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Neuropsychology of Children Exposed to Heavy Metals
Assessment and Intervention to ImproveExecutive Functions
Neander AbreuProfessor- Instituto de Psicologia – Universidade Federal da Bahia
- BrazilChrissie Carvalho
Posdoctoral Fellow – Psychology Department – Harvard University 1
Outline
Neuropsychological effects in
children exposed to Mn in Brazil
A program to stimulate Executive
Functioning in school-aged children: Heroes
of Mind - WORKSHOP
Vulnerability, Risk factors and
Executive Functions development
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Executive Functions and Life-Span Effects
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THAT’S WHAT EF ARE FORHigh order cognitive functions that controlautomatisms.
Goal directed behavior background
They may control attention, automatic reactions (in novelty contexts), planning and problem-solving
Working memory
Monitoring
Flexibility
InhibitionPlanning
Thinking and Action Regulation
Common Mecanism
EXECUTIVE FUNCTIONS
Diamond (2013)•Based on Structural equation modeling for
factorial analysis – Myiake•Core functions: working memory, cognitive
flexibility and inhibition control•Does not exclude other FE dimensions: planning,
thinking (high order)
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WHO SEEKS TO IMPROVE?
People with CNS Disorders• Developing specific and general cognition• Rehabilitation
Typical individuals wiht cognitive difficulties• Looks for stimulation (e.g. math, attention)• Looking for “acceleration” in specific domains
Typical individual looking for a better performance• Better results .• To avoid ou postpone ageing effects
EF AND LIFE-SPANA better mental capital mental
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EXECUTIVE FUNCTIONS
AND LIFE SPANDeficits and
Improvement
• Higher vulnerabilty• Social and educational problems• Sensibility to training• Better results
• OBESITY AND IMPULSIVITY• JOBS AND RELATIONSHIPS AT WORK
CONTEXT• ACADEMIC RESULTS• MARRIAGE AND DIVORCE• VIOLENCE• DECISION KMAKING
EXECUTIVE FUNCTIONS
Emmerges at first-year of age
Develops until end of adolescence.
Affected in a wide range of mental/CNS disorders.
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CORE EXECUTIVE FUNCTIONS
Working Memory
VERBAL WM
NON-VERBAL WM
INHIBITORY CONTROL
CONTROL over externaland internal influences, and prepotent response
Aimed and non-aimedbehaviors
COGNITIVE FLEXIBILITY
Working Memory: mental representation of cognitive
process.
High Complexity Executive Functions
Thinking Problem Solving Planning
Working Memory
Inhibition Control Cognitive
Flexibility
FLUID INTELLIGENCE
EF AND LIFE-SPANA better mental capital mental
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EXECUTIVE FUNCTIONS
AND LIFE SPANDeficits and
Improvement
• Higher vulnerabilty• Social and educational problems• Sensibility to training• Better results
• OBESITY AND IMPULSIVITY• JOBS AND RELATIONSHIPS AT WORK
CONTEXT• ACADEMIC RESULTS• MARRIAGE AND DIVORCE• VIOLENCE• DECISION KMAKING
Neuropsychological effects in children exposed to Mn
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Manganese and Child Neurodevelopment
Mn
Intelligence• Total IQ• Verbal IQ• Executive IQ
(Bouchard et al., 2011, 2018; Haynes et al., 2015; Menezes-Filho et al., 2011; Rahman et al., 2017; Riojas-Rodríguez et al., 2010; Wasserman et al., 2006)
Memory
Attention(Bhang et al., 2013; Carvalho et al., 2014; Ericson et al., 2007; Oulhote et al., 2014; Takser et al., 2003)
(Oulhote et al., 2014; Takser et al., 2003; Torres-Agustínet al., 2012; Wasserman et al., 2011; Woolf et al., 2002; Wright et al., 2006; Carvalho et al.,2018)
Behavior and Hyperactivity
(Bouchard et al., 2007; Farias et al., 2010; G et al., 1995; He et al., 1994; Khan et al., 2011; Menezes-Filho et al., 2014; Shin et al., 2015; Rodrigues et al., 2018).
School Achievement
Motor development
(Bhang et al., 2013; Khan et al., 2012)
(Henn et al., 2010; Hernández-Bonilla et al., 2011; Lucchini et al., 2012; Oulhote et al., 2014)
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20Menezes-Filho et al. 2011
Environmental exposure to Manganese in Bahia
Environmental exposure to Manganese in Bahia
Vila de Cotegipe – Simoes-Filho• Children’s MnH was negatively related to:– Full-Scale Intelligence Quotient (IQ) -5.78– Verbal IQ -6.72
• Maternal MnH was negatively associated with performance on the Raven’s
21Menezes-Filho et al. 2009, 2011.
