COMMENTARY

To solve existential brain challenges spanning neurology, mental health, education, workforce development, and neuroscience—we need a fresh approach to technologies and investing. We need a new investment opportunity: Brain Capital.

Human societies continue to be plagued by brain challenges, from mental health disorders and dementia to learning disabilities, the impact of long COVID, and disparities in educational health care access.1

Additionally, some of the most persistent social issues—homelessness, crime, death by despair—will be impossible to solve without attention to the root causes and address the treatment and support of individuals with brain disorders and vulnerabilities. If these brain health maladies are not definitively addressed, human communities will have a difficult time sustaining themselves both economically and socially.2

At the same time, deeply comprehending the human brain will make new achievements possible, with brains that thrive from better understanding mental processes such as creativity, innovation, leadership, and entrepreneurship.3

We need new ways to move the needle on these unprecedented challenges and opportunities. We need a cross-disciplinary, cross-functional, optimized approach to innovation with a new type of executive, new investment, and new governance.4

Enter Brain Capital.5

In the following article, we put forward our case forBrain Capital as a new investment category placing a premium on technological health care innovations that improve brain health and skills. We define Brain Capital Innovation as diverse neuroscience-inspired technologies addressing the confluence of mental health, neurology, education, workforce development, and positive psychology—including resilience, wisdom, and creativity (Figure 1).6 Brain Capital constitutes a promising new opportunity within the impact investment category, also known as environmental, social, and governance (ESG) investing.7

The Brain Capital Opportunity

Global brain challenges are worsening at a time when our economies and societies are becoming more turbulent. Dependence upon personal technologies is accelerating, with citizens struggling to keep up with unlimited access to massive amounts of information and data, creating increased stress and anxiety. There also have been positive developments, including increasing dependence on knowledge-intensive economic activity, neuroscience breakthroughs,8 and developments such as cognitive immunology,9 increasing attention to workplace mental health,10 a rush of venture capital activity driving innovation,11 and a higher number of unicorns (companies valued at over USD $1 billion).12 There are new, large-scale public-private partnerships aimed at tackling global mental health (Healthy Brains Global Initiative) and global Alzheimer disease issues (Davos Alzheimer’s Collaborative). Taken together, it can be argued that we are already living in a brain economy—a neuroscience-inspired, knowledge economy.13

Still, there are substantial limitations in our current system of innovation and investing to tackle these brain challenges.14 Approaches to screening, diagnosis, and treatment of mental health disorders are not optimized, compromising our ability to maximize societal brain health and brain skills. Scalable, technological solutions to successfully manage these issues have remained mostly piecemeal and siloed—higher education, business, the psychiatry profession, and tech and neurology innovators often do not communicate or collaborate beyond their own disciplines.15

While we can applaud emerging evidence-based digital health solutions as scalable, and often more equitable, these technological solutions are mostly at a population level, not personalized enough, and therefore not able to adequately address the diverse and complex nature of individual needs—a precondition to achieve improved outcomes and added value.

Conversely, personalized and biologically inspired technologies struggle to be consistently validated and integrated into clinical workflows and traditional reimbursement models.16 Our understanding of the fundamental neuroscience of these issues needs further advancement, but it is clear that brain disorders have many common neurobiological roots.17

Investment approaches such as the 2/20 general VC model18 can promote undue revenue pressures, create hype cycles that often lead to market failures14 and result in poor governance—especially given that investors cannot always clearly understand or keep pace with the ideas being pursued by technical founders.19 A majority of investments still favor expensive, reimbursed products and services over cost-efficiencies and value-based care. These governance approaches often create informational asymmetry, which is rife for abuse and mismanagement.19

But there are silver linings for addressing these global brain challenges.

Frontier neuroscience technologies—spanning omics, digital therapeutics, artificial intelligence, and devices—aim to improve access, screening, prevention, diagnosis, prognosis, and treatment. Concurrently, there is an increasing convergence of these types of solutions as experts, systems, and payors attempt to simplify workflows and minimize fragmentation of new products and services (Figure 2).

