Neuroplasticity Modulation: The Next Frontier in Brain Science?

On January 27, 2024, the inaugural Global Health Industry Innovation Forum hosted by the Institute for Global Health and Innovation at Tsinghua University (GHIC) was in full swing in a conference hall of a hotel in Haidian District, Beijing.

During the morning’s thematic session, Professor Hong Bo from the School of Medicine at Tsinghua University shared his team’s latest breakthrough in the world’s first implanted epidural electrode brain-computer interface. All attention in the room was fixed on his presentation slides.

Professor Hong Bo introduced that the team has completed theWireless Minimally Invasive Implantable Brain-Computer Interface NEO(Neural Electronic Opportunity)First-in-Human Clinical Implantation Trial, two coin-sized brain-computer interface processors were implanted into the patient's skull via a semi-invasive epidural approach.Successful Acquisition of Intracranial Neural Signals from Sensorimotor Cortical Regions。

After three months of home-based rehabilitation training, complete cervical spinal cord injury (ASIA Impairment Scale Grade A),Patients with long-term quadriplegia can now use pneumatic gloves driven by electroencephalographic activity., enabling brain-controlled functions such as autonomous drinking, with a grasping accuracy rate exceeding 90%.

Professor Hong Bo specially shared that the patient’s paralyzed arm showed conscious, slight finger movements after three months of learning and training. “Under intensive training and effort, the patient’s neurons may be establishing new connections.”

Although Professor Hong Bo stated that the underlying mechanisms warrant further investigation, this additional finding has clearly sparked new discussions within the industry.It also brought the concept of neuroplasticity back into the public eye.。

According to statistics from the National Health Commission and other institutions, in 2023, the number of Parkinson’s disease patients in China exceeded 3 million, the number of Alzheimer’s disease patients likely surpassed 10 million, the number of patients with central paralysis exceeded 23 million, and the number of stroke patients exceeded 28 million.

The growing number of patients with neurodegenerative diseases and acute neurological injuries has driven the market to pursue deeper exploration and higher standards for services and products aimed at improving cognitive function and treating neurological disorders. In this process,The Effects of Neuroplasticity Begin to EmergeSo, what is neuroplasticity? What are its characteristics, and what implications does it hold for the industry? What do the results of this NEO clinical trial reveal? Professor Li Yuanning from ShanghaiTech University, who has long focused on interdisciplinary research at the intersection of computational and cognitive neuroscience and machine learning, offers us unique insights.

“Traditional brain-computer interfaces (BCIs) based on open-loop neural decoding primarily focus on designing algorithms to decipher the encoding patterns of neural activity. In reality, however, most BCI systems operate in a closed-loop manner. For instance, in motor-control neuroprosthetics, human subjects can observe system outputs through visual feedback. Such BCIs rely heavily on neural learning by the subjects (humans or non-human primates) guided by sensory feedback and reward signals, rather than solely on fixed decoding algorithms trained on predefined datasets.”

Brain-Computer Interfaces Under Current Cognitive and Technological Conditions: Not a Unilateral Effort by Machine Algorithms, but a Bidirectional Engagement Between the Nervous System and Machines.

In layman's terms, neuroplasticity (neuro-plasticity)，It refers to the ability of the nervous system to alter its neural activity in response to intrinsic or extrinsic stimuli by reorganizing brain structural architecture, functions, or connections between neurons.。

Based on this definition, neuroplasticity can be further broken down as follows:

1. The brain's ability to change its structure or function based on experience;

2. Adaptive or regenerative capacity of the nervous system following trauma;

3. The ability of the central nervous system to undergo structural and functional changes in response to new experiences.

If we further differentiate based on forms of expression, it is as follows:

1. Functional Plasticity: The brain's ability to transfer functions from damaged areas to other undamaged areas;

2. Structural Plasticity: The brain's ability to tangibly alter its physical structure through learning and experience.

From this perspective, it seems possible to understand the potential for regained neural control observed in the NEO clinical trial. “Because the brain possesses redundancy and plasticity, such control may facilitate the formation of a new pathway or the strengthening of an existing one, particularly given sufficient time,” shared Professor Li Yuanning.

“Motor brain-computer interfaces (BCIs) mostly enable control of external mechanical movements with a few degrees of freedom through brain activity, such as two-degree-of-freedom planar cursor movement and three-degree-of-freedom spatial robotic arm movement. In contrast, current language BCI technologies based on sensorimotor cortex decoding involve controlling more complex, higher-degree-of-freedom movements of the articulatory organs via brain activity. For the human ‘native’ nervous system, both motor control and speech control are acquired skills; the progression from inability to proficiency relies entirely on neuroplasticity, with neural pathways and synaptic connections continuously formed and strengthened through repeated training. However, our current BCI technologies have not fully leveraged this plastic capacity of the brain.”

Based on this plasticity, aroundStroke rehabilitation, traumatic brain injury (TBI) rehabilitation, neurodegenerative diseases, learning and memory enhancement, and mental health disordersOnly then could hardware and software products and services in these specialized niches be deployed and applied in end-user settings such as homes, hospitals and clinics, research institutions and academic centers, and pharmaceutical and biotechnology companies.

Taking Parkinson’s disease (PD) patients as an example, approximately 90% of those with advanced PD develop motor disorders, including gait disturbances, balance problems, and gait rigidity, which severely impair their quality of daily life. Currently available therapies include dopamine replacement therapy and deep brain stimulation (DBS) of the subthalamic nucleus. While these approaches are effective for mild PD-related motor disorders, they have limited efficacy in treating severe motor disorders.

