Ultrasound as a next-generation brain interface

When you think of ultrasound, you probably imagine a pregnant woman in a clinic looking at her baby on a black-and-white display. The reality is that ultrasound devices have become pocket-sized and stream directly to clinicians’ phones, exploding in popularity during the pandemic among many different specialties. Rather than sending the patient to get costly and time-consuming imaging, ultrasound offers a real-time alternative.

Butterfly Networks, an ultrasound device manufacturer, is exploring how to further increase accessibility and lower the barrier to training so that patients can perform it largely on their own. Early pilots are showing that patients can obtain interpretable lung ultrasound images at home with guidance, which is particularly impactful for rural and remote regions.

Butterfly telemedicine platform enables a trained practitioner to connect with a novice at the bedside. Source.

Apart from its diagnostic potential, ultrasound technology has been showing promise as a therapeutic tool for brain conditions such as OCD, addiction, and depression. Startups like Attune and Nudge are rapidly overcoming the technical and clinical hurdles toward a future where safe, non-invasive neuromodulation is accessible to everyone.

Next-generation neuromodulatory technology

Research progress in transcranial ultrasound stimulation (TUS) has accelerated in the last few years, demonstrating its potential as a transformative technology for therapeutic applications.

To understand what makes it so compelling, let’s compare it to traditional neuromodulatory approaches:

deep brain stimulation (DBS) is an invasive procedure, considered the gold standard in delivering stimulation for therapeutic effects in neurological and psychiatric disorders.
transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive but don’t reach deep brain regions.

TUS offers a small form factor capable of non-invasive, whole-brain neuromodulation with high precision. The tradeoff is that its short-term effects appear to be less potent than directly applied electrical stimulation. In addition, the human skull interferes with its imaging capabilities, but computational techniques are being developed to account for this.

The biological mechanisms of ultrasound neuromodulation are not well understood. Focused sound waves are beamed at neurons, applying mechanical force as they pass through. This may influence the activity of cell membranes or ion channels, resulting in either excitation or inhibition depending on the ultrasound parameters used (pulse duration or intensity).

From clinical trials to home use

Before therapeutic TUS is mature enough for remote use, early applications will begin in clinical environments with strict protocols and trained technicians administering treatments. The pace of this trajectory will depend on proving successful outcomes for initially approved indications.

TUS can be thought of as a scalable, non-invasive version of DBS, which has found the most success with treating movement disorders such as essential tremor and Parkinson’s disease (more than 160,000 surgeries performed so far). These conditions are localized to a specific brain region, which makes them relatively straightforward to stimulate with both DBS and TUS.

The next step is the treatment of psychiatric disorders, such as OCD, depression, and addiction, which are disorders of multiple neural circuits. The assumption is that targeting multiple circuits may lead to more effective treatments. TUS is much better suited for multi-site stimulation compared to existing DBS treatments, which rely on ‘choke points’ that connect different circuits.

The therapeutic potential of TUS to treat these conditions will be investigated in a landmark NHS clinical trial using Forest-1, an ultrasound system capable of both high-resolution imaging and precise multi-target neuromodulation. This minimally invasive device is designed to be implanted beneath the skull but outside the brain, to overcome the limitations caused by skull signal interference. The trial will recruit 30 patients with brain injuries that needed part of their skull temporarily removed to relieve pressure buildup, which means the device can be implanted without surgery.

If safety and efficacy are shown in clinical settings, at-home TUS systems can be rolled out for the alleviation of chronic symptoms, such as neuropathic pain.

An initial clinic visit will be needed to get pre-treatment imaging (e.g. MRI) to configure the stimulation parameters and ensure that it’s stimulating the target neural circuit (Figure 1). This is expensive today, but emergent MRI technology will likely drive down costs enough for this to be scalable.

Figure 1. Adapted from Murphy and Fouragnan (2024). Source.

Enhancing cognitive function

Beyond medical applications of TUS, there will likely be considerations for enhancing cognitive function in healthy individuals. Safety will be a top priority; the risk/benefit calculation is quite different for treating debilitating brain conditions compared to enhancing normal function.

The small size and low cost will inevitably lead to self-experimentation efforts, as we’ve seen with the rollout of similar non-invasive technology like TMS and tDCS. The potential safety risks associated with these efforts may detract from public opinion about ultrasound neuromodulation.

Risks aside, a pilot study from Arizona’s SEMA lab has shown that stimulating the default mode network during meditation sessions may enhance people’s capacity to experience equanimity.

Generated with DALLE-3.

This suggests that in the future, you may get a multimodal assessment of your neurocognitive function and get “prescribed” a personalized set of mindfulness practices along with specific ultrasound stimulation parameters that will enhance the practice.