1. Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns: Einführung und Motivation(Teil 2) Priv.-Doz. Dr. Carsten Wolters Dr.rer.nat. Harald Kugel Dr.med. Gabriel Möddel Priv.Doz. Dr. med. Christoph Kellinghaus Priv.-Doz. Dr. Carsten Wolters Dr.rer.nat. Harald Kugel Dr.med. Gabriel Möddel Priv.Doz. Dr. med. Christoph Kellinghaus Vorlesung, 29.Oktober 2013

2. Carsten Wolters, IBB, WWU Münster Outline Updated planning for the lecture Further introduction to the lecture Serving as a subject in our DFG-project Updated planning for the lecture Further introduction to the lecture Serving as a subject in our DFG-project

3. Carsten Wolters, IBB, WWU Münster Aktuelle Vorlesungsplanung 15.Oktober: Vorbesprechung und erste Einführung und Motivation (Wolters) 22.Oktober: Einführung Magnetresonanztomographie (MRT) (Kugel) 29.Oktober: Weitere Einführung und Motivation zur Vorlesung (Vorwerk, Wagner, Lucka, Wolters) 5.Nov.: Einführung Magnetresonanztomographie (MRT), Teil 2 (DTI, fMRI, k-Raum) (Kugel) 12.Nov.: Mathematisch-physikalische Modellierungsgrundlagen zu EEG und MEG (Wolters) 19.Nov.: Grundlagen von Epilepsie und EEG (Kellinghaus) 26.Nov.: Epileptische Anfälle und ihre Behandlung (Kellinghaus) 3.Dez.: Registrierung von MRT: Teil 1 (Wolters) 10.Dez3.: Registrierung von MRT: Teil 2 (Wolters) 17.Dez.: Segmentierung von MRT (Wolters) 7.Jan.: Mathematik des EEG/MEG Vorwärtsproblems, Teil 1 (Wolters) 14.Jan.: Mathematik des EEG/MEG Vorwärtsproblems, Teil 2 (Wolters) 21.Jan.: Mathematik des EEG/MEG inversen Problems, Teil 1 (Wolters) 28.Jan.: Mathematik des EEG/MEG inversen Problems, Teil 2 (Wolters) 4.Feb.: Epilepsiechirurgie, Teil 3 (Möddel) 15.Oktober: Vorbesprechung und erste Einführung und Motivation (Wolters) 22.Oktober: Einführung Magnetresonanztomographie (MRT) (Kugel) 29.Oktober: Weitere Einführung und Motivation zur Vorlesung (Vorwerk, Wagner, Lucka, Wolters) 5.Nov.: Einführung Magnetresonanztomographie (MRT), Teil 2 (DTI, fMRI, k-Raum) (Kugel) 12.Nov.: Mathematisch-physikalische Modellierungsgrundlagen zu EEG und MEG (Wolters) 19.Nov.: Grundlagen von Epilepsie und EEG (Kellinghaus) 26.Nov.: Epileptische Anfälle und ihre Behandlung (Kellinghaus) 3.Dez.: Registrierung von MRT: Teil 1 (Wolters) 10.Dez3.: Registrierung von MRT: Teil 2 (Wolters) 17.Dez.: Segmentierung von MRT (Wolters) 7.Jan.: Mathematik des EEG/MEG Vorwärtsproblems, Teil 1 (Wolters) 14.Jan.: Mathematik des EEG/MEG Vorwärtsproblems, Teil 2 (Wolters) 21.Jan.: Mathematik des EEG/MEG inversen Problems, Teil 1 (Wolters) 28.Jan.: Mathematik des EEG/MEG inversen Problems, Teil 2 (Wolters) 4.Feb.: Epilepsiechirurgie, Teil 3 (Möddel)

4. Carsten Wolters, IBB, WWU Münster Outline Updated planning for the lecture Further introduction to the lecture Serving as a subject in our DFG-project Updated planning for the lecture Further introduction to the lecture Serving as a subject in our DFG-project

5. Carsten Wolters, IBB, WWU Münster EEG and MEG source analysis: Source model and the forward problem

6. Carsten Wolters, IBB, WWU Münster Gray and White Matter Gray matter (GM) Gray matter (GM) White matter (WM) T1 weighted Magnetic Resonance Image (T1-MRI) T1 weighted Magnetic Resonance Image (T1-MRI)

7. Carsten Wolters, IBB, WWU Münster + - - cell body sink source ~30 mm 2 = 5.5×5.5 mm 2 Size of Macroscopic Neural Activity Equivalent Current Dipole (Primary current) (~50 nAm) parameters: position : x 0 moment : M cortex synapse - + Microscopic current flow (~5×10 -5 nAm) The source model

