Michael Berk, MD, PhD

Elizabeth Holmes of the blood testing company Theranos, who is being tried for 12 charges of wire fraud and conspiracy to commit wire fraud, serves as a sobering reminder of the importance of due diligence.

 Theranos’s many esteemed investors were not unscrupulous, just unaware. Holmes’s case is one of information asymmetry, in which 1 party has information that the other does not. Holmes knew she was selling snake oil; her investors did not.

 is considered by economists as a major source of market failure.

 in the past years, this field needs sustained investment increases over the coming decades to seriously tackle 

multi-trillion dollar global brain health challenges

 Approaches to understand and then minimize information asymmetry between technical entrepreneurs and investors are key.

This asymmetry creates an imbalance of power and can lead to negative results, spanning from poor decision making on the part of the less informed party, all the way to providing an opportunity for exploitation and unethical behavior (

Table 1: Common Types of Information Asymmetry

The opportunity for information asymmetry to lead to fraud is particularly alarming. According to 

, 47% of companies experienced fraud in the past 24 months, and more than $4.5 trillion are lost to fraud each year globally.

 Concerning startups, fraud is most prevalent among small companies. According to the 

Association of Certified Fraud Examiners’ (ACFE) 2018 report

, organizations with fewer than 100 employees see the largest share of fraud cases and lose nearly twice as much per scheme compared to organizations with more than 100 employees.

We believe that brain health technologies will add monumental value to human society in the coming decades. However, if entrepreneurs and investors are not on the same page, information asymmetry could impede development of the brain health technology company space.

The problem of information asymmetry is exacerbated by ever-growing information overload. In 1971, before the advent of the internet and social media, the prominent Nobel Prize winning economist 

 noted “information…consumes the attention of its recipients…a wealth of information creates a poverty of attention and a need to allocate that attention efficiently among the overabundance of information sources that might consume it.”

 This problem has become increasingly apparent in our daily lives as a cacophony of online media competes for our attention. 

, there are more than 474,000 tweets, 400 hours of new video on YouTube, 3 million new posts on Facebook, 3.5 million Google searches, and over 15 million text messages delivered.

The problem of information overload is particularly acute in brain health technology investing. There has been a 

 in technological breakthroughs; basic, translational, and clinical neuroscience discoveries; and brain health technology company formations.

 Likewise, there has been substantial growth in investments—venture investors poured a 

 into brain health-related startups by the year-end of 2020.3 The brain health technology sector urgently needs sustained investment over decades. Further, the brain health technology market has the opportunity to tap into the 

 in global assets with environmental, social, and governance investment imperatives that could be harnessed by the brain health space if the market continues to mature.

The effect of such information overload is to amplify information asymmetry. Sunstein, in 

argues that less is often more, highlighting that in many cases, abundant information is neither necessary nor welcome, and can be an impediment to effective decision making.

 People typically make decisions by distilling redundant information rather than adding unnecessary complexity.

Because of the immense complexity of neuroscience, it is particularly vulnerable to such asymmetry. Complex neuroscience principles, technology, and 

 may be poorly understood by advisors, employees, and investors without a relevant technical or clinical background.

 Additionally, it is especially hard to develop an accurate sense of the product’s capabilities and scientific validity when it lacks peer review. 

As a result, investors and customers are arguably more reliant on views of others and are consequently vulnerable. Who do nontechnical investors turn to when evaluating a neuroscience company? In some cases, they may consult experts in the field. Often, however, they may simply trust the due diligence of earlier investors. Current capital markets and funds (private equity and venture capital) have so much money that free riding is increasingly common. Large firms count on the due diligence of smaller funds (or early-stage investors), who in turn count on the reputation of the big firms. Thus, mistakes and oversights from early investors might not always be rectified in future investment rounds.

Moreover, the rapidity of the current market environment maximizes asymmetries. Building a trusting and robust relationship with founders over time used to be the usual way for an investor to gain access to reliable and accurate information. Over time, investors observe consistencies and inconsistencies in narratives and presented factors and data. However, deals are closed so quickly and fear of missing out is widespread among investors, therefore effective diligence cannot be completed.

