Sam Gilbert Institute of Cognitive Neuroscience & Department of Psychology

1. Social versus nonsocial functions of rostral prefrontal cortex in typical development and autism spectrum disorders Sam Gilbert Institute of Cognitive Neuroscience & Department of Psychology

2. Rostral PFC (Area 10)

3. Gateway hypothesis (Burgess, Simons, Dumontheil & Gilbert, 2005; Burgess, Dumontheil & Gilbert, 2007) • BA 10 supports selection between stimulus-oriented and stimulus-independent thought

4. Direct test (Gilbert, Frith & Burgess, 2005; EJN) • Three separate tasks, which participants could accomplish either by using visually-presented information, or by doing the same task “in their head” • Participants alternate between “stimulus-oriented” and “stimulus-independent” phases

5. Direct test (Gilbert, Frith & Burgess, 2005; EJN) Stimulus-Oriented (SO) Stimulus-Independent (SI) Task 1 3-54s (mean: 11s)

6. Direct test (Gilbert, Frith & Burgess, 2005; EJN) Stimulus-Oriented (SO) Stimulus-Independent (SI) Task 1 3-54s (mean: 11s) ¿ A D G ? ? Task 2

7. Stimulus-Independent > Stimulus-Oriented: no active voxels Stimulus-Oriented > Stimulus-Independent: Direct test (Gilbert, Frith & Burgess, 2005; EJN) p < .05 corrected

8. Direct test (Gilbert, Frith & Burgess, 2005; EJN) • Medial BA10: focusing attention on the external environment • But how can we know that this region are causally involved in selection between stimulus-oriented and stimulus-independent thought? • Activity in medial BA10 has previously been attributed to task-unrelated thought processes during low-demand conditions (e.g. Mason et al., 2007; McKiernan et al., 2003; Wicker et al., 2003)

9. % signal change SI Daydreaming during (easy) stimulus-oriented conditions? (Gilbert, Simons, Frith & Burgess, 2006; JEP:HPP) Stimulus-Oriented (SO) > Stimulus-Independent (SI)

10. Daydreaming during (easy) stimulus-oriented conditions? (Gilbert, Simons, Frith & Burgess, 2006; JEP:HPP) % signal change Stimulus-Oriented (SO) > Stimulus-Independent (SI) Correlation with baseline RT SI

11. Mentalising / Theory of Mind Frith & Frith (2003) “the mentalizing region of the MPFC is engaged when we attend to our own mental states as well as the mental states of others”

12. Multi-Task Mentalising y=60 x=0 z=0 Functional specialization within BA 10 (Gilbert, Spengler, Simons, Steele, Lawrie, Frith & Burgess, 2006; JoCN)

13. Functional specialization within BA 10 (Gilbert, Spengler, Simons, Steele, Lawrie, Frith & Burgess, 2006; JoCN) Predictions of the classification algorithm: Multi-Task Episodic Retrieval Mentalising Prediction accuracy: 74% (p < .0000001)

14. Functional specialization within BA 10 (Gilbert, Spengler, Simons, Steele, Lawrie, Frith & Burgess, 2006; JoCN) % medial activations 32% (N=99) Emotion Mentalizing 0% (N=2) 96% (N=24) 37% (N=8) Medial activations associated with contrasts involving both mentalizing and emotional materials May play a role in attending to emotional states, rather than representing those emotional states themselves

15. 2 x 2 factorial design (cf. additive factors logic): Mentalising versus attention in medial rostral PFC (Gilbert, Williamson, Dumontheil, Simons, Frith & Burgess, 2007, SCAN) Attentional focus Mentalising

16. Mentalising versus attention in medial rostral PFC (Gilbert, Williamson, Dumontheil, Simons, Frith & Burgess, 2007, SCAN) Stimulus-Oriented (SO) Stimulus-Independent (SI) Task 1 ¿ A D G ? ? Task 2

17. A V D S Mentalising versus attention in medial rostral PFC (Gilbert, Williamson, Dumontheil, Simons, Frith & Burgess, 2007, SCAN) Helpful / Unhelpful? Spatial task Mentalising etc. ¿ Y G ? ? Alphabet task Non-mentalising Fast / Slow? Stimulus- independent (SI) Stimulus- oriented (SO) Stimulus- oriented (SO) Phase 3-18s (mean: 11s) 5s 21-39s (mean: 30s)

18. Mentalising versus attention in medial rostral PFC (Gilbert, Williamson, Dumontheil, Simons, Frith & Burgess, 2007, SCAN) “I was thinking about whether you could see if I was stuck … and what was coming up on your screen … I was more aware of the human element entering into the equation”