8. Carsten Wolters, IBB, WWU Münster EEG forward problem Compute the EEG Place a dipole Simulate quasistatic Simulate quasistatic Maxwell equations

9. Carsten Wolters, IBB, WWU Münster MEG forward problem Compute the MEG Place a dipole Simulate quasistatic Simulate quasistatic Maxwell equations

10. Carsten Wolters, IBB, WWU Münster A 5 compartment volume conductor model Skin0.33 S/m Skullanisotropic/ 3-layer CSF1.79 S/m Gray matter0.33 S/m White matteranisotropic

11. Carsten Wolters, IBB, WWU Münster Three-layered human skull

12. Carsten Wolters, IBB, WWU Münster Anisotropy of white matter (WM) Longitudinally: 9 Transversally: 1

13. Carsten Wolters, IBB, WWU Münster Volume conductor modeling Spherical shells GeometryConductivity Skinunreal. Skullunreal. CSFunreal. GMunreal. WMunreal. GeometryConductivity Skinrealistic Skullrealisticunreal. CSF unrealistic (1 isotropic value) GM WM Boundary element Finite Element (FE) GeometryConductivity Skinrealistic Skullrealistic CSFrealistic GMrealistic WMrealistic

14. Carsten Wolters, IBB, WWU Münster State-of-the-art finite element volume conductor model [Pursiainen, Lucka & Wolters, Phys Med Biol, 2012] [Drechsler, Wolters, Dierkes & Grasedyck, NeuroImage, 2009] [Lew, Wolters, Dierkes, Röer & MacLeod, Appl. Num. Math., 2009] [Wolters, Köstler, Möller, Härtlein, Grasedyck & Hackbusch, SIAM Journal on Scientific Computing, 2007] [Wolters, Anwander, Berti & Hartmann, IEEE Trans Biomed.Eng., 2007] [Wolters, Anwander, Reitzinger & Kuhn, Comp.Vis.Sci., 2002]

15. Carsten Wolters, IBB, WWU Münster Validation of forward and inverse modeling

16. Carsten Wolters, IBB, WWU Münster Multilayer sphere model 134 regularly distributed electrodes: On a sphere with radius: 92mm Needle electrode (“point in space”) 134 regularly distributed electrodes: On a sphere with radius: 92mm Needle electrode (“point in space”) 4-layer sphere model with 3-layer skull: Radii: 92, 86:84:82:80, 78mm; Cond.: 0.33, 0.0062:0.021:0.0049, 1.79, 0.33 S/m Sources: Depth from midpoint to CSF boundary 4-layer sphere model with 3-layer skull: Radii: 92, 86:84:82:80, 78mm; Cond.: 0.33, 0.0062:0.021:0.0049, 1.79, 0.33 S/m Sources: Depth from midpoint to CSF boundary

17. Carsten Wolters, IBB, WWU Münster Tetrahedra mesh: Coarse in brain, fine in CSF/skull/skin compartment: Nodes: 360,056 Elements: 2,165,281 Tetrahedra mesh: Coarse in brain, fine in CSF/skull/skin compartment: Nodes: 360,056 Elements: 2,165,281 Constrained Delaunay Tetrahedralization [Drechsler, Wolters, Dierkes, Si & Grasedyck, NeuroImage, 2009]

18. Carsten Wolters, IBB, WWU Münster Validation: FEM validated with analytic 4% 3% 1% 0% 2% 15% 10% 5% 0% [Drechsler, Wolters, Dierkes & Grasedyck, NeuroImage, 2009] [Lew, Wolters, Dierkes, Röer & MacLeod, Appl. Num. Math., 2009] [Wolters, Köstler, Möller, Härtlein, Grasedyck & Hackbusch, SIAM Journal on Scientific Computing, 2007] [Wolters, Anwander, Berti & Hartmann, IEEE Trans Biomed.Eng., 2007] [Wolters, Anwander, Reitzinger & Kuhn, Comp.Vis.Sci., 2002]

19. Carsten Wolters, IBB, WWU Münster Analytic forward, FEM based dipole fit inverse: localization error due to numerical error

20. Carsten Wolters, IBB, WWU Münster Evoked Potentials (EP) and Fields (EF)

21. Carsten Wolters, IBB, WWU Münster Auditory evoked potentials (AEP) and Fields (AEF)

22. Carsten Wolters, IBB, WWU Münster Evoked responses [Gazzaniga, Ivry & Mangun, Cognitive Neuroscience, 2nd ed., W.W.Norton & Company, 2002]

23. Carsten Wolters, IBB, WWU Münster Auditory evoked potential (AEP) [Gazzaniga, Ivry & Mangun, Cognitive Neuroscience, 2nd ed., W.W.Norton & Company, 2002] Only contralateral path is shown.

