Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Circulatory and Metabolic Correlates of Brain Function in Normal Humans

Marcus E. Raichle

10.1002/cphy.cp010516

Source: Supplement 5: Handbook of Physiology, The Nervous System, Higher Functions of the Brain

Originally published: 1987

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Methods
1.1 Tracer Strategies
1.2 Instrumentation
1.3 Anatomical Localization Procedures
1.4 Statistical Considerations
2 Relationship of Neuronal Activity to Blood Flow and Energy Metabolism
2.1 Neuronal Function and Energy Metabolism
2.2 Blood Flow and Energy Metabolism
2.3 Effect of Elementary Stimulus Variables
3 Resting Awake Brain: Changes in Blood Flow and Metabolism
3.1 Normal Features
3.2 Sleep
3.3 Anxiety
3.4 Age
3.5 Anatomical Asymmetries and Atrophy
4 Activated Brain: Changes in Blood Flow and Metabolism
4.1 Voluntary Motor Activity
4.2 Somatosensory Stimulation
4.3 Visual Stimulation
4.4 Auditory Stimulation
4.5 Speech and Language
4.6 Mental Work
5 Conclusions
Figure 1. Figure 1.

Whole‐brain, inert‐gas (nitrous oxide) technique for the measurement of blood flow and metabolism in humans. Drawings depict experimental setup with needles in femoral artery and jugular bulb for measurement of arteriovenous differences across the brain, gas delivery system, and manifolds of syringes for sampling arterial and venous blood. This technique and tracer principles upon which it is based provided the basis for all subsequent tracer techniques for study of regional brain circulation and metabolism as well as fundamental data on circulation and metabolism of the human brain.

From Kety and Schmidt 117
Figure 2. Figure 2.

Geometry of regional nontomographic techniques for measurement of blood flow and metabolism in the human brain. Techniques are based on external detection of radioactive tracers administered by intracarotid or intravenous injection or by inhalation. Geometry of monitored region(s) of the brain depends on number and size of radiation detectors and on energy of tracer. Left: multidetector system with many small detectors; right: large single detector. Dark shadows extending as truncated cones from surface of detectors depict origin of data obtained with lower energy (81 keV) 133Xe (left) and much higher energy (511 keV) of 15O‐labeled radiopharmaceuticals (right). Multidetector systems with 133Xe are widely used in studies of regional brain blood flow in humans.
Figure 3. Figure 3.

Detection scheme for positron emission tomography (PET). Radionuclides employed in PET decay by emission of positrons (β+) from a nucleus unstable because of deficiency of neutrons. Positrons lose their kinetic energy in matter after traveling a finite distance (∼1–6 mm) and, when brought to rest, interact with electrons (β–). The 2 particles are annihilated, and their mass is converted to 2 annihilation photons traveling at ∼180° from each other with an energy of 511 keV. Annihilation photons are detected by imaging device, using opposing radiation detectors connected by electronic coincidence circuits that record an event only when 2 photons arrive simultaneously. A major factor determining the ultimate resolution of PET is distance traveled by positron before its annihilation.

From Raichle 199, reproduced with permission from the Annual Review of Neuroscience, © 1983 by Annual Reviews Inc
Figure 4. Figure 4.

Geometry employed in positron emission tomography. Multiple radiation detectors (type depicted in Fig. 3) are arranged about subject's head and connected by coincidence circuits. Data from coincidence lines between detectors form quantitative image of distribution of radiopharmaceutical within the brain. Resulting image is equivalent to quantitative tissue autoradiogram obtained by exposing tissue containing radioactivity to X‐ray film. Spatial geometry of resulting image is very different from that obtained by multidetector, nontomographic systems (cf. Fig. 2).

From Raichle 286
Figure 5. Figure 5.