A number of boutique and thematic venture funds have arrived to help with brain challenges—the LSP Dementia Fund, the Dementia Discovery Fund, and the Alzheimer’s Drug Discovery Foundation (for dementia); the HEKA Fund and Re Mind Capital (for mental health); The Ontario Brain Institute’s Neurotech Early Research and Development (NERD) program (for neurotech); The Longevity Fund and Apollo Ventures (longevity); Primetime Partners (aging); and Learning Capital (education)—and there is much activity surrounding social determinants of health (SDoH). While this interdisciplinary work is a vital step forward, we must engineer new approaches and strategic frameworks to move the needle on these unprecedented, collective brain challenges. We need Brain Capital.

The Potential of Brain Capital

Sidebar 1: Promising Brain Capital Start-Ups

Digital Therapeutics

Pear Therapeutics builds prescription digital therapeutics (PDTs) to provide better outcomes for patients, smarter engagement and tracking tools for clinicians, and cost-effective solutions for payers. Pear’s lead product, reSET, for the treatment of substance use disorder, was the first PDT to receive market authorization from the FDA to treat disease. Pear’s second product, reSET-O, for the treatment of opioid use disorder, was the first PDT to receive Breakthrough Designation. Pear’s third product Somryst® for the treatment of chronic insomnia, was the first PDT submitted through the FDA’s traditional 510(k) pathway while simultaneously reviewed through FDA’s Software Precertification Pilot Program.

TALi is a digital health company aiming to help children reach their full potential by providing engaging training software clinically proven to improve core cognitive performance. Hence, this has value in education and mental health fields. TALi has been developed and validated through a series of pilot studies including randomized controlled trials for acquired brain injury (ABI) and attention in primary school classrooms.

Akili Interactive builds clinically validated cognitive therapeutics, assessments, and diagnostics that look and feel like video games. The company built EndeavorRx, a prescription digital therapeutic video game to help children aged 8 to 12 with attention deficit/hyperactivity disorder (ADHD) and the first game-based therapeutic to get FDA approval. This company has an impact in the mental health, neuroscience, and education realms. Akili has recently entered into a strategic licensing agreement with TALi to extend its offerings for early childhood attention impairments.

The “Cranky Uncle” game can be employed to improve brain function and teach individuals about logical fallacies and critical thinking in the context of climate change. In the game, players must identify the form of science denialism that matches the possible arguments of a climate denialist, such as “How can models predict climate 100 years out when they can’t get the forecast right next week?” and “Climate models are imperfect so they can’t be trusted.” Overcoming cognitive biases and improving brain function will be key to equipping us to prevent climate change, which conversely will help prevent significant harm to brain health.

Happify Health is a health care platform that combines prescription digital therapeutics (PDTx) and care delivery solutions to improve mental and physical health. Happify Health’s first prescription PDTx called Ensemble focuses on treating major depressive disorder (MDD) and generalized anxiety disorder (GAD).

Mobio Interactive has developed digital theragnostics, personalized with objective and scalable biomarkers, to prevent, measure, and treat mental illness.They use facial photoplethysmography (PPG) software and deep neural networks to personalize safe and effective gamified “measure-treat-measure” system has been clinically proven to reduce the risk of mental illness in cancer patients, as well as alleviate anxiety in young adults.

LUCID are producing real-world applications to establish music as medicine.They have curated and created therapeutic music using biometrics and AI for people looking to reduce stress and anxiety, increase focus, and unlock their full potential.They are also exploring their capabilities in the dementia space.

Extended Reality Therapies

Charisma is a flexible virtual platform combined with live, interactive cognitive coaching to enhance how individuals think, interact, and thrive socially. It has relevance and data for anxiety disorders, as well as social and emotional intelligence.