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Brazil – State of Bahia – Environmental Exposure to Mn
José Antonio Menezes-Filho
Neander Abreu
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23Carvalho et al. 2014, Neurotoxicology
• Combining the results • 617 children from studies in
Mexico, Brazil and Canada.• Decrease in total IQ of 2.62
points for each increase of 10 units MnH µg/g
(Roels et al., 2012)
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Carvalho et al. 2014, Neurotoxicology
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Carvalho et al. 2014, Neurotoxicology
Third tertile (higher levels of Mn)• Vocabulary• Visual Organization (EF)• Working Memory• Immediate visual memory
Sustained Attention• Commission errors – percentile <2
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Menezes-Filho et al. 2014, Neurotoxicology
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Inhibition:Inhibitory Control
Flexibility
InstrumentsNEPSY-II: Inhibition, word generation and List Memory .Grooved Pegboard Test (motor function) Conners Abbreviated Scale (answerd by teachers)
28Carvalho et al. 2018, Neurotoxicology
Results
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Associations with Mn in the hair:
• Verbal memory and learning
• Free Recall after Interference
• Delayed Effect
• Hiperactivity (Conners)
• Higher frequency of hyperactivitybehavior
Carvalho et al. 2018, Neurotoxicology
SEX DIFFERENCES
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Higher concentrations of MnH in boys were stronger associated with poor performance to recall words after the presentation of a new content
In girls higher concentrations of MnHwere associated to the Delay Effect, representing a higher rate of forgetting.
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Dispersion of pollutants from industrial activity and effects on the behavior of school children from the municipality of Simões Filho, Bahia.
Mn biomarkers• blood• Hair (1–2 months)• toenails (7–12 months)245 children225 biomarkers samples7-12 years old
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• The CBCL Total score correlated only with the Community Violence Score (ρ=0.265, p=0.024).
• Each ten-fold increase in Mn concentrations measured in toenail, reflects 10.2 point increase in the total score of behavioral problems in children.
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GAM MnTn concentration was significantly associated with: • the total score of behavioral
problems, • externalizing behavior, aggressive
behavior, rule breaking, thought problems and social problems.
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WHAT ARE THE FUNCTIONS TO INCLUDE
IN A NEUROPSYCHOLOGICAL
ASSESSMENT IN THIS CONTEXT?
SummaryMn
Attention and Inhibitory Control
Memory and learning;Working Memory
(Bhang et al., 2013; Carvalho et al., 2014; Ericson et al., 2007; Oulhote et al., 2014; Takser et al., 2003)
(Oulhote et al., 2014; Takser et al., 2003; Torres-Agustínet al., 2012; Wasserman et al., 2011; Woolf et al., 2002; Wright et al., 2006)
Behavior problems and hyperactivity
(Bouchard et al., 2007; Farias et al., 2010; G et al., 1995; He et al., 1994; Khan et al., 2011; Menezes-Filho et al., 2014; Shin et al., 2015)
Motor function
(Henn et al., 2010; Hernández-Bonilla et al., 2011; Lucchini et al., 2012; Oulhote et al., 2014)
Commission errors in sustained attention
• Less recall and interference effect children with higher levels of MnH
• Higher levels showed worse scores in verbal WM
No association
Positive association with Hair Mn: • CBLC - Total Score, attention and Externalizing behavior and
Conners - Hiperactivity• Girls – higher frequency of behavior problemPositive association with Tn Mn: • Total score of behavioral problems, • externalizing behavior and thought problems and social
problems.
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Intelligence• Negative association with IQ• Co-exposure with Pb is worse for
higher levels
VULNERABILITY, RISK FACTORS AND EXECUTIVE FUNCTIONS DEVELOPMENT
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This is John
Single parent Home
and low education
Bad quality of
education
Environmental
Exposure
Violence
Problems are increased in vulnerable and low
socioecomic environments
(Williford and Shelton, 2008).
Poverty – Threat and Deprivation
Sheridan e McLaughlin (2016)
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Schibli, Wong, Hedayati & D’Angiulli (2017), Ann. N. Y. Acad. Sci.
Bifurcated developmental trajectory (BiDeT) framework
Schibli, Wong, Hedayati & D’Angiulli (2017), Ann. N. Y. Acad. Sci.
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How cognitive training can influence thetrajectory of development?
Jolles & Crone, 2012
Programs that promote Executive Functions and Self-Regulation
Lynn Meltzer, 2010
Sarilhos do Amarelo– Self-regulation– Storytelling and
reflection – organizing,
imagination, reasoning and comprehension.