Diagram of components of modern positron emission tomography system and ways in which data collection and formatting are performed. Data are collected in a list mode that records both the position of the radioactive event in the tissue and the time at which it occurs (i.e., instrument can record number of events occurring every 10 ms for period of time). Resulting image of distribution of radioactivity can be reconstructed either as 1) a single image representing sum of all radioactive decay events occurring during the study or 2) a sequence of images gated to a recurring electrical event in the brain such as cortical evoked response. Latter data format, not yet widely used for research on the brain, can relate circulatory events to brain electrical activity that is recurring over millisecond time intervals and may be important for future studies of brain functional activity.
Figure 6. Figure 6.

Diagram of concept of spatial resolution used in studies with positron emission tomography (PET). A: spatial resolution of PET system is operationally defined as width of an observed distribution of radioactive counts, produced by single point source of radioactivity in field of view of PET scanner, at 1/2 its maximum value (full width at half maximum or FWHM). B: when 2 point sources of radioactivity occur simultaneously in a PET image they cannot be distinguished from each other unless separated by at least 1 FWHM. C: 2 sequentially occurring point sources, however, can be distinguished from each other at considerably less than a distance of 1 FWHM. This fact has important implications for design and interpretation of future studies of functional activity in the human brain with PET.
Figure 7. Figure 7.

[14C]deoxyglucose autoradiographs and stained histological sections of coronal brain sections (left) and pituitary sections (right) in control and dehydrated rats demonstrating location of functionally induced changes in metabolism (i.e., neuropil vs. cell bodies). A: results characteristic of control rats, allowed to drink water freely. B: illustration of positions of the supraoptic (SON) and paraventricular (PVN) nuclei in brain section shown in A after cresyl violet (Nissl) staining. Positions of posterior pituitary (PP) and anterior pituitary (AP) are on the right in B after toluidine blue staining. C: autoradiography of brain and pituitary typical of dehydrated rats given 2% NaCl to drink for 5 days. Note intense labeling in PP without comparable change in SON and PVN, indicating good correlation between neuronal activity and deoxyglucose uptake in nerve terminals but no correlation in cell bodies of origin. D: results characteristic of normal rats after intravenous injection of α‐blocker (phenoxybenzamine) ∼1 h before injection of [14C]deoxyglucose. Note intense labeling in region of SON and PVN (presumably reflecting activity in afferent nerve terminals) as well as intense labeling in PP.

From Schwartz et al. 247. Copyright 1979 by the American Association for the Advancement of Science
Figure 8. Figure 8.

Local blood flow response measured with positron emission tomography in striate cortex of normal humans as function of stimulus repetition rate. Blood flow in striate cortex varied systematically with stimulus rate with maximum response at 7.8 Hz. Two stimuli (patterned flash and reversing checkerboard) were chosen to determine whether stimulus luminance or stimulus frequency was responsible for observed increases in striate cortex blood flow previously observed during photic stimulation 36. Regional cerebral blood flow (rCBF) changes are expressed as percent of change in rCBF from initial unstimulated scan. Each point represents mean rCBF % change from initial unstimulated scan. Error bars indicate ± 1 SE. Response curves show nearly identical rates despite other differences between the two stimulus modalities. Shape of blood flow response curves probably reflects relationships of type depicted in Fig. 9 and underscores importance of understanding elementary stimulus variables in design of brain activation studies in experimental animals and in humans.

From Fox and Raichle 37
Figure 9. Figure 9.

Recordings of electrocorticogram (ECoG), local blood flow recorded with thermoelement (ThE) in cortical projection field of left forepaw in right sensorimotor cortex, systemic arterial blood pressure (SAP), and sensory evoked potential (EP) in cat under chloralose anesthesia during stimulation of left forepaw with 15‐V rectangular pulses 0.3 ms in duration. Output of stimulator (St) records stimulation time. Note relationship between EP and ThE. Changes in ThE do not appear until stimulus frequency reaches 3 Hz, reflecting the fact that average ThE during period of measurement is not appreciably affected at stimulation frequencies as low as 1 Hz. At stimulation frequencies >3 Hz in this particular system amplitude of EP and ThE decline in parallel.

K.‐A. Hossman, personal communication
Figure 10. Figure 10.

