The M/EEG inverse problem Gareth R. Barnes Format • What is an inverse problem • Prior knowledge- links to popular algorithms. • Validation of prior knowledge/ Model evidence Inverse problems aren’t difficult The forward problem Predicted 0.08 Prediction 0.06 0.04 0.02 M/EEG sensors 0 Lead fields (determined by head model) describe the sensitivity of an M/EEG sensor to a dipolar source at a particular location -0.02 -0.04 -0.06 -0.08 Lead fields (L) Head Model Model describes conductivity & geometry Dipolar source Measurement (Y) Prediction ( Y ) Predicted Measured 0.08 0.1 0.06 0.08 0.04 0.06 0.02 0.04 0 0.02 0 -0.02 -0.02 -0.04 -0.04 -0.06 Forward problem -0.06 -0.08 -0.08 Y LJ Generated source activity M/EEG sensors Prior info brain ? Current density Estimate J Measurement (Y) Prediction ( Y ) Predicted Measured 0.08 0.1 0.06 0.08 0.04 0.06 0.02 0.04 0 0.02 0 -0.02 -0.02 -0.04 -0.04 -0.06 -0.06 -0.08 -0.08 brain ? J WY Forward problem Generated source activity M/EEG sensors Y LJ Prior info Current density Estimate J Inversion depends on choice of source covariance matrix (prior information) ' 1 W CL ( R LCL ) ' Sensor Noise (known) sources 2 Lead field (known) sources 4 6 8 Generated source activity Source covariance matrix, One diagonal element per source 10 12 14 Prior information 16 2 4 6 8 10 12 14 16 Single dipole fit Y (measured field) PREDICTED Measured Predicted 0.1 0.02 0.08 0.015 0.06 0.01 0.04 0.005 0.02 0 0 -0.005 400 -0.02 -0.04 -0.01 -0.015 -0.08 -0.02 350 -0.06 200 250 time ms 300 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 11.21 (10.26) log-evidence = 53.1 -0.025 2 150 4 6 8 100 10 J 12 2 4 6 -0.2 50 16 -0.15 -0.1 -0.05 0 0.05 0.1 14 8 10 12 14 16 -0.1 -0.05 0 0.05 0.1 0.15 0.2 2 -0.15 4 -0.2 12 100 8 4 200 250 time ms 2 6 10 6 8 10 12 300 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 99.78 (91.33) log-evidence = 112.8 150 350 -0.02 -0.02 -0.04 -0.04 400 -0.06 -0.25 50 Y (measured field) Single dipole fit Measured 14 16 14 16 PREDICTED Predicted 0.1 0.08 0.08 0.06 0.06 0.04 0.04 0.02 0.02 0 0 -0.08 -0.06 -0.08 J -0.2 -0.15 -0.1 -0.05 0 0.05 0.1 0.15 0.2 12 100 8 4 200 250 time ms 2 6 16 2 4 6 8 300 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 99.78 (91.33) log-evidence = 112.8 150 350 400 -0.06 -0.25 50 Y (measured field) Two dipole fit Measured 14 10 12 14 16 PREDICTED 0.1 Predicted 0.08 0.08 0.06 0.06 0.04 0.04 0.02 0.02 0 0 -0.02 -0.02 -0.04 -0.04 -0.08 -0.06 -0.08 10 J Measured PREDICTED Predicted 0.1 0.1 0.08 0.08 0.06 0.06 0.04 0.04 0.02 0.02 0 0 -0.02 -0.0 400 -0.04 -0.06 -0.0 -0.08 200 250 time ms 300 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 98.49 (90.16) log-evidence = 93.1 350 -0.0 22 44 150 66 88 100 10 10 12 12 J -4 50 -3 16 16 -2 -1 0 1 2 14 14 3 4 Minimum norm Y (measured field) 22 44 66 88 10 10 12 12 14 14 16 16 Beamformer Y (measured field) PREDICTED Measured Predicted 0.1 0.1 0.08 0.06 0.08 0.04 0.06 0.02 0.04 0 0.02 -0.02 0 -0.04 -0.02 400 -0.06 -0.08 -0.04 350 -0.06 4 6 8 10 12 14 16 0 0.1 0.2 0.4 10 8 150 0.3 12 0.5 0.6 6 100 0.7 0.8 0.9 -0.02 -0.01 0 0.01 1 0.02 -0.03 50 2 0.03 4 *Assuming no correlated sources PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 