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These documents were presented by Dr. NATHAN A. FOX, UNIVERSITY OF MARYLAND at the session sponsored by The Nippon Foundation, Tokyo, Japan, in the international society for the prevention of child abuse and neglect conference in Nagoya, Japan, on September 14, 2014.

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  2. 2. OUTLINE OF TALK Principles of brain and behavioral development Sensitive periods Using the Bucharest Early Intervention Project to illustrate these principles Implications for policy
  3. 3. 3 Brains are built over time, starting in the earliest years of life. Simple skills come first; more complex skills build on top of them. Brain Architecture Supports Lifelong Learning, Behavior, and Health Cognitive, emotional, and social capabilities are inextricably intertwined throughout the life course. A strong foundation in the early years improves the odds for positive outcomes and a weak foundation increases the odds of later difficulties.
  4. 4. The Ability to Change Brains 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
  5. 5. Neural Circuits are Wired in a Bottom-Up Sequence FIRST YEAR -8-7-6-5-4-3-2-1123456789101112345678910111213141516171819 Birth (Months) (Years) Sensory Pathways (Vision, Hearing) Language Higher Cognitive Function Source: C.A. Nelson (2000)
  6. 6. birth 6 years 14 yearsExperience Shapes Brain Architecture by Over-Production Followed by Pruning(700 synapses formed per second in the early years)
  7. 7. Interaction shapes brain circuitry
  8. 8. 8 Young children naturally reach out for interaction through babbling, facial expressions, and gestures, and adults respond in kind. Serve & Return Builds Brains and Skills These “serve and return" interactions are essential for the development of healthy brain circuits. Therefore, systems that support the quality of relationships in early care settings, communities, and homes also support the development of sturdy brain architecture.
  9. 9. SENSITIVE PERIODS Are limited time periods during which the effect of experience on the brain is particularly strong Allow experience to instruct neural circuits to process information in an adaptive way Provide information that is essential for normal development and may alter performance permanently
  10. 10. Mechanisms of architectural change in the brain that underlie sensitive periods Knudsen, 2004
  11. 11. Lorenz and imprinted ducklings walking after him
  12. 12. Hubel and Weisel: Classic studies on early experience and sensitive periods Monocular deprivation in early infancy led to deficits in brain organization in visual cortex
  13. 13. Effects of unilateral and bilateral deprivation of patterned vision (Lewis & Maurer, 2005) Studies of infants born with bilateral cataracts—timing of surgical removal Daphne Maurer
  14. 14. Early experience establishes the neural substrate for capabilities that emerge at a much later point in development 14 years later children whose cataracts were removed late in infancy were deficient in face processing Sleeper effects as a function of sensitive period input
  15. 15. Janet Werker Effects of experience on perception of language (Werker & Tees, 2005) The timing and nature of experience with language affects perception of different languages Before 9-10 months of age, infants can discriminate the sounds of all languages. By the end of the first year of life, they are only able to discriminate the language(s) they hear in their environment
  16. 16. Werker & Tees (2005) Multiple sensitive periods across development for different domains Most probably there are different sensitive periods for different skills across the first years of life
  17. 17. Sensitive Periods for Integration of Auditory and Visual Information Eric Knudsen studies Barn Owls manipulating their early visual or auditory experience identifying sensitive periods for these inputs
  18. 18. People blind from birth hear language in their visual cortex A sensitive period for language in the visual cortex: Distinct patterns of plasticity in congenitally versus late blind adults Marina Bedny
  19. 19. (Hensch, 2005) Can we reopen sensitive periods in the visual system? The answer appears to be yes!! Takao Hensch
  20. 20. GENERAL CONCLUSIONS ABOUT SENSITIVE PERIODS Collectively, in most cases sensory/perceptual development proceed normally if such systems are “set”correctly during a sensitive period of development—(e.g. Hubel and Wiesel) There is also evidence for sensitive periods in specific domains of language and perception The human brain “expects” certain types of input at particular times in development. It is not clear what aspects of cognitive or social and emotional development require experience at particular (e.g., sensitive) points in time. Inferences drawn from intervention studies suggest some advantage to early experience.
