Altered White Matter Architecture in BDNF Met Carriers

• Published in: PloS one Vol. 8; no. 7; p. e69290
• Main Authors: Ziegler, Erik, Foret, Ariane, Mascetti, Laura, Muto, Vincenzo, Le Bourdiec-Shaffii, Anahita, Stender, Johan, Balteau, Evelyne, Dideberg, Vinciane, Bours, Vincent, Maquet, Pierre, Phillips, Christophe
• Format: Journal Article Web Resource
• Language: English
• Published: United States Public Library of Science 31.07.2013; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Algorithms; Alleles; Anterior commissure; Architecture; Artificial intelligence; BDNF; Biology; Brain; Brain - anatomy & histology; Brain - metabolism; Brain - physiology; Brain Mapping; Brain research; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Carriers; Cerebral cortex; Cerebral hemispheres; Computer Science; connectivity; Corona; Corpus callosum; Corpus Callosum - anatomy & histology; Corpus Callosum - metabolism; Corpus Callosum - physiology; Extreme values; Female; Forebrain; Gaussian process; Gene Frequency; Genotype; Genotype & phenotype; Genotypes; Human health sciences; Humans; Internal Capsule - anatomy & histology; Internal Capsule - metabolism; Internal Capsule - physiology; Linkage Disequilibrium; Magnetic Resonance Imaging - methods; Male; Medical imaging; Medical instruments; Medicine; Methionine - genetics; Models, Neurological; Nerve Fibers - metabolism; Nerve Fibers - physiology; Nerve Net - anatomy & histology; Nerve Net - metabolism; Nerve Net - physiology; Neural networks; Neuroimaging; Neurologie; Neurology; Permutations; Polar environments; Polar regions; Polymorphism, Single Nucleotide; Pruning; Pyramidal tracts; Sciences de la santé humaine; Sensorimotor system; Statistical analysis; Substantia alba; Thalamus; Valine - genetics; white matter; Young Adult; Belgium
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069290

Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin's activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture.