Transcript Becker et al 2008 Choo Presentation

Functional
Neuroanatomy of
Lexical processing in
children with cleft lip
and palate
(CCLP)
Becker et al., 2007
Background
Males are affected more often than females.
Incidence in:
• Asian population = 1 in 500 births.
• Caucasian and Hispanic populations = 1 in
1000 births.
• African American population = 1 in 2000
births.
(Altemus & Ferguson, 1965; Chung et al., 1986; Natsume & Kawai,
1986; Vanderas, 1987)
Cleft Lip & Palate
Cleft lip may occur in
isolation or together with
cleft palate and vice versa.
Incidence of cleft lip alone
(15-20%) is lower than the
incidence of cleft palate
only (30-35%) and cleft lip
and palate (50%).
(Coccia et al., 1969; Woolf et al., 1963)
Cleft Lip & Palate
• Occurrence of cleft
lip and palate
together is more
common in males.
• Cleft palate only is
more common in
females
(Calzolari et al., 1988;
Womersley & Stone, 1987)
Types of Clefts
Common
• Unilateral (9x as
common as bilateral
and occurs more often
on the left side)
• Bilateral
Unilateral
Often involve deformity
of the nose
Bilateral
Types of Clefts
Rare
• Median
• Facial
(DeMyer, 1971; Tessier, 1976)
When do they form?
Between fourth to
eight week of
embryonic
development.
Earlier
malformations are
more severe than
later ones
Causes
Genetic
Increased incidence in
children with a parent or
sibling who are similarly
affected ⇒ 1 in 131 (Melnick,
1986).
Orbital cleft
Note: Individuals with cleft palate only have higher
percentage of siblings that have other types of
malformations than individuals with cleft lip only or
cleft lip and palate (Meskin & Pruzansky, 1969.
(Malformations can occur in the orbital cleft, facial
asymmetry, middle ear defects, sternum).
Causes
Environmental
• Antiepileptic drug, phenytoin = 10-fold
increase in the incidence of clefts.
• Smoking during pregnancy = 50% to 70%
increase in clefting compared to those born
to nonsmoking mothers.
• Certain viruses (rubella and influenza)
increase risk of clefting.
Associated Anomalies
Clefting occurs in about 250
syndromes including Van
der Woude, Stickler
syndrome, microcephaly, etc.
Van der Woude
microencephaly
Stickler
Associated problems
1) Feeding
2) Ear infection- hearing
loss
3) Speech and language
disorders
4) Dental problems
Treatment
Surgery
NAM – Nasal
alveolar molding
Anatomical differences
Adult males with cleft palate display:
1) smaller cerebellum
2) smaller temporal lobe
3) smaller occipital lobes
4) larger frontal lobes
* Proportional gray and white matter
(Nopoulos et al., 2000)
Language Development
• Early deficits in cognitive development (Fox et al.,
1978; Snyder & Scherer, 2004; Speltz et al., 2000).
• Problems with syntax, short length of utterance
and delays in expressive language (Horn, 1972;
Morris, 1962; Withcomb et al., 1976).
• Articulation disorders, sometimes even after the
cleft is repaired (Jones et al., 2003; O’Gara & logemann,
1988).
Method
Participants
Experimental design
• Total of 6 runs.
• Each run consisted of 21 stimuli - one discrete
task and one modality.
Lexical task
Auditory
Visual
Rhyme
generation
Rhyme
generation
e.g. “mud” –”flood”
Verb
generation
Verb
generation
Opposite
generation
e.g. “cake”– “eat
Opposite
generation
e.g. “white” – “black”
* Presentation was jittered –
stimulus was presented every
2nd, 3rd, 4th MR frame in
pseudorandom fashion.
Movement analysis
Motion in the scanner can be a problem.
If more than 1.5 mm (RMS value) was needed to
realign head movement, the data was excluded.
Image analysis
General Linear Model for event related data.
Time = 7-level factor (BOLD measures every 3.08
seconds).
Removed outliers = time course that had greater
than 2% change in signal.
Overlap analysis
Compared with Brown et al. (2005) study.
Brown et al. 2005 (used the same tasks)
• Age-related regions = regions that showed
increased or decreased activity with age.
• Performance-related regions = regions that
were related to performance ability.
• Age-and performance-independent regions.
Developmental analysis
To determine if age had an effect.
Each CCLP was compared to an age-matched
cohort (group of 20 control individuals matched
within 2 years).
Statistical analysis
Repeated measures analysis – mixed model.
Between subject factor = condition or group (with
or without cleft lip and/or palate)
Within subject factor = time
Results
Results were based only on correct responses.
**Reaction time
(collapsed across task and modality)
Experimental: 1813 msec
Control: 1804 msec
** not statistically different
Main Effect of Time
To determine how reliably each voxel was activated by
the tasks.
Regions activated were similar to previous study
(Schlagger et al., 2002) looking at single word
processing.
Main effect: voxels reliably activated across all
subjects and all tasks
Group x time interaction
There were several regions that displayed
activation differences related to:
1) latency (CCLP > control)
2) duration (CCLP >control)
3) magnitude
Higher magnitude in CCLP
Right inferior frontal gyrus
Right parietal precuneus
Left superior medial frontal gyrus
Lower magnitude in CCLP
Right middle temporal gyrus
* Right lateral
prefrontal cortex – not
shown
Left inferior frontal gyrus
Similar in CCLP and controls
Left cingulate gyrus
* left paracentral lobule, right superior
temporal gyrus – not shown
Not activated in CCLP
Right middle frontal gyrus
Developmental Analysis
9 out of 12 CCLP showed regions that had
differences in BOLD responses from their agematched cohorts.
Older participants (>14.5 years) showed
differences consistently in the right frontal
cortex (n=2) and ACC (n=1) when compared to
controls.
Group x time: regions that were statistically
different in BOLD response between groups
Regions that corresponded to Brown et al., 2005
study.
* Functional differences between CCLP and
control increase with age.
Average number of regions where the
BOLD responses that differed from the
controls
Older (above 14.5 years) = 8.4
Younger (below 14.5 years) = 2.6
CCLP show substantial variability in activation regions
when compared to controls
lateral
medial
posterior
Pink: CCLP ≠ control (Are there more blue than pink regions in the older
posterior
participant?)
Blue: CCLP = control
Discussion
CCLP have similar but non-identical functional
neuroanatomy during language tasks at
comparable levels of performance.
Regional differences in functional neuroanatomy
are more apparent in age/performance related
areas.
CCLP display increasing differences in age-related
regions with increasing age.
CCLP display novel organization during language
tasks