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Increased Excitability Induced in the Primary Motor Cortex by Transcranial Ultrasound Stimulation

Benjamin C. Gibson, Joseph L. Sanguinetti, Bashar W. Badran, Alfred B. Yu, Evan P. Klein, Christopher C. Abbott, Jeffrey T. Hansberger, Vincent P. Clark

Frontiers in Neurology 2018, 9 · 10.3389/fneur.2018.01007

human healthyhealthyemg mepbehaviour

Abstract

Background: Transcranial Ultrasound Stimulation (tUS) is an emerging technique that uses ultrasonic waves to noninvasively modulate brain activity. As with other forms of non-invasive brain stimulation (NIBS), tUS may be useful for altering cortical excitability and neuroplasticity for a variety of research and clinical applications. The effects of tUS on cortical excitability are still unclear, and further complications arise from the wide parameter space offered by various types of devices, transducer arrangements, and stimulation protocols. Diagnostic ultrasound imaging devices are safe, commonly available systems that may be useful for tUS. However, the feasibility of modifying brain activity with diagnostic tUS is currently unknown. Objective: We aimed to examine the effects of a commercial diagnostic tUS device using an imaging protocol on cortical excitability. We hypothesized that imaging tUS applied to motor cortex could induce changes in cortical excitability as measured using a transcranial magnetic stimulation (TMS) motor evoked potential (MEP) paradigm. Methods: Forty-three subjects were assigned to receive either verum ( n = 21) or sham ( n = 22) diagnostic tUS in a single-blind design. Baseline motor cortex excitability was measured using MEPs elicited by TMS. Diagnostic tUS was subsequently administered to the same cortical area for 2 min, immediately followed by repeated post-stimulation MEPs recorded up to 16 min post-stimulation. Results: Verum tUS increased excitability in the motor cortex (from baseline) by 33.7% immediately following tUS ( p = 0.009), and 32.4% ( p = 0.047) 6 min later, with excitability no longer significantly different from baseline by 11 min post-stimulation. By contrast, subjects receiving sham tUS showed no significant changes in MEP amplitude. Conclusion: These findings demonstrate that tUS delivered via a commercially available diagnostic imaging ultrasound system transiently increases excitability in the motor cortex as measured by MEPs. Diagnostic tUS devices are currently used for internal imaging in many health care settings, and the present results suggest that these same devices may also offer a promising tool for noninvasively modulating activity in the central nervous system. Further studies exploring the use of diagnostic imaging devices for neuromodulation are warranted.

Abstract via europepmc.

Specieshuman
Subjects21 participants
Sessions per subject1
Randomisedyes
Blindingsingle
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsemg mep, behaviour10-item mood questionnaire (0-5 Likert) and 0-10 sensation questionnaire (itching, heat/burning, tingling) administered before and after stimulation
Direction of effectexcitatoryVerum tUS produced a significant increase in MEP amplitude (33.7% at 1 min, 32.2% at 6 min post-stimulation) relative to baseline and compared with sham, which showed no significant change from baseline.
Adverse eventsnone observedMechanical index during tUS was 0.67 (below FDA limit of 1.9) and thermal index was 2.6; no significant differences between verum and sham in itching, heat/burning, or tingling sensation ratings.

Exposures

Exposure 1: Verum tUS to primary motor cortex

Target: primary motor cortex — “motor cortex (abductor pollicis brevis motor hotspot)
Device: other named manufacturer · Phillips · CX50 Diagnostic Imaging Ultrasound System with S5-1 broadband plane sector transducer array

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)2,320✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)120✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)1,020✓✓
Free-field Isppa (W/cm²)34.96✓✓
Free-field Ispta (W/cm²)0.133✓✓
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Diagnostic tUS (B-mode with harmonics, focal depth 10 cm, unfocused/plane-wave field) was administered for 2 min to the motor hotspot; duty cycle was described only as '<1%' without an exact value being given.

Flags from extraction

  • n_subjects21 subjects were assigned to verum tUS, but after exclusions only 19 verum subjects were included in the final MEP analysis; enrolled (21) is reported here per rule, see 'A total of 40 subjects were used in the analysis, with 19 in verum (11 females) and 21 in sham (14 females).'
  • exposures[0].timing.duty_cycle_pctPaper states duty cycle only as '<1%', an inequality rather than an exact value, so left not_reported; see 'The low duty cycle of our device, <1%, ...' in protocol_description.
  • device.manufacturerManufacturer name spelled 'Phillips' in the source text (likely intended as Philips); recorded verbatim.
  • n_sessions_per_subjectSingle-session, between-subjects design inferred from the single-visit study design (experimental visit 70-100 min); paper does not state 'one session' as an explicit number.