BOLD fMRI John VanMeter, Ph.D. Center for Functional and Molecular Imaging Georgetown University Medical Center

2. Outline BOLD contrast fMRI conceptually Relationship between BOLD contrast and hemodynamics History of BOLD contrast Relationship between neuronal glucose metabolism and blood flow Theories about properties of BOLD contrast mechanisms

3. Neuronal Activity and Blood Flow Changes: Initial Hypothesis Roy and Sherrington hypothesize that local neuronal activity is related to regional changes in both cerebral blood flow and metabolism (1890). �There are, then, two more or less distinct mechanisms for controlling the cerebral circulation, viz. - firstly, an intrinsic one by which the blood supply of the various parts of the brain can be varied locally in accordance with local requirements, and secondly, an extrinsic, viz. - the vasomotor nervous system�� Awarded Nobel Prize in 1932 with Lord E. D. Adrian for their discoveries on the functions of neurons Coined the term Synapse in 1897 from the Greek "syn" meaning "together" and "haptein" meaning "to clasp." Knighted in 1922Awarded Nobel Prize in 1932 with Lord E. D. Adrian for their discoveries on the functions of neurons Coined the term Synapse in 1897 from the Greek "syn" meaning "together" and "haptein" meaning "to clasp." Knighted in 1922

4. Roy and Sherrington�s Experiments �� the increase in the volume of the brain which results from stimulation of the sensory nerves is mainly if not entirely due to passive or elastic distension of the its vessels as a result of the blood-pressure in the systemic arteries.� Oncograph output of Sherrington�s device measures changes in vertical thickness of the cerebrum Kymograph measures arterial pressure in femoral artery Fig 2. Shows changes during stimulation of sciatic nerveOncograph output of Sherrington�s device measures changes in vertical thickness of the cerebrum Kymograph measures arterial pressure in femoral artery Fig 2. Shows changes during stimulation of sciatic nerve

5. History of BOLD fMRI Initial discovery of magnetic properties of blood by Linus Pauling and graduate student Charles Coryell (1936): Magnetic properties of a blood cell (hemoglobin) depends on whether it has an oxygen molecule With oxygen ? zero magnetic moment Without oxygen ? sizeable magnetic moment

6. Initial In Vivo Measurement of Neuronal Activity Initial techniques used PET (positron emission tomography) PET uses injection of a radiotracers which are variants of physiological molecules that include a radio isotope FDG (2-fluoro-2deoxy-D-glucose) for glucose metabolism H2015 for blood flow

7. Functional Imaging - PET Sokoloff demonstrated that rCBF (blood flow) increases in visual cortex in proportion to photic stimulation using PET (1961). Demonstrated �coupling� between blood flow and metabolism (1981). Called 'the father of PET' because he first demonstrated the feasibility of measuring glucose metabolism Also earned a Lasker Award Coupling important since it demonstrates that flow can be used to infer activity. Energy metabolism is a function of individual cells whereas CBF serves regions of brain and is also sensitive to systemic factors, e.g., blood gas tensions, pH, etc. Measurement oflocal energy metabolism should, therefore, be expected to provide better resolution and specificity in response to altered local neuronal functional activity. Called 'the father of PET' because he first demonstrated the feasibility of measuring glucose metabolism Also earned a Lasker Award Coupling important since it demonstrates that flow can be used to infer activity. Energy metabolism is a function of individual cells whereas CBF serves regions of brain and is also sensitive to systemic factors, e.g., blood gas tensions, pH, etc. Measurement oflocal energy metabolism should, therefore, be expected to provide better resolution and specificity in response to altered local neuronal functional activity.

8. Relationship Between Glucose Metabolism and Blood Flow Sokoloff (1981) used autoradiography Measured both glucose metabolism and blood flow 39 brain regions in rat brain Correlation r=0.95 Slope m=2.6 Used metabolic acidosis to induce changes Metabolic acidosis is a pH imbalance in which the body has accumulated too much acid and does not have enough bicarbonate to effectively neutralize itUsed metabolic acidosis to induce changes Metabolic acidosis is a pH imbalance in which the body has accumulated too much acid and does not have enough bicarbonate to effectively neutralize it

9. First MRI-based Measurement of Neuronal Activity Belliveau (1990) used MRI contrast agent Gadolinium as an exogenous tracer Gadolinium locally disrupts MRI signal Perfusion weighted imaging (PWI)

10. Oxy- vs. Deoxy- Hemoglobin Oxygenated hemoglobin (Hb) is diamagnetic (zero magnetic moment) Deoxygenated hemoglobin (dHb) is paramagnetic (magnetic moment) Magnetic susceptibility of dHb is about 20% greater than Hb Magnetic susceptibility affects rate of dephasing - T2 and T2* contrast!

