Interview

Improving Early Detection and Intervention

Michael Georgieff, MD

Co-director of Masonic Institute for the Developing Brain

Please tell us about the mission of the Masonic Institute for the Developing Brain.

The mission of the Masonic Institute for the Developing Brain (MIDB) is to develop an innovative neurodevelopmental research, educational and clinical intervention institute in a single setting. As a shared facility, it will bring together clinical and academic experts from three entities, including: M Health Fairview Masonic Children’s Hospital and pediatric specialty clinics (M Health Fairview), the University of Minnesota College of Education and Human Development (College of Education and Human Development) and the University of Minnesota Medical School (Medical School).

The MIDB’s basic tenet is that investment in early childhood brain health is an investment in society going forward. The MIDB is unique in that it is not dedicated to any one neurobehavioral disorder, but instead seeks to discover basic processes by which the brain develops. This in turn informs us about many neurobehavioral disorders and helps clinicians bring responsive treatments to patients. In addition to being a leading-edge research facility, M Health Fairview is relocating the majority of its outpatient behavioral, developmental and mental health care to the facility—making it easier for clinicians and researchers to collaborate and for patients to get the care they need in one location.

The understanding of these developmental processes ranges from basic biologic underpinnings of brain development to clinical and policy interventions. The MIDB is based on the science that the brain is most responsive to interventions and environmental conditions during its periods of most rapid growth: the first 1,000 days post-conception with a second peak during adolescence. Thus, our programs focus on the best ways to identify risks to the brain, promote the most healthy brain growth possible and bring new and novel interventions and knowledge to the clinical, educational and policy arenas. The MIDB facilitates this process by having researchers, educators, policy makers and clinicians under one roof where they can collaborate.

Brain health is an investment in society going forward.

What can you share about how and why the Institute was founded?

The MIDB was the brainchild of Dean Jakub Tolar of the Medical School and Dean Emeritus Jean Quam of the College of Education and Human Development, both of whom put in an enormous amount of energy and monetary investment for the MIDB to be established.

The original seeds of the MIDB date back about 20 years with the founding of the Center for Neurobehavioral Development (CNBD) under the watch of President Robert Bruininks. CNBD was part of the birth of a new field at the time called neurobehavioral development. Its goal was to bring together researchers from basic science through policy to engage in collaborative interdisciplinary approaches in understanding neurobehavioral development, as well as solving or preventing neurobehavioral problems. The emphasis on early brain development reflected an emerging concept called “The Developmental Origins of Adult Health and Disease,” which showed that early life events set the brain on a life-long trajectory.

About five years ago, as part of the growth of CNBD, Professor Frank Symons, Associate Dean for Research in the College of Education and Human Development, and I approached Dr. Jakub Tolar, then head of the Stem Cell Institute, about the potential role of stem cell therapies in neurodevelopmental disorders. When Dr. Tolar became Dean of the Medical School, he and Dean Emeritus Quam were captivated by the idea of a larger institute that would integrate the research performed at CNBD, the education and policy initiatives at the Institute on Community Integration (ICI) and our M Health Fairview clinics that provided neurobehavioral care. They, in partnership with the University of Minnesota Foundation, rapidly secured a site for the MIDB along East River Road and major philanthropic support from Minnesota Masonic Charities and the Lynne and Andrew Redleaf Foundation. The effort was capped by the recruitment of Professor Damien Fair from Oregon Health Sciences University to co-found and co-direct the MIDB.

What is your role there and what does it entail?

I co-direct the MIDB with Professor Damien Fair, who brings his own remarkable research to the U of M. In our role as co-directors, we set the scientific and clinical agenda for the MIDB. We ensure that the pipeline of scientific information generated by the researchers reaches the clinics, the educators and the policy makers in a much more rapid time frame than has traditionally been possible. We do this through creating and overseeing core services that are designed to assist researchers and clinicians to facilitate their work. In Dean Tolar’s words, we are there to ensure that “collisions” happen among all the people participating in the MIDB so that everyone is aware of new knowledge that is coming down the pipeline as soon as it becomes available. This information may be in the form of novel therapies, new learning modules or new scientific concepts. Professor Fair and I have remarked that we are “the hosts at the party.” It is our job to make sure everyone knows what everyone else is doing and to foster new, productive collaborative teams to move the field forward faster and more efficiently.

