Mapping human cortical excitability through coupling between robotized TMS and EEG 1. IRMaGe / CNRS - UGA / Grenoble, France 2. Lab. of Psy. and NeuroCognition / CNRS - UGA / Grenoble, France 3. Gipsa-Lab / CNRS - UGA / Grenoble, France 4. Grenoble Neuosciences Institute / INSERM - UGA / Grenoble, France Time (ms) 0 10 20 30 40 P-value Local TEPs 0.05 0.5 1 0 3 5 1 2 3 Z-score Results Introduction Materials & Methods Conclusion Measuring cortical excitability (CE) of the motor cortex is a mandatory step prior to any experiment involving transcranial magnetic stimulations (TMS), because it determines both stimulation dose and safety limits [1]. However, generalization of the motor CE level to other cortical areas is not straightforward because of the very specific cytoarchitecture of the primary motor cortex. Combining TMS with concurrent electroencephalographic (EEG) recordings is a way to assess CE on any cortical areas, by studying the early components of the TMS evoked potentials (TEP) [2]. * Protocol design anatomical MRI motor CE TMS-EEG TMS-EEG EEG preparation 0h 0h45 1h45 2h 2h30 2h45 3h15 TMS parameters → Neuronavigated and robotized TMS → 18 cortical targets (9/hemisphere) → 80 single pulses per target (0.5-0.7Hz) → Intensity of 120%rMT (adjusted according to scalp-cortex distances) → rMT measured on the FDI hot spot EEG signal processing The EEG preprocessing was performed using the Fieldtrip toolbox for Matlab, and following the methodology described in [3], using two rounds of ICA. Computed TEPs showed spatio-temporal patterns specific to each cortical target: EEG parameters → 64 electrodes TMS-compatible cap → Sampling frequency: 512Hz Others → 22 healthy subjects → Active noise-canceling earphone + white noise → Stimulation targets: IFG, DLPFC, Middle Frontal Gyrus, SMA, M1, Superior Temporal Gyrus, Inferior and Superior Parietal Lobes, and Superior Occipital Lobe CE maps Local TEPs start to differ after 25 ms, where there is a significant effect of the stimulation site, regardless of the stimulation side. Maps variability and reproducibility Tested through the correlation product between the original local TEPs, and TEPs obtained with random subsets of subjects. Good reproducibility (r>0.9) achieved for groups of at least 13 subjects (r=0.75 for groups of 9). REFERENCES [1] Herbsman, T., Forster, L., Molnar, C., Dougherty, R., Christie, D., Koola, J., Ramsey, D., Morgan, P.S., Bohning, D.E., George, M.S., Nahas, Z., 2009. Motor Threshold in Transcranial Magnetic Stimulation: The Impact of White Matter Fiber Orientation and Skull-to-Cortex Distance. Hum Brain Mapp 30, 2044–2055. doi:10.1002/hbm.20649 [2] Rogasch, N.C., Fitzgerald, P.B., 2013. Assessing cortical network properties using TMS-EEG. Human Brain Mapping 34, 1652–1669. doi:10.1002/hbm.22016 [3] Rogasch, N.C., Thomson, R.H., Farzan, F., Fitzgibbon, B.M., Bailey, N.W., Hernandez-Pavon, J.C., Daskalakis, Z.J., Fitzgerald, P.B., 2014. Removing artefacts from TMS-EEG recordings using independent component analysis: Importance for assessing prefrontal and motor cortex network properties. NeuroImage 101, 425–439. doi:10.1016/j.neuroimage.2014.07.037 [4] Veniero, D., Bortoletto, M., Miniussi, C., n.d. On the challenge of measuring direct cortical reactivity by TMS-EEG. Brain Stimulation. doi:10.1016/j.brs.2014.05.009 From top to bottom: absolute amplitude of local TEPs for each stimulation site, CE maps and continuous ANOVA results, against time Number of remaining subjects 20 16 12 8 5 0.55 0.75 1 r Correlation coefficient and 95% CI ACKNOWLEDGMENTS This work was partly funded by - the French program “Investissement d’Avenir” run by the ‘Agence Nationale pour la Recherche’ ; grant ’Infrastructure d’avenir en Biologie Santé' – ANR-11-INBS-0006. - Grenoble Pôle Cognition Left Right Aims → Developing a method to map the TMS evoked EEG activity of the cortex → Studying the spatial homogeneity of the human CE Mapping feasibility → Cons: - expensive in terms of time and budget, regarding the whole procedure - preprocessing not fully data driven (choice of ICs to be rejected) → Pros: - the mapping in itself can be done in a fast and convenient way - low inter-subject variability Human CE maps The earliest components (0-25ms) are spatially homogeneous, but caution must be taken for the 0-15ms period (TMS artifacts), whereas the latter components (25-50ms) are spatially inhomogeneous, although activity from other intra-hemispheric connections might already be present [4]. → This mapping could bring useful information about regional differences in cortical excitability. It could be turned into a biomarker of cortical reactivity integrity. Average of the neighboring TEPs of each stimulation site (local TEPs, S i (t)) CE maps computation Maps were computed using the following processing pipeline: CE maps pcANOVA Z-score CE_map(t) Time (s) -0.04 0 0.04 0.08 0.12 0.16 0.2 0.24 0.28 0.32 0.36 0.4 S. Harquel 1,2 , A. Chauvin 2 , L. Beynel 2 , N. Guyader 3 , C. Marendaz 2 , O. David 4 15ms 30ms 40ms 50ms
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Mapping human cortical excitability through coupling between robotized TMS and EEG
1. IRMaGe / CNRS - UGA / Grenoble, France2. Lab. of Psy. and NeuroCognition / CNRS - UGA / Grenoble, France3. Gipsa-Lab / CNRS - UGA / Grenoble, France4. Grenoble Neuosciences Institute / INSERM - UGA / Grenoble, France
Time (ms)0 10 20 30 40
P-va
lue
Local TEPs
0.05
0.5
1
0
3
5
1
2
3
Z-sc
ore
Results
Introduction
Materials & Methods
Conclusion
Measuring cortical excitability (CE) of the motor cortex is a mandatory step prior to any experiment involving transcranial magnetic stimulations (TMS), because it determines both stimulation dose and safety limits [1]. However, generalization of the motor CE level to other cortical areas is not straightforward because of the very specific cytoarchitecture of the primary motor cortex.
