13. Integrative action of axon’s membrane explored by sub threshold stimulation of the peripheral...

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12. More pulses – lower thresholds? The efficacy of the number of pulses within a stimulus train to elicit MEPs—Dimitrios Kefalas, Andrea Szelényi (Neurosurgical Clinic, University Hospital Dues- seldorf, Germany) Introduction: The multipulse transcranial electrical stimulation (TES) is used intraoperatively to elicit motor evoked potentials (MEPs). In supratentorial surgeries a slightly suprathreshold stimu- lation is established to avoid deep white matter activation. Thus, stimulation paradigms are optimized to achieve lowest motor threshold (MT). However a systematic study on the effect of the number of pulses (NOP) on MT has not been performed and thus evaluated. Material and methods: In twenty-five patients (55 12 y.o., 10 females, normal motor status) underwent brain surgery, the MTs of the MEPs from the 1st interosseus muscle of the hand were mea- sured, after TES with 19 NOP. The stimulations were delivered by a constant current stimulator (maximum 220 mA) with the following montages: C-1 C2, C-1 C1, C3-Cz, C4-Cz, the interstimulus interval was 4 ms and the pulse width 0.5 ms. The thresholds of left vs right cortex stimulation, ‘affected’ vs ’unaffected’ hemisphere, stimulating montages and different NOP were compared (Student’s t-test). Results: MEPs were elicited in 5/25 patients (20%) with NOP = 1, in 24/25 patients (96%) with NOP = 2 and in all patients with NOP3. There is no significant difference of the MTs between left/right hemi- sphere (p>0.5), ‘affected’/‘unaffected’ hemisphere (p>0.5) and stim- ulating montages (p>0.5) for any number (2-9) of pulses. There is significant difference between NOP2/NOP5 (p<0.05), but not between NOP5/NOP8 (p>0.5). The MT averages (in mA) for 29 pulses are the following: MTNOP2: 79.3 ± 40.6, MTNOP3: 65.6 ± 26.9, MTNOP4: 60.7 ± 24.2, MTNOP5: 58.4 ± 23.2, MTNOP6: 57.0 ± 22.4, MTNOP7: 56.1 ± 21.7, MTNOP8: 55.3 ± 21.4, MTNOP9: 55.0 ± 21.4 (mean ± SD). The MT for any NOP can be well predicted (R2 = 0.9997), knowing just the MTNOP4 and MTNOP5, by the fol- lowing hyperbolic equation: MT (NOPx)=0.47 * MTNOP4 * (NOPx-1)- b + 0. 87 * MTNOP5, where b = MTNOP5/MTNOP4. Conclusion: This study shows that the stimulation with a train of more than five pulses does not lower efficiently the MT of the MEPs. The ‘MT-NOP’ curve can be approximated by a hyperbolic function. doi:10.1016/j.clinph.2013.12.015 13. Integrative action of axon’s membrane explored by sub threshold stimulation of the peripheral nerve fibres—Beatriz Arranz Arranz a , Javier Urriza b , Sedat Ulkatan c , Vedran Deletis c ( a Dept of Clin Neurophys, Virgen de la Arrixaca Hospital, Murcia, Spain, b Dept of Clin Neurophys, Pamplona-Navarra, Spain, c St. Luke’s Roosevelt Hospital, Intraoperative Neurophysiology, NY, United States) Introduction: Bostock et al. [J Physiol 564.3 93–1940, 2005] showed thatwhen the current of subthreshold intensity is applied to the peripheral nerve it will make the axon hyperexcitable. We experimented with a modified method of Bostock et al. by using multiple subthreshold stimuli to the median nerve. We were able to show integrative action of axon’s membrane. Method: In 6 healthy subjects and 17 patients who underwent monitoring for low spine surgery, we stimulated the median nerve at the wrist (in most of them bilaterally) with percutaneous elec- trodes, using near-the-threshold one to nine, constant-current stim- uli at a duration of 500 microseconds Interstimulus interval between stimuli was 2 ms. In the patient group recordings of the compound- muscle action-potential (CMAP) were done from opponens pollicis muscle using EEG needle electrodes, while in healthy subjects we used surface electrodes. TIVA without muscle relaxant was used in all patients and measurements were performed at the end of surgery. Result: In all healthy subjects and patients a single near-the- threshold stimulus did not generate CMAP. When the number of near-the-threshold stimuli was increased to two, five, seven, or nine stimuli and packed in a short train with inter stimulus intervals of 2 ms, this resulted in the successful eliciting of CMAP amplitude from 100 to 200 microvolts. Conclusion: We concluded that the described phenomenon might be explained by the integrative action of the axonal membrane which is capable of summating the trains of sub-threshold stimuli, increasing the resting potential to the firing level and consequently generating CMAP. This is due to the effect of sub threshold stimulus hyperexcitability. This phenomenon is not very well explored in clin- ical neurophysiology, and needs more attention. This could lead to explanations of some neurophysiologic phenomena during intraop- erative monitoring. doi:10.1016/j.clinph.2013.12.016 14. The new math of EEG: Symbolic transfer entropy, the effects of dimension—John McAuliffe (Cincinnati Children’s Hospital, United States) Introduction: Symbolic transfer entropy (STE) and transfer entropy (TE) has been proposed as a means to detect exchange of information between two signal sources, such as areas of the brain 1. The compu- tation of STE and TE assumes that the time series that make up the signals to be analysed have been properly embedded in a higher dimensional space. The significance of dimension is examined. Materials and methods: The analysis was conducted using simu- lated signals consisting of Gaussian noise, coupled Lorenz oscillators, sum-of-sinusoids and a combination of the Lorenz oscillators and sinusoids. Normalized STE was calculated according to 2 using a range of dimensions and delay values for data sets of 2500 data points. The data sets were padded with Gaussian noise in order to induce a time lag between the driver signal and the responding signal. Results: Gaussian noise posed the biggest challenge at D = 3 or 4. In both cases the calculated direction of information flow was + 1 or 1 for 60% of the data sets whereas 60% were correctly labelled a zero at D = 5. Otherwise D = 3 or 4 correctly identified the direction of information flow for the Lorenz data sets and the combination data sets. D = 5 performed best at identifying the lack of net informa- tion flow in the sum-of-sinusoids data sets. Increasing delay values, tau, resulted in proportionally greater increases in calculated reverse information flow than forward flow; this effect was more pro- nounced at higher dimension. NSTE was sensitive to the direction of information flow if as little as 15% the signal and the remainder being background. Conclusions: NSTE may be less sensitive to false neighbours than TE for complex reasons. The correct embedding dimension appears to be highly dependent on the characteristics of the information being analysed. References Anaesthesiology 2013;118:1264. J Neurophysiology 2007;97:2533. doi:10.1016/j.clinph.2013.12.017 Society Proceedings / Clinical Neurophysiology 125 (2014) e13–e24 e17

