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Preservation of general intelligence following traumatic brain injury: contributions of the Met66 brain-derived neurotrophic factor.

Barbey AK, Colom R, Paul E, Forbes C, Krueger F, Goldman D, Grafman J - PLoS ONE (2014)

Bottom Line: Val/Met did not differ from Val/Val genotypes in general cognitive ability before TBI.However, we found substantial average differences between these groups in general intelligence (≈ half a standard deviation or 8 IQ points), verbal comprehension (6 IQ points), perceptual organization (6 IQ points), working memory (8 IQ points), and processing speed (8 IQ points) after TBI.These results support the conclusion that Val/Met genotypes preserve general cognitive functioning, whereas Val/Val genotypes are largely susceptible to TBI.

View Article: PubMed Central - PubMed

Affiliation: Decision Neuroscience Laboratory, University of Illinois, Urbana, Illinois, United States of America ; Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, Illinois, United States of America ; Department of Internal Medicine, University of Illinois, Champaign, Illinois, United States of America ; Department of Psychology, University of Illinois, Champaign, Illinois, United States of America ; Department of Speech and Hearing Science, University of Illinois, Champaign, Illinois, United States of America ; Neuroscience Program, University of Illinois, Champaign, Illinois, United States of America.

ABSTRACT
Brain-derived neurotrophic factor (BDNF) promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes with intracellular trafficking, packaging, and regulated secretion of this neurotrophin. The human prefrontal cortex (PFC) shows lifelong neuroplastic adaption implicating the Val66Met BDNF polymorphism in the recovery of higher-order executive functions after traumatic brain injury (TBI). In this study, we examined the effect of this BDNF polymorphism on the preservation of general intelligence following TBI. We genotyped a sample of male Vietnam combat veterans (n = 156) consisting of a frontal lobe lesion group with focal penetrating head injuries for the Val66Met BDNF polymorphism. Val/Met did not differ from Val/Val genotypes in general cognitive ability before TBI. However, we found substantial average differences between these groups in general intelligence (≈ half a standard deviation or 8 IQ points), verbal comprehension (6 IQ points), perceptual organization (6 IQ points), working memory (8 IQ points), and processing speed (8 IQ points) after TBI. These results support the conclusion that Val/Met genotypes preserve general cognitive functioning, whereas Val/Val genotypes are largely susceptible to TBI.

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Related in: MedlinePlus

Lesion overlap map illustrating common and distinctive brain regions for Val/Val (blue) and Val/Met (yellow) genotype patients.Overlap between Val/Val and Val/Met genotype patients is illustrated in green. In each axial slice, the right hemisphere is on the reader's left.
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pone-0088733-g003: Lesion overlap map illustrating common and distinctive brain regions for Val/Val (blue) and Val/Met (yellow) genotype patients.Overlap between Val/Val and Val/Met genotype patients is illustrated in green. In each axial slice, the right hemisphere is on the reader's left.

Mentions: CT data were acquired during the Phase 3 testing period. Axial CT scans without contrast were acquired at Bethesda Naval Hospital on a GE Medical Systems Light Speed Plus CT scanner in helical mode (150 slices per subject, field of view covering head only). Images were reconstructed with an in-plane voxel size of 0.4×0.4 mm, overlapping slice thickness of 2.5 mm, and a 1 mm slice interval. Lesion location and volume were determined from CT images using the Analysis of Brain Lesion software [36], [37] contained in MEDx v3.44 (Medical Numerics) with enhancements to support the Automated Anatomical Labeling atlas [38]. Lesion volume was calculated by manual tracing of the lesion in all relevant slices of the CT image then summing the traced areas and multiplying by slice thickness. A trained neuropsychiatrist performed the manual tracing, which was then reviewed by an observer who was blind to the results of the neuropsychological testing. As part of this process, the CT image of each subject’s brain was spatially normalized to a CT template brain image. This template was created by spatial normalization of a neurologically healthy individual’s CT brain scan to MNI space using the Automated Image Registration program [39]. Lesion overlap maps for patients with the Val/Val or Val/Met genotypes are illustrated in Figures 1 and 2, respectively. Demographic and background data for the Val/Val and Val/Met patient groups are reported in Table S1 (see also [29]–[32]). No effects on test performance were observed in these patient groups on the basis of demographic variables (e.g., age, sex, ethnicity, years of education, and lesion size; see also [28]). A direct comparison of brain regions damaged in the Val/Val versus Val/Met genotypes is illustrated in Figure 3. The profile of brain damage among these patient groups primarily reflects common PFC subregions (highlighted in green) and entails the majority of damaged voxels (Val/Val = 62.02% shared with Val/Met; Val/Met = 76.33% shared with Val/Val). An additional analysis performed on a subset of the Val/Val patients whose lesion maps had maximal overlap with the full Val/Met patient group (84.94%) is reported in Table S3 and Figs. S1–S3, and replicates the findings of this study.