  21. 21. The Bucharest Early Intervention Project seeks to: •Examine the effects of psychosocial deprivation on brain and behavioral development of young children •Determine if these effects can be remediated through intervention, in this case: foster care •Examine the issue of timing of intervention or duration of deprivation and its effects on brain and behavior with an eye towards identifying sensitive periods in cognitive and social development
  22. 22. Project Background
  23. 23. CEAUSESCU’S LEGACY TO ROMANIA Communist Policy:1966 decree •Raise production by increasing population •Establishment of the MENSTRUAL POLICE -state gynecologists who conducted monthly checks of women of childbearing age who had not borne at least 5 children •Establishment of CELIBACY TAX - families received a stipend for having more than 2 children; were levied tax for having fewer than 5 children •OUTLAWED all contraception and abortion
  24. 24. •Child abandonment became a national disaster, as families could not afford to keep their children, and were encouraged to turn them over to the state. This destroyed the family unit and led to thousands of children being raised in institutions. THE RESULTS OF CEAUSESCU’S 1966 POLICY
  25. 25. •Poverty #1 reason for child abandonment •International media brought the plight of these children to the attention of the world •Large numbers of children adopted internationally, often by Western families unprepared for challenges that lay ahead •And then, Romania banned international adoption 1989: The fall of the Ceausescu regimeThe aftermath…. 100,000 children “warehoused”in state institutions
  26. 26. The Study
  27. 27. 1 2 6 3 4 5 Institutional Group FCG n=68 NIG n=72 CAUG n=68 After baseline assessment (pre-group assignment), comprehensive follow up performed at 30, 42, 54 months, 8 and 12 years BEIP Study design
  28. 28. DOMAINS OF ASSESSMENT IN BEIP •Physical Development •Language•Cognition•Language•Brain Function •Emotional reactivity •Caregiving Environment•Attachment •Social competence •Mental Health Problems •Genetics *Data derived from measures listed in boldand underlined will be discussed in this talk
  30. 30. BEIP FOSTER CARE Goal was to have foster care that was: •Effective •Affordable •Replicable •Culturally sensitive •Informed by latest clinical and research findings
  31. 31. THE FOSTER CARE TEAM –BEIP Comprised 3 social workers Match families and children Preparation of applications for foster care Appearances before the Commission Supervision of visits with biological family Management of challenging child behavior Permanency planning
  32. 32. –BUCHARESTSUPPORT SERVICES TO FOSTER PARENTS Caseload of 18-20 families Visits to foster parents every 10 –15 days •Intensive phone contact •Inquiry regarding child behavior/adjustment Foster Parent Support Group •Education/Support Supplies •Cribs, car seats, diapers, clothing
  33. 33. GENERAL HYPOTHESES OF THE BEIP STUDY •Institutional rearing will have profound effects upon children’s socio-emotional development •Removing children from the institution and placing them in family environments will remediate some of these deficits. •The age or timing of placement into foster care will be a significant factor explaining intervention effects (thought this may vary by domain)
  35. 35. COGNITIVE DEVELOPMENT (AT BASELINE) Smyke et al (2007)
  36. 36. IQ Scores of Foster Care and Institutionalized Groups at Follow-up Nelson et al (2007)