Transcript of 13. Integrative action of axon’s membrane explored by sub threshold stimulation of the peripheral...

12. More pulses – lower thresholds? The efficacy of the number ofpulses within a stimulus train to elicit MEPs—Dimitrios Kefalas,Andrea Szelényi (Neurosurgical Clinic, University Hospital Dues-seldorf, Germany)

Introduction: The multipulse transcranial electrical stimulation(TES) is used intraoperatively to elicit motor evoked potentials(MEPs). In supratentorial surgeries a slightly suprathreshold stimu-lation is established to avoid deep white matter activation. Thus,stimulation paradigms are optimized to achieve lowest motorthreshold (MT). However a systematic study on the effect of thenumber of pulses (NOP) on MT has not been performed and thusevaluated.

Material and methods: In twenty-five patients (55�12 y.o., 10females, normal motor status) underwent brain surgery, the MTsof the MEPs from the 1st interosseus muscle of the hand were mea-sured, after TES with �19 NOP. The stimulations were delivered by aconstant current stimulator (maximum 220 mA) with the followingmontages: C-1 C2, C-1 C1, C3-Cz, C4-Cz, the interstimulus intervalwas 4 ms and the pulse width 0.5 ms. The thresholds of left vs rightcortex stimulation, ‘affected’ vs ’unaffected’ hemisphere, stimulatingmontages and different NOP were compared (Student’s t-test).

Results: MEPs were elicited in 5/25 patients (20%) with NOP = 1, in24/25 patients (96%) with NOP = 2 and in all patients with NOP3.There is no significant difference of the MTs between left/right hemi-sphere (p>0.5), ‘affected’/‘unaffected’ hemisphere (p>0.5) and stim-ulating montages (p>0.5) for any number (2-9) of pulses. There issignificant difference between NOP2/NOP5 (p<0.05), but notbetween NOP5/NOP8 (p>0.5). The MT averages (in mA) for �29pulses are the following: MTNOP2: 79.3 ± 40.6, MTNOP3:65.6 ± 26.9, MTNOP4: 60.7 ± 24.2, MTNOP5: 58.4 ± 23.2, MTNOP6:57.0 ± 22.4, MTNOP7: 56.1 ± 21.7, MTNOP8: 55.3 ± 21.4, MTNOP9:55.0 ± 21.4 (mean ± SD). The MT for any NOP can be well predicted(R2 = 0.9997), knowing just the MTNOP4 and MTNOP5, by the fol-lowing hyperbolic equation: MT (NOPx)=0.47*MTNOP4*(NOPx-1)-b + 0. 87*MTNOP5, where b = MTNOP5/MTNOP4.