11. T1 & T2 Contrast Versus Oxygenated Hemoglobin

12. Demonstration of BOLD Contrast Seiji Ogawa (1990) manipulates oxygen content of air breathed by rats Results in variation of oxygenated state of blood Demonstrates effect on T2* contrast to make images of blood vessels

13. Ogawa�s Images of Blood Vessels Based on Oxygen Content Pure oxygen Normal Air 1st BOLD image!1st BOLD image!

14. Magnetic Susceptibility Greater on T2* than T2 Images Oxygenated Hemoglobin Deoxygenated Hemoglobin

15. Oxygenation vs Local Field Changes

16. Build Up to BOLD Contrast Hypothesis of relationship between blood flow and activity (Roy & Sherrington, 1890) Discovery of differential magnetic properties of oxygenated and deoxygenated hemoglobin (Pauling, 1936) Blood flow increases with activity (Sokoloff, 1961) Blood flow correlated with glucose metabolism (Sokoloff, 1981) Demonstration of blood flow measured using MRI with an exogenous tracer (Belliveau, 1990) Demonstration of effect of dHb on T2* contrast (Ogawa, 1990) use of blood as an endogenous tracer Generation of first BOLD images (Ogawa, 1990)

17. Basic Model of Relationship Between BOLD fMRI & Neuronal Activity

18. Disparity Between Blood Flow & Oxygen Consumption Fox & Raichle conducted PET experiments to measure glucose metabolism (CMRglu), blood flow (CBF), and rate of oxygen metabolism (CMRO2) Measured percent change between visual stimulation and rest Increase in CBF=50%, CMRglu=51% But increase in CMRO2 is only 5%!! Implies anaerobic metabolism of glucose Focal stimulation (visual stimulation) vs. Sokoloff�s global/systemic change in metabolismFocal stimulation (visual stimulation) vs. Sokoloff�s global/systemic change in metabolism

20. Disparity & MRI Signal Increase Upshot of Fox & Raichle: much more oxygen (CBF) is supplied than is used (CMRO2) While neuronal activity results in more deoxygenated hemoglobin much more oxygenated hemoglobin flows in flushing out deoxygenated hemoglobin Result is a decrease in dHB and thus an increase in MRI signal But there�s uncoupling of glucose metabolism and oxygen metabolism - WHY?

21. Uncoupling Problematic Fox & Raichle data nicely explains why MRI signal increases with neuronal activity But a new problem is presented: uncoupling of glucose and oxygen metabolism We expect a 6:1 ratio of oxygen-to-glucose (OGI) for aerobic glycolysis but F&R saw about 1:10 Implication is anaerobic glycolysis is used

22. Theories to Explain Uncoupling Found by Fox & Raichle Watering the Garden for the Sake of One Thirsty Flower Astrocyte-Neuron Lactate Shuttle Model Transit Time and Oxygen Extraction

23. Separate Measurement of Oxy & Deoxy Hemoglobin Malonek & Grinvald used optical imaging to measure Hb and dHb separately during visual stimulation ?dHb spatially focal and co-located to neuronal activity ?Hb more widely distributed

24. Implications of Differences in Concentration of Hb & dHb Rapid increase in dHb implies oxidative metabolism initially High spatial correspondence between initial dHb increase and neuronal activity Coarse spatial correspondence and greater extent of delivery of Hb

25. Watering the Garden According to this model uncoupling observed by Fox & Raichle does not imply anaerobic glycolysis Instead Malonek & Grinvald�s data shows huge excess of freshly oxygenated hemoglobin spread over a wide area displacing deoxygenated hemoglobin But CMRglu wasn�t measured; still haven�t explained why Fox & Raichle gets a 1:10 versus expected 6:1 OGI

26. Astrocyte-Neuron Lactate Shuttle Model Initially anaerobic glycolysis occurs producing excess glutamate (consistent with Fox & Raichle) Glutamate taken up by astrocyte to prevent toxicity and converted to glutamine which neuron can reuse Delicate balance is achieved by astrocyte through intake of Na+ produced by sodium-potassium pump of neuron Astrocyte uses 2 ATP molecules Great because that�s all the ATP available! But where�s the ATP for the neuron? Fast early anaerobic does not predict initial dip!Fast early anaerobic does not predict initial dip!

