Neural Activity induced by ultrasound: from mechano-electric transduction to brain stimulation prosthesis – NeurActiv

For a long time, the gold standard for artificially inducing brain activity was through electrical deep brain stimulation (DBS). This technique has been widely utilized for management of several diseases or neurological nature (Parkinson’s disease, pain, epilepsy). However, electrical stimulation techniques require surgical implantation of electrodes in subdural or deep regions of the brain which can be a highly invasive procedure. In recent years, various non- or minimally-invasive introduced techniques, such as electrical (tDCS) and magnetic (TMS) stimulations remain limited by spatial issues.
Several studies have highlighted the capabilities of Focused Ultrasound (FUS) in effectively stimulating or modulating neuronal activity in a non- or minimally-invasive manner. Early work in the 1970s and 1980s revealed a set of ultrasound parameters capable of superficially stimulating external neural structures (mechanoreceptors, auditory nerves) in human subjects. Nonetheless, no details regarding the mechanisms were ever validated. Recently, multiple teams across the globe have increasingly demonstrated that it is possible to stimulate cortical or deep regions of the brain of several in vivo animal models using low frequency transcranial FUS. Despite low frequency FUS exposures (0.3-0.6 MHz) yielding large focal zones as result of longer wavelengths, studies have shown in vitro that much higher ultrasound frequencies (40 MHz) are also effective for stimulating neural structures, thus offering the possibility of precise spatial selectivity. However, the biological mechanisms involved in this type of neurostimulation remain largely unknown and highly hypothetical.
A minimally invasive strategy for neurostimulation by FUS could represent a revolutionary advancement in this field. NeurActiv is a multidisciplinary project that will be piloted by the Laboratory of Therapeutic Applications of Ultrasound (LabTAU, INSERM, Lyon). Its general objective will be to lead and accelerate the development of FUS neurostimulation by exploring and enhancing current understanding of the biophysical mechanisms involved in this process while identifying a set of FUS parameters capable of stimulating neuronal networks in safe, selective, reproducible and controlled manner. To overcome these challenges, NeurActiv members come from 3 teams, LabTAU, CIRB (Collège de France, INSERM, CNRS, Paris) and GRC NeurON (Sorbonne University, Paris) including physicists, biologists and medical doctors who combine their world-renowned expertise in biomedical ultrasound research, cellular neurophysiology and clinical applications in neurosurgery. This multidisciplinary consortium will aim at developing a unifying framework of neurostimulation using neural models of increasing anatomical and physiological complexity, thus efficiently transitioning from in vitro to in vivo studies. We will address the spatio-temporal characteristics of brain responses evoked by FUS stimulations both at a cellular and network levels, compare it to electrical stimulations and attempt to unravel its mechanism focusing on astrocytes vs neuronal initiation, effects on membrane channels and neurotransmission. We will further validate that neuronal plasticity may be achieved by FUS. Then, the ultimate goal of NeurActiv is to design and develop a novel strategy for application of FUS through a cranial prosthesis, placed at the surface of the dura mater, capable of selectively targeting and stimulating specific neural bodies in the brain non-invasively for the brain. The NeurActiv project aims to treat profound deafness. These FUS prostheses, if successful, would provide a novel neurostimulation approach capable of improving the portability of neurostimulation systems and increasing the autonomy of the patient (no systemic MRI sessions required for planning of chronic treatments), in many neurological indications (e.g.: audition, vision, motor skills, pain, memory).