Brain-Computer Interfaces to Augment Brain Regeneration
Dan Lewis Foundation | Spring 2024

In prior newsletters, we’ve discussed research strategies that bring hope to persons with severe disabilities after a major brain injury.  We’ve discussed research focused on creating and transplanting new brain cells to replace damaged tissue [“cellular repletion” ].  We’ve reviewed progress towards stimulating the brain to regrow [“regeneration”] and rewire itself [“axonal repair”] as it seeks to compensate for damage.  We’ve explored evidence that the brain can be induced to regenerate new connections [ “synaptogenesis”].


This edition will discuss how biomechanical devices called brain-computer interfaces (“BCIs”) can help a person compensate for an injured brain.  We will also explore how new medicines may help a person maximize the benefits of BCIs. The idea of a direct connection between a person’s brain and the external world mediated by a computer sounds like an idea from science fiction.  Nevertheless, brain-computer interface devices have been developed and are beginning to be implanted in patients.



What is a BCI?

At its essence, a brain-computer interface is a system that allows direct communication between the human brain and the world, either for sensory inputs or motor outputs. Imagine typing a message, playing a song, controlling an artificial limb, or steering a wheelchair merely by thinking about it. Picture a blind person having a camera-like device that is hardwired to the visual cortex to enable sight or a glove that transmits sensory information directly to the cortex for interpretation.  More formally, a BCI is a type of prosthesis that allows regions of the brain to be reconnected to parts of the body or the outside world after the natural neuronal connections have been lost. BCIs connect the world to the brain for interpretation and the brain to the world for action.



How Do BCIs Work?

The magic behind BCIs lies in their ability to decode and encode the brain's electrical signals. Our thoughts and intentions spark neural activity, generating distinctive electrical patterns.  Our sensations exist as patterns of neuronal excitation in the brain.  BCIs can control limbs or external devices by detecting the electrical patterns of intentions and then translating these signals into commands that can control a prosthetic limb, a cursor on a screen, or the hand of a person whose spinal cord has been severed.  BCIs tap into the brain’s electrical activity using various sensors placed on the scalp (non-invasively) or directly within the brain (invasively) to detect and record these signals. Once these signals are captured, they are fed into a computer that interprets them using sophisticated algorithms. This process translates the brain's electrical activity into commands controlling external devices or encoding sensory information to be transmitted directly to the brain (see Figure 1).



The Potential Impact of BCIs:

There are numerous potential impacts of BCIs for persons who have suffered a severe brain injury.  A BCI can allow someone who is paralyzed to control a limb again.  BCIs may be used to stimulate regions of the brain to accelerate the brain’s reprogramming after a major injury.  Some will be able to use a BCI to directly control an external device by sending signals from the brain to an external device. For individuals living with paralysis or severe communication barriers, BCIs offer the hope of regaining some abilities to interact with the world. In the future, devices may enable the blind to see via a direct connection between an electronic device and the brain. 1 Brain-computer interfaces have begun to enable individuals with traumatic injuries of the central nervous system to regain components of lost neurologic function, restore communication and mobility, and gain more independence. 2   Here are two short video clips about BCIs to help you better understand the technology and its implications.  The first describes what these devices are and how they work [BCI overview]. The second demonstrates the benefit of such a device for a patient with ALS [BCI in ALS].



BCIs in Clinical Trials:

Several BCIs are being tested in clinical trials, each involving a few patients (see Table 1).   Different devices and trials target different capabilities.  One trial is focused on allowing a paralyzed patient to control a computer cursor by thought alone.  Several trials are using BCIs to bypass a spinal cord injury and restore (partial) control over a limb. 3  Finally, a range of devices are being developed or trialed to accelerate brain recovery after injury. 4



Biologic Augmentation of  BCI Benefits:

As discussed elsewhere, there is real hope that new medicines will be able to unlock the brain’s ability to regenerate after a devastating injury.  Future medicines that stimulate the formation of new neurons, repair of damaged axons, or the enhanced plasticity of synaptic connections are all likely to promote functional recovery without the use of a brain-computer prosthetic device.  These medicines may also be quite useful for recipients of BCIs.  More specifically, preconditioning the brain through stimulating neurogenesis, providing autologous-derived neurons, or enhancing plasticity may amplify the benefits of (BCIs) for recipients with traumatic brain injuries.  Even after the BCI is successfully implanted, the person will need protracted training and rehabilitation to learn how to use the device. Providing autologously derived neurons to replace lost tissue may be helpful for those whose injuries resulted in a substantial loss of viable brain tissue.