27. ANLS Model (cont�d) Astrocyte dumps resulting lactate, which diffuses into neuron that turns into pyruvate and into TCA cycle to give neuron 36 ATP molecules for neuron�s energy Thus, we�re back to aerobic glycolysis, which requires 6 molecules of oxygen Model hypothesizes early anaerobic followed by aerobic glycolysis Support for this comes from Mintun (2002) who showed uncoupling only occurs with initial onset of stimulus then coupling is reestablished with continued stimulation Lactate converted to pyruvate via enzyme lactate dehydrogenase-1Lactate converted to pyruvate via enzyme lactate dehydrogenase-1

28. Astrocyte-Neuron Lactate Shuttle Model

29. Transit Time and Oxygen Extraction Disputes that uncoupling implies anaerobic glycolysis as does Watering the Garden Model is based on limited time for extraction due to increase in velocity of blood flow with neuronal activity

30. Transit Time and Oxygen Extraction Model proposed by Buxton (1998) rests on four assumptions: Increased blood flow accomplished by increase in velocity as opposed pumping blood through more capillaries Virtually all oxygen is metabolized But not all of the glucose is metabolized Extraction of oxygen from blood by neurons is limited and proportional to transit time Transit time - how long it takes for blood to pass through a given area

31. Transit Time and Oxygen Extraction Wouldn�t limited time for extraction of oxygen due to increase in velocity of blood also limit glucose availability? Buxton - well actually glucose availability is even more limited than oxygen but less than half that is extract is actually used� Data from Gjedde (2002) supports glucose part

32. Balloon Model No uncoupling of CBF and CMRO2; difference between CBF and CMRO2 lowers oxygen extraction (E) [Fick Principle] Initial increase in blood flow increases blood volume (ballooning of venous capillary to accommodate) Predicts initial dip in BOLD signal

33. Theories to Explain Uncoupling Found by Fox & Raichle Watering the Garden for the Sake of One Thirsty Flower Astrocyte-Neuron Lactate Shuttle Model Transit Time and Oxygen Extraction (extended to Balloon Model) Aerobic glycolysis already near max at rest thus activity requires quick increase in energy via anaerobic glycolysis (Prichard, 1991)

34. Uncoupling Problem Debate continues to this day Uncoupling problem important to understanding the fundamental basis of fMRI signal fMRI is an indirect measure of blood flow and is not directly tied to glucose metabolism or even oxygen metabolism Relationship between mechanisms of metabolism and blood flow is important to understanding how closely related blood flow is to neuronal activity

35. Implications of Theories for Uncoupling �Watering the Garden� model posits widespread distribution of CBF increase ? poor fMRI spatial resolution �Transit Time� model implies excess oxygen rich blood passing over area of activity getting into venous system ? poor fMRI spatial resolution Both imply a �Draining Vein� problem with dHb flowing downstream of area of activity Frahm (1994) asked �Brain or Vein?� Uncoupling issue remains unresolved

36. Initial Dip Studies used very short TR (100ms) and visual stimulus for 10s at 4T or higher Examined time course of fMRI signal Menon (1995) found Initial Dip in fMRI signal before expected increase There�s also a post stimulus undershoot

37. Spatial Extent of Initial Dip Voxels with initial dip were more spatially restricted and localized to gray matter around calcarine sulcus

38. Implications of Initial Dip Menon suggested dip is directly related to oxygen extraction and thus more closely related to neuronal activity But dip could also result from temporary decrease in blood flow or increase in blood volume Initial dip if it occurs is contradictory with anaerobic glycolysis - Why? Balloon model predicts increase in blood volume and thus consistent with initial dip but for a different reason than Menon posits Menon posits anaerobic glycolysis causes initial dip Buxton�s balloon model says increase in blood flow leads to temporary increase in blood volume leading to build-up of dHb causing dipMenon posits anaerobic glycolysis causes initial dip Buxton�s balloon model says increase in blood flow leads to temporary increase in blood volume leading to build-up of dHb causing dip

