1. Asta K. Håberg Trondheim fMRI gruppe Department of Neuroscience Norwegian University of Science and Technology (NTNU) Human navigation abilities elucidated using functional MRI and virtual reality www.NTNU.no /fMRI

2. Navigation - Memory test (objects-places-events ++) - Ecologically valid - Impaired navigation abilities present in different disorders (Alzheimer’s disease, neurodevelopmental disorders) - Used extensively in animal research (translational potential)

3. Hippocampus Posterior (Back) Anterior (Front) Medial temporal lobe with hippocampus

4. Healthy Demented

5. Example of VR environment ~62 m ~74 m

6. Movement plots Target Start

8. Navigation activates a network of cortical and subcortical regions Xu et al., 2010

9. Size of the place fields along the hippocampal A-P axis Anterior- posterior axis of hippocampus

10. Navigation RESEARCH QUESTIONS: 1. Different demands during navigation period gives rise to different activity? 2. Can we find evidence for a difference along the anterior-posterior axis of the hippocampus? 3. Are there differences between men and women? 4. What distinguishes successful and unsuccessful navigation?

11. Navigation 1. Different demands during navigation period gives rise to different activity? 2. Can we find evidence for a difference along the anterior-posterior axis of the hippocampus? 3. Are there differences between men and women? 4. What distinguishes successful and unsuccessful navigation?

12. Landmarks removed Unaltered environment

13. 1. Different demands during navigation period gives rise to different activity? - Hippocampal activity throughout the navigation period only found in intact environment -Hippocampal activity highly specific for different periods -The specific demands of the different navigational periods affect the interaction of the hippocampus with other brain regions

14. Navigation 1. Different demands during navigation period gives rise to different activity? 2. Can we find evidence for a difference along the anterior-posterior axis of the hippocampus? 3. Are there differences between men and women? 4. What distinguishes successful and unsuccessful navigation?

15. Functional segregation of the representation of space along hippocampus A-P axis Spatial detail is represented by posterior hippocampus Spatial coherence (map like overview ) is represented in anterior hippocampus 2. Can we find evidence for a difference along the anterior-posterior axis of the hippocampus?

16. Navigation 1. Different demands during navigation period gives rise to different activity? 2. Can we find evidence for a difference along the anterior-posterior axis of the hippocampus? 3. Are there differences between men and women? 4. What distinguishes successful and unsuccessful navigation?

17. Success rate for reaching target, men and women

18. Trajectory mapping 1st target landmark

19. Differences in navigation strategy Men and women moved the same distance, but: 1.Men picked shortcuts 2.Men used a map-like representation of the environment 3.Men were better at making correct judgments wrt distance and direction between objects

20. Male>female Female>male During the entire navigation period men have more hippocampal activity than women

21. In men hippocampal activity is accompanied by increase interaction with orbitofrotal cortex and precuneus

22. 3. Are there differences between men and women? - Men and women use different navigation strategies - The male navigation strategy is more successful - Men use a map-like representation of space, and the direction and distance between objects are more correctly and precisely positioned. - The differences in navigation behavior is reflected in differences in hippocampal activity and hippocampal interaction with other brain regions.

23. Navigation 1. Different demands during navigation period gives rise to different activity? 2. Can we find evidence for a difference along the anterior-posterior axis of the hippocampus? 3. Are there differences between men and women? 4. What distinguishes successful and unsuccessful navigation?

24. Anterior hippocampusPosterior hippocampus BOLD signal time courses for successful and unsuccessful trials Target reached

25. Navigational success seems particularly dependent on activation of the anterior (front) of the hippocampus 4. What distinguishes successful and unsuccessful navigation?

26. Conclusions

27. Acknowledgement Funding: NTNU, MI lab (Norwegian Research Council), Women in sciences grant (NTNU), Department of Radiology (St. Olav’s Hospital) Postdoc PhD Hanne Lehn MD PhD Jian Xu Medical research student Carl WS Pintzka PhD student Hallvard R. Evensmoen

28. Thank you