The relationship between marketing and the product is another source of information asymmetry. Overemphasis on marketing without product development—a staple of the Silicon Valley “fake it till you make it” mentality—may distract from an unvalidated or poorly validated product. In some cases, as with Theranos, “the emperor has no clothes,” and the product is nonfunctional. Of course, when communications to customers and investors paints a rosier picture than the truth of product development, this leads to further information asymmetry. From a product-market fit perspective, there are many novel market segments and a rapidly evolving brain health landscape. Only select people may understand these product-market fit dynamics, enabling information asymmetry to arise between key stakeholders.

Entrepreneurs may have a monopoly of knowledge over the different market activities and thus spin or even withhold relevant and accurate information.

In particular, market activities are often overplayed by entrepreneurs. It is important for investors to discern the difference between conversations in the market, unpaid pilots, paid pilots, commercial contracts, and revenue from commercial contracts. However, entrepreneurs often inaccurately portray these activities in conversations with investors (eg, claim unpaid or one-off pilots as commercial contracts). Entrepreneurs may have a monopoly of knowledge over the different market activities and thus spin or even withhold relevant and accurate information.

The disconnect between revenue and valuation may also present information asymmetry between founders and employees. Potential employees without a comprehensive understanding of startups may not understand how a brain health technology company may be worth millions or billions of dollars, and yet have minimal or no revenue. Entrepreneurs also may charismatically explain inaccurate revenue projects and withhold information from potential employees. Subsequently, potential employees may accept jobs and take on more risk than they would otherwise feel comfortable with if they comprehensively understood the current state of the startup.

Finally, we would be remiss not to mention that cognitive biases may worsen information asymmetries. For instance, 

 could have a negative impact on our field in the long run.

 The increasingly high and speculative valuation dynamics embolden founders as well as investors to think that they have “got it.” It is important that overconfidence does not lead to insufficient diligence, and insufficient operational and governance activities.

Table 2: Solutions to Mitigate Information Asymmetry

Action is required to mitigate information asymmetry in brain health companies, or else brain health technology could suffer. For one, the field should encourage more advertising of failures and accurate analysis of how they could have been avoided. Additionally, to mitigate cognitive biases like overconfidence, training in 

, and associated self-reflection may be useful.

 Finally, information needs to be disseminated in a manner that is clear, simple and accurate, and minimizes jargon. We have developed a 

 that may apply in this situation to equip people to be more effective investors and board members.

 Specialist investment funds should be established in niche areas with highly skilled investors, operators, clinicians and scientists (eg, 

). Engaging clinicians and scientists with deep domain expertise, as independent experts, is additionally key to ensure 

investors and brain health practitioners are aligned

 Material incentives, reputation incentives, control incentives, and stock option incentives have also been found to be 

 to reduce information asymmetry, improve decision making, and lessen the investment risk of investors and entrepreneurs.

 Further details around these solutions are outlined in 

To work toward addressing the current global brain health challenges, continued investment and interest is needed in the brain health space. We cannot afford to turn a blind eye to problems stemming from information asymmetry. As with the case of 

, information asymmetry and fraud in one company can sour investor interest in the space for years to come.

 The brain health technology space cannot afford to be set back by information asymmetry and fraud due to the urgent need for innovation and sustained investment. The decisions made now to understand and mitigate information asymmetry between key stakeholders in brain health technology companies will have repercussions for decades to come.

 is a director at the PRODEO Institute, an Atlantic Fellow in Brain Health Equity at the Global Brain Health Institute (GBHI) at the University of California, San Francisco (UCSF) and a Thiel Fellow at Stanford University.

 is cofounder of the PRODEO Institute and CEO of PRODEO. 

 is a Senior Clinical Advisor for Cohen Veterans Bioscience’s Trauma Research Programs. She serves as Strategic Advisor co-leading CVB’s Suicide Strategy Initiative. 

 is an undergraduate studying neuroscience at Dartmouth College.

