Effects of Transcranial Focused Ultrasound on Human Primary Motor Cortex Using 7T fMRI
Condition: Ultrasound in MRI
Study type: Interventional

Summary: 
      Transcranial focused ultrasound (tFUS) is a form of neuromodulation that uses a single
      element transducer to produce highly focused low-intensity acoustic energy that can be used
      to affect cortical excitability in humans. This technology has an advantage over existing
      electric and electromagnetic technologies in that it has very high spatial resolution and can
      be focused deep to the cortical surface to target sub-cortical neural structures and
      circuits. Previous research has shown that tFUS can affect human tactile detection thresholds
      (Legon et al. 2014a) as well as functional measures of the electroencephalogram (EEG) (Legon
      et al. 2014a; Mueller et al. 2014a). However, EEG does not provide for detailed spatial
      mappings and thus the specific spatial extent of the effect of acoustic energy in the cortex
      is not yet understood. This is an important consideration for the advancement of tFUS as a
      non-surgical method of stimulation of discrete cortical circuits and small sub-cortical
      neural structures. Is the effect of tFUS limited to its beam maxima? Does the effect extend
      along the beam path? And if so, to what extent? These questions can be answered if tFUS is
      combined with magnetic resonance imaging (MRI).
    

Detailed description: 
      Background and Significance:

      MRI provides highly detailed spatial maps of cortical and sub-cortical activation. As such,
      delivering tFUS in the MR scanner can provide critical information on neural activation as a
      result of tFUS. It is unclear however, if tFUS can generate a detectable blood-oxygen level
      dependent (BOLD) response. Preliminary evidence in humans (Mueller et al. 2014b; Legon et al.
      2015) has demonstrated mostly negative results and highly variable responses perhaps due to
      the transducer or acoustic intensity levels used, the pulsing strategy employed and/or poor
      signal to noise ratios. We know from animal work it is possible to detect a change in BOLD
      response from tFUS if a known signal already exists. Yoo et al. (2011) showed focused
      ultrasound to attenuate the BOLD signal generated by visual stimuli in visual cortex of
      rabbits. Thus, it is reasonable to assume that this effect is transferable to humans as the
      underlying brain physiology producing the BOLD signal is the same.

      Here we plan to investigate the effect of tFUS on the BOLD signal in human primary motor
      (M1). M1 has been chosen for two fundamental reasons. 1) The use of muscle contraction to
      generate a BOLD signal in M1 allows for investigation tFUS on the peripheral electromyogram
      (EMG) and 2) spatially specific BOLD responses in the cortex can be generated depending upon
      the musculature used, thus allowing for precise spatial mapping of effect. The first point is
      of significant interest because if a detectable effect is demonstrated on peripheral
      musculature it provides important initial evidence that tFUS operates on cortical motor
      neurons and descending motor tracts similar to electric and electromagnetic stimulation thus
      hinting at the cellular populations and mechanisms affected by and responsible for tFUS
      neuromodulatory effect. The second point confirms with high precision the spatially selective
      effect of tFUS and if we can establish energy/effect functions from this data, this can also
      lead to scaling of tFUS energies to elicit specific effects such as inhibition or excitation.

      Together, this knowledge will further promote tFUS for cortical stimulation and progress tFUS
      for subcortical stimulation in humans. This last advancement is the great potential of tFUS.
      Imagine a small device that can simply be attached to the head for precise stimulation
      anywhere in the brain in lieu of surgery. This is the ultimate goal of this research,
      however, before this can be considered, the detailed data from this research proposal is
      necessary.
    

Intervention name(s): Focused Ultrasound
Intervention type(s): Other
Intervention description(s): Test ultrasound in 7T MRI scanner
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Basic Science