The neurocircuitry of underlying psychiatric disorders has been the subject of intense study, especially in cases of treatment-resistant issues such as depression or obsessive-compulsive disorder.

Arulpragasam AR, van ’t Wout-Frank M, Barredo J, et al. Low intensity focused ultrasound for non-invasive and reversible deep brain neuromodulation—a paradigm shift in psychiatric research. Front Psychiatry. 2022;13:825802.

 

Two modalities—transcranial magnetic stimulation (TMS) and transcranial electrical stimulation—are currently the most widely used treatments, but both lack a high degree of spatial focality. Other stimulation methods, such as deep brain stimulation, offer spatial precision but are invasive and therefore riskier.

An emerging technology known as low intensity focused ultrasound (LIFU) shows promise as a new method of brain stimulation. Unlike previous technologies, LIFU directly affects neuronal activity with high spatial precision.

 

Low-intensity ultrasound to modulate neuronal activity

 

At its simplest, ultrasound can be defined as an acoustic, or sound, wave occurring at frequencies undetectable to the human ear. Generally, these frequencies are greater than 20kHz.

At high intensity, ultrasound waves produce enough thermal energy to cause irreversible effects on proteins in brain tissue.

Darrow DP. Focused ultrasound for neuromodulation. Neurotherapeutics. 2019;16(1):88–99.

However, higher frequencies do not penetrate brain tissue as deeply even though they do have better spatial resolution.

 

Low intensity ultrasound uses ultrasonic intensity that matches or is less than that used in various diagnostic ultrasound applications.

Baek H, Pahk KJ, Kim H. A review of low-intensity focused ultrasound for neuromodulation. Biomed Eng Lett. 2017;7(2):135–142.

 

While the exact biophysical mechanisms impacted by and resulting from LIFU are unknown, researchers speculate that the heat produced from the absorption of acoustic energy may actually inhibit neuronal activity.

It is also possible that ultrasound may alter the state of mechanosensitive ion channels by causing conformational changes which induce the same channels to open. These changes may lead to fluctuations in ion levels, ultimately generating action potentials.

Another proposed mechanism of neuromodulation involves acoustic cavitation within the brain’s bilayer membrane, which results in the temporary enhancement of blood-brain barrier permeability.

 

LIFU safety considerations

 

Preliminary studies have not shown any brain injury or other serious adverse effects. However, biological effects resulting from ultrasound are still possible. Depending on the exposure parameters, coagulative necrosis may lead to irreversible cell death, although this has only been demonstrated using high intensity ultrasound.

Currently, the U.S. Food and Drug Administration and other regulatory authorities require practitioners to adhere to safety guidelines for diagnostic ultrasound examinations. While not directly applicable to LIFU, these guidelines should be treated as the minimum safety standards during ultrasonic neuromodulation procedures.

This new approach to treatment may eventually help many patients achieve manageable symptoms or even symptom remission without certain limitations associated with standard brain stimulation treatments.