Physiological Basis of fMRI (and Neuroanatomy, in brief)

1. Physiological Basis of fMRI(and Neuroanatomy, in brief) FMRI Undergraduate Course (PSY 181F) FMRI Graduate Course (NBIO 381, PSY 362) Dr. Scott Huettel, Course Director FMRI – Week 5 – MR Signal Scott Huettel, Duke University

2. I.NeurophysiologyWhat brain processes consume energy? FMRI – Week 5 – MR Signal Scott Huettel, Duke University

3. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

4. There are two primary types of information flow in the CNS: • Signaling via action potentials (axonal activity) and • Integration via dendritic activity FMRI – Week 5 – MR Signal Scott Huettel, Duke University

5. Action potential Depolarization opens CA2+ channels Vesicles fuse with presynaptic membrane Neurotransmitter release Neurotransmitters open ion channels on postsynaptic membrane Change in potential IPSP or EPSP FMRI – Week 5 – MR Signal Scott Huettel, Duke University

6. Energy Demands of Integration/Signaling Following activity, neurons require energy to restore concentration gradients of key ions. Sodium-Potassium pump takes sodium out of the cell while bringing potassium into the cell. Note that for action potentials, the movement of ions is along gradients. Key concept: activity of neurons does not itself require energy; restoring membrane potentials afterward does. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

7. What metabolites are the sources of that energy? FMRI – Week 5 – MR Signal Scott Huettel, Duke University

8. Oxygen (via hemoglobin) Glucose FMRI – Week 5 – MR Signal Scott Huettel, Duke University

9. Facts about energy supply to brain • 30-50 μmol/g/min of ATP for awake brain • 10 μmol/g/min of ATP for comatose brain • Information processing accounts for >75% of ATP consumption • 54mL/min of blood for each 100 g of brain tissue • Brain is ~3% of body weight, but demands 15-20% of blood flow and ~20% of blood oxygen FMRI – Week 5 – MR Signal Scott Huettel, Duke University

10. Data from rodent models (Attwell & Laughlin, 2001). In humans, integrative activity may be 50% greater. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

11. Why do neuroenergetics matter? • Information reduction necessitated by energy demands! • How could we increase information transmission? • Decrease membrane resistance  finer-resolution of dendritic activity (~200Hz) • Increase action potential rate (~100-300Hz) • Decreasing membrane resistance would increase maintenance costs • Increasing action potential rate would rapidly increase signaling costs • The energy available to the brain limits neural information processing Attwell and Gibb, 2005 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

12. How are energy sources (metabolites) delivered? FMRI – Week 5 – MR Signal Scott Huettel, Duke University

13. The brain does not store glucose and oxygen in appreciable quantities. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

14. Duvernoy, H. M., Delon, S., & Vannson, J. L. (1981). Cortical blood vessels of the human brain. Brain Research Bulletin, 7(5), 519-579. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

15. Arteries (1-25mm)Arterioles (10 - 300 microns)precapillary sphinctersCapillaries (5-10 microns)Venules (8-50 microns)Veins FMRI – Week 5 – MR Signal Scott Huettel, Duke University

16. Key concepts in vascular system • Vast change in scale from largest arteries to capillaries • Small changes in diameter result in large changes in flow (2x diameter = 16x flow) • Pulsatile flow in arteries smoothed out by resistance vessels (arterioles) • Surface area of capillaries is essential for O2 exchange • Neurons are usually within 20μm from a capillary • Capillaries are not always perfused! • Blood can bypass capillaries • Saves weight, cost (in blood), etc. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

17. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

18. (anastomosis of internal carotids and basilar artery) FMRI – Week 5 – MR Signal Scott Huettel, Duke University

19. ACA – Medial cortex MCA – Anterolateral cortex PCA – Posterior temporal and occipital lobes FMRI – Week 5 – MR Signal Scott Huettel, Duke University

20. Sinus. n. An separation of the dura mater in which blood drains into the venous system. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

21. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

22. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

23. Distribution of vascularization across cortical layers FMRI – Week 5 – MR Signal Scott Huettel, Duke University

24. Capillary structure FMRI – Week 5 – MR Signal Scott Huettel, Duke University

25. How does function map onto blood flow? FMRI – Week 5 – MR Signal Scott Huettel, Duke University

26. “[Mosso] relates of his female subject that one day whilst tracing her brain-pulse he observed a sudden rise with no apparent outer or inner cause. She however confessed to him afterwards that at that moment she had caught sight of a skull on top of a piece of furniture in the room, and that this had given her a slight emotion.” -James Principles… (1890) Iadecola, Nature Reviews Neuroscience, 2004 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