Summary of different regional cortical blood flow patterns obtained in normal human volunteers with regional nontomographic technique (see Fig. 2) and 133Xe administered by intracarotid injection or inhalation. Absolute mean blood flow (value in box, in ml·min−1·100 g−1) for each hemisphere is shown along with percent increase in hemisphere blood flow during the test (value below box). Filled and empty circles indicate approximate location of regional flow measurements 20% above or below mean flow, respectively. Top left: composite diagram of 30 resting measurements in normal subjects (CONTROLS: REST). Note typical resting pattern obtained with this technique, described as hyperfrontal. Electrical cutaneous stimulation of the contralateral hand (e.g., right hand stimulated when blood flow measured in left hemisphere) with a low‐intensity stimulus (SENS 1) gives a pattern roughly similar to the high‐intensity stimulation (SENS 2). SENS 2, however, which was experienced as slight pain, increased mean hemisphere flow by 16%, possibly as result of anxiety. Failure of somatosensory stimulation to produce distinctive focal changes in blood flow may reflect improper selection of elementary stimulus variables as somatosensory stimulation in other studies have produced intense focal areas of activation 38. Voluntary hand movements give expected increases in the sensorimotor hand area along with an increase in hemisphere blood flow. Talking and reading produced two similar patterns at about the same resting blood flow. Finally, a reasoning test (i.e., oral description of geometric figures) and the serial subtraction of one number from another produced focal increases in blood in pre‐ and postcentral areas.

From Ingvar 97
Figure 11. Figure 11.

Positron emission tomographic (PET) image of local cerebral blood flow in a resting awake subject with panic disorder, a severe form of anxiety. Left half of image is a quantitative representation of cerebral blood flow corresponding to left side of the calibrated color scale. Right half of image represents the difference between right and left hemispheres expressed as percent of the left hemisphere blood flow in right half of the calibrated color scale. Image is oriented with subject's left at 9:00 and anterior at 12:00. Note striking asymmetry in posterior aspect of image. With a complex localization technique this regional asymmetry was determined to reside in region of the parahip‐pocampal gyrus. Other asymmetries appearing in image vary randomly among subjects.

From Reiman et al. 208. Reprinted by permission from Nature, copyright 1984, Macmillan Journal Limited
Figure 12. Figure 12.

Measurements of regional cerebral blood flow with non‐tomographic, intracarotid, 133Xe technique in normal subject at rest (bottom) and during mental operations on information retrieved from memory (top). Subject was asked to start with 50 and continuously subtract 3, silently. Subject was told to go on even if he reached negative numbers. He was not allowed to speak. Actual values for local blood flow (ml · min−1 · 100 g−1) from 254 regions sampled are shown on color scale to right of images. Approximate anatomical orientation of blood flow changes is indicated by outline of data on left cerebral hemisphere.

From Roland and Friberg 229


Figure 1.

Whole‐brain, inert‐gas (nitrous oxide) technique for the measurement of blood flow and metabolism in humans. Drawings depict experimental setup with needles in femoral artery and jugular bulb for measurement of arteriovenous differences across the brain, gas delivery system, and manifolds of syringes for sampling arterial and venous blood. This technique and tracer principles upon which it is based provided the basis for all subsequent tracer techniques for study of regional brain circulation and metabolism as well as fundamental data on circulation and metabolism of the human brain.

From Kety and Schmidt 117


Figure 2.

Geometry of regional nontomographic techniques for measurement of blood flow and metabolism in the human brain. Techniques are based on external detection of radioactive tracers administered by intracarotid or intravenous injection or by inhalation. Geometry of monitored region(s) of the brain depends on number and size of radiation detectors and on energy of tracer. Left: multidetector system with many small detectors; right: large single detector. Dark shadows extending as truncated cones from surface of detectors depict origin of data obtained with lower energy (81 keV) 133Xe (left) and much higher energy (511 keV) of 15O‐labeled radiopharmaceuticals (right). Multidetector systems with 133Xe are widely used in studies of regional brain blood flow in humans.



Figure 3.

