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Transcranial Ultrasound (TUS) Effects on Mental States: A Pilot Study

Stuart Hameroff, Michael Trakas, Chris Duffield, Emil Annabi, M. Bagambhrini Gerace, Patrick Boyle, Anthony Lucas, Quinlan Amos, Annemarie Buadu, John J. Badal

Brain Stimulation 2013, 6, 409-415 · 10.1016/j.brs.2012.05.002

human patientchronic painclinical scaleautonomic physiology

Abstract

Background/objective Transcranial ultrasound (TUS) can modulate brain function. To assess possible TUS modulation of mental states, we investigated effects on subjective reports of pain and mood of sub-thermal TUS versus placebo applied to frontal scalp and brain of chronic pain patient volunteers. Methods With IRB approval and informed consent, subjects with chronic pain completed two visual analog scales for pain (NRS) and mood (VAMS/Global Affect), and their vital signs were recorded 10 min prior to, and 10 min and 40 min following exposure to either subthermal TUS (8 MHz) or placebo (in a double blind crossover study) using the 12L-RS probe of a LOGIQe ultrasound imaging machine (General Electric, USA). A physician, also blinded for TUS versus placebo, applied the probe (with gel) to scalp over posterior frontal cortex, contralateral to maximal pain, for 15 seconds. A second investigator operated the ultrasound machine, randomizing TUS versus placebo. The process was then repeated, applying the opposite modality (TUS or placebo). Results Subjective reports of Mood/Global Affect were improved 10 min (P = 0.03) and 40 min (P = 0.04) following TUS compared with placebo. NRS pain reports slightly improved following TUS (P = 0.07) at 40 min. Conclusion We found improvement in subjective mood 10 min and 40 min after TUS compared to placebo. TUS can have safe neurophysiological effects on brain function, and is a promising noninvasive therapy for modulating conscious and unconscious mental states and disorders. We suggest TUS acts via intra-neuronal microtubules, which apparently resonate in TUS megahertz range.

Abstract via europepmc.

Specieshuman
Subjects31 participants
Sessions per subject1
Randomisedyes
Blindingdouble
Sham / controlinactive transducer
Auditory controlpost hoc check
Readout timingoffline
Anaesthesianot applicable
Readoutsclinical scale, autonomic physiologyNumerical Rating Scale (NRS) for pain; Visual Analog Mood Scale (VAMS) yielding Global Affect and Global Vigor; vital signs (heart rate, systolic/diastolic blood pressure, oxygen saturation)
Direction of effectmixed or unclearTUS produced a significant improvement in Global Affect (mood) at 10 and 40 min versus placebo, a marginal reduction in pain (NRS) at 40 min, higher oxygen saturation at 10 min, and blunted the blood-pressure reduction seen with placebo at 10 min; Global Vigor and other vital signs were not significantly different.
Adverse eventsobservedOne subject experienced exacerbation of a headache following TUS which quickly subsided without sequelae and was included in the analysis; there were no other untoward effects during or after treatment or in follow-up phone interviews up to 4 months later.

Exposures

Exposure 1: 8 MHz diagnostic TUS to posterior frontal scalp/cortex

Target: frontal lobe — “posterior frontal scalp overlying frontal-temporal cortex (site 5, near the temporal window)
Device: other named manufacturer · General Electric · LOGIQe with 12L-RS probe

Pulse timing
Waveformnot reported
Fundamental frequency (kHz)8,000✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)15✓✓
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 estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Ispta, domain unspecified (W/cm²)0.152✓✓
Protocol, in the paper’s words

A diagnostic B-mode ultrasound machine (GE LOGIQe, 12L-RS probe) was applied with gel to the scalp, contralateral to the site of maximal pain, for 15 s per exposure, with settings of power 100%, depth 3.5 cm, harmonics on, cross-Xbeam on. Acoustic output values were MI 0.7, TIs 0.5, TIc 0.2 and a maximum acoustic output (AO) of 152 mW/cm2, well below FDA diagnostic ultrasound limits (MI 1.9, 720 mW/cm2).

Flags from extraction

  • n_sessions_per_subjectNot stated as an explicit number of TUS sessions; inferred as 1 from the crossover design in which each subject received one TUS exposure and one placebo exposure.
  • exposures[0].unspecified_domain.ispta_w_cm2Paper reports a console-derived 'acoustic output (AO)' value of 152 mW/cm2 compared against the 720 mW/cm2 FDA ISPTA limit, suggesting it represents ISPTA, but the paper never explicitly names it as ISPTA or states whether it is a free-field or derated in-situ value; placed in unspecified_domain.
  • exposures[0].timing.waveformDevice is a standard diagnostic B-mode imaging probe; no pulse duration, PRF or duty cycle for the imaging pulse sequence is disclosed, so waveform could not be classified.
  • auditory_controlPaper reports that a spectrum analyzer detected a faint 12.8 kHz signal from the probe during TUS but judged it inaudible to subjects and staff, and subjects reported detecting no sound; this is a post hoc inaudibility check rather than an active masking method, coded as 'other'.