19. Mentalising versus attention in medial rostral PFC (Gilbert, Williamson, Dumontheil, Simons, Frith & Burgess, 2007, SCAN) x = -8 x = -6 x = -4 Mentalising SO > SI Overlap x = 0 x = -2 x = +2 x = +6 x = +4 x = +8

20. Mentalising versus attention in medial rostral PFC (Gilbert, Williamson, Dumontheil, Simons, Frith & Burgess, 2007, SCAN) Direct comparison Meta-analysis Multiple-task co-ordination Mentalising Episodic Memory SO > SI Mentalising > Non-mentalising

21. Executive functions in autism spectrum disorders (Gilbert, G. Bird, Brindley, Frith & Burgess, in press, Neuropsychologia) • Neuroimaging studies investigating ASD suggest functional differences in medial rostral PFC during mentalizing tasks (e.g. Castelli et al., 2002). Will similar effects be seen in a different task that activates a similar region of medial PFC? • Rostral PFC has been implicated in executive function tests involving multitasking in ill-structured situations (e.g. Six Element Tests; Burgess, 2000). Abnormal performance in ASD has been reported particularly in such tasks (Hill & C. Bird, 2006).

22. Executive functions in autism spectrum disorders (Gilbert, G. Bird, Brindley, Frith & Burgess, in press, Neuropsychologia) p = .15 p = .75

23. Stimulus-Independent Phase Stimulus-Oriented Phase Stimulus-Oriented Phase A B Z P M F G A B C D E F G time

24. Stimulus-Oriented > Stimulus-Independent Control: ASD:

25. Stimulus-Oriented > Stimulus-Independent Control: ASD: ASD > Control:

26. Executive functions in autism spectrum disorders (Gilbert, G. Bird, Brindley, Frith & Burgess, in press, Neuropsychologia) Control SO > SI ASD

27. Executive functions in autism spectrum disorders (Gilbert, G. Bird, Brindley, Frith & Burgess, in press, Neuropsychologia) Control SO > SI ASD Control participants SO > SI Mentalising

28. A V D S Mentalising versus attention in ASD (Gilbert, Meuwese, Towgood, Frith & Burgess, submitted) Helpful / Unhelpful? Spatial task Mentalising etc. ¿ Y G ? ? Alphabet task Non-mentalising Fast / Slow? Stimulus- independent (SI) Stimulus- oriented (SO) Stimulus- oriented (SO) Phase 3-18s (mean: 11s) 5s 21-39s (mean: 30s)

29. Mentalising versus attention in ASD (Gilbert, Meuwese, Towgood, Frith & Burgess, submitted) • ASD group: N = 16, mean age = 32.2, mean FSIQ = 116 • Control group: N = 16, mean age = 30.9, mean FSIQ = 120 • 2x2x2x2 design: • Group (ASD, Control) • Task (Alphabet, Spatial) • Mentalizing (Mentalizing, Non-mentalizing) • Phase (SO, SI)

30. Imaging data Mentalizing > Non-mentalizing SO>SI

31. Imaging data ASD (Mentalizing – Non-mentalizing) > Control (Mentalizing – Non-mentalizing)

35. 0.34**

36. 0.34** 0.17*

37. 0.11 0.04 0.03 0.34** 0.17* -0.11

38. Present results

39. Present results

41. Mentalizing > Non-mentalizing SO>SI Alphabet task = - Spatial task

42. Mentalizing > Non-mentalizing SO>SI Alphabet task = - Spatial task

43. Mentalizing > Non-mentalizing SO>SI Alphabet task = - Spatial task = -

44. Mentalizing > Non-mentalizing SO>SI Alphabet task = - Spatial task = -

45. Mentalizing > Non-mentalizing SO>SI Alphabet task = - Spatial task = -

46. p = 0.4 p = 0.000003

47. ASD: increased functional specialisation in medial rostral PFC? lack of generalisation from one task to another ASD: reduced functional specialisation in medial rostral PFC? nothing to generalise from one task to another

48. Split-half analysis: p = .0004 p = .0005

49. Conclusions • Role of rostral PFC in selection between stimulus-oriented and stimulus-independent thought • This may underlie the involvement of rostral PFC in a wide variety of domains (e.g. prospective memory) • Considerable functional specialisation within rostral PFC: • Distinct roles of lateral versus medial subregions • Distinct regions of medial rostral PFC involved in social and nonsocial functions • Abnormal functional architecture of medial rostral PFC in autism spectrum disorders: functional specialisation may not generalise from one task to another

50. Future questions: Multi Voxel Pattern Analysis (MVPA) One voxel • MVPA involves examining the distribution of activation across a set of voxels, typically on a participant-by-participant basis, rather than the group-averaged peak voxel.