27. “These facts seem to us to indicate the existence of an automatic mechanism by which the blood supply of any part of the cerebral tissue is varied in accordance with the activity of the chemical changes which underlie the functional action of that part. Bearing in mind that strong evidence exists of localisation of function in the brain, we are of opinion that an automatic mechanism, of the kind just referred to, is well fitted to provide for a local variation of the blood supply in accordance with local variations of the functional activity.” [Roy and Sherrington, 1890, emphasis added] “Blood very likely may rush to each region of the cortex according as it is most active, but of this we know nothing.” [James, 1890] FMRI – Week 5 – MR Signal Scott Huettel, Duke University

28. Facts about blood flow • Aorta peak flow: 90 cm/s • Internal carotid flow: ~ 40 cm/s • Smaller arteries: ~10-250 mm/s • Capillaries: ~ 1 mm/s • Venules and small veins: ~10-250 mm/s FMRI – Week 5 – MR Signal Scott Huettel, Duke University

29. Stimulation of the sciatic nerve (in a rat) results in arteriole dilation in somatosensory cortex. There is a parallel change in blood velocity . But, blood pressure remains relatively constant. (This is a good thing.) Adapted from Ngai et al., 1988 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

30. Change in diameter of arterioles following sciatic (hindlimb) stimulation Adapted from Ngai et al., 1988 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

31. Change in arteriole dilation as a function of distance from active neurons Iadecola, Nature Reviews Neuroscience, 2004 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

32. What triggers changes in blood flow? • K+ : after synaptic activity • Adenosine : follows metabolic activity • Nitric oxide : released by active neurons • Causes smooth muscles surrounding arterioles to relax • NO inhibitors attenuate CBF, BOLD • Neuronal activity ? FMRI – Week 5 – MR Signal Scott Huettel, Duke University

33. Iadecola, Nature Reviews Neuroscience, 2004 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

34. How does the vascular system respond to neuronal activity? Physiological data suggests that blood flow changes may be associated with preponderance of dendritic activity, but disconnections are possible. Iadecola, Nature Reviews Neuroscience, 2004 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

35. 2 m 400 nm 2 m 400 nm Direct neuronal influences? On small capillaries, there are terminals of dopamine neurons. These appear to have slower influences than necessary for fMRI. Noradrenergic Dopamine Pial Arteries (i.e., larger vessels) 10 m Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

36. Challenges to Neurogenic Control • Slow time scale: DA effects = minutes • DA receptor blockade does not modulate CBF increases w/activation (e.g., Esaki et al., 2002) • Lack of spatial specificity of blood flow responses FMRI – Week 5 – MR Signal Scott Huettel, Duke University

37. Summary of Physiology • Information processing requires (substantial) energy • Energy is needed for restoring membrane potentials • Energy comes from Oxygen and Glucose • Minimal local availability • Metabolites supplied by vascular system • Changes in blood flow with activity • Changes may be disproportionate • Next week: Can we identify some aspect of this process that is measurable using MRI? FMRI – Week 5 – MR Signal Scott Huettel, Duke University

38. II. Neuroanatomy FMRI – Week 5 – MR Signal Scott Huettel, Duke University

39. Terminology: Planes of Section FMRI – Week 5 – MR Signal Scott Huettel, Duke University

40. Terminology: Labels FMRI – Week 5 – MR Signal Scott Huettel, Duke University

41. Brain in skull FMRI – Week 5 – MR Signal Scott Huettel, Duke University

42. Brain covered with dura mater FMRI – Week 5 – MR Signal Scott Huettel, Duke University

43. Gyri (bumps) Sulci (valleys) FMRI – Week 5 – MR Signal Scott Huettel, Duke University

44. corpus callosum falx skull hypothalamus occipital lobe frontal lobe sinus thalamus midbrain pons cerebellum medulla spinal cord FMRI – Week 5 – MR Signal Scott Huettel, Duke University

45. A midsagittal MRI of the human head FMRI – Week 5 – MR Signal Scott Huettel, Duke University

46. parietal lobe central sulcus superior parietal lobule precentral gyrus parieto-occipital sulcus occipital lobe frontal lobe Sylvian fissure cerebellum temporal lobe FMRI – Week 5 – MR Signal Scott Huettel, Duke University

47. frontal lobe olfactory nerves Optic chiasma Parahippocampal gyrus circle of Willis fusiform gyrus inferior temporal gyrus basilar artery brain stem substantia nigra vertebral arteries spinal cord occipital lobe Fig 2.15 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

48. frontal lobe anterior corpus callosum caudate ventricle thalamus posterior corpus callosum occipital lobe Fig 2.17 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

49. Caudate Corpus Callosum Putamen Internal Capsule Globus Pallidus Anterior Commissure (Collectively, these are known as the basal ganglia) FMRI – Week 5 – MR Signal Scott Huettel, Duke University

50. Insula FMRI – Week 5 – MR Signal Scott Huettel, Duke University