  37. 37. How does IQ differ for children in foster care as a function of age of placement? Age at placement 70 75 80 85 90 95 0-18 18-24 24-30 30+ DQ/IQ N 0-18 14 18-24 16 24-30 22 30+ 9 * Nelson, et al (2007)
  38. 38. CHANGE IN GROUP ASSIGNMENT OVER TIME/SUBJECT ATTRITION (AS OF 96 MONTHS) Randomized (n=136) Assessed for Eligibility (n=187) Excluded (n=51) Allocated to Foster Care (n=68) Allocated to Care as Usual (n=68) Placement at 96 months (n=60) -31 MacArthur Foster Care -7 adopted -8 Government Foster Care -12 Returned to Bio Family -2 Social Apartments Discontinued Participation (n=8) Placement at 96 months (n=56) -15 Institutional Care -4 adopted -18 Government Foster Care -18 Returned to Bio Family -1 Family Placement Discontinued Participation (n=12) Analyzed (n=53) Excluded from analysis (n=7) -WISC data not available Analyzed (n=50) Excluded from analysis (n=6) -WISC data not available Participation Analysis Allocation Enrollment
  39. 39. WISC DATA AT 96 MONTHS OF AGE 70 72 74 76 78 80 82 84 86 88 90 Verbal Perceptual Working Memory Processing Speed Full Scale IQ CAU (n=41) FCG (n=48) * Note: *p = .05 Fox et al (2011) JCPP
  40. 40. COMPARING CURRENT PLACEMENT IN INSTITUTIONS, GOVERNMENT FOSTER CARE AND MACARTHUR FOSTER CARE 0 20 40 60 80 100 V PR WM PS FSIQ Institution (n=12) Gov't FC (n=23) Mac FC (n=28) Note: V = Verbal Comprehension, P = Perceptual, WM = Working Memory, PS = Processing Speed, FSIQ = Full Scale IQ; *p < .05, **p < .01. * * ** * Fox et al (2011) JCPP
  41. 41. 0 20 40 60 80 100 120 VCI PRI WMI PSI Full IQ CAUG FCG 12-YEAR IQ COMPOSITESBY GROUP * ** * p<.05, **p<.01
  42. 42. INTERIM SUMMARY: IQ Young children living in institutions show significant delays in IQ Removal from institutions, particularly prior to 24 months of age, and placement into families remediates IQ deficits Stability of family placement over age is an important factor in IQ outcomes Remarkably, 10 years after the intervention began there are still positive effects on IQ
  43. 43. LANGUAGE
  45. 45. UTTERANCE LENGTH (42 MONTHS) 0 2 4 6 8 10 IG FCG>24 FCG<24 NIG Mean length of utterance words morphemes
  46. 46. -2 -1.5 -1 -0.5 0 z score Reading (8years) (Single word identification) IG (N=47) FCG>24 (N=31) FCG<24 (N=24) This figure includes all children, assigning a zero score to (mainly IG) children who could not read.
  47. 47. INTERIM SUMMARY: LANGUAGE Young children living in institutions have significant delays in expression and receptive language Removal from institutions, particularly before 24 months of age, is associated with remediation of language These effects continue through age 8.
  48. 48. BRAIN ACTIVITY-EEG Beta 10-18 Hz Alpha 6-9 Hz Theta 3-5 Hz Delta <3 Hz CAT CAT CAT Cat cat CAT CAT CAT Cat
  49. 49. INSTITUTIONALIZATION & BRAIN ACTIVITY Institution Community Proportion 0.58 0.46 Theta, 3-5 Hz McLaughlin et al, 2010, Biological Psychiatry Marshall, Fox, and BEIP (2007)
  50. 50. INSTITUTIONALIZATION & BRAIN ACTIVITY Institution Community Alpha, 6-9 Hz McLaughlin et al, 2010, Biological Psychiatry Proportion 0.58 0.46 Marshall, Fox & BEIP group (2007)
  51. 51. 2.44μV2 3.80μV2 Brain Activity (EEG) Changes as a function of intervention and timing (8 years of age) CAUG FCG > 24 NIG FCG < 24 Vanderwert et al (2010)
  52. 52. BRAINEFFECTS OF EARLY PSYCHOSOCIAL DEPRIVATION Initial reports on post institutionalizedchildren reported reduced metabolic activity in temporal and frontal cortex; In one study Tottenham et al. show enlarged amygdala volumes, whereas Hanson/Pollak et al. show smaller amygdala volume. In both cases, however, must keep in mind potential for sample bias.