24. Carsten Wolters, IBB, WWU Münster Combined EEG/MEG measurement in lying position Combined EEG/MEG measurement in lying position presentation of 800ms sine tones presentation of 800ms sine tones 350, 1400 and 5600Hz 350, 1400 and 5600Hz Stimulus Offset Asynchrony (SOA) of 3.5 to 4.5sec Stimulus Offset Asynchrony (SOA) of 3.5 to 4.5sec 3rd order synthetic gradiometer 3rd order synthetic gradiometer Baseline correction using -200ms to 0ms Baseline correction using -200ms to 0ms 1-20 Hz filter 1-20 Hz filter Voltage-threshold-based eye artefact rejection Voltage-threshold-based eye artefact rejection Tonotopy in auditory cortex: Preliminary results

25. Carsten Wolters, IBB, WWU Münster MGFP

26. SNR

27. Example Signals A0206 350 Hz 1400 Hz 5600 Hz MEG SNR: 8.3 EEG SNR: 12.5 MEG SNR: 14.0 EEG SNR: 18.2 MEG SNR: 14.5 EEG SNR: 13.9

28. Carsten Wolters, IBB, WWU Münster Example Topographies A0206 5600 Hz 350 Hz 1400 Hz

29. Carsten Wolters, IBB, WWU Münster Two dipole Solution

30. Carsten Wolters, IBB, WWU Münster Auditory tonotopy: Preliminary results Discussion and outlook Result1: 2 of 3 subjects show a trend of more medially localized dipoles with increasing frequency, in agreement with findings of (Pantev et al., 1988; Yamamato et al., 1988; Lütkenhöner et al., 1998).Result1: 2 of 3 subjects show a trend of more medially localized dipoles with increasing frequency, in agreement with findings of (Pantev et al., 1988; Yamamato et al., 1988; Lütkenhöner et al., 1998). Result2: No trend was observed for inferior-superior or anterior- posterior locations.Result2: No trend was observed for inferior-superior or anterior- posterior locations. Outlook: Additional subjects will be studied to obtain statistically more significant results.Outlook: Additional subjects will be studied to obtain statistically more significant results.

31. Carsten Wolters, IBB, WWU Münster Somatosensory evoked potentials (SEP) and Fields (SEF)

32. Carsten Wolters, IBB, WWU Münster SEP/SEF source analysis using the FEM

33. Carsten Wolters, IBB, WWU Münster EEG/MEG calibration using SEP/SEF data EEG SNR: 24dB MEG SNR: 30dB Brain conductivity of 0.332 S/mBrain conductivity of 0.332 S/m Skull conductivity of 0.0133 S/m (=> brain:skull ratio of 25)Skull conductivity of 0.0133 S/m (=> brain:skull ratio of 25) Explained variance; SEP 93%, SEF 96.1%Explained variance; SEP 93%, SEF 96.1% [Wolters, Lew, Hämäläinen & MacLeod, Proc. DGBMT, 2010]

34. Carsten Wolters, IBB, WWU Münster SEP/SEF source analysis results SEP dipole (red) and SEF dipole (blue) [Lanfer, diploma thesis, 2007]

35. Carsten Wolters, IBB, WWU Münster S1 and M1 homunculi

36. Carsten Wolters, IBB, WWU Münster Clinical applicability of SEP/SEF source analysis [Roberts, Poeppel and Rowley, MEG and magnetic source imaging, Neuropsychiatry Neuropsych.Behav.Neurol., 11, pp.49-64, 1998] Tumor near the central sulcus

37. Carsten Wolters, IBB, WWU Münster Clinical applicability of SEP/SEF source analysis [Roberts, Poeppel and Rowley, MEG and magnetic source imaging, Neuropsychiatry Neuropsych.Behav.Neurol., 11, pp.49-64, 1998] Tactile stimulation of the right index finger: SEF (left) and fitted dipole (right)

38. Carsten Wolters, IBB, WWU Münster Clinical applicability of SEP/SEF source analysis [Roberts, Poeppel and Rowley, MEG and magnetic source imaging, Neuropsychiatry Neuropsych.Behav.Neurol., 11, pp.49-64, 1998] Tumor (green) and MEG dipole fits (red) for continuous stimulation of fingers and toes

39. Carsten Wolters, IBB, WWU Münster Outline Literature for this lecture Introduction to the lecture Serving as a subject in our DFG-project Literature for this lecture Introduction to the lecture Serving as a subject in our DFG-project

40. Carsten Wolters, IBB, WWU Münster Serving as a subject for our epilepsy project Institut für Biomagnetismus und BiosignalanalyseMalmedyweg 15Direkt hinter der HNO Klinikhttp://biomag.uni-muenster.decarsten.wolters@uni-muenster.de

41. Carsten Wolters, IBB, WWU Münster Thank you for your attention!