Rosário, Nuñes e González-Pienda, 2007
ClassroomTeaching strategies
Dawson e Guare, 2010Teaching strategies
• Pre-school• Tools of the Mind – Executive Function and Self-Regulation Curriculum(Blair & Raver, 2014; Bodrova & Leong, 2001; Diamond, Barnett, Thomas, & Munro, 2007)
• PATHS – Socio and Emotional Competence(Arda & Ocak, 2012; Domitrovich, Cortes, & Greenberg, 2007)
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ELEVATED AIRBORNE MANGANESE AND THE PROMOTION OF EXECUTIVE FUNCTIONING IN SCHOOL-AGED CHILDREN
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Objective
To develop and implement a School Program to promote Executive Function in children chronic exposed to airborne Mn.
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The Curricula Program – 7-10 years old
• Comic Book with 6 Stories.• Four specific modules.
• Clear instructions and goals to beimplemented by teachers in theclassroom.
• 42 activities including:• card games• pencil and paper activities• Thinking strategies
Carvalho & Abreu, (in prep.)
The Intervention Program: Heroes of the Mind
1. Organizing and Planning
• Daily schedule
• Learning to make plans
• Calendar support
• Time Management
• Organizing space and ideas
2. Attention, Inhibitory control and Cognitive flexibility
• Tasks requiring cognitive flexibility to switch
between a rule and another: spell words, mimic
play and solving problem (alternative answers).
• Exploring sentences and ambiguous words.
• Categorization.
3. Working Memory
• Self-checking
• Add rules to known games and try to
keep the information.
• Remembering activities with calendar
support
• Play memories games with
interference.
4. Emotions and Self-regulation• Identification and expression of emotions
• Use photos and body games to express
emotions.
• Prosocial behavior and empathy.
• Self-regulation strategies
Metacognition and self-monitoringHeroes of the Mind
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Planning
Inhibitory and Flexibility Card Game
Self-Regulation
What is missing?Working Memory Game
Say the namesRemember
Check-List and monitoring
Pre – Post test Design Study.
Mn - Control Regular Curriculum27 children (8,3 ±1.3 YO)
Mn – Intervention19 children (7,9 ±1.4 YO)
Typical development –Intervention17 children (9,4 ±0.5 YO)
EnvironmentalExposure to Manganese
Sociovulnerable Children – Public Schools
No history of exposure
May - August
July - September
Pre-test
Neuropsychological Assessment
Group 1
Group 2
Group 3
Post-test
9 months – 12 months
• Nuclear EF• Working Memory• Inhibitory Control• Flexibility
• Higher EF• Verbal Fluency• Decision Making
• Attention• Intelligence
Environmental Exposure in Schools
SchoolControl Group 1
SchoolIntervention Group 2
Samplers were set mid July and collected mid August/2015
SchoolIntervention without history of exposed to manganeseGroup 3
SchoolControl Group 1
SchoolIntervention Group 2
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Results – Intelligence
Decrease in Control Mn Group52
Raven's Coloured Progressive Matrices
Intelligence - Raven
Nuclear Executive Function: Working Memory
Visual:Significant improvement of
Experimental Mn Group.
Post-test: reach same levels as
typical Group 53
Verbal: Significant improvement of Experimental
Mn Group (Effect size higher)
Improvement of Control-Mn (Effect size
medium)Carvalho & Abreu, (in prep.)
Nuclear Executive Function: Inhibitory Control and Cognitive Flexibility
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Experimental typical:
improvement in speed processing in
both.
Experimental-Mn:Less errors in both
and higher ES.
Control Group-Mn:only marginal effects
and ES smaller.
Carvalho & Abreu, (in prep.)
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Higher level Executive Function: Verbal Fluency and Decision Making
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Experimental-Mn(higher ES)
Only Experimental-Typical improve significantly
Performance close to typical
Advantageous Choices Minus Disadvantageous Choices (CGT)
Carvalho & Abreu, (in prep.)
Results – Attention
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Experimental-Mn improved moreNarrow the gap
Sustained Attention: No differences between groups.
Carvalho & Abreu, (in prep.)
Conclusions
• OnlyMn control children decreased in Fluid intelligence .
• Improvement in nuclear and higher EF in children fromHeroes ofMind Program.
• Results are consistent with studies using interventions basedschool curriculum (Blair & Raver, 2014; Bodrova & Leong, 2001;Dias & Seabra, 2013; Domitrovich et al., 2007; Meltzer, 2010)
• Improvement in tasks that demands more EF, for instanceflexibility (Diamond et al., 2007; Dias & Seabra, 2015).
• Vulnerable children benefit more from intervention (Diamond &Ling, 2016). Decreasing in the neurodevelopment gap betweenthe exposed group and typical children.
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Neander Abreu [email protected]
Chrissie [email protected]
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Interdisciplinary Lab of HumanNeurodevelopment (LINHA)
UCSAL - Brazil
Harvard Lab for Developmental Studies
Research Lab of Clinical and Cognitive Neuropsychology - UFBA