Smileyscope is a virtual reality digital therapeutic for pain and anxiety. Through patented, targeted techniques, its VR experiences have been shown to reduce pain up to 60%, anxiety up to 40%, and need for restraints by 48% in parallel randomized controlled trials. This company has an impact in mental health, education, and neuroscience.

FloreoVR is leveraging the power of VR to provide a method of teaching social, behavioral, communication, and life skills for individuals with autism spectrum disorder (ASD) and related diagnoses. FloreoVR has gone through a usability and initial feasibility pilot study that supports the technology’s ability to improve fundamental joint attention skills in ASD.

Artificial Intelligence-Based Technologies

Stroke affective computing technology built by researchers at Penn State and Houston Methodist leverages machine learning to aid in the diagnosis of strokes using a smartphone to detect abnormalities in speech and face muscle movements. The app aims to enable caregivers and patients to detect the stroke earlier, enabling better options for the patient. The technology was developed and validated from a dataset of 80 patients having stroke symptoms at Houston Methodist, and it achieved 79% accuracy

Muse has developed an electroencephalogram headband that detects brain signals and applies machine learning algorithms to provide insights into attention levels, meditation, and sleep. This has applications in neurology and neuroscience.

Digital Mental Health Care Platforms

Real is redesigning the mental health therapy experience. It makes evidence-based group therapy available on-demand. Real’s digital platforms allow users access to different therapy pathways, group therapy sessions, journal prompts, and other resources available anytime at their fingertips.

Brain-Computer Interface Technologies

Synchron is developing a platform of brain interface technology that transmits data in and out of the brain via devices implanted inside cerebral blood vessels using minimally invasive endovascular procedures. Synchron’s flagship product, the Stentrode™, is a minimally invasive brain-computer interface that serves as a motor neuroprosthesis for the treatment of paralysis. It is designed to circumvent the dysfunctional neural pathway to convert attempts to move to control digital devices. A first-in-human clinical trial was conducted to evaluate the safety and efficacy of the Strentrode to improve functional independence for individuals with paralysis.

Neuralink develops ultra-high bandwidth brain-machine interfaces to connect humans and computers. Neuralink is currently going through extensive studies with the aim to create the future of brain interfaces by building devices that help individuals with paralysis and inventing new technologies that will expand people’s abilities and the larger community and world.

Innovative Education Startups

Blinkist is an online learning and education platform that delivers non-fiction, author-driven content by turning bestselling books into bite-sized audio and reading content. By distilling the essence of world literature into 15-minute “Blinks,” the company is adapting to today’s fast-paced society with seamless integration of learning opportunities into everyday life.

Tomorrow’s Education is redesigning higher education by delivering personalized, flexible, and remote-first online degrees in entrepreneurship, sustainability, and technology. Students are mentored by real-world experts and industry leaders, and receive tailored curricula with a focus on creating a more sustainable society.

Patient Reported Outcomes Tools

BiAffect is utilizing keystroke behavior to predict episodes of bipolar disorder. The technology tracks smartphone keystrokes and extracts patterns that can impact mood, thereby predicting mood changes and mood risk.

Blueprint is moving traditional in-office, paper patient reported outcome scales to the patient’s smartphone with the ability to track mood over time and deliver directly to the patient’s provider.

Brain Capital has the potential to introduce a paradigm shift to our economic understanding and agency in brain health. By placing a premium on brain health and skills in the economy, Brain Capital technology can be defined as neuroscience-inspired technologies that integrate and optimize for mental health, brain health, education, and positive psychology (including resilience, wisdom, and creativity).6,20 As an example of complex issues at the confluence of multiple fields, depression is not just a mental disorder—it also constitutes a major risk factor for absenteeism and presenteeism at work, dementia, worsening comorbidities, poor education attainment, cognitive dysfunction, sleep dysregulation, and economic hardship. Severe mental illness drives social injustice syndromes such as homelessness, transgenerational disadvantage, poverty, and crime. Similarly, early childhood trauma predisposes to poor educational attainment, reduction in occupational capacity, neurological dysfunction, depression, and dementia, often with transgenerational impacts.21 Later on in neurodegenerative disorders, like Alzheimer disease, Parkinson disease, multiple sclerosis, stroke, and epilepsy, after the onset of the disease, researchers see some similarities, which are probably the result of the neurodegeneration rather than the causes for these disorders. These include problems with speech, gait and unsteadiness, and motor movements in general.

