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Neurobehavioral Patterns Across the
Spectrum in FASD
Dr. Ana Hanlon-Dearman
Developmental Pediatrician
Clinic for Alcohol and Drug Exposed Children
Assistant Professor Pediatrics and Child Health
University of Manitoba
Winnipeg, MB
September 2007
Clinic for Alcohol and Drug
Exposed Children
Goals of Session:
 Brain: To review current research on anatomic and
neurotransmitter correlates of brain function
 Behavior: To describe at neurodevelopmental
correlates of brain function in FASD
 Across the spectrum
 Over time
 Promising questions for future research
September 2007
Clinic for Alcohol and Drug
Exposed Children
Brain in FASD
• Integration of molecular, cellular,
chemical, anatomic, and behavioral
research
September 2007
Clinic for Alcohol and Drug
Exposed Children
Brain plasticity and neurodevelopment
• Traditionally:
– fixed number of adult
neurons
– synaptogenesis
– neurotransmitter
functions (receptors,
release of
neurochemicals)
http://www.utexas.edu/research/asrec/synapse_m.html
September 2007
Clinic for Alcohol and Drug
Exposed Children
Novel processes of neuronal development
Neural Stem cells
Mood
Neurogenesis
Learning
Sensory Processing
Memory
Behavior
September 2007
Clinic for Alcohol and Drug
Exposed Children
Alcohol and neuronal development
• Does alcohol exposure affect neuronal
development?
• Could this damage be repaired?
September 2007
Clinic for Alcohol and Drug
Exposed Children
Alcohol and regulation of neurogenesis
• Genetics influences responses to alcohol
• Environment affects plasticity
Alcohol
Genetics
Stress
Environment
September 2007
Clinic for Alcohol and Drug
Exposed Children
Alcohol
Physiology and Function
Cognitive Function
Sensory regulation
Neurotransmitters
Growth Factors
Motor function
September 2007
?Circadian regulation
Clinic for Alcohol and Drug
Exposed Children
What does that mean over the
spectrum?
• Fetal neural stem cells are highly
susceptible to alcohol toxicity (Luo and Miller.
1998)
• Alcohol affects neurogenesis in high doses,
as well as moderate chronic doses
September 2007
Clinic for Alcohol and Drug
Exposed Children
With this in mind…
• Discuss our clinical research into
– specific manifestations of alcohol toxicity
on learning structures and their function
– alcohol effects on circadian rhythm and
sleep
– neurodevelopmental functions over time
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Clinic for Alcohol and Drug
Exposed Children
What is the neurodevelopmental
spectrum of alcohol effects?
FASD
September 2007
•
•
•
•
•
•
•
Language
Executive function
Attention
Memory
Visual spatial skills
Motor coordination
Cognitive
processing
Clinic for Alcohol and Drug
Exposed Children
Attention
Sensorimotor
Language
Executive Function
Structural
malformation
Memory
Cognitive Function
Academic Achievement
Adaptive
September 2007
Clinic for Alcohol and Drug
Exposed Children
Some of our questions…
• Can we define specific learning impairments?
• Can we define specific sensory impairments?
• What about ARND?
• What happens over time?
September 2007
Clinic for Alcohol and Drug
Exposed Children
Learning…
September 2007
Clinic for Alcohol and Drug
Exposed Children
September 2007
Clinic for Alcohol and Drug
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encoding
Working Memory
retrieval
retaining
Central Executive
Visual + spatial
Phonological
Episodic buffer
September 2007
Clinic for Alcohol and Drug
Exposed Children
Participants
Methods
• 14 children with
FASD:
– FAS
n=3
– pFAS n=6
– ARND n=5
• 10 adults with
FASD:
• N-back test
• Self-ordered pointing
task (SOPT)
• Continuous
Performance Test
• Wisconsin Card Sorting
Task
– FAS
n=3
– pFAS n=1
– ARND n=6
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Clinic for Alcohol and Drug
Exposed Children
N back task
N=0
N=1
N=2
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Clinic for Alcohol and Drug
Exposed Children
Results: Mean scores in each n-back task
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Clinic for Alcohol and Drug
Exposed Children
Results: 1 Back minus Simple -- 11 year
old children
FAS
pFAS
Control
September 2007
Clinic for Alcohol and Drug
Exposed Children
Results: 11 year old children
• FASD:
• Controls:
– Increased functional
activation in inferiormiddle frontal and orbital
gyrus
– Greater activation in
cingulate cortex in
inferior slices
– Greater activation in
cingulate and frontal
areas in superior slices
– Greater parietal activity
– Increased frontal lobe
activity with increasing
task difficulty
– Decreased frontal lobe
activity with increasing
task difficulty
September 2007
Clinic for Alcohol and Drug
Exposed Children
Results: One Back minus Simple Task
26 y ARND
25 y FAS
26 y Control
September 2007
Clinic for Alcohol and Drug
Exposed Children
Results: Adults
• Adults with FASD showed greater orbital and inferiormiddle frontal activation during blank test
• In general, trend toward greater brain activity with
increased task difficulty
• Greater parietal and frontal activations with
increasing task difficulty in both FASD and control
(FASD<control)
• Pattern less consistent in adults
September 2007
Clinic for Alcohol and Drug
Exposed Children
Conclusions:
• FASD:
– dysfunction in prefrontal areas
– ?decreased parietal function relative to
controls (link to accuracy and effort)
– Activation in cingulate (link to affective behaviors,
executive function)
Impairment in spatial working memory
– Independent of cognitive and response
inhibition
September 2007
Clinic for Alcohol and Drug
Exposed Children
Sensory….
