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The BDNF Val/Met Polymorphism Is Linked With Children's Reading And Language Skills And Neural Activation Patterns In The Brain's Reading Network
Kaja Jasińska1, Peter Molfese1, W. Einar Mencl1, Kenneth Pugh123, Elena Grigorenko3 & Nicole Landi123 1Haskins Laboratories, 2University of Connecticut, 3Yale University, Child Study Center
RESEARCH QUESTIONS Does common genetic variation influence reading and language skills and the underlying developing brain’s network for reading and language? The BDNF (Brain Derived Neurotrophic Factor) Gene is important to context-dependent brain plasticity and is associated with learning, memory and higher cognition A common single nucleotide polymorphism (SNP) in BDNF resulting in a Val-to-Met substitution (located at rs6265) is associated with changes in activity-dependent BDNF release and associated functional neural changes BDNF is variably expressed over early life – during periods critical for linguistic and cognitive development
METHODS Participants 86 children ages 6-10 years of age (mean = 8y) DNA Oragene kits (DNA Genotek) were used to collect saliva After extraction of DNA from samples we used the Applied Biosystems Inc. (ABI) Taqman protocol for SNP genotyping Behavioral Assessments Word and non-word reading, phonological processing, short-term memory, reading speed and comprehension, spelling, verbal and performance IQ fMRI task
BEHAVIORAL RESULTS DISCUSSION
FUNCTIONAL BRAIN RESULTS
The BDNF gene is associated with reading and reading related linguistic skills, specifically, reading comprehension and phonological memory.
Children with Val/Val and Val/Met* polymorphisms show both structural and functional brain differences: Structure: Children who have the Val/Val combination show greater cortical thickness than children who have the Val/Met or Met/Met combination in regions associated with language and reading function (e.g. bilateral IFG, posterior STG). Function: Children who have the Val/Val combination, but not the Val/Met or Met/Met combination, show reading skill modulated patterns of neural activation in regions associated with language and reading function (including LIFG, STG, IPL)
Implications
Single nucleotide polymorphisms in genes involved in brain maturation (BDNF) impact both the structure and function of the developing brain in ways that may modulate children’s language and reading abilities.
CONTACT
This work was supported by NIH grant: R01 HD 048830 (K. Pugh, PI) PO1 HD052120, (R.Wagner, PI) P01 HD 01994 (C. Fowler, PI) R03HD053409 (N. Landi, PI)
STRUCTURAL BRAIN RESULTS
Val/Val > Val/Met*
Val/Met*
Val/Val
SNP by Group Interaction
p <.05 min 300 clusters
FWE
*Significant predictors reported controlled for effects of age, gender and parent report of child hyperactivity
*Val/Met = Val/Met &Met/Met
Skilled > Less-Skilled
SNP: Val/Val & Val/Met*
Group: Skilled & Less-Skilled
p <.01 FWE
LANGUAGE PLASTICITY: GENES, BRAIN, COGNITION, COMPUTATION
I G E R T INTEGRATIVE GRADUATE EDUCATION & RESEARCH TRAINEESHIP
HYPOTHESIS The BDNF Val/Met SNP is important for structural and functional development of the brain’s hippocampal network, which may downstream impact developing language circuits including left-hemisphere frontal, temporoparietal and occipitotemporal regions involved in reading) as thus also the development of reading and language abilities
Val/Val > Val/Met*
LH RH
Cortical thickness differences were observed
between Val/Val and Val/Met* groups
0
20
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60
80
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Passage Comprehension
Phonological Memory
Verbal IQ
Sta
ndar
d S
core
Val/Val
Val/Met*
p < .05
p <.01 FWE
Genotype groups (Val/Val and Val/Met) and reading groups (skilled and less-skilled—based on median split) were compared on indicators of behavioral performance across printed non-matching pseudowords Planned contrasts within an ANCOVA (using IQ and gender as covariates) were used to compare groups for the main effect of print processing (pseudowords) at each voxel separately
(uncorrected)
Kaja Jasinska, PhD [email protected] www.haskins.yale.edu www.haskins.yale.edu/staff/jasinska