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Associative stimulation of the supraorbital nerve fails to induce timing-specific plasticity in the human blink reflex.

Zeuner KE, Knutzen A, Al-Ali A, Hallett M, Deuschl G, Bergmann TO, Siebner HR - PLoS ONE (2010)

Bottom Line: On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD).We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone.All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Christian-Albrechts-University Kiel, Kiel, Germany. k.zeuner@neurologie.uni-kiel.de

ABSTRACT

Background: Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS(LTP)) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS(LTD)) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006).

Methodology/principal findings: We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD). Controls also received (iv) HFS(LTD) alone and (v) a non-intervention protocol. In BEB patients, HFS(LTP) followed by HFS(LTD) was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment.

Conclusion/significance: Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex.

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R2 response of each individual subject at baseline and after HFSLTP.Individual results of each subject before and immediately after HFSLTP for each protocol starting with HFSLTP (i.e. HFSLTP, HFSLTP-LTD, HFSLTP-LTP) are presented.
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pone-0013602-g006: R2 response of each individual subject at baseline and after HFSLTP.Individual results of each subject before and immediately after HFSLTP for each protocol starting with HFSLTP (i.e. HFSLTP, HFSLTP-LTD, HFSLTP-LTP) are presented.

Mentions: We were interested to explore the inter-subject variability in the acute changes of the R2 response after the first HFSLTP intervention. When plotting the immediate change in R2 response after HFSLTP in the three interventional sessions, some subjects showed a marked increase in one experimental session, but this R2 facilitation could not be replicated in the other sessions (Fig. 6). In healthy controls, inter-subject variability of changes in R2 area after HFSLTP was within the range of spontaneous fluctuations in the R2 response observed in the HFSNO session (Fig. 7). To further increase the sensitivity to detect any facilitatory effects of the HFSLTP protocol we reduced the variability by calculating the percent change between baseline and the 30 min measurement averaged across HFSLTP, HFSLTP-LTD and HFSLTP-LTP protocols. A one-sided one-sample t-test detected a mild facilitatory effect of 7% only in patients (T10 = 2.46; p = 0.017), but not in controls (p>0.4). A two-tailed independent sample t-test between patients and controls, however, showed no significant difference between the two groups (p>0.6).


Associative stimulation of the supraorbital nerve fails to induce timing-specific plasticity in the human blink reflex.

Zeuner KE, Knutzen A, Al-Ali A, Hallett M, Deuschl G, Bergmann TO, Siebner HR - PLoS ONE (2010)

R2 response of each individual subject at baseline and after HFSLTP.Individual results of each subject before and immediately after HFSLTP for each protocol starting with HFSLTP (i.e. HFSLTP, HFSLTP-LTD, HFSLTP-LTP) are presented.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2964285&req=5

pone-0013602-g006: R2 response of each individual subject at baseline and after HFSLTP.Individual results of each subject before and immediately after HFSLTP for each protocol starting with HFSLTP (i.e. HFSLTP, HFSLTP-LTD, HFSLTP-LTP) are presented.
Mentions: We were interested to explore the inter-subject variability in the acute changes of the R2 response after the first HFSLTP intervention. When plotting the immediate change in R2 response after HFSLTP in the three interventional sessions, some subjects showed a marked increase in one experimental session, but this R2 facilitation could not be replicated in the other sessions (Fig. 6). In healthy controls, inter-subject variability of changes in R2 area after HFSLTP was within the range of spontaneous fluctuations in the R2 response observed in the HFSNO session (Fig. 7). To further increase the sensitivity to detect any facilitatory effects of the HFSLTP protocol we reduced the variability by calculating the percent change between baseline and the 30 min measurement averaged across HFSLTP, HFSLTP-LTD and HFSLTP-LTP protocols. A one-sided one-sample t-test detected a mild facilitatory effect of 7% only in patients (T10 = 2.46; p = 0.017), but not in controls (p>0.4). A two-tailed independent sample t-test between patients and controls, however, showed no significant difference between the two groups (p>0.6).

Bottom Line: On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD).We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone.All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Christian-Albrechts-University Kiel, Kiel, Germany. k.zeuner@neurologie.uni-kiel.de

ABSTRACT

Background: Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS(LTP)) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS(LTD)) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006).

Methodology/principal findings: We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD). Controls also received (iv) HFS(LTD) alone and (v) a non-intervention protocol. In BEB patients, HFS(LTP) followed by HFS(LTD) was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment.

Conclusion/significance: Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex.

Show MeSH
Related in: MedlinePlus