99.18 (90.78) log-evidence = 99.9 14 200 250 time ms 2 16 at 57, -26, 9 mm 300 Projection onto lead field* -0.08 fMRI biased dSPM (Dale et al. 2000) Y (measured field) Measured PREDICTED Predicted 0.1 0.1 0.08 0.06 0.08 0.04 0.06 0.02 0.04 0 0.02 -0.02 0 -0.04 -0.02 -0.06 -0.04 400 -0.08 -0.06 200 250 time ms estimated response - condition 1 at 57, -26, 9 mm 300 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 99.18 (90.78) log-evidence = 99.9 350 -0.08 2 2 4 4 6 1 0.9 0.8 0.7 6 8 0.6 150 8 10 0.5 10 0.4 100 12 12 14 0.3 0.2 fMRI data 12 14 16 16 2 4 -0.02 10 -0.01 8 0 6 0.01 4 0.02 0.03 2 6 8 -0.03 50 14 16 10 0.1 12 14 16 0 Maybe… Some popular priors 2 4 6 8 10 12 14 16 0 16 0.1 14 2 0.2 12 0.3 4 0.4 0.5 8 0.6 Minimum norm 8 SAM,DICs Beamformer 10 6 6 10 0.7 4 0.8 12 0.9 2 14 1 16 2 4 6 8 10 12 14 16 1 2 2 0.9 4 4 0.8 6 6 Dipole fit 8 0.7 LORETA 0.6 8 0.5 10 10 12 12 14 14 0.2 16 0.1 0.4 16 2 4 6 8 10 12 14 0.3 16 2 1 2 0.9 4 0.8 fMRI biased dSPM 8 10 12 14 16 2 6 4 0.5 8 10 0.4 10 12 0.3 6 ? 8 12 10 0.2 14 14 12 0.1 16 2 4 6 8 10 12 14 16 0 0 4 0.6 8 6 2 0.7 6 4 16 2 14 16 4 6 8 10 12 14 16 Summary • MEG inverse problem requires prior information in the form of a source covariance matrix. • Different inversion algorithms- SAM, DICS, LORETA, Minimum Norm, dSPM… just have different prior source covariance structure. • Historically- different MEG groups have tended to use different algorithms/acronyms. See Mosher et al. 2003, Friston et al. 2008, Wipf and Nagarajan 2009, Lopez et al. 2013 Software • SPM12: http://www.fil.ion.ucl.ac.uk/spm/software/spm12/ • DAiSS- SPM12 toolbox for Data Analysis in Source Space (beamforming, minimum norm and related methods), developed by collaboration of UCL, Oxford and other MEG centres.https://code.google.com/p/spmbeamforming-toolbox/ • Fieldtrip : http://fieldtrip.fcdonders.nl/ • Brainstorm:http://neuroimage.usc.edu/brainstorm/ • MNE: http://martinos.org/mne/stable/index.html Which priors should I use ? • Compare to other modalities.. fMRI Singh et al. 2002 MEG beamformer • Use model comparison… rest of the talk. x 10 -4 50 -3 -2 -1 0 -0.031 50 -0.02 2 3 4 -0.01 0 -3 100 100 150 300 200 250 time ms 300 200 250 time ms 6 8 10 0.02 0.015 0.01 0.005 0 96% 12 14 16 300 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 98.49 (90.16) log-evidence = 93.1 150 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 99.18 (90.78) log-evidence = 99.9 150 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 99.78 (91.33) log-evidence = 112.8 estimated response - condition 1 at 65, -21, 11 mm 200 250 time ms 4 1 100 0.9 -0.25 0.01 50 0.8 2 Predicted 2 11 % 16 0.7 Y 14 4 Predicted 12 0.6 0.02 10 6 -0.2 14 8 -0.15 512 dipoles Percent variance explained 11.21 (10.26) log-evidence = 53.1 8 0.5 6 16 350 350 350 0.4 4 0.3 2 12 10 14 0.2 12 400 400 400 0 16 10 12 8 16 8 14 10 6 12 6 10 14 4 8 Variance explained -0.08 4 6 J 2 0.06 0.04 0.02 0 -0.005 -0.02 -0.01 -0.04 -0.015 -0.06 -0.08 97% 4 Prior -0.06 2 0.1 -0.04 2 Measured 16 Y (measured field) How do we chose between priors ? 