1. Dynamic Causal Models Will Penny Olivier David, Karl Friston, Lee Harrison, Andrea Mechelli, Klaas Stephan Mathematics in Brain Imaging, IPAM, UCLA, USA, July 22 2004. V1V5SPC V1 V5 SPC Wellcome Department of Imaging Neuroscience, ION, UCL, UK.

2. Contents Neurodynamic model Hemodynamic model Model estimation and comparison Attention to visual motion Single word processing Friston et al.(2003) Neuro- Image, 19 (4), pp. 1273-1302.

3. Contents Neurodynamic model Hemodynamic model Model estimation and comparison Attention to visual motion Single word processing

4. Single region u2u2 u1u1 z1z1 z2z2 z1z1 u1u1 a 11 c

5. Multiple regions u2u2 u1u1 z1z1 z2z2 z1z1 z2z2 u1u1 a 11 a 22 c a 21

6. Modulatory inputs u2u2 u1u1 z1z1 z2z2 u2u2 z1z1 z2z2 u1u1 a 11 a 22 c a 21 b 21

7. Reciprocal connections u2u2 u1u1 z1z1 z2z2 u2u2 z1z1 z2z2 u1u1 a 11 a 22 c a 12 a 21 b 21

8. Neurodynamics Inputs Change in Neuronal Activity Neuronal Activity Intrinsic Connectivity Matrix Modulatory Connectivity Matrices Input Connectivity Matrix V1 V5 SPC

9. Contents Neurodynamic model Hemodynamic model Model estimation and comparison Attention to visual motion Single word processing

10. Hemodynamics Hemodynamic variables For each region: Hemodynamic parameters Seconds Dynamics

11. Hemodynamic saturation Sub-linear and super-linear responses to pairs of stimuli Equivalent input-output functions Neuronal impulse Neuronal impulses

12. Why have explicit models for neurodynamics and hemodynamics ? For 4 event types u 1, u 2, u 3, u 4 : In a GLM for a single region, y=X  +e, with 3 basis functions per event type (canonical,shifter, stretcher) there are 12 parameters to estimate. These relate hemodynamics directly to each stimulus. In a (single region) DCM there are 4 neuronal efficacy parameters relating neuronal activity to each stimulus And 5 hemodynamic parameters relating neuronal activity to the BOLD signal. A total of 9 parameters.

13. DCM Priors Hemodynamics Rate of signal decay: 0.65 Elimination rate: 0.41 Transit time: 0.98 Grubbs exponent: 0.32 Oxygenation fraction: 0.34 E[h] Cov[h] Neurodynamics Stability priors ensure principal Lyapunov exponent is less than zero with high probability.

14. Contents Neurodynamic model Hemodynamic model Model estimation and comparison Attention to visual motion Single word processing

15. Bayesian Estimation Relative Precision Weighting Normal densities

16. Multiple parameters One-step if C e, C p and  p are known General Linear Model

17. Nonlinear models Gauss-Newton ascent with priors Linearization Current Estimates Friston et al.(2002) Neuro- Image, 16 (2), pp. 513-530.

18. Model Comparison I V1 V5 SPC Model, m Parameters: Prior Posterior Likelihood Evidence Laplace, AIC, BIC approximations Model fit + complexity Penny et al. (2004) NeuroImage, 22 (3), pp. 1157-1172.

19. Model Comparison II V1 V5 SPC Model, m Parameters: Prior Posterior Likelihood Prior Posterior Evidence Parameter Model

20. Model Comparison III V1 V5 SPC Model, m=i V1 V5 SPC Model, m=j Model Evidences: Bayes factor: 1 to 3: Weak 3 to 20: Positive 20 to 100: Strong >100: Very Strong

21. Contents Neurodynamic model Hemodynamic model Bayesian estimation Attention to visual motion Single word processing

22. Attention to Visual Motion STIMULI 250 radially moving dots at 4.7 degrees/s PRE-SCANNING 5 x 30s trials with 5 speed changes (reducing to 1%) Task - detect change in radial velocity SCANNING (no speed changes) 6 normal subjects, 4 100 scan sessions; each session comprising 10 scans of 4 different condition 1.Photic 2.Motion 3.Attention Experimental Factors Buchel et al. 1997

23. Specify regions of interest Identify regions of Interest eg. V1, V5, SPC GLM analysis V1 V5 SPC Motion Photic Att Model 1

24. V1 V5 SPC Motion Photic Att Model 1 V1 V5 Estimation SPC Time (seconds)

25. Posterior Inference B 3 21 P(B 3 21 |y)  How much attention (input 3) changes connection from V1 (region 1) to V5 (region(2)

26. V1 V5 SPC Motion Photic Att Model 1 Motion Photic Att V1 V5 SPC Model 2 Bayes Factor B 12 > 10 19 Very Strong

27. V1 V5 SPC Motion Photic Att Model 1 V1 V5 SPC Motion Photic Att Model 3 Bayes Factor B 13 =3.6 Positive

28. V1 V5 SPC Motion Photic Att Model 1 Motion Photic Att V1 V5 SPC Model 4 Bayes Factor B 14 =2.8 Weak Penny et al. (2004) NeuroImage, Special Issue.

29. Contents Neurodynamic model Hemodynamic model Bayesian estimation Attention to visual motion Single word processing

30. SPM{F} “dog” “radio” “gate” …. 10,15,30, 60 and 90 words per minute

31. A2 WA A1 0.92 0.38 0.47 -0.62 -0.51 0.37 Input 1: Word Presentation Input 1 Estimated Model Intrinsic connections: Full connectivity assumed – only significant connections shown. Modulatory connections: modulation of all self-connections, only A1 and WA significant

32. Hemodynamic saturation in A1 Seconds y Summed individual responses Response to pair Individual Stimuli Pair of Stimuli

33. Neuronal Saturation in A1 Seconds ztzt modulation of A1 self connection With or without A1 -0.62

34. Identifiability Estimation of relative intrinsic connections and modulatory connections is robust to errors in estimation of hemodynamics due to eg. slice timing problems Indeterminacy in neurodynamic and hemodynamic time constants is soaked up in  u2u2 z1z1 z2z2 u1u1 -- c a 12 a 21 b 21 --

35. Summary Neurodynamic model Hemodynamic model Bayesian estimation Attention to visual motion Single word processing

36. Neuronal Transients and BOLD 300ms500ms More enduring transients produce bigger BOLD signals Seconds

37. BOLD is sensitive to frequency content of transients Seconds Relative timings of transients are amplified in BOLD Neurodynamics Hemodynamics