Altered White Matter Architecture in BDNF Met Carriers |
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Authors: | Erik Ziegler Ariane Foret Laura Mascetti Vincenzo Muto Anahita Le Bourdiec-Shaffii Johan Stender Evelyne Balteau Vinciane Dideberg Vincent Bours Pierre Maquet Christophe Phillips |
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Institution: | 1. Cyclotron Research Centre, Université de Liège, Liège, Belgium.; 2. Department of Human Genetics, CHU Sart Tilman, Liège, Belgium.; 3. Department of Neurology, CHU Liège, Liège, Belgium.; 4. Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium.; Institut National de la Santé et de la Recherche Médicale (INSERM U901), France, |
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Abstract: | 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. |
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