0.1 0.08 0.06 0.04 0.02 0 -0.02 2 4 6 10 8 12 14 16 2 Predicted 4 6 8 10 12 0.08 -0.02 -0.025 -0.08 98% 14 16 0.1 0.08 Predicted 0 0.06 0 0.04 0 0.02 0 0 0 -0.02 0 -0.04 - -0.06 - - Y Prediction ( Measurement (Y) Forward problem Generated source activity Eyes True recipe J ) Estimated recipe J Use prior info (possible ingredients) Y Prediction ( 2 4 6 8 10 Diagonal elements correspond to ingredients 12 14 16 2 4 6 8 10 12 14 16 ) Forward problem Generated source activity Measurement (Y) J 2 4 6 8 10 12 14 16 16 14 12 10 8 6 4 C 2 2 4 6 8 10 12 B 14 16 2 4 6 8 10 12 14 16 2 4 2 6 4 8 6 10 8 12 10 A 14 12 16 2 14 4 6 8 10 12 14 16 16 2 Possible priors 4 6 8 10 12 14 Which is most likely prior (which prior has highest evidence) ? Y Prediction ( 2 A 4 6 8 10 ? 12 14 16 16 10 12 14 14 8 16 12 6 0 J 0.1 10 8 B 12 0.2 0.3 0.4 0.5 0.6 2 6 0.7 4 4 C 0.8 6 2 0.9 1 10 4 8 2 6 14 4 16 2 8 10 12 14 16 2 4 6 8 10 12 14 16 ) Forward problem Generated source activity Measurement (Y) Consider 3 generative models 2 4 6 8 10 12 14 16 2 0 16 4 0.1 14 6 0.2 0.3 12 0.4 10 8 10 0.5 8 12 0.6 6 14 0.7 10 12 14 16 1 8 0.9 6 0.8 P(Y) 4 2 2 4 16 2 Evidence 4 6 8 10 12 14 16 2 4 6 8 10 12 14 16 Area under each curve=1.0 Space of possible datasets (Y) Complexity Cross validation or prediction of unknown data Prediction (Y ) 2 A 4 6 Forward problem Generated source activity Measurement (Y) 8 10 ? 12 14 16 16 10 12 14 14 8 16 12 6 0 J 0.1 10 8 B 12 0.2 0.3 0.4 0.5 0.6 2 6 0.7 4 4 C 0.8 6 2 0.9 1 10 4 8 2 6 14 4 16 2 8 10 12 14 16 2 4 6 8 10 12 14 16 Polynomial fit example 4 parameter fit y Training data 2 parameter fit x The more parameters in the model the more accurate the fit (to training data). Polynomial fit example 4 parameter fit y 2 parameter fit test data x The more parameters the more accurate the fit to training data, but more complex model may not generalise to new (test) data. Fit to training data 0.4 Training data 0.2 Predicted 0.08 0.06 0.04 2 0 -0.02 -0.04 -0.06 -0.08 Predicted 0.02 4 0 6 O 8 10 12 14 -0.2 GS IID 16 2 4 6 8 10 12 14 16 2 4 -0.4 6 x 8 10 12 -0.6 -0.6 14 16 -0.4 -0.2 0 Measured 0.2 0.4 2 4 6 8 10 Measured 0.1 0.08 0.06 0.04 0.02 0 -0.02 -0.04 -0.06 -0.08 More complex model fits training data better 12 14 16 Fit to test data 0.4 Predicted 0.2 0.08 0.06 0.04 2 0.02 4 -0.02 -0.04 -0.06 -0.08 Predicted 0 6 0 O 8 10 12 14 16 -0.2 2 GS IID -0.4 4 6 8 10 12 14 16 2 4 6 x 8 10 12 14 -0.6 -0.6 16 2 -0.4 -0.2 0 Measured 0.2 0.4 Measured 0.1 0.08 0.06 0.04 0.02 0 -0.02 -0.04 -0.06 -0.08 Simpler model fits test data better 4 6 8 10 12 14 16 Relationship between model evidence and cross validation 2 4 1 6 8 2 0.9 4 0.8 Random priors 0.7 6 10 0.6 0.5 10 14 20 1 8 12 2 4 6 8 10 12 14 16 0.9 4 0.8 0.4 0.3 12 16 2 0.7 0.2 6 14 0.6 0.1 8 0.5 16 2 4 6 8 10 12 14 16 0 10 0.4 12 0.3 log Model evidence 0.2 14 15 0.1 16 2 4 6 8 10 12 14 0 16 1 10 2 0.9 4 0.8 0.7 6 0.6 8 0.5 10 0.4 12 0.3 0.2 14 5 0.1 16 2 4 6 8 10 12 14 16 0 1 0 0.37 2 0.9 4 0.8 0.7 0.4 0.39 0.38 Cross Cross validation validation accuracy error 0.41 6 0.6 8 0.5 10 0.4 12 0.3 0.2 14 0.1 16 2 Can be approximated analytically… 4 6 8 10 12 14 16 0 -0.02 2 3 4 -0.01 0 -4 50 -3 -2 -1 0 -0.031 50 x 10 -3 100 100 100 150 300 200 250 time ms 300 200 250 time ms 12 0.02 0.015 0.01 0.005 0 Dip 2 14 16 300 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 