39. Physiological Mechanisms for Regulation of Blood Flow How is blood flow controlled? Arterioles well upstream need to respond to produce local changes in blood flow Mechanism for accomplishing this is largely unknown Possible candidates include nitrous oxide synthesis, potassium accumulation, generation of lactate, or acetylcholine activity

40. First fMRI BOLD in Human Kwong (1992) demonstrated first BOLD-contrast fMRI in human visual cortex

41. Blood Flow vs BOLD Changes Kwong also showed how changes in BOLD corresponded to changes in blood flow Important to show that BOLD and blood are related

42. HDR (Hemodynamic Response)HRF (Hemodynamic Response Function) Change in MR signal related to neuronal activity (HRF) Has multiple components Changes delayed by 1-2 sec (lags activity) Initial dip (not always seen) Influx of Hb greater than needed for activity 5-6 sec time to peak Undershoot follows ~6s later

43. Typical HDR for Long Stimulus (Block) Peak is sustained with prolonged stimulation Block is also referred to as an epoch Brief stimulus is referred to as an event

44. Undershoot Arises from rapid return to baseline of CBF but delayed return of CBV Delay in CBV return to baseline results in an accumulation of dHb

45. BOLD vs Neuronal Activity Logothetis, et al., 2001 recorded LFP, MUA, and BOLD simultaneously BOLD response best explained by changes in LFP Suggests BOLD reflects �incoming input and local processing rather than spiking activity� �The BOLD contrast mechanism directly directly reflects the neural responses elicited by a stimulus.� Stimulus duration varied from a) 24s, b) 12s, c) 4sStimulus duration varied from a) 24s, b) 12s, c) 4s

46. Open Questions about Basis of BOLD fMRI Uncoupling problem - Why does it occur? To what extent? Is there an Initial Dip? What causes the dip? Is it more localized than the expected signal increase? What about �Draining Veins�? How does arterial system upstream know when and by how much to increase blood flow?

47. Factors Affecting BOLD Signal Physiology Cerebral blood flow (baseline and change) Metabolic oxygen consumption Cerebral blood volume Equipment Static field strength Field homogeneity (e.g. shim dependent T2*) Pulse sequence Gradient vs spin echo Echo time, repeat time, flip angle Resolution From Daniel Bulte�s talk Centre for Functional Magnetic Resonance Imaging of the Brain, University of OxfordFrom Daniel Bulte�s talk Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford

48. Physiological Baseline Baseline CBF changes (up for hypercapnia, down for hypocapnia) But ?CBF ?CMRO2 unchanged (probably) (Brown et al JCBFM 2003) BOLD response ? (probably) From Daniel Bulte�s talk Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford From Daniel Bulte�s talk Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford

49. Spatial & Temporal Properties of BOLD Spatial resolution - ability to distinguish unique changes in activity from one location to the next Temporal resolution - ability to distinguish changes across time Linearity vs Nonlinearity - does combined response to 2 or more events with short ISI (inter-stimulus interval) lead to sum in BOLD response?

50. Image Resolution (2D) FOV - Field of View, prescribed area that will be covered in the acquisition Matrix size - how many voxels will be acquired in each dimension Rectangular FOV possible Voxel dimension (size) = FOV/matrix

51. Example FOV = 192mm x 192mm Matrix = 64x64 What is the voxel size in-plane? 3mm x 3mm

52. Slice Thickness Defines 3rd Dimension Does not have to match size of in-plane resolution Voxels are referred to as isotropic when all three sides have the same size Gaps between slices can be used to cover more of the brain 3D Acquisition has a 2nd phase encode for through plane dimension and effectively 3rd FOV dimension but usually presented on console as slice thickness

53. Problems With Increasing Spatial Resolution Increased spatial resolution results in smaller voxels Fewer protons so less MRI signal Less dHb thus more noise in BOLD fMRI signal Degree of activation varies by brain region with greater activation in sensorimotor areas and less in frontal and association cortices Smaller voxels ultimately make detecting changes harder

54. Spatial vs Temporal Resolution Acquisition time per slice goes up as voxel size goes down Number of phase encode lines increases thus more time required to cover k-space Decreasing slice thickness will require increasing number of slices to maintain same coverage again increasing acquisition time