  53. 53. Magnetic Resonance Imaging (MRI)
  54. 54. STRUCTURAL MRI Performed in Bucharest on 1.5T Siemens machine DTI also obtained on 80% of the children
  55. 55. STRUCTURAL MRI •FreeSurferused to automatically detect grey/white matter borders and identify: –Total grey matter –Total white matter –Hippocampus –Amygdala –Basal ganglia : caudate, putamen, globuspallidus, nucleus accumbens –Corpus callosum andsubdivisions –Thalamus Sheridan et al, (2012) PNAS
  56. 56. TOTAL CORTICAL GREY MATTER * IG B= -39.9, t= -3.01, p= .004 FCG B= -38.5, t= -2.79, p= .007 Regression controlling for age and gender * Sheridan et al (2012), PNAS
  57. 57. TOTAL CORTICAL WHITE MATTER * IG B= -24.1, t= -2.17, p= .03 FCG B= -18.1, t= -1.5, p= .12 Regression controlling for age and gender n.s. Sheridan et al (2012), PNAS)
  58. 58. a + t = 1.8, p = .06 b * t = 2.9, p = .005 d + t = 1.9, p=.06 e n.s. t = 1.4, p = 15 c + t = 1.9, p = .06 Regression Analysis: Group, Age, Gender
  59. 59. INSTITUTIONALIZATION & NEURAL STRUCTURE •Institutionalization associated with: •Total grey matter * •Total white matter* •Hippocampus •Amygdala •Basal ganglia: caudate, putamen, globus pallidus, nucleus accumbens •Corpus callosum* •Thalamus
  60. 60. MRISUMMARY Dramatic reduction in grey and white matter among ever institutionalized children No intervention effect for grey matter Possible (modest) intervention effect for white matter
  61. 61. STRUCTURE AND FUNCTION •Associations between institutionalization and reductions in alpha power are fully mediated by white matter integrity •White matter variation in typical adults accounts for individual differences in EEG alpha power1 •Damage to white matter results in decreases in EEG alpha power2 1. Valdés-Hernández et al., 2010; 2. Claudio Babiloni et al., 2006
  63. 63. INCIDENCE OF MENTAL HEALTH PROBLEMS The caregiver was administered the Romanian version of the Preschool Age Psychiatric Assessment (Romanian PAPA) when the children in the BEIP were 54 months old The PAPA is a comprehensive structured psychiatric interview assessing mental health symptoms and disorders in children ages 2 through 5 years old
  64. 64. PREVALENCE OF ADHD IN THE BEIP STUDY 0 5 10 15 20 25 Institution Foster Care Community Prevalence of ADHD (Zeanah et al 2009)
  65. 65. Intervention Effects on Internalizing Disorders * 0 10 20 30 40 50 60 CAU FC CAU FC Girls Boys Prevalence of Internalizing Disorders WHITEW WHITEW
  66. 66. SUMMARY OF FINDINGS ON PSYCHIATRIC DISORDERS In general, children raised in institutions display greater internalizing and externalizing disorders compared to community controls. But children removed from institutions and placed into foster care homes display significantly less internalizing problems compared to those randomized to remain in the institution. •This was particularly true for girls There was no intervention effect for externalizing problems— specifically ADHD
  67. 67. INTERIM SUMMARY Early exposure to severe psychosocial deprivation is associated with higher slow wave and lower high frequency EEG activity and heightened internalizing and externalizing problems Foster care intervention (particularly if it occurs early in life) remediates this pattern of EEG activity and internalizing problems. It does not remediate externalizing problems— specifically ADHD EEG activity early in life is associated with lower internalizing problems and mediates the relation between early experience and later problems with ADHD
  68. 68. ATTACHMENT
  70. 70. BEIP: SSP CLASSIFICATIONS Community •76.7% secure •3.6% avoidant •0.0% resistant •19.7% disorganized •0.0% unclassifiable Institution •16.8% secure •4.7% avoidant •0.0% resistant •65.4% disorganized •13.1% unclassifiable Zeanah, et al 2005
