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From Neuronal to Hemodynamic Activity

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Presentation on theme: "From Neuronal to Hemodynamic Activity"— Presentation transcript:

1 From Neuronal to Hemodynamic Activity
Gregory McCarthy Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

2 Shulman and Rothman PNAS, 1998
In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) methods, which localize brain activities. These functional imaging methodologies map neurophysiological responses to cognitive, emotional, or sensory stimulations. The rapid experimental progress made by using these methods has encouraged widespread optimism about our ability to understand the activities of the mind on a biological basis. However, the relationship between the signal and neurobiological processes related to function is poorly understood, because the functional imaging signal is not a direct measure of neuronal processes related to information transfer, such as action potentials and neurotransmitter release. Rather, the intensity of the imaging signal is related to neurophysiological parameters of energy consumption and blood flow. To relate the imaging signal to specific neuronal processes, two relationships must be established… The first relationship is between the intensity of the imaging signal and the rate of neurophysiological energy processes, such as the cerebral metabolic rates of glucose (CMRglc) and of oxygen (CMRO2).    The second and previously unavailable relationship is between the neurophysiological processes and the activity of neuronal processes. It is necessary to understand these relationships to directly relate functional imaging studies to neurobiological research that seeks the relationship between the regional activity of specific neuronal processes and mental processes. Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

3 Shulman and Rothman PNAS, 1998
Psychology Image Signal Mental CMRglc Neuroenergetics CMRO2 CBF Neuronal Neuroscience Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

4 What brain processes consume energy?
And what is the source of that energy? Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

5 Neuronal Activity fmri-fig-06-02-0.jpg
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

6 Ion channels and pumps fmri-fig-06-03-0.jpg
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

7 Synapses and neurotransmitter release.
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

8 Anaerobic and aerobic glycolysis.
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

9 The energy budget of the (rodent) brain.
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

10 Roy and Sherrington (1890) Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

11 Positron emission tomography (PET) imaging.
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

12 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

13 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

14 The Vascular System Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

15 fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

16 fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

17 fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

18 fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

19 Arteries Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

20 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

21 Microcirculation of the human brain.
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

22 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

23 fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

24 Arterioles ( microns) precapillary sphincters Capillaries (5-10 microns) Venules (8-50 microns) Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

25 fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

26 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

27 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

28 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

29 fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

30 Models to account for decoupling
‘Watering the whole garden for the sake of one flower’ (Grinvald) Astrocyte shuttle (Shulman, Magestretti) Transit time (Buxton) Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

31 From Malonek and Grinvald et al., 1996
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

32 Phosphorescence Decay Time
(Oxyphor R2 oxygen tension-sensitive phosphorescent probe) Vanzetta and Grinvald, Science, 286: , 1999 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

33 Vanzetta and Grinvald, Science, 286: 1555-1558, 1999
deoxy Hb Oxy Hb Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

34 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

35 Astrocyte-Neuron Lactate Shuttle
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

36 from Magestretti et al, Science, 2002
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

37 The Initial (Negative) Dip
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

38 Different Concentrations of Hb and dHB
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

39 Berwick et al, JCBFM, 2002 Optical imaging of rat barrel cortex
Hb02= oxyhemoglobin, Hbr = deoxyhemoglobin, Hbt = total blood flow Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

40 Early Response in fMRI Hu, Le, Ugurbil MRM, 1997
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

41 Functional Imaging of the Monkey Brain
N. Logothetis, Nature Neuroscience, 1999 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

42 Transit Time and Balloon Model
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

43 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

44 Brain or Vein? Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

45 Evoked changes in blood flow
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

46 The relation between sensory stimulation and local blood flow changes
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

47 The change in diameter of arterioles following sciatic stimulation.
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

48 Change in arteriole dilation as a function of distance from active neurons.
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

49 What triggers blood flow?
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

50 Tissue factors K+ H+ Adenosine Nitric oxide
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

51 Neuronal Control of the Microcirculation
C. Iadecola, Nature Neuroscience, 1998 Commentary upon Krimer, Muly, Williams and Goldman-Rakic, Nature Neuroscience, 1998 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

52 Pial Arteries Noradrenergic Dopamine 10 m
Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

53 Dopamanergic terminals associated with small cortical blood vessels
Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

54 Dopamanergic terminals associated with small cortical blood vessels
400 nm 2 m 400 nm Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

55 Perivascular iontophoretic application of dopamine
Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

56 Neuroanatomy Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

57 eyeball optic nerve spinal cord
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

58 corpus callosum falx skull hypothalamus occipital lobe frontal lobe
sinus thalamus midbrain pons cerebellum medulla spinal cord Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

59 fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

60 parietal lobe central sulcus superior parietal lobule precentral gyrus
parieto-occipital sulcus occipital lobe frontal lobe Sylvian fissure cerebellum temporal lobe Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

61 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 Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

62 central sulcus cingulate gyrus parietal lobe corpus callosum
occipital lobe calcarine sulcus fornix thalamus posterior commissure cerebellum pons medulla Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

63 corpus collosum white matter lateral ventricles Sylvian sulcus
thalamus Insula temporal lobe mamillary body amygdala Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

64 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

65 anterior corpus callosum
frontal lobe anterior corpus callosum caudate ventricle thalamus posterior corpus callosum occipital lobe Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

66 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

67 corona radiata sagittal stratum thalamus
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

68 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

69 Week 6: Physiological Basis of the BOLD Response
Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University

70 The cytoarchitectonic map of Brodmann
fmri-fig jpg Week 6: Physiological Basis of the BOLD Response Gregory McCarthy, Duke University


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