical voltage spikes) at a pulse repetition rate of 150 kHz to a small region of the CA1 hippocampal slice, continuously for periods of 2 to 15 min (mean 9.4 min for the fiber-volley experiments; mean 7 min for the dendritic-potential experiments), while electrical stimulation of the Schaffer/Commissural afferents was delivered once every 20 s throughout baseline, ultrasound exposure, and (in some experiments) a recovery period.

Flags from extraction

  • exposures[0].timing.pulse_repetition_frequency_hzA stated pulse repetition rate of 150 kHz together with a ~6 microsecond pulse duration implies pulses repeating almost back-to-back (~90% duty cycle), which is unusual for a device described as delivering discrete 'pulses'; the paper does not reconcile this, so the stated PRF is recorded as-is without independently computing a duty cycle.
  • exposures[0].free_field.ispta_w_cm2The Methods state the calibrated ISPTA is 'no greater than 82 W/cm2', while the Abstract restates this as 'about 80 W/cm2'; the more precise Methods value (82) is recorded here.
  • n_subjectsReported as the four per-set experiment counts (6, 6, 1, 9); the paper never states a combined total number of slice preparations used.