1. Emmanuel A Stamatakis Centre for Speech, Language and the Brain, Department of Experimental Psychology, University of Cambridge School of Psychological Sciences & Division of Imaging Science and Biomedical Engineering, School of Medicine, University of Manchester Hemispheric connectivity in ageing

2. Cognitive functions underpinned by an anatomically distributed neural system in which different neuronal regions are connected e.g.: Language

3. Hemispheric connectivity in ageing Emphasis on understanding cognition and the ageing brain is in terms of regional changes i.e. which brain regions show age-related changes

4. Hemispheric connectivity in ageing Need to examine age related changes in connectivity to determine whether related to impaired/preserved function

5. Hemispheric connectivity in ageing To address questions of age related changes in connectivity and relationship to changes in cognitive function we combine: a) Cognitive performance  Behavioural data (studies based on cognitive models) b) Functional MRI  Use fMRI with s ubtractive designs e.g. condition A – Baseline  Establish interactions (influences, modulations) between regions with functional connectivity analysis c) Structural MRI  Establish region-specific grey/white matter atrophy d) Diffusion Tensor MRI  Establish white matter tract integrity & subcortical pathways

6. The language system Activity within this system modulated by different linguistic processes Important that language is strongly left-lateralised; gives us an opportunity to look at RH contributions with age How does language processing change with age?

7. Example from Language: Processing word structure Core aspect of language processing: To decompose complex words into stem + affix (jump+ed) This process engages a fronto-temporal system (when compared to words that do not require this kind of decomposition e.g. slept) 20-40y n=14 0 14 L>R R>L LIFG MTG STG

8. Example from Language: Processing word structure Core aspect of language processing: To decompose complex words into stem + affix (jump+ed) This process engages a fronto-temporal system (when compared to words that do not require this kind of decomposition e.g. slept) 20-40y n=14 0 14 L>R R>L LIFG MTG STG ACC

9. Functional Connectivity: The method Jumped vs. Slept: How do regions within the network influence each other in time? LIFG ? *

10. Processing word structure: Functional Connectivity The pattern of connectivity between regions differs for the two kinds of words (jumped vs. slept) * Predictor time series Stamatakis et al., NeuroImage, 2005 The ACC modulates fronto-temporal connectivity (> jumped) Interactions left lateralised L R ** ACC LIFG L STS L MTG R STS Young: 20-40y n=14

11. Functional Connectivity underpinned by Anatomical Connections? Anatomical Connectivity: Diffusion Tensor Imaging Measure white matter integrity by Fractional Anisotropy (FA) FA measures directionality of tracts and integrity of WM tissue Higher FA values have been related to increases in WM organization/integrity DTI images used to calculate WM tracts

12. Measure white matter integrity by Fractional Anisotropy (FA) FA measures directionality of tracts and integrity of WM tissue Higher FA values have been related to increases in WM organization/integrity DTI images used to calculate WM tracts Functional Connectivity underpinned by Anatomical Connections? Anatomical Connectivity: Diffusion Tensor Imaging

13. Anatomical Connectivity: DTI Anterior-posterior, Left-right, Feet-head Directional FA

14. Anterior-posterior, Left-right, Feet-head SLF ILF Anatomical Connectivity: DTI Directional FA

15. DTI: Hemispheric comparison DTI: More coherence in white matter tracts in LH This may explain functional connectivity between regions In preparation

16. DTI, Contribution of white matter tracts White matter tracts connecting areas activated in fMRI study ( words which need to be decomposed - jumped vs. those that do not - slept ) L In progress * * 1 6 Fronto-temporal connectivity supported by anatomical connectivity SLF LIFG LMTG L R * * ACC LIFG L MTG

17. Processing word structure in young Summary Primarily L fronto-temporal system -Modulated by different linguistic processes e.g. decomposition -Anatomically distinct regions connected functionally -Underpinned by white matter tracts - especially ILF and SLF -What happens to this system as we age?