 is a corporate attorney, a professor of law at University of Surrey and an adjunct professor with the UCLA David Geffen School of Medicine. 

isa senior advisor to the Organisation for Economic Co-Operation and Development (OECD) Secretary General, head of the New Approaches to Economic Challenges Unit (NAEC), and co-lead of the OECD-PRODEO Institute Neuroscience-inspired Policy Initiative (NIPI).

 is Chief Commercial Officer with Stanford University’s Brainstorm Lab and adjunct faculty with the Massachusetts General Hospital, affiliated with Harvard University.

 is a technologist, venture capitalist and an adjunct professor in engineering at Stanford University. 

 is venture capitalist, founder and managing partner at Newfund Capital. 

 is Alfred Deakin Professor of Psychiatry at Deakin University and director of IMPACT at Deakin University (Institute for Mental and Physical Health and Clinical Translation). 

 is a venture capitalist and an adjunct faculty member at UC Berkeley and Singularity University. 

 is a venture capitalist, managing director at Newline Ventures and Adjunct Professor in Management Science & Engineering and Civil & Environmental Engineering, Stanford University.

 is an undergraduate studying computer science at Stanford University.

 is cofounder of the PRODEO Institute, colead of the OECD NIPI, and holds adjuncts roles with IMPACT at Deakin University, GBHI at UCSF and Baylor College of Medicine.

Bad Blood: Secrets and Lies in a Silicon Valley Startup

The control strategies for information asymmetry problems among investing institutions, investors, and entrepreneurs in venture capital.

3. Jennings K. Venture funding for mental health startups hits record high as anxiety, depression skyrocket. 

 June 7, 2021. Accessed October 8, 2021. 

https://www.forbes.com/sites/katiejennings/2021/06/07/venture-funding-for-mental-health-startups-hits-record-high-as-anxiety-depression-skyrocket/?sh=5f56a6f21116

4. Eyre H, Carson J, Smith E, et al. Boosting brain health after COVID-19: a convergence solution. 

https://www.psychiatrictimes.com/view/boosting-brain-health-after-covid-19-a-convergence-solution

6. PwC’s Global Economic Crime and Fraud Survey 2020. Accessed October 8, 2021. 

https://www.pwc.com/gx/en/services/forensics/economic-crime-survey.html

7. Association of Certified Fraud Examiners’ (ACFE) 2018 report. Accessed October 8, 2021. 

https://www.acfe.com/report-to-the-nations/2018/default.aspx

Why Herbert Simon matters for policymaking. 

9. Schultz J. How much data is created on the internet each day? MicroFocus. August 6, 2019. Accessed October 8, 2021. 

https://blog.microfocus.com/how-much-data-is-created-on-the-internet-each-day/

10. Altimus CM, Marlin BJ, Charalambakis NE, et al. 

11. Baker S. Global ESG-data driven assets hit $40.5 trillion. 

https://www.pionline.com/esg/global-esg-data-driven-assets-hit-405-trillion

Too Much Information: Understanding What You Don’t Want to Know. 

“Black box” pharmacogenetic decision-support tools in psychiatry.

14. Baker HK, Nofsinger JR, eds. Behavioral finance: investors, corporations, and markets. Kolb Series in Finance. Accessed October 8, 2021. 

https://oedf.eu/wp-content/uploads/2019/11/KENT-BAKER-H.-NOFSINGER-J.R.-sous-la-direction-de-Behavioral-Finance-Investors-Corporations-and-Markets-Wiley-2010..pdf

15. UPMC Western Behavioral Health. What are cognitive distortions? (with 10 examples). UPMC Health Beat. May 13, 2021. Accessed October 8, 2021. 

https://share.upmc.com/2021/05/cognitive-distortions/

16. Eyre HA, Berk M, Smith E, et al. Brain health executives: a transdisciplinary workforce innovation—a commentary. 

https://innovationscns.com/brain-health-executives-transdisciplinary-workforce-innovation/

17. Carson J, Noori S, Dunn A, Eyre HA. Buyer beware: why investors and mental health practitioners must sit on the same side of the table. 

