In this Q&A, the professor discusses his groundbreaking work on creating artificial systems that can stimulate the nervous system or record its activities to restore lost functions.
Silvestro Micera splits his time among three laboratories: the first at the Scuola Superiore Sant’Anna in Pisa, where he serves as a Full Professor of Electronic and Computer Bioengineering; the second at the IRCCS Ospedale San Raffaele in Milan, where he collaborates with the Unit of Neurosurgery and Stereotactic Radiosurgery; and the third at the École Polytechnique Fédérale (EPFL) in Lausanne. What connects these three research centers, in addition to the frequent travels of this fifty-three-year-old bioengineer from Taranto, is a shared mission: “We work to create artificial structures that enable us to stimulate the nervous system or record its activities,” explains the professor. “In this way, we aim to replicate functions that have been disrupted due to a traumatic event or a neurological condition”.
Can you provide us with an example?
If we have an individual who can no longer walk due to a spinal cord injury, we can implant electrodes on the spinal cord below the site of the injury. This generates an artificial current that activates the neuromuscular system. When stimulated appropriately, the spinal cord can activate and generate a response in the peripheral nerves, which in turn stimulate the muscles, enabling the person to walk. However, there are other examples as well”
Please continue?
“We also work with individuals who use a prosthetic limb following an amputation. In this case, we utilize residual muscle activity to control the prosthetic device. Additionally, we can stimulate the peripheral nerves to provide sensory feedback. This approach effectively replaces the sensors in the foot, which, during walking, send information to the spinal cord and brain, enabling us to adjust our movements based on the type of terrain and helping us avoid falls”.
Do you also work with individuals who have neurodegenerative diseases?
“No, not yet but many groups in the world are carrying out interesting studies. For example, they focus on individuals with Amyotrophic Lateral Sclerosis (ALS), who experience a form of lockdown because they remain cognitively aware but are unable to speak. For these individuals, they implant brain microchips — like those that Elon Musk frequently discusses in relation to Neuralink — which record cortical activity and convert it into an artificial voice, thereby restoring their ability to communicate”.
How will you create tailored spaces for individuals?
“We begin with the understanding that people with different abilities require distinct environments. We will analyze individuals’ behaviors using tools such as virtual and augmented reality, which allow us to predict behavior within various spaces. We have already made progress in this area. For instance, sometime ago, we collaborated with mechanical engineers from the Lecco Campus to simulate the movements of a person with cataracts within a specific environment. Our findings revealed that the optimal lighting conditions and arrangement of objects that benefit a healthy individual are critical for someone with this condition”.
Is this an inventions that influences the intention to move?
“Of course, because articulating the mouth to express a concept is a deliberate intention to communicate. Notably, researchers like Sergey Stavisky from the University of California and others who study language decoding engage with areas of the brain responsible for the motor production of language, such as Broca’s area and Wernicke’s area. Our focus is on the motor actions involved in producing words and the ability to articulate the mouth to express concepts. This understanding is crucial from a rehabilitative perspective as well”.
In the past twenty years, neuroengineering has made remarkable advancements.
“I agree. It has established a series of foundational components that allow us to stimulate and record activity in the cerebral cortex, as well as in the deeper regions of the brain and the spinal cord. We are now beginning to combine these components in targeted ways to facilitate actions that are motor, sensory, and cognitive in nature”.
From a design perspective, what requirements must these electrodes meet to function correctly?
“First and foremost, they must be biocompatible. They should not cause any damage, although some reaction is always expected. When an electrode is implanted into the nervous system, it invariably triggers a response that results in the formation of fibrous tissue, which serves to protect the body from the foreign object. The electrodes must also interface with the targeted area that I wish to stimulate or from which I want to record activity with the necessary selectivity. By selectivity, I mean the ability to establish a very intimate and specific connection. For instance, in Deep Brain Stimulation—a technique used to treat conditions such as Parkinson’s disease—the electrodes must stimulate a deep region of the brain known as the subthalamic nucleus, which is approximately the size of a walnut. The goal is always to minimize the volume of tissue that is activated or recorded, with variations that naturally depend on the type of application”.
Are there any other requirements?
“We need to develop implantable systems for chronic use that can last over time, ideally for at least 15 years”.
An implantable system requires an appropriate control system to function effectively, correct?