98.49 (90.16) log-evidence = 93.1 150 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 99.18 (90.78) log-evidence = 99.9 150 PPM at 188 ms (100 percent confidence) 512 dipoles Percent variance explained 99.78 (91.33) log-evidence = 112.8 estimated response - condition 1 at 65, -21, 11 mm 200 250 time ms 0.9 -0.25 0.01 50 0.8 0.02 10 1 8 Predicted 2 -0.2 6 0.7 4 4 Dip 1 2 0.6 Y 16 6 -0.15 14 8 Predicted 12 0.5 10 350 350 350 0.4 8 0.3 6 0.2 4 16 10 14 12 14 400 400 400 0.1 2 12 0 12 16 16 10 14 8 12 8 10 10 6 8 6 6 Log model evidence 14 4 0.06 0.04 0.02 0 -0.005 -0.02 -0.01 -0.04 -0.015 -0.06 -0.08 BMF 4 J 2 4 2 Prior 2 16 512 dipoles Percent variance explained 11.21 (10.26) log-evidence = 53.1 How do we chose between priors ? 2 4 6 8 10 12 14 16 2 Predicted 4 6 8 10 12 14 0.08 -0.02 -0.025 -0.08 30 20 10 0 Min Norm 16 0.1 Predicted 0.08 0 0.06 0 0.04 0 0.02 0 0 0 -0.02 0 -0.04 - -0.06 - - Muliple Sparse Priors (MSP), Champagne Candidate Priors Prior to maximise model evidence l1 l2 l3 ln 0 0 -2 -0.5 Multiple0 Sparse priors -0.5 -0.5 -1 So now construct the priors to maximise model evidence -1 -1 (minimise cross validation error). -1.5 8 10 -1.5 -1.5 -4 -6 -2 -8 0 100 200 -2 300 0400 time ms 500 100 600 200 -2 700 300 4000 time ms 500 100 600 200 700 300 400 time ms 0 100 500 200 600 300 400 time ms 700 500 6 10 PPM at 229 ms (100 percent confidence) PPM at 229 ms (100 percent confidence) 512 dipoles 512 dipoles Percent variance explained 99.15 (65.03)Percent variance explained 99.93 (65.54) log-evidence = 8157380.8 log-evidence = 8361406.1 4 Free energy Accuracy Accuracy Free Energy Complexity Compexity PPM at 229 ms (100 percent confidence) 512 dipoles Percent variance explained 99.87 (65.51) log-evidence = 8388254.2 10 PPM at 229 ms (100 percent confidence) 512 dipoles Percent variance explained 99.90 (65.53) log-evidence = 8389771.6 2 10 0 50 100 Iteration 150 6 Conclusion • MEG inverse problem can be solved.. If you have some prior knowledge. • All prior knowledge encapsulated in a source covariance matrix. • Can test between priors (or develop new priors) using cross validation or Bayesian framework. References • • • • Mosher et al., 2003 J. Mosher, S. Baillet, R.M. Leahi Equivalence of linear approaches in bioelectromagnetic inverse solutions IEEE Workshop on Statistical Signal Processing (2003), pp. 294–297 • • • • Friston et al., 2008 K. Friston, L. Harrison, J. Daunizeau, S. Kiebel, C. Phillips, N. Trujillo-Barreto, R. Henson, G. Flandin, J. Mattout Multiple sparse priors for the M/EEG inverse problem NeuroImage, 39 (2008), pp. 1104–1120 • • • • Wipf and Nagarajan, 2009 D. Wipf, S. Nagarajan A unified Bayesian framework for MEG/EEG source imaging NeuroImage, 44 (2009), pp. 947–966 Thank you • • • • • • Karl Friston Jose David Lopez Vladimir Litvak Guillaume Flandin Will Penny Jean Daunizeau • • • • • • Christophe Phillips Rik Henson Jason Taylor Luzia Troebinger Chris Mathys Saskia Helbling And all SPM developers Analytical approximation to model evidence • Free energy= accuracy- complexity What do we measure with EEG & MEG ? From a single source to the sensor: MEG MEG EEG
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