To be clear, the path towards useful BCIs will be challenging. Ethical considerations, technological limitations, and the need for personalized rehabilitation strategies remain pivotal areas requiring further exploration and refinement. Despite these hurdles, the trajectory of BCI technology is undeniably promising, driven by ongoing research, clinical trials, and the real promise of restoring meaningful ability to those who have suffered a devastating brain injury.



Table 1: Selected BCI Trials

Company/Lad Device Essential Technology Function Served Reference/Link
BrainGate Co. BrainGate Intracortical brain-computer interface Enables individuals with paralysis to control assistive devices BrainGate
Neuralink Corp. Neuralink High-bandwidth neural interface Aims to facilitate direct communication between the brain and electronic devices Neuralink
Synchron, Inc. Stentrode™ Minimally invasive stent-based electrode Restores functional independence for severe paralysis patients by enabling them to control digital devices Synchron
Duke University Center for Neuroengineering Walk Again Project Non-invasive BCI with exoskeleton Restores walking ability in patients with severe spinal cord injuries Walk Again Project
Blackrock Neurotech MoveAgain BCI Implantable BCI for motor control Restores functional independence by enabling motor control of devices and potentially limbs Blackrock Neurotech

Figure 1: A BCI Example 5


References



  1. Hart, Robert. 2024. “Elon Musk Teases First Neuralink Products After Company Implants First Brain Chip In Human.”Forbes Magazine, January 30, 2024.https://www.forbes.com/sites/roberthart/2024/01/30/elon-musk-teases-first-neuralink-products-after-company-implants-first-brain-chip-in-human/.
  2. Pulse, Ieee. 2023. “The Future of Brain–computer Interfaces.” IEEE Pulse. January 25, 2023.https://www.embs.org/pulse/articles/the-future-of-brain-computer-interfaces/.
  3. Samejima, Soshi, Abed Khorasani, Vaishnavi Ranganathan, Jared Nakahara, Nicholas M. Tolley, Adrien Boissenin, Vahid Shalchyan, Mohammad Reza Daliri, Joshua R. Smith, and Chet T. Moritz. 2021. “Brain-Computer-Spinal Interface Restores Upper Limb Function After Spinal Cord Injury.”IEEE Transactions on Neural Systems and Rehabilitation Engineering: A Publication of the IEEE Engineering in Medicine and Biology Society 29 (July): 1233–42.
  4. Simon, Colin, David A. E. Bolton, Niamh C. Kennedy, Surjo R. Soekadar, and Kathy L. Ruddy. 2021. “Challenges and Opportunities for the Future of Brain-Computer Interface in Neurorehabilitation.”Frontiers in Neuroscience 15 (July): 699428.
  5. Vansteensel, Mariska J., Elmar G. M. Pels, Martin G. Bleichner, Mariana P. Branco, Timothy Denison, Zachary V. Freudenburg, Peter Gosselaar,et al.2016. “Fully Implanted Brain–Computer Interface in a Locked-In Patient with ALS.”The New England Journal of Medicine 375 (21): 2060–66.
A gold trophy with a laurel wreath around it.
By Dan Lewis Foundation April 2, 2025
For the third consecutive year, the Dan Lewis Foundation for Brain Regeneration is proud to announce the DLF Prize competition. The 2025 DLF Prize, a $20,000 award, will recognize an outstanding early career scientist (2 to 5 years post-doc) conducting innovative research in neuroscience, pharmacology, or biotechnology. This prestigious prize honors researchers whose work aligns with the DLF mission to drive breakthroughs in neural regeneration and repair. The current research priorities of the DLF are: Pharmacological Reactivation of Neural Repair: Research into pharmacological methods of reactivating or augmenting synaptogenesis, neurogenesis or axonal repair. Cell-Based Cortical Repair: Investigating the potential of derived cortical neurons to restore function in damaged cortical regions. Transcriptomics of Neural Recovery: Characterizing transcriptomic profiles of cortical neurons in the recovery phase following brain injury to identify pathways that drive repair. Molecular Inhibitor Targeting: Advancing anti-sense oligonucleotides (ASO’s) or small-molecule therapeutics designed to downregulate inhibitors of neural regeneration in the cortex or spinal cord. Application for the 2025 DLF Prize can be made by going to our website— danlewisfoundation.org —and clicking on the Tab “ 2025 DLF Prize ”. This will bring you into the application portal. The application portal opened in March, 2025 and will remain open through May 31st. Once in the portal, you will find complete information about the DLF prize, eligibility requirements, and an application form which can be filled in and submitted online. The winner of the 2023 DLF Prize, Dr. Roy Maimon, continues his research indicating that downregulation of PTBP1, an RNA-binding protein, can convert glial cells into neurons in the adult brain (Maimon et al. 2024) .