18. Ageing 19

19. Ageing 30

20. Ageing 50

21. Ageing 68

22. Ageing 80

23. Ageing 90

24. Ageing 90 19

25. Ageing, statistical assessment of grey matter atrophy A voxel by voxel statistical analysis is used to detect regional differences in the amount of grey matter between populations

26. Ageing: Evidence of neural atrophy Neural atrophy increases with age (Structural MRI evidence) How does this affect cognition? L R 4 t-scores 12 Volunteers aged 20-75y old (n=28) Stamatakis & Tyler, 2006 Extent of age-related changes in grey matter for this group

27. Effect of neural atrophy on cognition with age? e.g. processing word structure Reaction time difference for words which need to be decomposed compared to those that do not Takes longer to recognise a word that needs to be decomposed (jump+ed), and this is the same across age. -150 -100 -50 0 50 100 150 200 olderyounger RT differences (ms) Stamatakis & Tyler, 2006

28. Effect of neural atrophy on cognition with age? e.g. processing word structure Reaction time difference for words which need to be decomposed compared to those that do not -150 -100 -50 0 50 100 150 200 olderyounger RT differences (ms) Stamatakis & Tyler, 2006 In spite of neural atrophy, no cognitive deficit. Is this evidence for plasticity?

29. Processing word structure (jumped vs. slept) Older volunteers (60-75y old) Decomposing complex words into stem + affix (jump+ed) activates fronto-temporal system in older group No differences between old and young in regions involved 60-75y n=14 Is cognitive preservation associated with changes in functional connectivity? L R L S/MTG R S/MTG ACC LIFG Old-Young L R

30. Processing word structure (jumped vs. slept) All volunteers (20-75y old) L R Stamatakis & Tyler, 2006 ACC LH seeds Older (60-75) RH seeds Younger (20-40) * * LIFG ACC * * LIFG ACC * * RIFG ACC * * RIFG * Predictor time series L R Does functional connectivity change with age?

31. Processing word structure (jumped vs. slept) All volunteers (20-75y old) Does functional connectivity change with age? L R Stamatakis & Tyler, 2006 ACC LH seeds Older (60-75) RH seeds Younger (20-40) * * LIFG ACC * * LIFG ACC * * RIFG ACC * * RIFG * Predictor time series L R

32. Processing word structure (jumped vs. slept) All volunteers (20-75y old) L R Stamatakis & Tyler, 2006 ACC LH seeds Older (60-75) RH seeds Younger (20-40) * * LIFG ACC * * LIFG ACC * * RIFG ACC * * RIFG * Predictor time series L R Does functional connectivity change with age?

33. Processing word structure (jumped vs. slept) All volunteers (20-75y old) * Predictor time series L R Stamatakis & Tyler, 2006 ACC LH seeds Older (60-75) RH seeds Younger (20-40) * * LIFG ACC * * LIFG ACC * * RIFG ACC * * RIFG Left Lateralised Bi-Lateral Does functional connectivity change with age?

34. White matter changes with age All volunteers n=28 (20-75y old) DTI - decreased integrity with increasing age Does this affect functional connectivity? In preparation

35. Ageing: Evidence of neural atrophy Neural atrophy increases with age (Structural MRI evidence) How does this affect cognition? L R 4 t-scores 12 Volunteers aged 20-75y old (n=28) Stamatakis & Tyler, 2006 Extent of age-related changes in grey matter for this group

36. Ageing: Evidence of neural atrophy Neural atrophy increases with age (Structural MRI evidence) How does this affect cognition? L R 4 t-scores 12 Volunteers aged 20-75y old (n=28) Stamatakis & Tyler, 2006 Extent of age-related changes in grey matter for this group

37. Summary 1.Regions involved in this linguistic process show significant atrophy with age 2.Preserved cognitive function 3.Similar networks appear to be activated in young and old BUT changes in fronto-temporal functional connectivity -becomes more bilateral

38. Summary Changes in connectivity with increasing age: Due to grey and/or white matter deterioration In spite of neural deterioration, cognitive performance on this task is preserved across the life-span Due to recruitment of RH ?

39. Thank you Lorraine K. Tyler William Marslen-Wilson Billi Randal Meredith Shafto