September 2007
Clinic for Alcohol and Drug
Exposed Children
Sleep Characteristics of Young Alcohol
Affected Children: A Quantitative and
Qualitative Study
A. Hanlon-Dearman, CADEC Team
September 2007
Clinic for Alcohol and Drug
Exposed Children
I used to hear him constantly, just moving
all the time…he would mumble and whine
or whatever but nothing that I could make
out. That’s if he wasn’t waking up crying or
screaming…anywhere from once to two to
three times per night. (Interview #1)
September 2007
Clinic for Alcohol and Drug
Exposed Children
Methods:
• N=9 children
• household matched controls
• Tools:
– actigraphy and sleep log
– sleep questionnaire
– interviews
September 2007
Clinic for Alcohol and Drug
Exposed Children
Actigraphy results:
repeated measures ANOVA FASD vs Controls
Sleep episodes
(number)
21.1+/-0.8
19.0 +/0.9
5.63
0.0214
*Significant
Wake Episodes
(number)
21.3+/-0.8
19.2+/-0.9
5.40
0.0241
*Significant
Mean Duration
Wake Episodes
(min)
6.9+/-0.4
8.2+/-0.4
7.81
0.0072
*Significant
September 2007
Clinic for Alcohol and Drug
Exposed Children
Questionnaire results
• FASD sleep related concerns OR 35.29 (p=0.009)
– Talking (44%)
– Difficulty settling (33%)
– Daytime fatigue (11%)
• Nightime wakenings: 23 times more likely to wake
related to own movements (OR 23.22 p=0.0294)
• Daytime behavior concerns: hyperactivity OR 3.0
(p=0.009)
September 2007
Clinic for Alcohol and Drug
Exposed Children
Conclusions
• First objective study of sleep characteristics in FASD
children
• Confirms significantly disrupted nighttime sleep
– Increased frequency and length of night wakenings
• Parental report of concerns re: sleep is significantly
greater than those related to hyperactivity
September 2007
Clinic for Alcohol and Drug
Exposed Children
He needed to be bundled for quite a long time…We have these
sort of rough, massaging type of gloves that we rub him down
with, and he really likes that with some gel. Before this, he
gets a bath with a calming lavender bath from the
States…Then we do the rub down with the gloves, and he
really likes that. Then, we go into the rocking chair and we
rock him for about 15-20 minutes. Then, we go up to his
room where we read him a story, and then he knows he has to
lie down or play quietly. (Interview #4)
September 2007
Clinic for Alcohol and Drug
Exposed Children
Sleep and Sensory Processing in Young
Children (0-36 months) with FASD -A pilot study
A. Hanlon-Dearman, B. Fjeldsted, CADEC Team
September 2007
Clinic for Alcohol and Drug
Exposed Children
Alcohol teratogenicity
Neurotransmitters
Sensory Processing
Sleep
September 2007
Clinic for Alcohol and Drug
Exposed Children
Methods
• N=20 children with FASD
Tools used:
• Infant/Toddler Sensory Profile (Dunn and
Daniels, The Psychological Corporation, 2002)
• Brief Infant Sleep Questionnaire (BISQ)
developed by Sadeh (2004)
September 2007
Clinic for Alcohol and Drug
Exposed Children
Results:
• Significant Correlations :
– total daytime sleep and sensation seeking
(raw) rs=-0.56 (p=0.0103)
– pm wakefulness and sensation avoiding
rs=0.46 (p=0.0421)
– pm wakefulness and oral (raw) rs=-0.44
(p=0.0494)
September 2007
Clinic for Alcohol and Drug
Exposed Children
Conclusions
• First study to correlate sleep dysfunction with
sensory processing abnormalities in FASD
• Sensory processing abnormalities correlated
with both daytime and nighttime dysfunction
September 2007
Clinic for Alcohol and Drug
Exposed Children
Neurodevelopmental patterns over
time…
September 2007
Clinic for Alcohol and Drug
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Background
• 20 years of longitudinal studies have
shown persistent behavioral, learning, and
adaptive difficulties into adulthood (Spohr,
2007; Autti-Ramo, 2000; Spohr, 1993; Streissguth, 1991)
• Deficits in social/adaptive behavior may
become more significant with age (Whaley et
al. 2001)
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Clinic for Alcohol and Drug
Exposed Children
Factors influencing outcomes
Family
Dose
Individual
factors
Alcohol
Environment
Timing
September 2007
School
Community
Clinic for Alcohol and Drug
Exposed Children
Age related Neurodevelopmental
Abnormalities in Children with pFAS
and ARND
S. Longstaffe, A. Hanlon-Dearman, K. Penner, and
CADEC Team
September 2007
Clinic for Alcohol and Drug
Exposed Children
Method
•
•
•
Retrospective analysis of clinical data
N=60
Children were grouped into 2 categories:
–
–
6-9 years (n=32)
10 - 12 years (n=28).