  71. 71. CONTINUUM OF ATTACHMENT 5 --ABCD patterns of attachment 4 --Patterns of attachment with behavioral anomalies 3 --Clear preference but passive 2 --Preference discernible 1 --No attachment behaviors evident
  72. 72. DEGREE TO WHICH CHILDREN LIVING IN INSTITUTIONS HAVE FORMED ATTACHMENTS TO THEIR CAREGIVERS Romanian Community Romanian Institution 1=No attachment 0% 9.5% 2=Some differentiation 0% 25.3% 3=Some preference 0% 30.5% 4=Attachment with anomalies 0% 31.6% 5=Clearly recognizable attachment patterns 100% 3.2% Zeanah et al (2005)
  73. 73. Intervention Effects at 42 Months
  75. 75. Security of attachment as a function of age of entry
  76. 76. SUMMARY OF SSP FINDINGS Large differences at baseline IG vs. NIG •Security •Organization •Large intervention effects, but incomplete recovery Timing effects on security and organization •More children secure if placed before 22-24 months •More children organized earlier they were placed
  77. 77. STRANGER AT THE DOOR Caregiver/mother and child answer door (pre-arranged). RA: “Come with me, I have something to show you.” Walk out the door and around the corner to find RA from previous home visit.
  78. 78. STRANGER AT THE DOOR 54 MONTHS Gleason et al (2013)
  79. 79. EFFECTS ON TIMING OF PLACEMENT ON INDISCRIMINATE BEHAVIOR Children placed into families before 24 months of age showed absence of indiscriminate behavior across follow-up
  80. 80. DOMAINS WITH SENSITIVE PERIOD IQ Attachment EEG power Social skills (teacher report) Indiscriminate behavior DOMAINS WITH NO SENSITIVE PERIOD (BUT INTERVENTION EFFECTS) Psychiatric outcomes (anxiety) Positive emotional reactivity Peer social competence
  81. 81. DOMAINS SEEMINGLY UNAFFECTED BY EARLY ADVERSITY Face processing Emotion recognition Face recognition DOMAINS UNAFFECTED BY INTERVENTION Externalizing problems Executive function
  82. 82. SENSITIVE PERIODS AND BEIP Both language and EEG activity show sensitive periods in development Cognition (IQ) does not but does show an intervention effect even 10 years after the start of the intervention. Early experience affects different domains and intervention has differential effects depending on timing
  83. 83. OVERALLCONCLUSIONS Children raised in institutions during early development demonstrate significantly impaired physical, cognitive, language, social-emotional, and brain development compared to community children. •Here we demonstrate specific cognitive deficits and neural neural compromises that may be associated with these deficits Insofar as we have been able to look at our data, our model of foster care as an intervention appears to effectively ameliorate many of the negative sequelae of institutionalization… Although not all…for example, we are seeing only small effects on executive functions….and only at 12 years of age Some aspects of brain development (i.e. certain white matter tracts) are remediated in children placed into foster care, whereas others are not (i.e. total gray matter, certain white matter tracts)
  84. 84. IMPLICATIONS FOR POLICY Brains develop as a function of expected environmental experience In the absence of expected experience brain and behavioral develop are derailed Children living in conditions of neglect are likely to suffer from the absence of stimulation (warm, responsive, contingent interaction) Removing children from conditions of neglect (and the earlier the better) is good for their brain development and good for their behavioral development
  85. 85. INVESTIGATIVE TEAM Principal Investigators Charles Zeanah, MD, Tulane University Nathan A. Fox, Ph.D., University of Maryland Charles A. Nelson, Ph.D., Harvard Medical School/Children’s Hospital Boston Funding: •John D. and Catherine T. Macarthur Foundation •NIMH MH091363-01