Detection scheme for positron emission tomography (PET). Radionuclides employed in PET decay by emission of positrons (β+) from a nucleus unstable because of deficiency of neutrons. Positrons lose their kinetic energy in matter after traveling a finite distance (∼1–6 mm) and, when brought to rest, interact with electrons (β–). The 2 particles are annihilated, and their mass is converted to 2 annihilation photons traveling at ∼180° from each other with an energy of 511 keV. Annihilation photons are detected by imaging device, using opposing radiation detectors connected by electronic coincidence circuits that record an event only when 2 photons arrive simultaneously. A major factor determining the ultimate resolution of PET is distance traveled by positron before its annihilation.

From Raichle 199, reproduced with permission from the Annual Review of Neuroscience, © 1983 by Annual Reviews Inc


Figure 4.

Geometry employed in positron emission tomography. Multiple radiation detectors (type depicted in Fig. 3) are arranged about subject's head and connected by coincidence circuits. Data from coincidence lines between detectors form quantitative image of distribution of radiopharmaceutical within the brain. Resulting image is equivalent to quantitative tissue autoradiogram obtained by exposing tissue containing radioactivity to X‐ray film. Spatial geometry of resulting image is very different from that obtained by multidetector, nontomographic systems (cf. Fig. 2).

From Raichle 286


Figure 5.

Diagram of components of modern positron emission tomography system and ways in which data collection and formatting are performed. Data are collected in a list mode that records both the position of the radioactive event in the tissue and the time at which it occurs (i.e., instrument can record number of events occurring every 10 ms for period of time). Resulting image of distribution of radioactivity can be reconstructed either as 1) a single image representing sum of all radioactive decay events occurring during the study or 2) a sequence of images gated to a recurring electrical event in the brain such as cortical evoked response. Latter data format, not yet widely used for research on the brain, can relate circulatory events to brain electrical activity that is recurring over millisecond time intervals and may be important for future studies of brain functional activity.



Figure 6.

Diagram of concept of spatial resolution used in studies with positron emission tomography (PET). A: spatial resolution of PET system is operationally defined as width of an observed distribution of radioactive counts, produced by single point source of radioactivity in field of view of PET scanner, at 1/2 its maximum value (full width at half maximum or FWHM). B: when 2 point sources of radioactivity occur simultaneously in a PET image they cannot be distinguished from each other unless separated by at least 1 FWHM. C: 2 sequentially occurring point sources, however, can be distinguished from each other at considerably less than a distance of 1 FWHM. This fact has important implications for design and interpretation of future studies of functional activity in the human brain with PET.



Figure 7.

[14C]deoxyglucose autoradiographs and stained histological sections of coronal brain sections (left) and pituitary sections (right) in control and dehydrated rats demonstrating location of functionally induced changes in metabolism (i.e., neuropil vs. cell bodies). A: results characteristic of control rats, allowed to drink water freely. B: illustration of positions of the supraoptic (SON) and paraventricular (PVN) nuclei in brain section shown in A after cresyl violet (Nissl) staining. Positions of posterior pituitary (PP) and anterior pituitary (AP) are on the right in B after toluidine blue staining. C: autoradiography of brain and pituitary typical of dehydrated rats given 2% NaCl to drink for 5 days. Note intense labeling in PP without comparable change in SON and PVN, indicating good correlation between neuronal activity and deoxyglucose uptake in nerve terminals but no correlation in cell bodies of origin. D: results characteristic of normal rats after intravenous injection of α‐blocker (phenoxybenzamine) ∼1 h before injection of [14C]deoxyglucose. Note intense labeling in region of SON and PVN (presumably reflecting activity in afferent nerve terminals) as well as intense labeling in PP.

From Schwartz et al. 247. Copyright 1979 by the American Association for the Advancement of Science


Figure 8.