ONWARD Medical, headquartered in the Netherlands with R&D facilities in Switzerland, specializes in innovative therapies for spinal cord injury. Its implantable device adheres closely to the spine and delivers electrical pulses to help restore muscle function, enabling paralyzed patients to walk again. On March 4, 2024, ONWARD Medical received its 10th Breakthrough Device designation from the U.S. Food and Drug Administration (FDA).

“This is a typical example of directly influencing the neuroplasticity of loop circuits,” introduced Professor Li Yuanning.

Since beginning his postdoctoral research with the Edward Chang team at UCSF, Professor Li Yuanning has been dedicated to exploring the fundamental neural mechanisms of language and applying these insights to restore speech impaired by neurological damage. His work now provides novel solutions and deep learning frameworks for brain-computer interfaces (BCIs) targeting the Chinese language and for research in neurolinguistics.

“The learning process relies entirely on neuroplasticity and the formation of new synaptic circuits. In patient rehabilitation, whether for motor or language functions, we facilitate the reformation or strengthening of synaptic circuits through a series of neuromodulatory interventions. Underlying all these efforts is the mechanism of neuroplasticity. With repetitive, high-intensity training, the connectivity of neural pathways can be reinforced. How to understand, leverage, and guide such plasticity processes remains an incompletely resolved question in the field of brain-computer interfaces.”

Represented by ONWARD’s innovative therapies for spinal cord injury and NEO, developed by Professor Hong BoInvasive Hardware ProductsProvides scarce rehabilitation services in the market for patients with severe motor dysfunction.

Another major category for optimizing neuroplasticity isNon-invasive hardware and digital therapeutics products, focusing on rehabilitation, cognition, mental health, and more.

MindMaze, a Swiss company, integrates digital therapeutics, artificial intelligence, motion analysis, and cloud technology to help stroke patients restore brain health through training, aided by VR and brain imaging. Since its inception, the company has raised over $300 million in cumulative funding, with the most recent round being a $105 million investment led by Concord Health Partners in 2022. The funds will continue to be used for the research and development of digital therapeutic solutions as well as the development and expansion of clinical channels.

In the realm of software and digital therapeutics, Posit Science and CogniFit are representative companies offering gamified cognitive enhancement training. Since its inception, Posit Science has received funding from the U.S. Department of Defense and the National Institutes of Health (NIH). The company was founded by American neuroscientist Michael Merzenich, a leading scholar in neuroplasticity and one of the inventors of the cochlear implant.

It is worth noting that, compared with clinical trials, software and digital therapeutics in this field are subject to more stringent product and therapeutic standards; their actual efficacy in cognitive enhancement still requires further exploration and rigorous systematic evaluation to demonstrate long-term effectiveness.

Professor Li Yuanning stated, “Whether in terms of software or hardware, invasive or non-invasive,”One of the ultimate goals of brain science is to modulate and enhance the brain.”

According to data released by Coherent Market Insights, the market size of industries related to neuroplasticity reached $6.51 billion in 2023 and is projected to reach $35.4 billion by 2030, at a CAGR of 27.3%.

Among these, the primary market driver is the growing global number of patients with neurological disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. Additionally, the integration of diverse therapeutic approaches and emerging technologies has further fueled this growth.

AR and VR technologies are increasingly being integrated into neuroplasticity-based interventions. These immersive technologies provide realistic and interactive environments for cognitive training, rehabilitation, and sensory stimulation. VR and AR can enhance engagement, motivation, and neuroplasticity by creating rich sensory experiences and promoting active participation in therapy. In addition to MindMaze, which provides VR rehabilitation training for stroke patients as mentioned earlier, Cognixion ONE Axon, approved by the FDA in May 2023, offers an AR-based communication solution for patients with ALS who are completely or severely paralyzed.

Real-time neurofeedback monitoring of brain activity is garnering cutting-edge attention as a neuroplasticity-based intervention. Advances in neuroimaging and wearable sensors have enabled real-time monitoring of brain activity, providing new observational metrics for clinical practice. NeuroVigil, founded by Harvard Medical School Professor Philip Low, had its early core product, iBrain 1, used by Stephen Hawking. The company’s technologies in real-time monitoring have achieved breakthrough applications in identifying biomarkers for neurological disorders, pathology, and sleep monitoring.

Research on neuroplasticity underscores the importance of personalized treatment approaches. By tailoring therapies and interventions to meet patients’ specific needs based on factors such as genetics, neurological profiles, and environmental influences, more effective and targeted therapeutic outcomes can be achieved. Neuroplast, a clinical-stage biotechnology company based in the Netherlands, is dedicated to providing personalized neuromodulation therapies for patients with traumatic spinal cord injury through stem cell therapy.

The rise of digital therapeutics and mobile health applications has also created opportunities for remote, on-demand, neuroplasticity-based therapeutic interventions. The integration of mobile apps, wearable devices, and virtual platforms enables more personalized rehabilitation training programs, making therapeutic interventions more convenient and accessible.

As a unique characteristic of the human nervous system, its potential changes can influence product applications across multiple niche sectors.

At present, numerous preclinical studies are focused on the modulation and application of neuroplasticity. More research evaluations are still needed in the market to assess changes from microscopic to macroscopic regulation and clinical safety, with the aim of bridging the gap between scientific research and commercialization. However, given its immense potential across multiple subfields of brain science, mastering this characteristic is undoubtedly disruptive for the industry.

As Professor Li Yuanning shared with us, “Neuroplasticity is a highly significant topic in neuroscience and an area that will inevitably be subjected to in-depth investigation as the field advances. It is already being addressed to varying degrees in cutting-edge research and will become increasingly important in the future.”