* Dr. Maimon, currently a post-doc at the University of California, San Diego is currently interviewing for a faculty position at several prominent neuroscience departments. The winner of the 2024 DLF Prize, Dr. William Zeiger is a physician-scientist in the Department of Neurology, Movement Disorders Division, at UCLA. Dr. Zeiger has expertise in interrogating neural circuits using a classic “lesional neurology” approach. He states, “Our lab remains focused on understanding how neural circuits become dysfunctional after lesions to the cortex and on investigating novel circuit-based approaches to reactivate and restore damaged cortex”. * Maimon, Roy, Carlos Chillon-Marinas, Sonia Vazquez-Sanchez, Colin Kern, Kresna Jenie, Kseniya Malukhina, Stephen Moore, et al. 2024. “Re-Activation of Neurogenic Niches in Aging Brain.” BioRxiv. https://doi.org/10.1101/2024.01.27.575940.
By Dan Lewis Foundation April 2, 2025
Alan was injured in 2021, at age 42. An art teacher in Lakewood, Colorado, Alan was riding his bicycle after school and was crossing at an intersection when a truck turned into the crosswalk area and hit him. Alan reports no memory of the event but has been told this is what happened. Alan says “My frontal lobe took the brunt of the impact, particularly the left frontal lobe”. Alan had a 2 ½ week stay at a nearby hospital where he, “re-learned to talk, to walk, and drink”-- although again he reports no memory of his stay there. Alan was then transferred to Craig Rehabilitation Hospital, in Englewood, Colorado. Alan says, “The only reason I knew I was at Craig is that I rolled over in bed and saw “Welcome to Craig” on the dry erase board.” During this stage of recovering, Alan repeatedly denied that he had been in an accident. Twice he tried to leave Craig on his own accord despite his wife’s and his therapists’ assurances that it was important for him to stay to recuperate from his injuries. Alan’s wife was 8 months pregnant at the time of his accident and gave birth to their son while Alan was an inpatient at Craig. Alan’s wife brought his newborn son to visit him days after the birth and Alan held him while sitting in his wheelchair, but Alan wistfully reports this is another thing he can’t remember. Alan reports that he still has significant difficulties with memory. Alan has also experienced several other neuropsychological difficulties. He states that for months after his injury, he could not experience emotion. “I could not laugh, I couldn’t cry.” Even after three years, his emotional experience is constricted. However, an emotion that is sometimes elevated is irritation and anger. Sometimes, dealing with people can be difficult because he may have temper flare-ups with little reason. This is something that Alan regrets and he is working hard with his neuropsychologist to improve the regulation of his emotions. Alan also has difficulty with organization, motivation, and distractibility. Earlier in his recovery, he had trouble sequencing and had difficulty carrying out personal and household routines. Alan has benefited greatly from therapy and his own hard work to make improvements in these areas. A chief reason that Alan works so hard in his recovery is so that he can be a good father to his son who is now almost 3 years old. He recognizes that it is important not to get frustrated when it seems that he can’t provide what his son wants or needs at a given moment. “I’m trying to raise my son the best I can…he’s at such a pivotal time in his life.” Alan’s financial situation was helped for a time by Social Security Disability Insurance payments but these payments ended. He is trying to get SSDI reinstated but the process of doing so is confusing and is taking a lot of time. Alan returned to work about 11 months ago at a liquor store (after about 2 years of not being able to work), the same store where he previously worked part time while teaching. He works in the wine department. “I sell wine and make recommendations.” When asked for advice to other brain injury survivors, Alan’s words were: “No matter how confused or upset you are or how frustrated you get, keep pressing on and moving forward because there is light at the end of the tunnel even though it may seem long. Keep moving forward and don’t give up no matter what anyone says to you”. Alan added that supports for individuals with brain injury are very important. He has found support groups, retreats, and seminars/events where brain injury survivors can share their experience to be very helpful. The volunteer work he does at Craig Hospital has been valuable for him. Alan is an inspiring individual. Despite having scarce memory of his accident and some confusion about the functional losses he has experienced, Alan has worked hard to make his recovery as complete as possible. He continues to work hard to progress and to express gratitude for those who have assisted him along the way.