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Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

Mastroeni C, Bergmann TO, Rizzo V, Ritter C, Klein C, Pohlmann I, Brueggemann N, Quartarone A, Siebner HR - PLoS ONE (2013)

Bottom Line: The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene.Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions.Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Christian-Albrechts-University, Kiel, Germany.

ABSTRACT
Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

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Effects of the three TBS-TBS protocols and BDNF polymorphism on corticospinal excitability over time: (A) MEPbi amplitude independent of polymorphism, (B) MEPbi amplitude divided by polymorphism, (C) MEPmo amplitude independent of polymorphism, (D) MEPmo amplitude divided by polymorphism.Asterisks indicate significant changes from baseline in the expected direction as revealed by one-sided one-sample t-tests (#P<0.05, *P<0.01, **P<0.001, ***P<0.0001, ****P<0.00001, *****P<0.000001; please note that p-values indicated by one or more asterisks are also significant when applying two-sided t-tests).
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pone-0057957-g002: Effects of the three TBS-TBS protocols and BDNF polymorphism on corticospinal excitability over time: (A) MEPbi amplitude independent of polymorphism, (B) MEPbi amplitude divided by polymorphism, (C) MEPmo amplitude independent of polymorphism, (D) MEPmo amplitude divided by polymorphism.Asterisks indicate significant changes from baseline in the expected direction as revealed by one-sided one-sample t-tests (#P<0.05, *P<0.01, **P<0.001, ***P<0.0001, ****P<0.00001, *****P<0.000001; please note that p-values indicated by one or more asterisks are also significant when applying two-sided t-tests).

Mentions: Figure 2 displays MEP amplitude throughout all TBS-TBS sessions as percent of the initial baseline measurements (note that all statistics in this section also rely on these percent values). One-sampled t-tests confirmed that iTBS consistently induced an increase and cTBS consistently induced a decrease in both MEPbi and MEPmo amplitude relative to pre-TBS baseline. In the i-iTBS session, mean MEPbi amplitude was facilitated after the 1st iTBS (5 min: T27 = 3.42, P = 0.001; 25 min: T27 = 3.97, P<0.001) as well as after the 2nd iTBS (5 min: T27 = 4.33, P<0.0001; 25 min: T27 = 4.76, P<0.0001). In the c-iTBS session, mean MEPbi amplitude was reduced after the 1st cTBS (5 min: T28 = 3.52, P<0.001; 25 min: T28 = 1.81, P<0.04) and facilitated after the 2nd iTBS (5 min: T28 = 4.68, P<0.0001; 25 min: T28 = 5.33, P<0.00001) relative to pre-TBS baseline. In the c-cTBS session, mean MEPbi amplitude decreased after the 1st cTBS (5 min: T26 = 3.92, P<0.001; 25 min: T26 = 2.51, P<0.01) but did not differ from baseline after the 2nd cTBS (5 min: P = 0.1; 25 min: P>0.1). The same pattern was evident when the mean MEPmo amplitude was used as index of corticospinal excitability. In the i-iTBS session, mean MEPmo amplitude was facilitated after both the 1st iTBS (10 min: T27 = 6.10, P<0.000001) and the 2nd iTBS (10 min: T27 = 4.35, P<0.0001). In the c-iTBS session, mean MEPmo amplitude was attenuated after the 1st cTBS (10 min: T28 = 5.77, P<0.00001) and facilitated after the 2nd iTBS (10 min: T28 = 3.03, P<0.01). In the c-cTBS session, mean MEPmo amplitude was reduced after the 1st cTBS (10 min: T26 = −2.03, P<0.05) but showed no difference after the 2nd cTBS (10 min: P>0.1).


Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

Mastroeni C, Bergmann TO, Rizzo V, Ritter C, Klein C, Pohlmann I, Brueggemann N, Quartarone A, Siebner HR - PLoS ONE (2013)

Effects of the three TBS-TBS protocols and BDNF polymorphism on corticospinal excitability over time: (A) MEPbi amplitude independent of polymorphism, (B) MEPbi amplitude divided by polymorphism, (C) MEPmo amplitude independent of polymorphism, (D) MEPmo amplitude divided by polymorphism.Asterisks indicate significant changes from baseline in the expected direction as revealed by one-sided one-sample t-tests (#P<0.05, *P<0.01, **P<0.001, ***P<0.0001, ****P<0.00001, *****P<0.000001; please note that p-values indicated by one or more asterisks are also significant when applying two-sided t-tests).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585283&req=5

pone-0057957-g002: Effects of the three TBS-TBS protocols and BDNF polymorphism on corticospinal excitability over time: (A) MEPbi amplitude independent of polymorphism, (B) MEPbi amplitude divided by polymorphism, (C) MEPmo amplitude independent of polymorphism, (D) MEPmo amplitude divided by polymorphism.Asterisks indicate significant changes from baseline in the expected direction as revealed by one-sided one-sample t-tests (#P<0.05, *P<0.01, **P<0.001, ***P<0.0001, ****P<0.00001, *****P<0.000001; please note that p-values indicated by one or more asterisks are also significant when applying two-sided t-tests).
Mentions: Figure 2 displays MEP amplitude throughout all TBS-TBS sessions as percent of the initial baseline measurements (note that all statistics in this section also rely on these percent values). One-sampled t-tests confirmed that iTBS consistently induced an increase and cTBS consistently induced a decrease in both MEPbi and MEPmo amplitude relative to pre-TBS baseline. In the i-iTBS session, mean MEPbi amplitude was facilitated after the 1st iTBS (5 min: T27 = 3.42, P = 0.001; 25 min: T27 = 3.97, P<0.001) as well as after the 2nd iTBS (5 min: T27 = 4.33, P<0.0001; 25 min: T27 = 4.76, P<0.0001). In the c-iTBS session, mean MEPbi amplitude was reduced after the 1st cTBS (5 min: T28 = 3.52, P<0.001; 25 min: T28 = 1.81, P<0.04) and facilitated after the 2nd iTBS (5 min: T28 = 4.68, P<0.0001; 25 min: T28 = 5.33, P<0.00001) relative to pre-TBS baseline. In the c-cTBS session, mean MEPbi amplitude decreased after the 1st cTBS (5 min: T26 = 3.92, P<0.001; 25 min: T26 = 2.51, P<0.01) but did not differ from baseline after the 2nd cTBS (5 min: P = 0.1; 25 min: P>0.1). The same pattern was evident when the mean MEPmo amplitude was used as index of corticospinal excitability. In the i-iTBS session, mean MEPmo amplitude was facilitated after both the 1st iTBS (10 min: T27 = 6.10, P<0.000001) and the 2nd iTBS (10 min: T27 = 4.35, P<0.0001). In the c-iTBS session, mean MEPmo amplitude was attenuated after the 1st cTBS (10 min: T28 = 5.77, P<0.00001) and facilitated after the 2nd iTBS (10 min: T28 = 3.03, P<0.01). In the c-cTBS session, mean MEPmo amplitude was reduced after the 1st cTBS (10 min: T26 = −2.03, P<0.05) but showed no difference after the 2nd cTBS (10 min: P>0.1).

Bottom Line: The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene.Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions.Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Christian-Albrechts-University, Kiel, Germany.

ABSTRACT
Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

Show MeSH
Related in: MedlinePlus