BDNF Val⁶⁶Met Polymorphism Is Related to Motor System Function After Stroke

Background The val⁶⁶met polymorphism in brain-derived neurotrophic factor (BDNF) has been associated with poorer outcomes after stroke. The mechanism for this finding remains uncertain but might be related to the reduced motor system activation associated with this polymorphism in healthy people.

Objective The current study examined whether the presence of the BDNF val⁶⁶met polymorphism is associated with reduced motor system activation after stroke.

Design and Methods Forty-two patients with stroke who were enrolled in 1 of 2 studies of robot-assisted arm motor therapy participated in the study. All participants were tested for the BDNF val⁶⁶met polymorphism followed by functional magnetic resonance imaging during affected hand movement.

Results Participants averaged 12 months poststroke and had wide-ranging motor deficits (Fugl-Meyer scale scores=14–60). Brain activation in participants without the BDNF val⁶⁶met polymorphism (n=26) spanned bilateral motor networks with a larger volume (total=334 cc) than that found in participants with this polymorphism (n=16) (97 cc). Regional analyses were consistent. Participants without this polymorphism showed larger ipsilesional primary sensorimotor cortex activation volume and magnitude compared with those in whom the polymorphism was present.

Limitations The extent to which these findings generalize to other populations of people with stroke, such as those with stroke <7 days prior, remains uncertain.

Conclusions Functional magnetic resonance imaging during affected hand movement showed decreased brain activation among participants with the BDNF val⁶⁶met polymorphism compared with those lacking this polymorphism, especially in the ipsilesional primary sensorimotor cortex contralateral to movement. These results echo findings in healthy people and suggest that genetic factors affecting the normal brain continue to be operative after stroke. The findings suggest a potential imaging-based endophenotype for the BDNF val⁶⁶met polymorphism's effect on the motor system that may be useful in a clinical trial setting.