Summary: Transcranial focused ultrasound (tFUS) can help elevate mood and decrease activity in brain networks associated with psychiatric disorders when directed at the ventrolateral prefrontal cortex.
Source: University of Arizona
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.
Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans
Transcranial focused ultrasound (tFUS) is an emerging method for non-invasive neuromodulation akin to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). tFUS offers several advantages over electromagnetic methods including high spatial resolution and the ability to reach deep brain targets. Here we describe two experiments assessing whether tFUS could modulate mood in healthy human volunteers by targeting the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. In a randomized, placebo-controlled, double-blind study, participants received 30 s of 500 kHz tFUS or a placebo control. Visual Analog Mood Scales (VAMS) assessed mood four times within an hour (baseline and three times after tFUS). Participants who received tFUS reported an overall increase in Global Affect (GA), an aggregate score from the VAMS scale, indicating a positive shift in mood. Experiment 2 examined resting-state functional (FC) connectivity using functional magnetic resonance imaging (fMRI) following 2 min of 500 kHz tFUS at the rIFG. As in Experiment 1, tFUS enhanced self-reported mood states and also decreased FC in resting state networks related to emotion and mood regulation. These results suggest that tFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex.