March 4, 2019 At the center of contemporary political debate are the record numbers of migrant families and children at the U.S.-Mexico border. As these parents and children flee the trauma of violence in their native countries, they are now experiencing the trauma of navigating an increasingly hostile immigration system. What can neuroscience tell us about the effects of these traumatic experiences on the brains of the children and adults? And how might the neuroscience of trauma and brain development affect legal cases? Can advances in mobile neuroimaging provide practitioners with real-time brain evidence of trauma? Does neuroscience have a larger role to play in shaping our nation’s immigration policies? This panel session brought together scientists and lawyers to start a dialogue on neuroscience, trauma, and justice. This event was free and open to the public. Part of the Project on Law and Applied Neuroscience, a collaboration between the Center for Law, Brain & Behavior at Massachusetts General Hospital and the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School. Learn more on the website: https://petrieflom.law.harvard.edu/events/details/trauma-at-the-border

1. Image by Juliendn
The Effects of Early Life
Adversity on Development:
Implications for Understanding
Trauma at the Border
Charles A. Nelson, Ph.D.
Professor of Pediatrics and Neuroscience,
Professor of Psychiatry in Psychology,
Harvard Medical School
Professor of Education,
Harvard University
Richard David Scott Chair in
Pediatric Developmental Medicine Research
Boston Children’s Hospital
Trauma at the Border, Harvard Law School, 4 March 2019

2. Outline
Summary of Brain Development
The Role of Experience in Brain Development
The Effects of Early Adversity
– Neglect/parent-child separation

3. 15 ½ weeks 22 weeks 23 weeks ~25 weeks
27 weeks Full term brain Adult
Age of viability
Part I: Brain Development
http://medstat.med.utah.edu

4. Summary of Brain Development
Source:
Thompson and
Nelson (2001).
Figure provided
by Heckman
(2013).

5. Part II: The Role of Experience in
Brain Development

6. Factors that Shape Development
Healthy experiences facilitate healthy brain
development; by contrast….
Adverse experiences can negatively impact
brain development.

7. …And timing matters
– Adverse experiences may have different effects depending on the
timing and duration of their exposure
– If a child is exposed to adverse events during a critical period (when
the brain is particularly responsive to experience – generally the first
few years of life; see next slide) OR
– If they move through a critical period without exposure to experiences
they expect to occur (e.g., someone who talks to them, holds them
when they cry, etc.), development can be derailed.
– Thus, early experience matters

8. Motor /
Language
Higher Cognition
Sensory
Birth
environment
critical periodgenes behavior
in utero adulthood
Early Windows of Experience
Shape Brain Function
Hensch, T. K., & Bilimoria, P. M. (2012). Re-opening Windows:
Manipulating Critical Periods for Brain Development. Cerebrum: The
Dana Forum on Brain Science, 2012, 11.

9. A final point about experience
Brain plasticity changes with age; in some
domains change is possible throughout the
life span (e.g., learning and memory),
whereas in others, change is much more
difficult (e.g., we don’t learn to see better).
This is illustrated in the next slide

10. The ability to change the brain
decreases over time
Source: Levitt (2009)
Birth 10 20 30
Physiological “Effort” Required to
Enhance Neural Connections
Normal Brain Plasticity
Influenced by Experience
Age (Years)
40 50 60 70

11. Summary
Early experience matters
Atypical experiences or lack of experiences
(i.e., neglect) during critical periods matters a
lot

12. Part III: Effects of Early Adversity
Some can be healthy
and adaptive
Others can be “toxic” and negatively
impact development

13. Psychosocial adversities
Income
Parental
education
Housing
conditions
Stressful
life events
Parenting
behaviors
Continuum of normal experiences

14. Severe psychosocial adversities
Neglect (emotional and physical)Traumatic events
Parental psychopathology (compromised caregiving)Maltreatment (physical, emotional, sexual)

15. Biological adversities
Malnutrition
(micro and macronutrient deficiencies)
Environmental toxins
(heavy metals, pollutants, toxins)
Infection (systematic and enteric)