Local blood flow response measured with positron emission tomography in striate cortex of normal humans as function of stimulus repetition rate. Blood flow in striate cortex varied systematically with stimulus rate with maximum response at 7.8 Hz. Two stimuli (patterned flash and reversing checkerboard) were chosen to determine whether stimulus luminance or stimulus frequency was responsible for observed increases in striate cortex blood flow previously observed during photic stimulation 36. Regional cerebral blood flow (rCBF) changes are expressed as percent of change in rCBF from initial unstimulated scan. Each point represents mean rCBF % change from initial unstimulated scan. Error bars indicate ± 1 SE. Response curves show nearly identical rates despite other differences between the two stimulus modalities. Shape of blood flow response curves probably reflects relationships of type depicted in Fig. 9 and underscores importance of understanding elementary stimulus variables in design of brain activation studies in experimental animals and in humans.

From Fox and Raichle 37


Figure 9.

Recordings of electrocorticogram (ECoG), local blood flow recorded with thermoelement (ThE) in cortical projection field of left forepaw in right sensorimotor cortex, systemic arterial blood pressure (SAP), and sensory evoked potential (EP) in cat under chloralose anesthesia during stimulation of left forepaw with 15‐V rectangular pulses 0.3 ms in duration. Output of stimulator (St) records stimulation time. Note relationship between EP and ThE. Changes in ThE do not appear until stimulus frequency reaches 3 Hz, reflecting the fact that average ThE during period of measurement is not appreciably affected at stimulation frequencies as low as 1 Hz. At stimulation frequencies >3 Hz in this particular system amplitude of EP and ThE decline in parallel.

K.‐A. Hossman, personal communication


Figure 10.

Summary of different regional cortical blood flow patterns obtained in normal human volunteers with regional nontomographic technique (see Fig. 2) and 133Xe administered by intracarotid injection or inhalation. Absolute mean blood flow (value in box, in ml·min−1·100 g−1) for each hemisphere is shown along with percent increase in hemisphere blood flow during the test (value below box). Filled and empty circles indicate approximate location of regional flow measurements 20% above or below mean flow, respectively. Top left: composite diagram of 30 resting measurements in normal subjects (CONTROLS: REST). Note typical resting pattern obtained with this technique, described as hyperfrontal. Electrical cutaneous stimulation of the contralateral hand (e.g., right hand stimulated when blood flow measured in left hemisphere) with a low‐intensity stimulus (SENS 1) gives a pattern roughly similar to the high‐intensity stimulation (SENS 2). SENS 2, however, which was experienced as slight pain, increased mean hemisphere flow by 16%, possibly as result of anxiety. Failure of somatosensory stimulation to produce distinctive focal changes in blood flow may reflect improper selection of elementary stimulus variables as somatosensory stimulation in other studies have produced intense focal areas of activation 38. Voluntary hand movements give expected increases in the sensorimotor hand area along with an increase in hemisphere blood flow. Talking and reading produced two similar patterns at about the same resting blood flow. Finally, a reasoning test (i.e., oral description of geometric figures) and the serial subtraction of one number from another produced focal increases in blood in pre‐ and postcentral areas.

From Ingvar 97


Figure 11.

Positron emission tomographic (PET) image of local cerebral blood flow in a resting awake subject with panic disorder, a severe form of anxiety. Left half of image is a quantitative representation of cerebral blood flow corresponding to left side of the calibrated color scale. Right half of image represents the difference between right and left hemispheres expressed as percent of the left hemisphere blood flow in right half of the calibrated color scale. Image is oriented with subject's left at 9:00 and anterior at 12:00. Note striking asymmetry in posterior aspect of image. With a complex localization technique this regional asymmetry was determined to reside in region of the parahip‐pocampal gyrus. Other asymmetries appearing in image vary randomly among subjects.

From Reiman et al. 208. Reprinted by permission from Nature, copyright 1984, Macmillan Journal Limited


Figure 12.

Measurements of regional cerebral blood flow with non‐tomographic, intracarotid, 133Xe technique in normal subject at rest (bottom) and during mental operations on information retrieved from memory (top). Subject was asked to start with 50 and continuously subtract 3, silently. Subject was told to go on even if he reached negative numbers. He was not allowed to speak. Actual values for local blood flow (ml · min−1 · 100 g−1) from 254 regions sampled are shown on color scale to right of images. Approximate anatomical orientation of blood flow changes is indicated by outline of data on left cerebral hemisphere.