What does the vision for collaboration outside the medical community include?

The ICI is a major partner for the MIDB programs and within the MIDB building. They are dedicated to educational and policy agendas as these relate to individuals with disabilities and have been recognized for their work in this non-medical space for over 40 years. Their leader, Dr. Amy Hewitt, has been instrumental in promoting the MIDB agenda, and ICI will also play a role in shaping clinical care within the MIDB. For example, we know that autism spectrum disorder (ASD) diagnoses and the number of families seeking care are increasing nationwide. Researchers from ICI are working with M Health Fairview providers to develop telehealth interventions that families can start with their children at home even while awaiting diagnosis.

One of the MIDB cores I mentioned previously is the Community Engagement and Education Core, led by Dr. Anita Randolph, a research neuroscientist, community organizer and educator, who was recruited to the U of M to lead the core. The goals of this core are also to ensure that critical supports are available for early intervention and treatment and to engage children and adolescents in programs that foster brain development. The MIDB engages with U of M Extension Services, multiple community programs, the Itasca Project’s First 1,000 Days Initiative and potentially with the legislature.

We recently published an article about the Itasca Project. What role does the MIDB play in this work? 

The MIDB provides neuroscience expertise and community engagement information to the Itasca Project (Itasca) through biweekly meetings with representatives. From a neuroscience perspective, we think it is important that the arguments set forward by Itasca to support early childhood—the first 1,000 days—efforts be grounded in sound neuroscience principles. These principles prove early life environment, including stress reduction, nutrition and supportive environments, set developing brains on a positive life course trajectory and prevent later neurobehavioral problems. Itasca’s First 1,000 Days Initiative gives us the opportunity to share the science with Itasca partners across the state who play a role in early childhood education, legislative policy, employment policies and more. Together, our ultimate goal is to make Minnesota a destination for excellent early childhood brain development.

What can you share about your work with Neuromodulation?

I am involved in research that plans to use neuromodulation to treat infants after brain injury at birth, specifically newborn strokes. Based on the work of former MIDB member Dr. Bernadette Gillick, neuromodulation appears effective in improving physical outcomes when applied to older children, aged 8-16-years old, who had strokes at birth. Arguably, the therapy would be more effective if applied during the period of maximal brain plasticity shortly after birth. This ground-breaking work continues in collaboration with Dr. Gillick at UW-Madison. Our research group thinks that ultimately the combination of neuromodulation and cellular replacement therapy may work the best. This therapy has also been prototyped as an option for neonatal brain injury. Neuromodulation is a great example of one of multiple innovative therapies being developed at the U of M to treat the developing brain.

At the MIDB, we’ll have the capacity to translate this research into future patient care at established clinics devoted to supporting children with neurodevelopmental concerns through their first 1,000 days. For example, the M Health Fairview Birth to Three Program will relocate to the the MIDB when it opens to patients Nov. 1.

Please tell us about the work with Human Phenotyping.

The Measurement and Human Phenotyping (MAP) core is at the heart of the clinical research program. It plays a vital role in making sure that the researchers in the MIDB are using the most precise and current assessment tools in their studies. One can assess the developing brain in multiple ways, including anatomically and functionally. Of course, ultimately families are most interested in function, i.e., behavior, but the period of maximum plasticity for the developing brain is characterized by infants and children who have a very limited behavioral repertoire.