Conclusion: This study shows that the stimulation with a train ofmore than five pulses does not lower efficiently the MT of the MEPs.The ‘MT-NOP’ curve can be approximated by a hyperbolic function.

doi:10.1016/j.clinph.2013.12.015

13. Integrative action of axon’s membrane explored by subthreshold stimulation of the peripheral nerve fibres—BeatrizArranz Arranz a, Javier Urriza b, Sedat Ulkatan c, Vedran Deletis c

(a Dept of Clin Neurophys, Virgen de la Arrixaca Hospital, Murcia,Spain, b Dept of Clin Neurophys, Pamplona-Navarra, Spain, c St.Luke’s Roosevelt Hospital, Intraoperative Neurophysiology, NY,United States)

Introduction: Bostock et al. [J Physiol 564.3 93–1940, 2005]showed thatwhen the current of subthreshold intensity is appliedto the peripheral nerve it will make the axon hyperexcitable. Weexperimented with a modified method of Bostock et al. by usingmultiple subthreshold stimuli to the median nerve. We were ableto show integrative action of axon’s membrane.

Method: In 6 healthy subjects and 17 patients who underwentmonitoring for low spine surgery, we stimulated the median nerveat the wrist (in most of them bilaterally) with percutaneous elec-trodes, using near-the-threshold one to nine, constant-current stim-uli at a duration of 500 microseconds Interstimulus interval betweenstimuli was 2 ms. In the patient group recordings of the compound-muscle action-potential (CMAP) were done from opponens pollicismuscle using EEG needle electrodes, while in healthy subjects we

used surface electrodes. TIVA without muscle relaxant was used inall patients and measurements were performed at the end ofsurgery.

Result: In all healthy subjects and patients a single near-the-threshold stimulus did not generate CMAP. When the number ofnear-the-threshold stimuli was increased to two, five, seven, or ninestimuli and packed in a short train with inter stimulus intervals of2 ms, this resulted in the successful eliciting of CMAP amplitudefrom 100 to 200 microvolts.

Conclusion: We concluded that the described phenomenon mightbe explained by the integrative action of the axonal membranewhich is capable of summating the trains of sub-threshold stimuli,increasing the resting potential to the firing level and consequentlygenerating CMAP. This is due to the effect of sub threshold stimulushyperexcitability. This phenomenon is not very well explored in clin-ical neurophysiology, and needs more attention. This could lead toexplanations of some neurophysiologic phenomena during intraop-erative monitoring.

doi:10.1016/j.clinph.2013.12.016

14. The new math of EEG: Symbolic transfer entropy, the effectsof dimension—John McAuliffe (Cincinnati Children’s Hospital,United States)

Introduction: Symbolic transfer entropy (STE) and transfer entropy(TE) has been proposed as a means to detect exchange of informationbetween two signal sources, such as areas of the brain 1. The compu-tation of STE and TE assumes that the time series that make up thesignals to be analysed have been properly embedded in a higherdimensional space. The significance of dimension is examined.

Materials and methods: The analysis was conducted using simu-lated signals consisting of Gaussian noise, coupled Lorenz oscillators,sum-of-sinusoids and a combination of the Lorenz oscillators andsinusoids. Normalized STE was calculated according to 2 using arange of dimensions and delay values for data sets of 2500 datapoints. The data sets were padded with Gaussian noise in order toinduce a time lag between the driver signal and the respondingsignal.

Results: Gaussian noise posed the biggest challenge at D = 3 or 4.In both cases the calculated direction of information flow was + 1or �1 for 60% of the data sets whereas 60% were correctly labelleda zero at D = 5. Otherwise D = 3 or 4 correctly identified the directionof information flow for the Lorenz data sets and the combinationdata sets. D = 5 performed best at identifying the lack of net informa-tion flow in the sum-of-sinusoids data sets. Increasing delay values,tau, resulted in proportionally greater increases in calculated reverseinformation flow than forward flow; this effect was more pro-nounced at higher dimension. NSTE was sensitive to the directionof information flow if as little as 15% the signal and the remainderbeing background.

Conclusions: NSTE may be less sensitive to false neighbours thanTE for complex reasons. The correct embedding dimension appearsto be highly dependent on the characteristics of the informationbeing analysed.

References

Anaesthesiology 2013;118:1264.J Neurophysiology 2007;97:2533.

doi:10.1016/j.clinph.2013.12.017

Society Proceedings / Clinical Neurophysiology 125 (2014) e13–e24 e17