. May 18, 2021. Accessed October 8, 2021. 

https://www.psychiatrictimes.com/view/buyer-beware-why-investors-mental-health-practitioners-must-sit-same-side-table

18. Griffith E. They still live in the shadow of Theranos’s Elizabeth Holmes. Updated October 6, 2021. Accessed October 8, 2021. 

https://www.nytimes.com/2021/08/24/technology/theranos-elizabeth-holmes.html

Articles

Information asymmetry occurs when one party has more or better information than the other party. Asymmetry and fraud will sour investor interest in the field.  

Sustaining Investment in Brain Health: The Dangers of Information Asymmetry 

“What if a game of peek-a-boo could change the world?” Seven-year-old Molly Wright, one of the youngest-ever TED speakers, posed this profound question in her July 2021 viral video.

 Why peek-a-boo? Because, as Molly so clearly articulated in her UNICEF and Minderoo Foundation-supported talk, this simple game captures the essence of what we know about young children’s healthy brain development: All of the everyday, back-and-forth interactions between caring responsive adults and babies serve to stimulate their senses, build social interaction skills, foster language development, and teach object permanence. These are all foundational brain-based skills.

Games like peek-a-boo are thus invaluable when it comes to brain building and supporting strategies that will help prepare today’s children to navigate a rapidly changing, increasingly complex, and globally connected world. With respect to the developing brain, early childhood is a time of particularly rapid change, with up to 90% of brain growth taking place by age 5. In other words, when it comes to strategic brain- and skill-building, these early years are critical for lifelong learning and well-being.

Building brains in the very earliest stage of life may ultimately be the best way to brace our societies for and empower our children to face a panoply of future challenges. Complex issues already impacting our societies today only stand to become more difficult as our children grow older.

Presently, rates of stress, depression, and anxiety are spiking due to the vicissitudes of COVID-19 (which still seems to have no end in sight for the globe).

 Further, COVID-19 seems to have exacerbated advanced cognitive skill deserts—areas characterized by low scores in standardized tests and poor educational infrastructure.

 This is concerning given that jobs are becoming increasingly knowledge-intense as automation subsumes lower-skilled roles. 

Current and future challenges related to climate change

 present issues to where we live, work, play, and eat. Taking action to tackle these issues is harder due to misinformation propagation, a global phenomenon spreading virally and accelerating radical and radicalizing conspiracy theories.

 Political and social divisions are increasingly stark and volatile. All in all, we have a collision of issues which, at their core, seem to be worsened by the overwhelming, overloading, or dysfunction of our brains and minds.

Of course, in the immediate term, one of the best strategies for ensuring the conditions needed for healthy early childhood brain development is rapid, global, vaccine-based herd immunity from COVID-19. This would allow economies, families, and communities to return to a normal life where, among other things, the mental health and safety of both young children and their caregivers is protected. But it is imperative that we are prepared to address what many predict will be the long-term detrimental 

 on our children, adolescents, and their families as well.

We are buoyed by the US President’s planned human infrastructure agenda, which both recognizes the importance of and provides supports for the boosting of brain-based skill development in early childhood.

 These proposed investments include childhood poverty reduction, universal pre-kindergarten, a child tax credit for low- and middle-income families, and a national paid leave program. If funded and executed well, these large-scale programs will facilitate early childhood brain development. We hope other 

 around the world take note of these ambitious plans.

Aligned with the planned human infrastructure agenda, poverty reduction is of the utmost value to early child brain development. 

 (ACEs) are associated with alterations in psychological, cognitive, and neurobiological development. From a brain-based skills perspective, executive function skills (encompassing skills such as cognitive flexibility and critical thinking), are clearly recognized to be of lifelong importance. Given that their most rapid rate of development occurs between the ages of 3 and 5, it is particularly concerning, but no surprise, that poverty has been found to increase the risk for executive functioning difficulties.

 Thus, efforts to better brain health go hand in hand with strategic investments in early childhood and measures to reduce childhood poverty, as well as other ACEs.