55. Designing an fMRI Protocol Tradeoffs Increased spatial resolution requires Increased TR (scan time) Less coverage (fewer slices) Increased temporal resolution requires Decreased spatial resolution (larger voxels) Less coverage (fewer slices) Reducing amount of k-space acquired (less SNR) Increased SNR (signal-to-noise ration) requires Decreased spatial resolution and/or Increased scan time via averaging

57. Partial Volume Effects Any given voxel will be a mix of tissue types Boundaries with sulci will include CSF Both can lead to a reduction in overall fMRI BOLD signal

58. Spatial Correspondence Disbrow, 2000, performed in monkeysDisbrow, 2000, performed in monkeys

59. Theoretical Lower Bound on Spatial Resolution Ultimately determined by the size of capillaries 1mm in length ~100 microns between capillaries Theoretical lower bound for any hemodynamic based measurement is 100 microns

60. Mapping Ocular Dominance Columns Menon, 1997 presented visual stimulus to alternating eyes Expect to see side-by-side alternating areas of activation in V1 corresponding to columns first shown by Hubel & Wiesel Acquired at 4T using a single slice with 547?m x 547?m resolution

61. fMRI of Ocular Dominance Columns Spatial location was not stable over sessions�Spatial location was not stable over sessions�

62. Ocular Dominance Columns - Take 2 Cheng, 2001 used 4T with 470?m2 resolution, single slice Each slice required 32-RF pulses to get enough SNR (averaging), scan time for 1 slice was 10s! Stimulus was 2min monocular presentation of light interspersed with 1min darkness

63. Replication Within Subject & C) show the same subject on 2 different sessions D) shows overlay of boundaries from session 1 overlaid on session 2& C) show the same subject on 2 different sessions D) shows overlay of boundaries from session 1 overlaid on session 2

64. Ocular Dominance Columns - Take 3 Done at 7T; C is based on the voxels that agree in all three sessionsDone at 7T; C is based on the voxels that agree in all three sessions

65. fMRI Data Processing & Spatial Resolution Typical processing includes Motion correction which will reslice the data (reslicing of data requires averaging of voxels to reformat data) Spatial Normalization (transforming into atlas space) again reslices data Spatial smoothing (blurring) Net result is reduction in effective spatial resolution

66. Temporal Resolution TR in fMRI refers to time needed to collect one volume of data Long TR (>3s) good for detecting differences in activation but not differences in HRF (hemodynamic response function) characteristics Where is activity occurring? Shorter TR (<2s) gives better estimate of differences in HRF characteristics What are the differences in activity between two stimuli activating in the same area?

68. �Jitter�Interleaved Stimulus Presentation Instead of locking stimulus presentation to the TR jitter it Effectively gives more data on HRF curve than locked to the TR Thus, effective temporal resolution is increased Downside is multiple presentations of the same stimulus type are required to achieve this extra granularity in the HRFDownside is multiple presentations of the same stimulus type are required to achieve this extra granularity in the HRF

69. Duration of Cognitive Processing & BOLD Response Psychophysical experiments looking at mental rotation have shown that the greater the differences in angle between two figures the longer the response time What happens to BOLD response?

70. BOLD Response Duration Increases Trial A had smaller angle and thus shorter response time than Trial B; as response time increased so did duration of HRFTrial A had smaller angle and thus shorter response time than Trial B; as response time increased so did duration of HRF

71. Timing Between Brain Regions Move joystick from one target to another Measured reaction time and difference in time to peak between different brain regions V1-SMA differences suggests decision pathway SMA-M1 flatness suggests simple execution Latency in response in V1 was shorter than in SMA and this difference grew as the response time went upLatency in response in V1 was shorter than in SMA and this difference grew as the response time went up

72. Latency of BOLD Response Examination of the latency (time to peak) in voxels with significant activation Blue shortest Yellow longest Output from V1 (slices a & c) feeds fusiform gyrus (slices b & d) As hoped response delayed in fusiform relative to V1 Subjects presented 500ms visual stimulus Example from 2 subjects: data from subject 1 in a) & b); subject 2 c) & d) a) & c) show calcarine (V1) has shorter latency than fusiform gyrus b) & d)Subjects presented 500ms visual stimulus Example from 2 subjects: data from subject 1 in a) & b); subject 2 c) & d) a) & c) show calcarine (V1) has shorter latency than fusiform gyrus b) & d)

73. Linearity of Hemodynamic Response? Linearity would imply there is additive effect of two stimuli presented close enough in time HRF scales with stimulus intensity HRF response to two or more stimuli equal summation of response to individual stimuli Under what conditions is HRF linear?

