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Val66Met BDNF gene polymorphism influences human motor cortex plasticity in acute stroke.

ABSTRACT: BDNF gene polymorphism impacts human motor cortex function and plasticity.Using transcranial magnetic stimulation (TMS), we investigated whether BDNF polymorphism influences cortical plastic changes in acute stroke.Twenty patients were recruited within 10 days of their first-ever ischemic stroke and genotyped for BDNF polymorphism. Blinded to the latter, we evaluated the excitability of the affected and unaffected hemisphere by measuring resting and active motor threshold and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation, a protocol of repetitive TMS inducing LTP-like activity. We also computed laterality indexes to assess inter-hemispheric excitability imbalance.Demographics, threshold and amplitude of motor-evoked potentials did not differ between those with (8 patients) and without polymorphism. Excitability of the unaffected hemisphere was significantly higher than the excitability of the affected hemisphere as probed by each measure. This imbalance was exaggerated in those without polymorphism; laterality indexes of rest motor thresholds were 0.016 ± 0.050 and 0.139 ± 0.028 for patients with and without polymorphism [t = 2.270, P = 0.036]. Exaggerated hemispheric imbalance also persisted after intermittent theta burst stimulation, which failed to induce any difference between groups.Our results suggest that inter-hemispheric imbalance with greater excitability over unaffected hemisphere, is several times stronger in stroke patients without, as opposed to with, polymorphism.

SUBMITTER: Di Lazzaro V

PROVIDER: S-EPMC4813754 | biostudies-literature | 2015 Jan-Feb

REPOSITORIES: biostudies-literature

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Val66Met BDNF gene polymorphism influences human motor cortex plasticity in acute stroke.

Di Lazzaro Vincenzo V Pellegrino Giovanni G Di Pino Giovanni G Corbetto Marzia M Ranieri Federico F Brunelli Nicoletta N Paolucci Matteo M Bucossi Serena S Ventriglia Maria C MC Brown Peter P Capone Fioravante F

Brain stimulation 20140823 1

<h4>Background</h4>BDNF gene polymorphism impacts human motor cortex function and plasticity.<h4>Objective/hypothesis</h4>Using transcranial magnetic stimulation (TMS), we investigated whether BDNF polymorphism influences cortical plastic changes in acute stroke.<h4>Methods</h4>Twenty patients were recruited within 10 days of their first-ever ischemic stroke and genotyped for BDNF polymorphism. Blinded to the latter, we evaluated the excitability of the affected and unaffected hemisphere by meas ...[more]

PMID: 25241287

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Project description:The val(66)met 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.The current study examined whether the presence of the BDNF val(66)met polymorphism is associated with reduced motor system activation after stroke.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 val(66)met polymorphism followed by functional magnetic resonance imaging during affected hand movement.Participants averaged 12 months poststroke and had wide-ranging motor deficits (Fugl-Meyer scale scores=14-60). Brain activation in participants without the BDNF val(66)met 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.The extent to which these findings generalize to other populations of people with stroke, such as those with stroke <7 days prior, remains uncertain.Functional magnetic resonance imaging during affected hand movement showed decreased brain activation among participants with the BDNF val(66)met 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 val(66)met polymorphism's effect on the motor system that may be useful in a clinical trial setting.

Project description:The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.

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Val66Met BDNF gene polymorphism influences human motor cortex plasticity in acute stroke.

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Val66Met BDNF gene polymorphism influences human motor cortex plasticity in acute stroke.

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