Combining TMS with concurrent electroencephalographic (EEG) recordings is a way to assess CE on any cortical areas, by studying the early components of the TMS evoked potentials (TEP) [2].
*Protocol design
anatomicalMRI
motorCE TMS -EEG TMS -EEGEEG
preparation
0h 0h45 1h45 2h 2h30 2h45 3h15
TMS parameters → Neuronavigated and robotized TMS → 18 cortical targets (9/hemisphere) → 80 single pulses per target (0.5-0.7Hz) → Intensity of 120%rMT (adjusted
according to scalp-cortex distances) → rMT measured on the FDI hot spot
EEG signal processing
The EEG preprocessing was performed using the Fieldtrip toolbox for Matlab, and following the methodology described in [3], using two rounds of ICA.
Computed TEPs showed spatio-temporal patterns specific to each cortical target:
EEG parameters → 64 electrodes TMS-compatible cap → Sampling frequency: 512Hz
Others → 22 healthy subjects → Active noise-canceling earphone +
white noise → Stimulation targets: IFG, DLPFC,
Middle Frontal Gyrus, SMA, M1, Superior Temporal Gyrus, Inferior and Superior Parietal Lobes, and Superior Occipital Lobe
CE maps
Local TEPs start to differ after 25 ms, where there is a significant effect of the stimulation site, regardless of the stimulation side.
Maps variability and reproducibility
Tested through the correlation product between the original local TEPs, and TEPs obtained with random subsets of subjects. Good reproducibility (r>0.9) achieved for groups of at least 13 subjects (r=0.75 for groups of 9).
REFERENCES
[1] Herbsman, T., Forster, L., Molnar, C., Dougherty, R., Christie, D., Koola, J., Ramsey, D., Morgan, P.S., Bohning, D.E., George, M.S., Nahas, Z., 2009. Motor Threshold in Transcranial Magnetic Stimulation: The Impact of White Matter Fiber Orientation and Skull-to-Cortex Distance. Hum Brain Mapp 30, 2044–2055. doi:10.1002/hbm.20649[2] Rogasch, N.C., Fitzgerald, P.B., 2013. Assessing cortical network properties using TMS-EEG. Human Brain Mapping 34, 1652–1669. doi:10.1002/hbm.22016[3] Rogasch, N.C., Thomson, R.H., Farzan, F., Fitzgibbon, B.M., Bailey, N.W., Hernandez-Pavon, J.C., Daskalakis, Z.J., Fitzgerald, P.B., 2014. Removing artefacts from TMS-EEG recordings using independent component analysis: Importance for assessing prefrontal and motor cortex network properties. NeuroImage 101, 425–439. doi:10.1016/j.neuroimage.2014.07.037[4] Veniero, D., Bortoletto, M., Miniussi, C., n.d. On the challenge of measuring direct cortical reactivity by TMS-EEG. Brain Stimulation. doi:10.1016/j.brs.2014.05.009
From top to bottom: absolute amplitude of local TEPs for each stimulation site, CE maps and continuous ANOVA results, against time
Number of remaining subjects
20 16 12 8 5
0.55
0.7
5
1
r
Correlation coefficient and 95% CI
ACKNOWLEDGMENTS
This work was partly funded by - the French program “Investissement d’Avenir” run by the ‘Agence Nationale pour la Recherche’ ; grant ’Infrastructure d’avenir en Biologie Santé' – ANR-11-INBS-0006.- Grenoble Pôle Cognition
LeftRight
Aims
→ Developing a method to map the TMS evoked EEG activity of the cortex → Studying the spatial homogeneity of the human CE
Mapping feasibility
→ Cons: - expensive in terms of time and budget, regarding the whole procedure - preprocessing not fully data driven (choice of ICs to be rejected)
→ Pros: - the mapping in itself can be done in a fast and convenient way - low inter-subject variability
Human CE maps
The earliest components (0-25ms) are spatially homogeneous, but caution must be taken for the 0-15ms period (TMS artifacts), whereas the latter components (25-50ms) are spatially inhomogeneous, although activity from other intra-hemispheric connections might already be present [4].
→ This mapping could bring useful information about regional differences in cortical excitability. It could be turned into a biomarker of cortical reactivity integrity.
Average of the neighboring TEPs of each stimulation site (local TEPs, S
i(t))
CE maps computation
Maps were computed using the following processing pipeline:
CE maps
pcANOVA
Z-sc
ore
CE_map(t)
Time (s) -0.04 0 0.04 0.08 0.12 0.16 0.2 0.24 0.28 0.32 0.36 0.4
S. Harquel1,2, A. Chauvin2, L. Beynel2, N. Guyader3, C. Marendaz2, O. David4
15ms
30ms
40ms
50ms
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