16. Developmental trajectory
• Early setbacks
compound social
disadvantage
• Biological
change
embedded
in behavior
Early childhood adversity Biological change Adult outcomes
Genetic variants alter
susceptibility to
specific adversities
(“gene x
environment
interaction”)
• Depriving environments (e.g. poverty,
low quality institutional care)
• Adverse birth outcomes (e.g.
prematurity, SGA, LBW, IUGR)
• Malnutrition (including under- and
overnutrition)
• Infectious and noninfectious
inflammation (e.g. maternal
inflammation, environmental
enteropathy, other infectious
diseases, toxin exposure)
• Psychosocial stressors (e.g.
caregiver insensitivity, exposure
to violence)
Early environment disrupts normal biology:
Sensitive period effects Adversity impacts key domains
most when concurring with
periods of rapid development
Increased risk of:
• Cognitive
deficits (e.g.
lower IQ,
poorer short-
term memory,
semantic
fluency, and
executive
function)
• Mental &
somatic illness
Genetic endowment
Berens, Jensen, & Nelson (2017), BMC Medicine, 15(135): 1-12
Epigenetic
changes
(e.g. DNA & histone
modification causing
altered gene expression;
telomere shortening)
Altered
homeostatic
systems
(e.g. derangements in
microbiome and
metabolic, immune, and
stress regulatory axes)
Excess inflammation
(e.g. due to stress
response dysregulation
during fetal or postnatal
development, or
environmental
enteropathy)
Neurodevelopmental
disruption
(e.g. due to aberrant or
absent stimulation;
disturbed hormonal
or inflammatory
environments)
How to model the biological embedding of adversity

17. World-wide prevalence of early
adversity
• The Centers for Disease Control (US) estimates 1/3rd of the
world’s children <18 years old experience physical or harsh
punishment or abuse
• The United Nations (UN) estimates that at least 133–275
million children globally witness violence between primary
caregivers
• 223 million children are victims of sex trafficking each year.
• 59% of children in developing countries had been victims of
physical, emotional, or sexual violence (excluding corporal
punishment) in the preceding year.
• Finally, if we consider caregiver mental health, depression
represents the leading cause of disease-related disability
globally per World Health Organization (WHO) estimates.

18. Effects of Early Adversity are Long
Lasting
• Increased risk of mental (e.g.,
anxiety and depression) and
physical health (e.g.,
cardiovascular disease; diabetes)
disorders
• It is theoretically possible for
effects to biologically cascade
from one generation to the next
(epigenetic effect)
• The financial and human
capital costs to society are
enormous

19. What happens when children
are neglected/fail to receive
adequate caregiving?
Why neglect is bad for the brain:
– Brain expects input it doesn’t receive, so its
wiring is altered
– Particularly egregious if experiences expected
to occur during a sensitive period fail to occur
(e.g., patterned light, sound, caregiving)

20. Early Institutionalization - A model
system for understanding profound
neglect?

21. Children reared in institutions*…
…are at dramatically increased risk for a variety of cognitive, social, and
behavioral problems:
• disturbances of social relatedness and attachment
• externalizing behavior problems
• inattention/hyperactivity
• deficits in IQ and executive functions
• syndrome that mimics autism
• growth stunting (next slide)
….and these outcomes also apply to children who experience familial
neglect – that is, they are not limited to children experiencing
institutional care
* There are currently 140 million orphans around the world, 8 million of whom are growing up in
institutions

22. Institutionalized children lose ~1 month of linear growth for every ~1 month in an institution
(pictures courtesy of Dana Johnson, MD, Ph.D)
Effects of institutionalization on
growth
17 year old girl 14 year old girl

23. High Level Summary of Behavioral
Findings Through Age 16 Years
Children in institutions:
• Lower IQ
• Reduced language function
• Poorer attachment
• Impairments in executive
functions and peer
relationships
• High rates of psychopathology
(particularly ADHD and acting
out behavior in adolescence)

24. High Level Summary of Behavioral
Findings Through Age 16 Years (con’t)
Children in high quality
foster care:
• higher IQ
• Better language
• Better relationships
• Lower rates of
psychopathology
• BUT….largest benefits
experienced by those
placed <2 years

25. Effects on brain and physiology
EEG
Stress physiology

26. EEG Activity at Baseline
Marshall, Fox, et al (2004) J. of Cog Neuro
IG
NIG
institutionalized
children
never
institutionalized
children

27. 2.44μV2
3.80μV2
CAUG
NIG
FCG < 24
FCG > 24
Does Brain Activity (EEG) Change as a
function of intervention and timing? Age 8
Vanderwert et al (2010) PLoS One

28. Summary
Children in institutional care displayed deficits in
brain electrical activity compared to the children
randomized to foster care intervention (FCG).
Children who received the foster care intervention
continued to show typical levels of brain activity
through age 16.
The age of placement into foster care is associated
with better outcomes; specifically, foster care
placement before 24 months results more robust
improvements in brain activity. Marshall PJ, Fox NA, Bucharest Early Intervention Project Core Group (2004). A comparison of the electroencephalogram between
institutionalized and community children in Romania. Journal of Cognitive Neuroscience, 16, 1327-1338.
Marshall P, Reeb BC, Fox NA, BEIP Core Group (2008). Effects of early intervention on EEG power and coherence in previously
institutionalized children in Romania. Development and Psychopathology. 20, 845-859.
Vanderwert, R.E., Marshall, P.J., Nelson, C.A., Zeanah, C.H., & Fox, N.A. (2010). Timing of intervention affects brain electrical activity
in children exposed to severe psychosocial neglect. PlosONE, , 5(7): 1-5.
Vanderwert R+, Fox NA, Nelson CA, & Zeanah CH (2016). Normalization of EEG activity among previously institutionalized children
placed into foster care: A 12-year follow-up of the Bucharest Early Intervention Project. Developmental Cognitive Neuroscience, 17: 68-
75.

29. Stress response

30. Trier Social Stress Test
• Delivered a speech about what makes a
good friend in front of two teachers they
have never met before
• Record various
Physiological (e.g., heart
Rate) and hormonal
(e.g., cortisol) responses
McLaughlin KA, Sheridan M+, Tibu F, Fox NA, Zeanah CH, & Nelson CA (2015).
Proceedings of the National Academy of Sciences, 112 (8), 5637-5642

31. Cortisol reactivity
0
2
4
6
8
10
12
14
Cortisolnmol/L
CAUG
FCG
NIG
FCG vs
CAUG
t = 2.58, p = .010

32. 0
2
4
6
8
10
12
14
Cortisolnmol/L
< 24
months
> 24
months
Timing of placement (FCG only)

33. Summary
Children placed into foster care <2 years show
normalized stress response; children placed
>2 years show response similar to
institutionalized children

34. Conclusions
• The effects of early adversity (including neglect)
can have far reaching consequences on brain,
biological and psychological development
• As a rule, the earlier in life the adversity begins,
and the longer it lasts, the more profound the
effects.
• If we want to reduce the burden of “disease”
(both physical and psychological) in adults, we
should take steps to address children growing up
in adverse circumstances

35. So how do we translate science to
policy?

36. Implications beyond Romania:
Parent-child separation at US-Mexican border

37. What about the assertion Margaret
Sheridan and I made in the NY Times?
https://www.nytimes.com/2018/05/30/opinion/how-to-turn-
children-into-criminals.html

38. Children with High Callous
Unemotional Traits
Humphreys et al., 2015 Journal of the American
Academy of Child and Adolescent Psychiatry
Girls Boys

39. A View from Above
In this light, there are powerful lessons here for the millions of children
who have experienced maltreatment and forceful/prolonged separation
from parents (for recent news reports see):
PBS News Hour: What we learned from congressional hearing on family separations
USA Today: Despite ban, separating migrant families at the border continues in some
cases
Vox: Hundreds of families are still being separated at the border
PRI: Why is the US still separating migrant families at the border?
HHS Official Says He Would Never Have Supported "Zero Tolerance" Family Separation
Policy
What Are the Long-Term Effects of Separating Immigrant Children from Their Parents?
Google News Roundup on Sexual Abuse of Migrant Youth
HHS docs show thousands of alleged incidents of sexual abuse against
unaccompanied minors in custody
*
Detention center in Texas Romania Orphanage
A little girl at the border being
separated from mother

40. Bottom Line
• Let’s learn from the science
• Let’s inform policy makers, politicians, and clinicians
about the short- and long-term effects of adversity, but
in particular, that…
• Early and prolonged adversity can have life-long effects
on both psychological and physical development
• Duration of time spent in adversity powerfully influences
later development
• Age of child when removed from adverse environment
will influence the outcome
• Forceful separation of children from parents elevates risk
of adverse outcomes – for both children and parents

41. THE END
charles_nelson@harvard.edu