At a societal level, the high prevalence and lasting burden of such issues result in a major strain on economic capacity, leading the World Health Organization, the World Economic Forum, and Harvard Medical School to declare investment in this area an economic “best buy.”22 Chronic noncommunicable diseases—including cardiovascular disease, diabetes, and obesity—are risk factors for depression, anxiety, cerebrovascular accidents (CVAs), and dementia. Vice versa, mental health disorders such as depression predispose to cardiometabolic disorders. Brain Capital technology has the potential to simultaneously address and mitigate these multisystemic, interdependent, and complex issues. This technology can save the system a fortune in the long run while significantly reducing human suffering—a huge win-win.

Brain Capital technology can also leverage a human-centered approach toward solution development. In other words, Brain Capital technology can utilize a “hybrid” approach that combines the best of technology with the best of human capabilities. For example, many existing Brain Capital technologies have started to combine human coaches with otherwise automated delivery of brain health interventions.23,24 This approach increases the viability of Brain Capital technologies in numerous ways. It enables a global cohort of advocates for brain health (eg, the coaches and community health workers) to be empowered to deliver brain health advice with both a human touch and advanced technology.

Moreover, responsible innovation and regulation of technology are important guarantors of brain health. While loneliness and lack of purpose remain large sources of poor brain health amplified by the increasingly exploitive uses of technology, Brain Capital technologies that integrate value-driven technology development and a human-centered approach might minimize these issues. Additionally, as many technologies generate large communities of users, the Brain Capital technology approach can be harnessed to accelerate, enrich, and ground these communities in human-centered values. As another example, brain-computer interfaces (BCIs) fuse human capabilities with technology, spanning from health applications (such as managing stroke and movement disorders) to optimizing human performance (such as increasing empathy).

Select examples of promising Convergent Brain Capital startups are outlined in Sidebar 1.

Sustaining Brain Health

As we previously noted, robust operational, governance, and investment innovations will be required to sustain the brain health technology sector.14 We need to bring diverse stakeholders together to form a common language and align on the main value drivers and strategic frameworks as this emerging industry evolves.

There is the opportunity and potential to address the massive underutilization of Brain Capital, especially from older people and meaningfully involve citizens in debate and dialogue about what is needed and possible to support Brain Capital.

To ensure greater replicability of brain research and promote evidence-based approaches translations of the science to benefit humanity, a major push toward standardization for data sharing, curation, and federation is needed. Brain Capital technologies require this foundational infrastructure to be successful. Further, larger validation and real-world studies will be needed to generate critical and dependable foundational data. Philanthropy, health systems, and venture capital must recognize and support this.

On the private investment level, existing ESG approaches have driven positive business and societal value; however, they are incomplete. Incorporating Brain Capital into ESG frameworks—ie, shifting to “B-ESG”—would provide a more comprehensive, robust approach to create long-term positive impacts for the economy, the environment, and all stakeholders.7

Brain Capital is an exemplar of the increasing importance of the impact investing space, and a clear sign of the evolution and expansion of ESG. Concurrently, the changing political and social atmosphere has brought more institutional investor interest to ESG: investment firms, foundations, and family offices are increasingly dedicating significant portions of their portfolios to “impact” investments.

Historically, ESG choices have been slim, and scalability was considered nearly impossible. Conversely, addressing the interdisciplinary, multisectoral nature of mental, neurologic, and substance use (MNS) disorders and the fostering of brain performance would make such investing inherently broader and more scalable.

