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Introduction and Background¹

Humans are potentially exposed to more than 80,000 toxic chemicals in the environment,² yet their impacts on brain health and disease are not well understood (Hamblin, 2014). The sheer number of these chemicals has overwhelmed the ability to determine their individual toxicity, much less potential interactive effects. Early life exposures to chemicals can have permanent consequences for neurodevelopment and for neurodegeneration in later life (Bellinger, 2013). Toxic effects resulting from chemical exposure can interact with other risk factors such as prenatal stress, and persistence of some chemicals in the brain over time may result in cumulative toxicity. Because neurodevelopmental and neurodegenerative disorders—such as attention-deficit hyperactivity disorder and Parkinson’s disease—cannot be fully explained by genetic risk factors alone, understanding the role of individual environmental chemical exposures is critical (Berkowitz, 2020; Ellis et al., 2011).

Workshop co-chair Deborah Cory-Slechta, professor of environmental medicine at the University of Rochester Medical Center, referred to environmental chemical exposures as “the ignored environmental risk factors for

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¹ The planning committee’s role was limited to planning the workshop, and the Proceedings of a Workshop was prepared by the workshop rapporteurs as a factual summary of what occurred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and have not been endorsed or verified by the National Academies of Sciences, Engineering, and Medicine. They should not be construed as reflecting any group consensus.

² For more information, see https://www.epa.gov/laws-regulations/summary-toxic-substances-control-act (accessed August 12, 2020).

neurodevelopmental disease and disorders.” However, as recognition has grown about the substantial vulnerability of the nervous system to environmental effects, environmental neuroscience is emerging as an important topic in neuroscience, said Frances Jensen, professor and chair of neurology at the University of Pennsylvania Perelman School of Medicine. This has fueled a proliferation of clinical neuroscience research around the role of chemical pollutants and other kinds of environmental threats to the nervous system. The purpose of this workshop, hosted by the National Academies of Sciences, Engineering, and Medicine’s Forum on Neuroscience and Nervous System Disorders on June 25, 2020, was to lay the foundation for future advances in environmental neuroscience, said Jensen (see Box 1-1).

Workshop co-chair Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke, added that the workshop was designed to explore new opportunities to bridge the gap between what is known about the genetic contribution to brain disorders and what is known, and not known, about the contribution of environmental influ-

ences, as well as to discuss what is known about how genetic and environmental factors interact. Noting that the problem spans variable types of environmental influences as well as multiple types of brain conditions, Koroshetz added that the workshop would focus on new technologies that allow previously unapproachable questions to be answered regarding chemicals and particular toxicants and their effects on neurodevelopmental and neurodegenerative conditions.

Held virtually in the shadow of the coronavirus disease 2019 (COVID19) pandemic, the workshop also provided a unique and timely opportunity to discuss how pathogen-driven infections may interact with environmental toxicants. Moreover, behavioral changes in response to COVID-19 that have altered some environmental exposures, such as reducing air pollution in various cities, have provided new research opportunities, said Tracey Woodruff, the Alison S. Carlson Endowed Professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco. Cory-Slechta added that because both COVID-19 and toxic environmental exposures preferentially affect communities of color and low socioeconomic status, issues related to environmental justice must also be considered in discussions of environmental neuroscience.

WORKSHOP OBJECTIVES

A goal of the workshop, said Koroshetz, was to bring the fields of mechanistic and clinical neuroscience closer together with the fields of neurotoxicology and environmental health sciences. By building evidence from observational, population-based, and epidemiological studies and combining that evidence with neurobiological mechanistic studies, scientists from these two fields, working together, may find the central issue of causation. Thus, an aim of the workshop was to discuss a pathway to achieving that goal, said Koroshetz.

The discussions focused on four major themes: (1) What toxicants are of most concern? (2) What is the biology of toxicant interaction with the nervous system? (3) What is known about particular toxicants as drivers of abnormal development or neurodegeneration? and (4) What are the implications of this knowledge for policy and future research, including identifying gaps and opportunities to bridge those gaps? While the impact of neurotoxicants on neuropsychiatric and other neurological disorders is also a critical issue, it was not included in this 1-day workshop in the interest of time.

ORGANIZATION OF THE PROCEEDINGS

The organization of these proceedings reflects the fact that the topics discussed are intimately linked and cannot be discussed in isolation. Thus, Chapter 2 focuses on the neurotoxicants themselves; Chapter 3 considers what is known about how neurotoxicants impact neurological disorders; and Chapter 4 focuses through the lens of these disorders. Research gaps and opportunities are summarized in Chapter 5, and frameworks for moving forward as well as opportunities for multidisciplinary collaboration are discussed in Chapter 6.