In considering the interplay between mental health, adversity, and early brain development further, research on the neural mechanisms underlying emotional processing in individuals of differing socioeconomic status (SES) point towards differences in brain structure and function as a link between mental health and SES.

 Innovative studies like the NIH- and philanthropically-funded Baby’s First Year Study aim to understand the impact of monthly, unconditional cash transfers to low-income 

 in the first 3 years of the child’s life.

 Currently underway, the Baby’s First Year Study is examining how poverty reduction affects early childhood development and the family processes known to support children’s healthy development.

Highlighting the cross-sector nature of this work, others suggest the need for social work to critically engage with the first 3 years, shifting focus from the individual and family to a more systems-level community and public health focus. Based on the old but sturdy Bronfenbrenner concept of socioecological influences on child development, we believe it is important to build skills at all levels: individual, family, community, service provision, policy, and systems. Targeting multiple levels of influence fosters mutually reinforcing positives effects on child development.

In addition to poverty reduction, interactional behaviors like serve-and-return (well demonstrated in a game of peek-a-boo), conversational turn-taking (see Harvard University’s 

), and child-directed speech are particularly important in early life. These early relational health behaviors build core life skills such as executive function/self-regulation, self-efficacy, trust, and resilience that serve to help buffer against adversity and better equip children (and their brains) to take advantage of future learning opportunities.

 It is worth noting that parenting behaviors like serve and return do not happen in a vacuum. Studies show that social and structural factors affect parental behaviors. We know that ongoing stress makes it difficult for parents to strengthen and use the executive function skills so central to providing nurturing, responsive, safe, and stimulating environments in which children and adolescents can thrive.

 In contrast, we also know that the presence of a caring responsive adult stands to serve as a protective buffer against the neurotoxic (and other harmful) effects of poverty.

Given the significant importance of the caregiver to early relational health, adequately addressing postpartum depression is also critically important. Simply put, better prevention, identification, and treatment of postpartum depression is key to boosting baby’s brain health and development. Not doing so proves to be both economically and individually quite costly. A recent study found that the state of Texas alone is losing $2.2 billion by not treating mothers’ mental health from pregnancy through their child’s first 5 years.

 Postpartum depression has also been found to have both maternal and infant consequences, including negatively affecting physical health, sleep, motor, cognitive, language, emotional, social, and behavioral development in the infant.

The impact of healthy brain development during the early years applies not only to physical and mental health, but early learning as well. Early childhood sets individuals up for lifelong learning. With converging accelerations in technology, globalization, and climate, lifelong learning is no longer desirable, lifelong learning is essential.

 The Organisation for Economic Co-Operation and Development (OECD) recently released the 

OECD Skills Outlook 2021: Learning for Life.

 This report noted that lifelong learning starts in childhood and youth, continuing throughout adulthood and old age. It encompasses formal learning in settings such as schools and training centers, informal and nonformal learning derived from colleagues and workplace trainers, and unintentional learning stemming from spontaneous social interactions.

In recognizing the impact of the early years to what ultimately becomes lifelong learning, the Minderoo Foundation’s Thrive by Five program engages with government, research institutes, and other stakeholders to advocate for effective policy and investment in early learning systems.

 This representative program has initial activities in Australia, with global ambitions. And while little formal research has been done to understand the effects of different parenting styles such as free range, helicopter, authoritative, or permissive parenting on brain development, in the brain-building context of early relational health and serve-and-return interactions, what is increasingly clear is that interactions shape brain development, and parents stand to serve as chief architects. With this in mind, The Minderoo Foundation’s Thrive by Five program also recently launched a new parenting app which leverages ground-breaking research into the early years to assist parents in developing their child’s life skills while going about their daily routines.

Though there is also an intrinsic link between education and early childhood brain development, more research is needed to better understand, build, and optimize education innovations that may bolster development. For example, German forest schools, known as 

, began in 1960 and encourage children to play, explore, and learn in a forest environment where adults assist rather than lead.

 The forest school model has spread to many locations around the world. Though research has elucidated the benefits of this model of education,

 little has been studied on the neurological affects.

