Differential Relationship between Microstructural Integrity in White Matter Tracts and Motor Recovery following Stroke Based on Brain-Derived Neurotrophic Factor Genotype

Eunhee Park, Jungsoo Lee, Won Hyuk Chang, Ahee Lee, Friedhelm C Hummel, Yun-Hee Kim, Eunhee Park, Jungsoo Lee, Won Hyuk Chang, Ahee Lee, Friedhelm C Hummel, Yun-Hee Kim

Abstract

Objective: The relationship between white matter integrity and the brain-derived neurotrophic factor (BDNF) genotype and its effects on motor recovery after stroke are poorly understood. We investigated the values of fractional anisotropy (FA) in the corticospinal tract (CST), the intrahemispheric connection from the primary motor cortex to the ventral premotor cortex (M1PMv), and the interhemispheric connection via the corpus callosum (CC) in patients with the BDNF genotype from the acute to the subacute phase after stroke.

Methods: The Fugl-Meyer assessment, upper extremity (FMA-UE), and tract-related FA were assessed at 2 weeks (T1) and 3 months (T2) after stroke using diffusion tensor imaging (DTI). Fifty-eight patients diagnosed with ischemic stroke were classified according to the BDNF genotype into a Val (valine homozygotes) or Met (methionine heterozygotes and homozygotes) group.

Results: The Val group exhibited a larger reduction of FA values in the ipsilesional M1PMv than the Met group from T1 to T2. The FMA-UE at T2 was negatively correlated with FA of the contralesional M1PMv at T2 in the Val group but was positively correlated with FA of the ipsilesional CST and CC at T2 in the Met group.

Conclusions: The integrity of the intra- and interhemispheric connections might be related to different processes of motor recovery dependent on the BDNF genotype. Thus, the BDNF genotype may need to be considered as a factor influencing neuroplasticity and functional recovery in patients with stroke. This trial is registered with http://www.clinicaltrials.gov: NCT03647787.

Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Copyright © 2020 Eunhee Park et al.

Figures

Figure 1
Figure 1
Template tract. Three template tracts were conducted by probabilistic tractography in 26 healthy subjects. The longitudinal tracts are shown in (a); the blue template is the corticospinal tract. The corticocortical connections are shown in (b); the pink template is intrahemispheric corticocortical connections from the primary motor cortex to the ventral premotor cortex, and the green template is interhemispheric corticocortical connections from both primary motor cortices.
Figure 2
Figure 2
Individual lesion masks were drawn and then spatially normalized to the Montreal Neurological Institute (MNI) space. The decision to flip all left lesions to the right was arbitrary. The lesion masks of (a) valine (Val) homozygotes of the BDNF genotype and (b) methionine (Met) allele carriers of the BDNF genotype superimposed onto MNI space. Colored bars represent levels of overlap in each lesion. Red indicates infrequent overlap, while white indicates frequent overlap.
Figure 3
Figure 3
The absolute values of fractional anisotropy (FA) in the (a) ipsilesional, the (b) contralesional, and the (c) interhemispheric motor-related tracts between two weeks and three months after stroke in each BDNF genotype. CC: corpus callosum; CST: corticospinal tract; M1PMv: intrahemispheric corticocortical connection from the primary motor cortex to the ventral premotor cortex; Met group: BDNF methionine (Met) allele carriers; T1: two weeks after stroke onset; T2: three months after stroke onset; Val group: BDNF valine (Val) homozygotes. ∗P < 0.05.
Figure 4
Figure 4
Correlations between upper limb motor function at three months after stroke and tract-related fractional anisotropy at three months after stroke in (a) valine (Val) homozygotes and (b) methionine (Met) allele carriers of BDNF genotype. “r” represents the partial correlation coefficient. Asterisks indicate significant differences (∗P < 0.05). CC: corpus callosum; CST: corticospinal tract; FA: fractional anisotropy; FMA-UE: Fugl-Meyer assessment, upper extremity; M1PMv: intrahemispheric corticocortical connection from the primary motor cortex to the ventral premotor cortex; r: partial correlation coefficient; T1: two weeks after stroke onset; T2: three months after stroke onset.

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