Joseph L Sanguinetti, Stuart Hameroff, Ezra E Smith, Tomokazu Sato, Chris MW Daft, William J Tyler, John JB Allen (2020) Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans  Frontiers in Human Neuroscience  

Newswise — A team of researchers at the University of Arizona has found that low-intensity ultrasound waves directed at a particular region of the brain’s prefrontal cortex in healthy subjects can elevate mood, and decrease connectivity in a brain network that has been shown to be hyperactive in psychiatric disorders. The method uses transcranial focused ultrasound (‘tFUS’), a painless, non-invasive technique to modulate brain function comparable to transcranial magnetic stimulation (‘TMS’), and transcranial direct current stimulation (‘tDCS’). This study shows, for the first time, a correlation between tFUS-induced mood enhancement, and reorganization of brain circuits.   

Commonly used for medical imaging, ultrasound consists of mechanical vibrations in the range of ‘megahertz’, a million waves per second, well above human auditory threshold at 20 thousand waves per second. The waves echo off internal body surfaces including unborn babies to provide dynamic anatomical images. Low intensity ultrasound has also long been used as a therapy, e.g. to reduce pain, inflammation and peripheral nerve dysfunction all over the body. Regarding the brain, ultrasound is attenuated by the skull, but passes through sufficiently to focus on specific brain regions at desired depths. At low intensities,, tFUS has been shown to be safe, and able to modulate brain activity, behavior and human mental states.  

In the present study, researchers aimed tFUS at the right ventrolateral pre-frontal cortex, specifically the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. For example increased activity there correlates with reduced negative emotional experience.         

In a randomized placebo-controlled double blind study, 51 healthy student volunteers (27 female, 24 male, mean age 19.7 years) received 30 seconds of either tFUS at 500 kilohertz (0.5 megahertz), or placebo exposure, by a transducer held to the scalp over the temporal window, aimed at rIFG. 

Subjects completed mood surveys before, and up until 30 minutes after tFUS, and results showed that, compared to those receiving placebo, mood scores (‘Global Affect’) for subjects receiving tFUS were significantly higher 20 and 30 minutes later and, anecdotally, up to one hour.  

In a second experiment in healthy volunteers, tFUS mood-elevating effects were replicated, and functional magnetic resonance imaging (fMRI) done before and 20 minutes after tFUS aimed at rIFG. Results showed decreased functional connectivity between rIFG and a number of cortical areas, and decreased connectivity within the default mode network (DMN), a circuit involved in self-referential thinking, mind-wandering and worrying. 

The mechanisms by which tFUS acts in the brain to alter mental states and neuronal connectivity are unknown, as is that by which TMS and tDCS act, and how mental states arise in the brain at all. At the cellular level, ultrasound has been proposed to act on membranes, receptors, extra-cellular matrix and intra-neuronal cytoskeletal microtubules. With known resonances in megahertz, microtubules play prominent roles in synaptic plasticity, and have been theoretically proposed as a substrate for consciousness.       

Decreasing connectivity within DMN suggests the possibility of less self-referential thinking, such as worrying or rumination, and may correlate with being more ‘in the moment’. Indeed a temporary reduction in this network could be particularly useful and lead to longer term neural plasticity if combined with reinforcing therapy, like mindfulness meditation or other modalities 

Lead author Jay Sanguinetti commented: "We're not trying to stimulate neurons to fire, nor simply activate pleasure areas, but to modulate plasticity and enable brain circuits to ‘re-tune’ toward being more mindful ‘in the moment’. 

tFUS as well as unfocused transcranial ultrasound (‘TUS’) are safe, painless, relatively inexpensive, and extremely promising for a variety of mental and cognitive disorders including traumatic brain injury, Alzheimer’s disease, depression, Parkinson’s, chronic pain and addiction.