“Yes, the software is designed to operate the system as efficiently as possible. An implantable system for the spinal cord typically features 32 electrodes, strategically placed based on our understanding of their effectiveness. However, after implantation, my role is to determine which of these electrodes can elicit the best motor response for the individual patient”.
How do you achieve this optimization?
“We do it manually, but we are progressing towards utilizing artificial intelligence. We employ what are known as ‘sparse data’: with 32 electrodes, the goal is to develop models and algorithms that enable us to characterize at least 15 of them, and then understand how to utilize the remaining electrodes, even in combination. The quicker I can complete this characterization and select the appropriate contacts, the faster the patient’s functional recovery will be, allowing me to move on to the next case sooner”.
Is it accurate to believe that the faster a device is developed, the greater the chances of patient recovery?
“A person who has experienced a stroke or a spinal cord injury typically undergoes a period of neuroplasticity lasting approximately six months, known as the sub-acute phase. During this time, the patient has the potential to recover independently, while those engaged in rehabilitation exert maximum effort. Our intervention with implants occurs later, at a point when the patient has already reached a plateau in their clinical progress. It is evident that we aim to act swiftly: to discharge the patient as soon as possible and, as I mentioned, to move on to the next case”.
Why do you only intervene after six months?
“We work with patients whose clinical conditions are already very delicate, and therefore we need scientific evidence. Ethical committees and regulatory authorities seek clarity because our work introduces additional risks for these vulnerable individuals. Furthermore, developing an implantable system is a significant undertaking that involves various professionals, making it extremely challenging for a hospital to manage two cases simultaneously. However, I am confident that we will expedite the process: one day, a person with a spinal cord injury will undergo surgery to stabilize the spine while simultaneously receiving an electrode implant”.
With these devices, we also aim to reconfigure the central nervous system. How is it controlled?
“We know for certain that implantable systems induce changes within the central nervous system; however, these modifications are currently neither controllable nor augmentable by us. As I mentioned, the first six months represent a highly favorable period characterized by significant plasticity, which, to some extent, persists even afterward. In fact, thanks to our technologies, we continue to achieve positive outcomes. One of the key areas we are focusing on is the enhancement and prolongation of neuronal plasticity”.
How are you working to achieve this?
“If I told you, it would be akin to thinking out loud. We have some ideas, but we are still uncertain about their feasibility. Let me give you another example: Stem cells have long been regarded as the Holy Grail of medical research. Unfortunately, for nearly twenty years, progress has been stymied because they either fail to function as intended or, conversely, work too effectively and become tumorigenic. Often, concepts that appear straightforward are challenging to implement. The spinal cord has a highly complex structure. Furthermore, in research, animal models are commonly utilized; one of the leading experts in this field is Professor Grégorie Courtine from the École Polytechnique Fédérale de Lausanne (EPFL), with whom I have been collaborating for some time. However, the translational leap from rodent models to human applications remains exceedingly difficult”.
Beyond the challenges, what are the prospects?
“We are working on implanting an electrical circuit composed of multiple interconnected nodes. The fundamental principle remains the same: to bypass the injury. We are developing a system that primarily understands the user’s intentions. It records their thoughts and the desire to move, decoding this information based on the activity of the cerebral cortex. Depending on the task, the system transmits data below the site of the peripheral or spinal injury, activating the muscles required for that action. To complete the circuit, I would also need to find a method to stimulate the sensory cortex, providing the patient with tactile feedback”.
What are the other future perspectives for closure?
“The next step is to transition from the temporary solutions we have developed for amputees to a chronic implant that can be used at home. At the beginning of next year, we plan to submit a project in collaboration with INAIL, the Institute of Technology in Genoa, and the University of Singapore. This initiative aims to provide certain patients with the opportunity to receive a fully implanted prosthesis equipped with a pacemaker that conveys tactile information regarding touch, position, and temperature. Ultimately, we aspire to extend our efforts at the IRCCS Ospedale San Raffaele not only to patients with spinal cord injuries but also to those suffering from non-traumatic paraplegia, such as that caused by infectious diseases”.
Is it a collaborative effort?
“Absolutely. All of this is only possible if strong, multidisciplinary, and cohesive teams are formed, where individuals collaborate effectively. For instance, at the IRCCS Ospedale San Raffaele and Ospedale Careggi in Florence, bioengineers work alongside neurosurgeons, physiatrists, physiotherapists, and neurologists. It took us twenty years to realize this, but we can only address the problem by working together”.
