Characteristic depressive episodes are the most common mental disorders worldwide. One in five people will suffer from depression in their lifetime, with suicidal risk responsible for several thousand deaths a year in France. A new study published in the journal Brain Stimulation and conducted by researchers from GHU Paris, Inserm, CNRS, Université Paris Cité and ESPCI Paris-PSL reveals promising results with a treatment over five consecutive days using low-intensity focused ultrasound to modulate the activity of deep brain regions involved in depression .
In 2021, a health barometer conducted by Santé Publique France revealed that 12.5% of people aged 18 to 85 had experienced a major depressive episode in the previous year [1] . Despite advances in the drug treatment of depression, the therapeutic effects of antidepressants take several weeks to take effect, and around a third of patients do not respond adequately to these drugs [2].
It is therefore essential to develop new therapeutic approaches offering a faster onset of action. One strategy for treating drug-resistant depression is brain stimulation of the deep brain regions involved in the disorder, such as the subcallosal cingulate region, but until now this has only been possible with intracerebral electrode implantation, an invasive procedure associated with significant neurosurgical risk, limiting its accessibility to a small number of patients.
A new study involving researchers and physicians from GHU Paris, Inserm, CNRS, Université Paris Cité and ESPCI Paris-PSL, published in the journal Brain Stimulation , shows promising results from a treatment over five consecutive days based on the use of low-intensity focused ultrasound. This innovative technology can modulate the activity of deep brain regions involved in depression, but this time in a non-invasive way. Ultrasound has the property of propagating through human tissue and remotely stimulating the brain area on which it is focused, by mechanical action, triggering the opening of mechano-sensitive channels. However, the irregular thickness of the skull, which deflects ultrasound and limits its ability to focus precisely on the area to be targeted, prevented the development of this technology for several decades. At the GHU Paris site Sainte-Anne, psychiatrists and researchers Marion Plaze and David Attali, in Dr Thierry Gallarda’s department, helped develop and implement an innovative portable device based on the use of acoustic lenses that concentrate ultrasound with unprecedented precision. These lenses compensate for the distortion of ultrasound waves as they pass through the cranial cavity. In fact, the researchers were able to model the effect of the skull on ultrasound and deduce the optimal shape of these acoustic lenses, uniquely manufactured and customized for each patient. The lens technology was developed at the Physics Institute for Medicine (Inserm, ESPCI Paris - PSL, CNRS) by researchers and engineers Jean-Francois Aubry (CNRS), Thomas Tiennot (ESPCI) and Mickael Tanter (Inserm), co-authors of the study.study, who have patented the technology and co-founded the startup SonoMind with Jeremy Bercoff, President, and Philippe Chapuis, Technical Director, with the aim of accelerating the clinical transfer of this technology.
The resulting precision transcranial ultrasound stimulation represents a major technological advance in personalized medicine and neuroscience. For the first time, it enables targeted, precise and non-invasive stimulation of deep brain structures, such as the subcallosal cingulate region, with a transportable device.
The clinical trial involved 5 consecutive days of ultrasound treatment of this brain area. The protocol was carried out on 5 patients suffering from severe, drug-resistant depression, with the aim of testing the safety of this new approach. The results were encouraging, with no serious adverse events and excellent tolerance: patients reported no discomfort or pain during the sessions. Depression severity scores were also progressively reduced over the course of treatment days, with an average reduction of over 60% in depression severity by the fifth day of the protocol.
" Although the results are encouraging, they must be interpreted with caution, as this is a first safety study on a limited number of patients and without a placebo group ," say the researchers.
Further studies are needed, and already planned, on larger cohorts of patients. If the rapid and marked therapeutic effects are confirmed, as well as the technique’s safety profile and persistence of effects over time, transcranial ultrasound stimulation could see its applications multiply over the next few years and extend to psychiatry, addictionology and neurology, to the benefit of many patients.
This work is the culmination of 25 years of research into methods for focusing ultrasound through the skull, 15 years into the modulation of brain activity by ultrasound, and 7 years of collaboration between psychiatrists-researchers at GHU Paris and the Institut de Psychiatrie et Neurosciences de Paris (Inserm/Université Paris Cité), and researchers at the Physics Institute for Medicine (CNRS/ESPCI Paris-PSL/Inserm).
The research has received ongoing support from Inserm, CNRS and ESPCI Paris-PSL, GHU Paris and Université Paris Cité, as well as financial backing from Fondation Bettencourt Schueller, Agence nationale pour la recherche and innovative funding from Inserm (Programme d’impulsion en Neurotechnologies and Accélérateur de Recherche Technologique en Ultrasons). The clinical trial received financial support from the Focused Ultrasound Foundation (Charlottesville, VA, USA).
[1] Prevalence of depressive episodes in France among 18-85 year-olds: results of the 2021 Health Barometer
2 Rush et al, American Journal of Psychiatry, 2006