September 2007
Clinic for Alcohol and Drug
Exposed Children
Assessment Tool
NEPSY: A neuropsychological assessment tool for
children ages 3-12
–
–
27 subtests assessing 5 domains:
Attention/Executive Function, Language,
Sensorimotor, Visuospatial, Memory and Learning
Qualitative analysis of motor function, error
patterns and critically significant core domain
discrepancies
September 2007
Clinic for Alcohol and Drug
Exposed Children
A NEPSY PROFILE





September 2007
Male 11.8 yrs presents with
history of increasing school
failure, externalizing,
internalizing, & ADHD
problem behaviors.
Nondysmorphic, well grown
In group home following
family and multiple
placement breakdowns.
Artistic, qualitative motor
concerns, “doesn’t listen”.
Final Dx: ARND
Clinic for Alcohol and Drug
Exposed Children
S c o r e s
Results:
Core Domain Standard Scores
Comparison 6-9 & 10 - 12 yr olds.
S ta n d a r d
110
100
90
80
70
AE
L
SM
Domain
6-9 yrs
September 2007
V
10-12 yrs
Clinic for Alcohol and Drug
Exposed Children
M
Auditory vs Visual:
Attention and Memory
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Exposed Children
Frequency of Significant Domain
Discrepancies
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Clinic for Alcohol and Drug
Exposed Children
• Visual spatial domain a consistent strength
•
Attention/executive function, language and
memory core domains were globally
significant weaknesses
•
N=54, p<0.05
September 2007
Clinic for Alcohol and Drug
Exposed Children
Error patterns

Increasing disorganization and difficulty
processing complex auditory, but not visual
information
Qualitative analysis: error patterns
Percent ranking @ <10th percentile.
70
P e rc e n t
60
50
40
30
20
10
0
simple ommission
co mplex co missio n
simple co missio n
co mplex o mission
AUD
September 2007
VIS
Clinic for Alcohol and Drug
Exposed Children
Conclusions
• Changes in NEPSY scores occur over time
•
Specific deficits in language, memory and
attention, at various age groups
•
Refining the Canadian Diagnostic Guidelines
may be needed to consider possible differential
expression of core deficits over time
September 2007
Clinic for Alcohol and Drug
Exposed Children
What are we learning?
September 2007
Clinic for Alcohol and Drug
Exposed Children
• FASD includes a complex profile of
neurodevelopmental deficits that persists and
perhaps evolves with time
•
•
•
•
Adaptive
Executive
Sensory
Sleep
• ARND is underrepresented
and significantly affected
September 2007
Clinic for Alcohol and Drug
Exposed Children
Questions….
• Why are there differences in presentation?
Impact of genetics? Impact of environment?
• What is the impact of one brain domain on
another? How can we assess more fluidly
and functionally?
September 2007
Clinic for Alcohol and Drug
Exposed Children
Final questions…
• Can we influence the toxicity of alcohol?
• Can we prevent these comorbidities?
• Can we prevent this disorder?
September 2007
Clinic for Alcohol and Drug
Exposed Children
Acknowledgements
• CADEC Team:
• Medical Director Dr. Sally Longstaffe
• Clinic Coordinator: Mary Cox Millar
• Developmental Pediatricians: Dr. Terri Benoit, Dr. Nancy Bowman,
Ana Hanlon-Dearman
• Geneticists: Dr. Albert Chudley, Dr. Sandra Marles, Dr. Aziz Mhanni
• Speech and Language Therapist: Shelley Proven
• Occupational Therapist: Brenda Fjeldsted
• Neurodevelopmental Consultant: Karen Penner
• Community Liason: Dorothy Schwaab
• Social Work: Sharon Wazny-Prendergast
• Administrative Assistant: Shirley Dion
Dr.
• Children’s Hospital Research Foundation/Manitoba Institute
of Child Health
• National Research Institute for Biodiagnostics
September 2007
Clinic for Alcohol and Drug
Exposed Children