The challenge is to find ways to assess the health of the brain and its functionality early enough that any interventions will have their greatest impact. Some ways we do that is by using an MRI to assess how well the brain looks anatomically and how it is hooked up, using connect to me techniques. We can record high density EEG output by the brain to assess responses to tasks that we have children perform even if they are too young to respond behaviorally or verbally. We can use eye-tracking to assess pre-autism social interactions in at-risk children well before the typical age for the diagnosis of autism. We are developing biomarkers— nutritional, stress and brain functionality—that can be measured in the urine, saliva or blood and tell us about an individual’s brain status. Finally, we develop and use new behavioral assessment tools that can give us early readouts of very specific areas of the brain, rather than relying on more generalized behavioral testing. The MAP advises researchers and physically assists investigators on the use of these tools. The tools can detect early neurodevelopmental problems well prior to clinical symptoms and can monitor response to interventional therapies. With our multidisciplinary clinicians and researchers working side-by-side, families will have easy access to both clinical care and the latest research, such as human phenotyping. Our goal is to improve both early detection capabilities and early intervention for patients.

What are you doing in the area of Translational Neuroscience?

One of our missions is to shorten the timeline from when fundamental developmental neuroscience discoveries are made in the laboratory, then go into clinical trials and ultimately clinical care. We have a group of about 20 researchers representing multiple departments on the U of M Twin Cities campus who are researching the biological underpinnings of typical and atypical neurodevelopment. Their research areas span the developmental topics like nutrition, stress, obesity, infection, toxins, addiction, autism and schizophrenia. Because their laboratories are not located on the MIDB campus, their interaction with clinical researchers and clinicians is facilitated by the Translational Neuroscience Core. This core is responsible for putting together research teams of pre-clinical and clinical researchers around the developmental topics noted above. This powerful interdisciplinary approach allows us to pinpoint the important biological factors that underlie the diagnosis and treatment of many neurodevelopmental disorders. Providing biological plausibility and proof is key to sharpening our approaches to treating neurodevelopmental disorders. It is key because we can be more specific in our therapies and the timing of those therapies when we know the biology. Many of our M Health Fairview clinicians at the MIDB are also researchers and educators at the U of M . They’re immersed in these discoveries, and we hope the Translational Neuroscience Core will even further expand collaboration across university departments and into medical care.

What are some of the longer term goals for the MIDB?

The most important goals are to shorten the timeline from discovery to intervention and to engage the community in brain development activities. As Dr. Fair has pointed out, the discovery to intervention process can take as long as 17 years, and that is simply unacceptable for our rapidly growing and developing children. We believe that the new efficiency of putting the researchers, educators, policy makers and clinicians in a single setting will facilitate speeding up that timeline. Ultimately, we want to learn from every patient’s experience to make our approaches better for the next patient who comes along. From a community perspective, engaging underrepresented individuals in neuroscience and helping those patients with difficulty in accessing consistent, effective and individualized neurobehavioral services are main focal points. Building these programs will take time, but will pay off in the long run because ultimately prevention of mental health problems through early detection and intervention far outweighs the cost of diagnosing and treating them later in life.

What would you like physicians in Minnesota to know about how they can become involved with the MIDB?

It is estimated that up to 50% of physician visits for children involve discussion, diagnosis and treatment of behavioral issues. When primary care physicians need additional consultation, there are multiple subspecialties which assess and potentially treat neurodevelopmental issues: pediatric neurologists, neuropsychologists, developmental pediatricians and child and adolescent psychiatrists. Yet fundamentally all of these subspecialists are assessing brain health and function. The MIDB brings all of these disciplines together in a single setting with a concise approach so that each child can potentially be evaluated by team members from all of these disciplines. From that intake, an individualized plan can be crafted to address a child’s needs, fueled by new knowledge and innovative approaches. Long term we hope to be a learning resource for physicians in Minnesota so they can leverage the knowledge generated by and tested in the MIDB in their own practices.

Michael Georgieff, MD, is the co-director of Masonic Institute for the Developing Brain and a professor at the U of M Medical School and College of Education and Human Development. He is a neonatologist at M Health Fairview Masonic Children’s Hospital.