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Modulation of the functional state of the brain with the aid of focused ultrasonic action

V. A. Velling, S. P. Shklyaruk

Neuroscience and Behavioral Physiology 1988, 18, 369-375 · 10.1007/bf01193880

other vertebratelarge animalhealthyeeg meginvasive electrophysiology

Abstract

We investigated the possibility of modifying the functional state of the brain with the aid of focused ultrasound and studied various regimes of its action. A specific pattern in the effect of focused ultrasonic action was discovered with regard to its intensity: the effect is absent at low (less than 0.1 mW/cm2) intensities; activation of bioelectrical activity in the brain takes place at intensities from 1 to 100 mW/cm2; and suppression of the ECoG takes place at intensities from 1 to 100 W/cm2. On the basis of our own data and the data in the literature, we suggest that the mechanism of ultrasound action is based upon changes in the permeability of neuronal membranes leading, after a chain of intracellular molecular reactions, to a subsequent general de- or hyperpolarization of the membranes of neuronal populations and to a change in the bioelectrical activity of the brain.

Abstract via europepmc.

Speciescat; rabbit
Subjectsnot reported animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingboth
Anaesthesiaboth
Readoutseeg meg, invasive electrophysiologyECoG (electrocorticogram) via implanted tungsten electrodes; visual evoked potentials to light flashes; thresholds for motor activity to direct electrostimulation of motor cortex
Direction of effectbidirectionalLow intensities (1-100 mW/cm2) activated/increased ECoG amplitude and cortical excitability, higher intensities (1-100 W/cm2) suppressed the ECoG and produced pathological 'peak-wave' activity, and intensities below 0.1 mW/cm2 produced no effect; the direction of the ECoG and excitability change depended on intensity, duration and modulation frequency.
Adverse eventsnot reported

Exposures

Exposure 1: Acute experiments: ultrasonic action through a trepanned opening in cats

Target: sensorimotor cortex, temporal lobe, parietal lobe — “temporal, sensorimotor, and parietal cortex
Device: custom-built

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)not reported
Pulse duration (ms)0.1, 100swept✓✓
Pulse repetition frequency (Hz)1, 20swept✓✓
Duty cycle (%)not reported
Sonication duration (s)5, 600swept✓✓
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 estimatesimulationsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)0.000001, 1,400swept✓✓
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Ultrasound was delivered through a trepanned skull opening to cats under light nembutal anaesthesia, focused with a micromanipulator-mounted emitter onto temporal, sensorimotor and parietal cortex sites. Regimes studied ranged from individual short pulses (0.1-100 ms, up to 100 repeated pulses) to extended trains ('packets of pulses' at 1-20 pulses/s) lasting from seconds to many minutes; short single pulses at intensities up to 1400 W/cm2 produced no ECoG change, whereas trains longer than about 10 s produced graded ECoG suppression (1-100 W/cm2) or a biphasic activation/suppression response (10-100 mW/cm2) depending on modulation frequency and duration.

Exposure 2: Chronic experiments: ultrasonic action through intact skull bone in awake rabbits

Target: cerebral cortex — “neocortex
Device: custom-built

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)not reported
Pulse duration (ms)0.1, 100swept✓✓
Pulse repetition frequency (Hz)6, 10swept✓✓
Duty cycle (%)not reported
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 estimatesimulationsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)0.001, 0.1swept✓✓
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

In chronic experiments, the ultrasound focus was fixed to the intact skull of awake rabbits with the focus 1.5-2.0 mm below the dura at a selected neocortical site. Regimes ranged from individual pulses (0.1-100 ms) to trains at 1-20 pulses/s. Intensities of 1-100 mW/cm2 with modulation at 6-10 Hz produced a stable increase in ECoG amplitude for exposures lasting up to 20 min; within this range, 10-100 mW/cm2 lowered cortical excitability (reduced evoked-potential amplitude, raised electrostimulation threshold) while 1-10 mW/cm2 increased excitability.

Flags from extraction

  • exposures[0].fundamental_frequency_khzNo carrier/fundamental ultrasound frequency (MHz) is stated anywhere in this paper for either the acute or chronic experiments.
  • exposures[1].fundamental_frequency_khzSame as exposures[0]: fundamental frequency is never reported.
  • n_subjects17 cats are stated for the acute experiments, but the number of rabbits used in the chronic experiments is never given, so a study-wide n_subjects cannot be determined.
  • exposures[0].timing.pulse_duration_msThe 'various regimes' sentence describing pulse duration, repetition rate and intensity range appears once in the Methods and is applied here to both the acute (cat) and chronic (rabbit) exposures because the paper does not clearly separate the parameter ranges used in each series.
  • exposures[0].in_situ.isppa_w_cm2Classified as in_situ/simulation because the text specifies 'intensity at the focus' (i.e. at the target) and describes it as 'calculated' rather than measured in water; however the paper does not explicitly describe a derating or simulation method, so this domain assignment is uncertain.
  • exposures[1].in_situ.isppa_w_cm2Same uncertainty as exposures[0].in_situ.isppa_w_cm2.