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.
By Dan Lewis Foundation | Spring 2024 11 Apr, 2024
Graham Dempsey, Ph.D., is a founder and Chief Scientific Officer (CSO) at Quiver Bioscience, a Cambridge, Massachusetts-based biotechnology company focused on the development of medicines for disorders of the nervous system. Dr. Dempsey and his team are working to develop treatments for some of the most challenging unsolved medical issues patients and their families face. Using advanced technologies in human stem cell biology, optogenetics, machine learning, and drug screening, progress is being made to develop medicines that will one-day treat conditions that have been largely untreatable. As the lead scientist for Quiver, formerly Q-State Biosciences, Dr. Dempsey enjoys working with world-class teams to invent, develop, and apply cutting-edge technologies to solve the most difficult challenges in biopharma for the betterment of patients. Dr. Dempsey’s inspiration to dedicate his professional life to science and medicine started at the early age of seven with the tragic loss of his father to an aggressive form of cancer, an experience that has deeply motivated him to this day. He completed his undergraduate studies at the University of Pennsylvania and his doctorate at Harvard University. As a graduate student in the biophysics program at Harvard Medical School, he co-developed ‘Stochastic Optical Reconstruction Microscopy’ or STORM , a light microscope with the ability to resolve nanometer (billionth of a meter, e.g. a hair is 100,000 nanometers thick) scale details of biological materials, an achievement that had been thought to be impossible for over a century. STORM has enabled what researchers call ‘super-resolution imaging’ for visualizing the intricate details of life’s most fundamental unit, the cell. Understanding the inner workings of a cell provides a path to a deeper understanding of the ways in which life is constructed and diseases can manifest. The technology was commercialized by Nikon Instruments for researchers worldwide. Dr. Dempsey left academic science to join Q-State Biosciences as the first hired employee with the goal of bringing advanced technologies developed at Harvard to the study of the brain. The brain, arguably the most complex structure in the known universe, works through electrical communication between brain cells or neurons. This communication is disrupted in all brain disorders but has been near impossible to study for the purposes of effectively developing medicines. Dr. Dempsey and his team over the course of ten years built a technology system that creates human brain models from patient stem cells (i.e. a ‘disease-in-a-dish’) and converts electrical activity of those brain cells into light signals that can be detected with ultra-sensitive microscopes. The resulting signals are analyzed using machine learning to find the patterns of how electrical activity is altered in disease, which can be used to find medicines that correct those changes. The team at Quiver is deploying this technology to take on previously untreatable brain conditions, including rare genetic diseases, such as certain seizure and neurodevelopmental disorders, to common conditions, such as chronic pain and Alzheimer’s disease. Dr. Dempsey’s passion outside of science starts with his family, his wife (and high school sweetheart) and three young daughters, be it traveling the globe to experience new cultures (or simply stare at the ocean), cooking elaborate meals on a Saturday evening, night-time reading of novels to his daughters, or attending live music around Boston. As a native of NJ, he celebrates his roots with visits to family near the Jersey Shore and, whenever possible, attendance at Springsteen concerts and Giants games. Dr. Dempsey is an avid student of history’s great entrepreneurs, spending the sparse remaining minutes of the day reading biographies and listening to podcasts, looking to extract every bit of learning towards taking on the challenges of building a great business while staying true to his family, his Quiver teammates, and his professional mission.
By Dan Lewis Foundation | Spring 2024 11 Apr, 2024
Sheryl Suzanne Nibbs, a legal secretary in a top law firm, started the process of becoming a paralegal as she approached her 40th birthday. She was fancy in her appearance, always making sure her hair, nails, and clothing were in order, a well-kept person, an avid traveler, and her mother’s best friend.
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