Preservation of general intelligence following traumatic brain injury: contributions of the Met66 brain-derived neurotrophic factor.

Barbey AK, Colom R, Paul E, Forbes C, Krueger F, Goldman D, Grafman J - PLoS ONE (2014)

Lesion overlap map illustrating common and distinctive brain regions for Val/Val (blue) and Val/Met (yellow) genotype patients.Overlap between Val/Val and Val/Met genotype patients is illustrated in green. In each axial slice, the right hemisphere is on the reader's left.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935849&req=5

pone-0088733-g003: Lesion overlap map illustrating common and distinctive brain regions for Val/Val (blue) and Val/Met (yellow) genotype patients.Overlap between Val/Val and Val/Met genotype patients is illustrated in green. In each axial slice, the right hemisphere is on the reader's left.
Mentions: CT data were acquired during the Phase 3 testing period. Axial CT scans without contrast were acquired at Bethesda Naval Hospital on a GE Medical Systems Light Speed Plus CT scanner in helical mode (150 slices per subject, field of view covering head only). Images were reconstructed with an in-plane voxel size of 0.4×0.4 mm, overlapping slice thickness of 2.5 mm, and a 1 mm slice interval. Lesion location and volume were determined from CT images using the Analysis of Brain Lesion software [36], [37] contained in MEDx v3.44 (Medical Numerics) with enhancements to support the Automated Anatomical Labeling atlas [38]. Lesion volume was calculated by manual tracing of the lesion in all relevant slices of the CT image then summing the traced areas and multiplying by slice thickness. A trained neuropsychiatrist performed the manual tracing, which was then reviewed by an observer who was blind to the results of the neuropsychological testing. As part of this process, the CT image of each subject’s brain was spatially normalized to a CT template brain image. This template was created by spatial normalization of a neurologically healthy individual’s CT brain scan to MNI space using the Automated Image Registration program [39]. Lesion overlap maps for patients with the Val/Val or Val/Met genotypes are illustrated in Figures 1 and 2, respectively. Demographic and background data for the Val/Val and Val/Met patient groups are reported in Table S1 (see also [29]–[32]). No effects on test performance were observed in these patient groups on the basis of demographic variables (e.g., age, sex, ethnicity, years of education, and lesion size; see also [28]). A direct comparison of brain regions damaged in the Val/Val versus Val/Met genotypes is illustrated in Figure 3. The profile of brain damage among these patient groups primarily reflects common PFC subregions (highlighted in green) and entails the majority of damaged voxels (Val/Val = 62.02% shared with Val/Met; Val/Met = 76.33% shared with Val/Val). An additional analysis performed on a subset of the Val/Val patients whose lesion maps had maximal overlap with the full Val/Met patient group (84.94%) is reported in Table S3 and Figs. S1–S3, and replicates the findings of this study.

Bottom Line: Val/Met did not differ from Val/Val genotypes in general cognitive ability before TBI.However, we found substantial average differences between these groups in general intelligence (≈ half a standard deviation or 8 IQ points), verbal comprehension (6 IQ points), perceptual organization (6 IQ points), working memory (8 IQ points), and processing speed (8 IQ points) after TBI.These results support the conclusion that Val/Met genotypes preserve general cognitive functioning, whereas Val/Val genotypes are largely susceptible to TBI.

View Article: PubMed Central - PubMed

Affiliation: Decision Neuroscience Laboratory, University of Illinois, Urbana, Illinois, United States of America ; Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, Illinois, United States of America ; Department of Internal Medicine, University of Illinois, Champaign, Illinois, United States of America ; Department of Psychology, University of Illinois, Champaign, Illinois, United States of America ; Department of Speech and Hearing Science, University of Illinois, Champaign, Illinois, United States of America ; Neuroscience Program, University of Illinois, Champaign, Illinois, United States of America.

ABSTRACT
Brain-derived neurotrophic factor (BDNF) promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes with intracellular trafficking, packaging, and regulated secretion of this neurotrophin. The human prefrontal cortex (PFC) shows lifelong neuroplastic adaption implicating the Val66Met BDNF polymorphism in the recovery of higher-order executive functions after traumatic brain injury (TBI). In this study, we examined the effect of this BDNF polymorphism on the preservation of general intelligence following TBI. We genotyped a sample of male Vietnam combat veterans (n = 156) consisting of a frontal lobe lesion group with focal penetrating head injuries for the Val66Met BDNF polymorphism. Val/Met did not differ from Val/Val genotypes in general cognitive ability before TBI. However, we found substantial average differences between these groups in general intelligence (≈ half a standard deviation or 8 IQ points), verbal comprehension (6 IQ points), perceptual organization (6 IQ points), working memory (8 IQ points), and processing speed (8 IQ points) after TBI. These results support the conclusion that Val/Met genotypes preserve general cognitive functioning, whereas Val/Val genotypes are largely susceptible to TBI.

Show MeSH
Related in: MedlinePlus