The fact that impact investments and ESG are still in the early stages of becoming mainstream investment areas, means the use of early-stage startups is also the path with the most upside and potentially lucrative returns for investors. As such, investors can take a relatively inexpensive, large position in companies while assuming a more active role in their development and governance. Likewise, accelerators can engage as early movers to provide a boost to the growth and ultimate success of brain tech companies.25

Channeling even a small percentage of the existing $40.5 trillion aligned to ESG into Brain Capital innovations and solutions as part of a B-ESG is expected to result in an unprecedented impact.26 A B-ESG approach would also allow us to leverage the financial markets to develop and scale Brain Capital technologies and reduce brain challenges. Finally, a B-ESG approach would send a signal for more investment in venture capital-type vehicles to fund the scaling of neuroscience-backed solutions.

Building on this emerging asset class, it is conceivable that a Brain Capital “exchange traded fund” (ETF) could be developed. ETFs are a type of security that track an index, sector, or commodity and can be purchased or sold on a stock exchange like regular stocks. Such thematic ETFs have already been established for areas such as longevity, psychedelics, and sustainable development goals. For a Brain Capital ETF, rules—optimized for brain health and skills building—would need to be generated to determine which company stocks are included and excluded. Potential companies engaged in Brain Capital-building activities may include pharmaceutical and biotech companies, technology companies, health systems and health insurers, educational technology companies, and many others.

Brain Capital Foundry

The neuroscience innovation market is often riddled with perverse incentives at the detriment of brain health (in social media, for example), as companies and shareholders chase returns. We need a new model to link brain-based innovation with economics—a disciplined approach, methodology, and a set of services for accelerating responsible innovation. To this end, we have developed a “Brain Capital Foundry” model that specifically aims to create and integrate neuroscience advances, policy, diplomacy, economic theories, responsible innovation, and the development and deployment of financial instruments.27

Concluding Thoughts

We believe that in the 21st century, there are no brains without capital, and no capital without brains. Therefore, a novel approach to building Brain Capital and mitigating global brain challenges is critical to ensuring and improving societal health and for economic growth and prosperity. Brain Capital technology and investment, carefully interwoven into our economy, will advance neuroscience and bring lasting, high-value, durable benefits to our global community. Brain Capital is perhaps the first foray into a new field of “financial engineering in the pursuit of brain building.”

We invite you to consider this Brain Capital framework as you innovate, invest and tackle social challenges.

Dr Eyre is co-lead of the OECD-PRODEO Institute Neuroscience-inspired Policy Initiative (NIPI) supported by the Meadows Mental Health Policy Institute. He holds adjunct or advisory roles with IMPACT (Institute for Mental and Physical Health and Clinical Translation) at Deakin University, the Heka Fund (pro bono), Brain Health Nexus at Cohen Veterans Bioscience, the Global Brain Health Institute (GBHI) at the University of California at San Francisco, Baylor College of Medicine, Latin American Brain Health (BrainLat), Universidad Adolfo Ibáñez, Chile, University of Texas Health Sciences Center at Houston, and the Davos Alzheimer’s Collaborative. Mr Faulkenberg is a managing director of investment management at Boomtown Accelerators. Mr Das is a senior financial and business executive. He was CEO of Caliber Home Loans and was prior CEO of CitiMortgage. Mr Hackett is a leader in energy management and investing, a faculty member at Rice University and the University of Texas, and a cofounder of a mental health policy center and an Emmy Award-winning mental health web channel. Ms Chen is a general partner at IOVC, and faculty at UC Berkeley and Singularity University. She is also appointed by California Governor Gavin Newson to serve as 1 of 13 voting members on California’s Mental Health Commission. Mr Véron is a general partner at Newfund, a cross-Atlantic early-stage firm with investments in health, mental health, edtech, and foodtech. Mr Swieboda is CEO of EBRAINS and director-general of the Human Brain Project of the European Union. Dr Ling is a professor of neurology, neurosurgery, anesthesiology, and critical care medicine at Johns Hopkins University and the Uniformed Services University of the Health Sciences, and an attending neuro critical care physician at Johns Hopkins Hospital. He serves as co-leader of The BrainHealth Project. Mr Bennett is chief investment officer of Tolleson Wealth Management. He was founding executive director of the Brain Performance Institute at the Center for BrainHealth. Dr Saxena is professor of practice of global mental health in the Department of Global Health and Population at the Harvard T. H. Chan School of Public Health. He was previously director of the Department of Mental Health and Substance Abuse at the World Health Organization. Mr Carnevale is a venture capital investor and technology executive. He is founder and co-chair of the Advisory Board of the UCSF Dyslexia Center, and a Californian Mental Health Commissioner. Mr Powell is Founder of Impact Shares and Principal and Chief Investment Officer with Brookmont Capital Management. Ms Smith is an Atlantic Fellow for Equity in Brain Health at GBHI, a Thiel Fellow at Stanford University, and a Steering Committee member for OECD NIPI. Mr Heinemeyer is CEO of PRODEO and co-founder of the PRODEO Institute. Dr Robertson is a T. Boone Pickens Distinguished Scientist at the Center for BrainHealth, a co-director at GBHI, professor emeritus at Trinity College Dublin, and founding director of its Institute of Neuroscience. Dr Ibanez is director of BrainLat and Senior Atlantic Fellow at the GBHI at University of California, San Francisco (UCSF), San Francisco, California, and Trinity College Dublin, Dublin, Ireland. Dr Wong is the John S Dunn Sr. Presidential Distinguished Chair, founding chair of Systems Medicine and Bioengineering Department, director of T.T. & W.F. Chao Center for BRAIN and associate director of Houston Methodist Cancer Center, Houston Methodist. He is a professor of radiology, neuroscience, pathology, and laboratory medicine at Weill Cornell Medicine. Dr Abbott is a professor of law and health sciences at University of Surrey; adjunct assistant professor of medicine at the David Geffen School of Medicine at UCLA; partner at Brown, Neri, Smith & Khan, LLP; and a mediator and arbitrator with JAMS, Inc. Dr Storch is professor, vice chair, and McIngvale Presidential Endowed Chair in the Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine. Dr Chan is a pediatric physician, CEO, and cofounder of Smileyscope, a VR/AR digital therapeutics company focused on pain and anxiety. Dr Tomori is vice president of medical affairs at Akili Interactive. He also currently serves on the National Advisory Board of the University of Michigan Depression Center. He is an adjunct professor of psychiatry with the New Mexico School of Medicine. Dr Soares serves as professor and Pat R. Rutherford, Jr. Chair in Psychiatry at McGovern Medical School and as executive director of UTHealth Harris County Psychiatric Center. Dr Winter is a physician-scientist, social entrepreneur, and health policy analyst. Besides training in neurology at the Charité University Hospital and Berlin Institute of Health, Germany, he is a postdoctoral researcher at the Massachusetts General Hospital at Harvard Medical School, Boston, USA. Dr Chapman is founder and chief director of the Center for BrainHealth at UT Dallas. She is a distinguished professor at UT Dallas. Ms Budinskaya is Scientific Leader in Neurology at GE Healthcare. Dr Brown is Founder and Principal Consultant at Great Scott! Consulting. Dr Corner is Director of VOICE Global (Valuing Our Intellectual Capital and Experience) and COO of the UK’s National Innovation Centre for Ageing, based at Newcastle University, UK. Dr Nylen isVice President for Integrated Discovery and Information at the Ontarion Brain Institute (OBI). Dr Smith is Vice President for Business Development and Partnerships at the OBI. Dr Mikkelsen is President and Scientific Director of the OBI. Dr Berk is a NHMRC senior principal research fellow, Alfred Deakin professor of psychiatry at Deakin University, and director of the IMPACT Institute at Deakin University.

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