Similarly, the Montessori method, developed in the 1900s by prominent psychiatrist and pediatrician Maria Montessori, MD, promotes independence through self-directed activities in a specially prepared environment and discourages conventional measures of achievement like tests and grades.

 Extensive connections between the Montessori method and early childhood brain development have been described and theorized, and research points towards many benefits of this model of education.

 However, more research is needed to understand the neuroscientific grounds of the Montessori method and how education can better facilitate brain development.

Better understanding is also needed for high-tech approaches to brain development in childhood. For example, leading baby-brain researcher Patricia Kuhl, PhD, demonstrates, through her research, how neuroscience can better inform our understanding of brain development, how children learn, and the way children are taught. One of her studies made use of magnetoencephaography (MEG) scans to monitor sensory and motor-sensory brain activation in infants from English-speaking families who were exposed to Mandarin.

 only when they were exposed to the novel language in live interaction, but not from television or audio-listening. This study suggests that neuroscience can guide us—both as to how and when technology should (or should not) be leveraged in education, and with respect to important aspects of foundational language development and bilingualism.

The value of investing in early childhood is unequivocal. Led by Nobel laureate and economist James Heckman, PhD, “The Lifecycle Benefits of an Influential Childhood Program” determined that high quality birth-to-5 programs for disadvantaged children can deliver as much as a 13% per year return on investment.

 Significant gains were realized for both children and mothers through better outcomes in education, health, IQ, crime reduction, social behaviors, future earnings, and employment.

 These early childhood programs work, in part, because they provide children with the skills they need to learn and socialize in primary school.

Developing transformative neuroscience insights which can generate new ways to understand, screen, diagnose, and treat brain disorders is also key. In this regard, we applaud new projects such as Advanced Research Projects Agency for Health (ARPA-H), which is a large-scale effort to accelerate medical innovation in areas such as autism.

Another of ARPA-H’s first 3 focus areas is Alzheimers disease—further exploration is needed into the value of starting dementia prevention strategies in childhood, which emerging evidence points to as promising.

Now more than ever, as nations across the globe are looking to build back better in a world facing globally complex challenges—from 

 to climate change and beyond—it is important that we do so strategically. According to International Monetary Fund Managing Director Kristalina Georgieva, PhD, the best investment in times of rapid change are investments in human capital.

 We agree. Based on all that the neuroscience now tells us about the importance of early brain and child development, we believe that achieving the goal of building back better must therefore include investments in child human capital. Actually, make that our children’s brain capital.

is a director at the PRODEO Institute, an Atlantic Fellow in Brain Health Equity at the Global Brain Health Institute (GBHI) at the University of California, San Francisco (UCSF) and a Thiel Fellow at Stanford University.

is a senior advisor to the Organisation for Economic Co-Operation and Development (OECD) Secretary General, head of the New Approaches to Economic Challenges Unit (NAEC), and co-lead of the OECD-PRODEO Institute Neuroscience-inspired Policy Initiative (NIPI).

is an economist, researcher at the IESE Business School, and president of the Venezuelan Alliance.

Paul Ramsay Foundation Fellow and Adjunct Professor, Queensland University of Technology (QUT) and convenor, Thriving Qld Kids Partnership.

is an advisor to ARACY (Australian Research Alliance for Children and Youth) and convener of the Brains Builders Alliance.

adjunct professor in engineering at Stanford University.

is professor and head of psychology at Baylor College of Medicine.

is a child and adolescent psychiatry fellow at UCLA.

is a pediatrician and professor with the Penn State Edna Bennett Pierce Prevention Research Center.

is Alfred Deakin Professor of Psychiatry at Deakin University and director of IMPACT at Deakin University (Institute for Mental and Physical Health and Clinical Translation).

s cofounder of the PRODEO Institute, co-lead of the OECD NIPI, and holds adjuncts roles with IMPACT at Deakin University, BrainLat, GBHI at UCSF and Baylor College of Medicine.

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In order to face the rapidly changing, increasingly complex, and globally connected world, we need to focus on the importance of early brain and child development.

Michael Berk, MD, PhD

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