74. Linearity of HRF - Theoretical Give two stimuli close in time does the HRF reflect a sum of the HRF for each stimulus?

75. Nonlinearity Via Attenuation - Theoretical Or is there some attenuation (reduction) in the response to the 2nd stimulus? Refractory effects - change in response to 2nd stimulus based on presence of first?

76. Does HRF Scale with Stimulus Magnitude?

77. Superposition of HRF ?

78. Evidence for Linearity Boynton, 1996 Presented several short stimuli for various durations Found response scaled with contrast Found good correspondence between actual response and predicted thus linearity held Stimulus (moving, reversing checkerboard) duration varied between 3s, 6s, 12s, and 24s (y-axis) followed by 24s gray background; also varied stimulus contrast As hypothesized amplitude of response scaled with increasing contrast Figure shows actual BOLD response (blue) and response predicted if multiple stimuli had been presented for 3s, 6s, 12s (x-axis) compared to actual duration (y-axis) Very good correspondence for between predicted and actual response when stimulus duration of predictor was >=6s; Less correspondence between actual and predicted response when stimulus was 3sStimulus (moving, reversing checkerboard) duration varied between 3s, 6s, 12s, and 24s (y-axis) followed by 24s gray background; also varied stimulus contrast As hypothesized amplitude of response scaled with increasing contrast Figure shows actual BOLD response (blue) and response predicted if multiple stimuli had been presented for 3s, 6s, 12s (x-axis) compared to actual duration (y-axis) Very good correspondence for between predicted and actual response when stimulus duration of predictor was >=6s; Less correspondence between actual and predicted response when stimulus was 3s

79. Superposition Boynton found good correspondence between predicted and actual measured response However, when adding 2 or more 3s stimuli - got smaller than predicted response Attributed to adaptation of neurons leading to reduced activity Support for linearity & superposition

80. Response to Multiple Trials Dale & Buckner, 1997 Three identical trials presented ISI was either 2s or 5s Each trial gives additive effect Presented 1, 2, or 3 trials back-to-back with ISI�s of 2s or 5s Presented 1, 2, or 3 trials back-to-back with ISI�s of 2s or 5s

81. Separation of Response to Multiple Trials Recovered HRF for 2nd and 3rd trials quite closely match that of the first Again at shorter ISI�s of 2s results were reduced amplitude and greater latency Evidence of nonlinearity at short ISI�s Testing to see if ISI is long enough if adaptation can be eliminated Superposition (ie. additive effect of multiple stimuli) held for 5s ISI but not as well for 2s ISI (shown); response to later stimuli is delayed and has less amplitude Testing to see if ISI is long enough if adaptation can be eliminated Superposition (ie. additive effect of multiple stimuli) held for 5s ISI but not as well for 2s ISI (shown); response to later stimuli is delayed and has less amplitude

82. HRF as a Function of Interstimulus Interval Huettel, 2000 used visual stimuli separated by a variable amount of time Found reduction in amplitude of response and increase in latency as ISI decreased

83. Linearity of HRF and Refractory Period Linearity seems to hold for combinations of stimuli with ISI�s 5-6s or longer Much evidence of a refractory period during which additional presentation of stimuli produces smaller and delayed response Is this a bad? Can we take advantage of this?

84. fMRI Adaptation (fMRI-A) Grill-Spector & Mallach, 2001 Presented same face with different sizes, positions, shading, and angles Response was reduced during conditions where size and position was varied Signal recovered when shading or angle was varied! Conclusion - fusiform recognizes identity regardless of size or position but treats shading and angle changes as �different� face

86. fMRI Adaptation Top graph - release of response to attributes other than color thus this area preferentially responds to changes in physical characteristics Bottom graph - release of response only to vehicle type thus this area preferentially responds to complex object categories

87. Summary fMRI BOLD signal arises from increase in blood flow Blood flow is primary means for delivering oxygen and glucose to neurons for production of energy Aerobic and anaerobic glycolysis implies different amounts of ATP (energy) production and oxygen requirements Definitive linkage of blood flow and neuronal energy metabolism still elusive