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 & PalateCleft 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 CleftsCommon • Unilateral (9x as
common as bilateral and occurs more often on the left side)
• Bilateral
Often involve deformity of the nose
Unilateral
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
CausesGenetic Increased incidence
in children with a parent or sibling who are similarly affected ⇒ 1 in 131 (Melnick, 1986).
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).
Orbital cleft
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 AnomaliesClefting occurs in
about 250 syndromes including Van der Woude, Stickler syndrome, microcephaly, etc.
Van der Woude
microencephalyStickler
Associated problems
1) Feeding2) Ear infection-
hearing loss3) Speech and
language disorders
4) Dental problems
TreatmentSurgery NAM – Nasal
alveolar molding
Anatomical differences
Adult males with cleft palate display:1) smaller cerebellum 2) smaller temporal lobe3) smaller occipital lobes4) 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
Lexical task
Auditory Visual
Rhyme generation
Verb generation
Opposite generation
Rhyme generation
Verbgeneration
Opposite generation
e.g. “cake”– “eat
e.g. “white” – “black”
e.g. “mud” –”flood”
* Presentation was jittered – stimulus was presented every 2nd, 3rd, 4th MR frame in pseudorandom fashion.
•Total of 6 runs.•Each run consisted of 21 stimuli - one
discrete task and one modality.
Movement analysisMotion 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 analysisGeneral 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 analysisCompared 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 analysisTo 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 analysisRepeated 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 msecControl: 1804 msec** not statistically different
Main Effect of TimeTo 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 interactionThere were several regions that
displayed activation differences related to:
1) latency (CCLP > control)2) duration (CCLP >control)3) magnitude
Higher magnitude in CCLP
Left superior medial frontal gyrus
Right parietal precuneusRight inferior frontal gyrus
Lower magnitude in CCLP
Left inferior frontal gyrus* Right lateral prefrontal cortex – not shown
Right middle temporal 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 age-matched 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 controlsOlder (above 14.5 years) = 8.4Younger (below 14.5 years) = 2.6
CCLP show substantial variability in activation regions when compared to
controls
lateral
medial
posteriorPink: CCLP ≠ control (Are there more blue than pink regions in the older
participant?)
Blue: CCLP = control
posterior
DiscussionCCLP 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