I want to talk about focused ultrasound and its potential role in psychiatry. Right now, it is not an established psychiatric treatment, but it is being actively studied and I think there is a good chance it becomes part of our clinical toolkit in the next several years (albeit perhaps only at academic centers initially). Small clinical trials are already underway, and the technology itself is further along than many people realize.

Let me start with the basics.

Most of us are familiar with diagnostic ultrasound, where sound waves are sent into tissue and the reflected signals are used to build an image of internal structures. With focused ultrasound the goal is to concentrate ultrasound energy at a specific point in the brain. Once you can reliably focus that energy, you can either modulate neural activity at that point or, at higher intensities, create a lesion by heating and destroying tissue.

Broadly speaking, there are two categories people talk about: low intensity focused ultrasound, often called LIFU, and high intensity focused ultrasound, or HIFU. There is not a universally agreed upon cutoff that separates the two. Some papers mention specific power levels like 100 watts as the boundary, but in practice the distinction is really about intent and biological effect. LIFU aims for reversible neuromodulation without permanent tissue damage. HIFU is used when the goal is thermal ablation and permanent lesioning.

The reason I am especially interested in LIFU is that it may address some of the inherent limitations of TMS. TMS is a great tool, but it has an inherent physical tradeoff between depth and focality. The deeper you try to stimulate, the less focal the stimulation becomes. If we want to target specific circuits, focality matters a lot. With TMS, once you move beyond superficial cortex, you quickly lose precision.

Focused ultrasound has the theoretical advantage of reaching deep brain structures while still maintaining millimeter scale focality. The exact focal size depends on a number of factors, including frequency and skull properties, but in general it can be more precise at depth than what we can do with standard TMS.

One of the most interesting aspects of LIFU is that it can modulate neural activity without causing lesions. Interestingly, the exact mechanism for this is not known. Ultrasound is fundamentally a mechanical pressure wave, so the question becomes how mechanical energy influences neurons. There is evidence that mechanosensitive ion channels play a role. For example, certain potassium channels located at the nodes of Ranvier appear to respond to mechanical forces, which could alter neuronal excitability. That said, this is still an active area of research and there are likely multiple mechanisms involved.

Depending on the stimulation parameters, LIFU has been shown to either enhance or suppress neural activity. Pulse duration, frequency, and intensity all matter. Many studies have demonstrated inhibitory effects, almost like creating a temporary functional lesion, but excitatory effects have also been reported. At this stage, the field is still mapping out which parameters reliably produce which outcomes.

There is also a fascinating physics angle when focused ultrasound is used inside a strong magnetic field, such as in an MRI scanner. In that setting, the motion of charged particles induced by ultrasound can interact with the magnetic field to produce a small electrical effect. In simple terms, ultrasound physically moves ions, and in the presence of a magnetic field that motion can be converted into an electrical influence on neurons. This concept is sometimes referred to as transcranial magneto acoustic stimulation.

A brief dive into the physics is worth it. The key idea comes from something called the Lorentz force, which describes how charged particles behave in electric and magnetic fields.

F = q(E + v × B)

F is the Lorentz force, which in this context is the force acting on a charged particleq is the charge of the particle (e.g. could be +1 or -1 or 0)E is the electric fieldv is the velocity of the charged particleB is the magnetic field

You do not need to follow the math in detail, but the equation gives us some helpful intuition if you just pay attention to cases where the force is 0 vs non-zero. If there is no charge, there is no force. If there is no electric field and no motion, there is no force. But if charged particles are moving in the presence of a magnetic field, they will experience a force, even in the absence of an electric field.

In neurons, the charged particles are ions. In a strong magnetic field like an MRI scanner, there is usually no meaningful electric field being applied. But if we use ultrasound, we are physically moving those ions back and forth. That motion in the magnetic field can generate tiny forces on the ions, leading to local and small electrical effects. In other words, mechanical energy from ultrasound can be converted into electrical influences on neural tissue.

The takeaway is that focused ultrasound in a magnetic field may offer a way to modulate neural activity through both mechanical and electrical mechanisms, which is part of what makes this technology so intriguing.

It is not yet a clinical tool, but it highlights how versatile this technology might become.

Another promising application of focused ultrasound is temporarily opening the blood brain barrier. When ultrasound is applied alongside microbubbles, it can safely and transiently increase the permeability of blood vessels in targeted brain regions. This allows medications that normally do not cross the blood brain barrier to enter the brain more easily. This approach is being actively studied in humans, especially in brain tumor treatment, though it is still largely investigational rather than standard clinical practice. There is also experimental work looking at targeted drug delivery where ultrasound helps release medications in specific regions, which could eventually have psychiatric applications.

High intensity focused ultrasound is already in clinical use for certain neurological conditions. The most established example is the treatment of medication refractory essential tremor. In this case, focused ultrasound is used to create a small lesion in a specific thalamic target, typically the ventral intermediate nucleus. This is done with MRI guidance, and one of the remarkable features is that temperature can be monitored in real time using MRI thermometry. The tissue is gradually heated into a range that produces thermal ablation, usually in the mid to high 50s Celsius, while carefully observing both imaging and clinical effects.

There has also been research using focused ultrasound lesioning for severe, treatment refractory psychiatric conditions. For example, capsulotomy targeting the anterior limb of the internal capsule has been studied in obsessive compulsive disorder and, to a lesser extent, major depressive disorder. These are small studies so far, but they are part of a broader resurgence of interest in carefully targeted neurosurgical interventions for psychiatric illness (“psychosurgery”).

One practical limitation of focused ultrasound is skull anatomy. The skull can distort and absorb ultrasound energy, and not everyone is an ideal candidate. A measure called skull density ratio is often used to estimate how well ultrasound will transmit. Depending on specific intervention, roughly twenty percent of patients may not reach therapeutic temperatures with current technology for HIFU.

Overall, I am very excited about focused ultrasound being used for psychiatric purposes. Focused ultrasound offers a combination of depth, focality, and flexibility that is hard to achieve with other noninvasive techniques. There is still a great deal we need to learn about optimal parameters, mechanisms of action, and long term safety.

For now, it is something worth keeping an eye on.

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