Low intensity focused ultrasounds to combat depression: this is the bet of French researchers who publish the promising results of a small security study in Brain Stimulation.
The characterized depressive episodes are the most frequent mental disorders, and would affect one in five people during their lifetime. In France, according to the France public health barometer in 2021, 12.5 % of people aged 18 to 85 had experienced a depressed episode characterized during the previous year. Despite progress in drug treatment, antidepressants have a period of action of several weeks and approximately a third of patients do not respond enough. Hence the interest of diversifying the therapeutic arsenal.
Faced with resistant depression, one of the tracks is the brain stimulation of the deep brain regions, such as the subcalular cingular region. But it presupposes the establishment of intracerebral electrodes, that is to say an invasive procedure associated with a significant neurosurgical risk, which limits its accessibility.
Treatment of five consecutive days
The technology developed by researchers and doctors of GHU Paris, Inserm, CNRS, Paris Cité University and ESPCI Paris-PSL makes it possible to modulate the activity of the deep brain regions involved in depression, but this time in a non-invasive manner. This, thanks to the ultrasound, which have the property of spreading in human tissues and stimulating the brain area on which they are concentrated, by mechanical action, by triggering the opening of mechano-sensitive channels. But it was first necessary to remove an obstacle: to avoid the deviation of the ultrasound (and therefore the loss of their precision), caused by the irregularities of the thickness of the skull.
The portable device described in Brain is based on the use of acoustic lenses (Metal’s In English) which concentrate ultrasound with unprecedented precision: these lenses, developed by the physical institute for medicine*, manage to compensate for the distortions of the waves induced by the crossing of the cranial box. This, thanks to a work of modeling the effect of the skull on ultrasound, in order to deduce the optimal shape of these acoustic lenses, made in a unique and personalized manner for each patient.
-Average reduction of more than 60 % of the severity of depression
The clinical trial consisted in five consecutive days of ultrasound treatments in this brain area (5 minutes of pulsed ultrasound, five times a day). This protocol was carried out on five patients with severe and drug-resistant depression, aged 23 to 75, taken care of at Sainte-Anne hospital, in order to test the safety of this new approach. The authors observe the absence of a serious unwanted event and excellent tolerance: the patients reported not feeling no discomfort or pain during the sessions. The severity scores of depression (on the MADRS scale) have gradually decreased over the days, with an average reduction of 60.9 % of the severity of depression on the fifth day of the protocol. On the fifth day, four of the five patients were considered to be responders (≥50 % decrease on the MADRS scale), two of which testified to a remission (Madrs ≤ 10).
“Ultrasonoric transcranial stimulation of precision thus obtained represents a leading technological advance; It allows for the first time to stimulate in a targeted, precise and non-invasive manner the deep brain structures, such as the subcalular cingular region, with a transportable device ”, Salt an Inserm press release. The authors also highlight the speed of the effect, incomparable with the time of action of antidepressants or even electroconvulsive therapy or esketamine (3 weeks).
“Although the results are encouraging, they must be interpreted with caution, because it is a first safety study on a limited number of patients and without placebo group”, they nevertheless nuance.
Researchers at the Physical Institute for Medicine have patented technology and co-founded the Sonomind startup in order to accelerate the clinical transfer of this technology. Studies are planned on larger cohorts of patients, with hope, if the results are confirmed, to develop the application of transcranial stimulation by ultrasound in psychiatry, addictology and neurology.
*(Inserm, ESPCI Paris-PSL, CNRS) by researchers and engineers Jean-François Aubry (CNRS), Thomas Tiennot (ESPCI) and Mickael Tanter (Inserm), co-authors of study