From Roland and Friberg 229
References
 1. Ackerman, R. F., D. M. Finch, T. L. Babb, and J. Engel. Increased glucose metabolism during long‐duration recurrent inhibition of hippocampal pyramidal cells. J. Neurosci. 4: 251–264, 1984.
 2. Astrup, J., D. Heuser, N. A. Lassen, B. Nilsson, K. Norberg, and B. Siesjö. Evidence against H+ and K+ as main factors for the control of cerebral blood flow: a micro‐electrode study. In: Cerebral Vascular Smooth Muscle and Its Control. New York: Elsevier/North‐Holland, 1978, p. 313–331. (Ciba Found. Symp. 56.)
 3. Auker, C. R., R. M. Meszler, and D. O. Carpenter. Apparent discrepancy between single‐unit activity and [14C]‐deoxyglucose labeling in optic tectum of the rattlesnake. J. Neurophysiol. 49: 1504–1516, 1983.
 4. Baron, J. C., P. Lebrun‐Grandie, P. Collard, C. Crouzel, G. Mestelan, and M. G. Bousser. Noninvasive measurement of blood flow, oxygen consumption, and glucose utilization in the same brain regions in man by positron emission tomography: concise communication. J. Nucl. Med. 23: 391–399, 1982.
 5. Batini, C., F. Benedetti, C. Buisseret‐Delmas, P. G. Montarolo, and P. Strata. Metabolic activity of intracer‐ebellar nuclei in the rat: effects of inferior olive inactivation. Exp. Brain Res. 54: 259–265, 1984.
 6. Bergstrom, M., W. Martin, D. Li, J. Rogers, and B. Pate. Correlation of PET, CT, and NMR images in the same patient. Neurology 34, Suppl. 1: 282, 1984.
 7. Brodersen, P., O. B. Paulson, T. G. Bolwig, Z. E. Rogon, O. J. Rafaelsen, and N. Lassen. Cerebral hyperemia in electrically induced epileptic seizures. Arch. Neurol. 28: 334–338, 1973.
 8. Buchsbaum, M. S., H. H. Holcomb, J. Johnson, A. C. King, and R. Kessler. Cerebral metabolic consequences of electrical cutaneous stimulation in normal individuals. Hum. Neurobiol. 2: 35–38, 1983.
 9. Carmon, A., S. Lavy, H. Gordon, and Z. Portnoy. Hemispheric difference in rCBF during verbal and nonverbal tasks. In: Brain Work: The Coupling of Function, Metabolism and Blood Flow in the Brain, edited by D. H. Ingvar and N. A. Lassen. Copenhagen: Munksgaard, 1975, p. 414–423. (Alfred Benzon Symp. 8.)
 10. Carter, C. C., J. O. Eichling, D. O. Davis, and M. M. Ter‐Pogossian. Correlation of regional cerebral blood flow with regional oxygen uptake using 15O method. Neurology 22: 755–762, 1972.
 11. Celesia, G. G., R. D. Polcyn, J. E. Holden, R. J. Nickles, J. S. Gatley, and R. A. Koeppe. Visual evoked potentials and positron emission tomographic mapping of regional cerebral blood flow and cerebral metabolism: can the neuronal potential generators be visualized? Electroencephalogr. Clin. Neurophysiol. 54: 243–256, 1982.
 12. Cobb, S., and J. H. Talbott. Studies in cerebral capillaries. II. A quantitative study of cerebral capillaries. Trans. Assoc. Am. Physicians 45: 255–262, 1927.
 13. Cohen, L. B., and P. De Weer. Structural and metabolic processes directly related to action potential propagation. In: Handbook of Physiology. The Nervous System, edited by J. M. Brookhart and V. B. Mountcastle. Bethesda, MD: Am. Physiol. Soc., 1977, sect. 1, vol. I, pt. 1, chapt. 5, p. 137–159.
 14. Cooper, R., D. Papkostopoulos, and H. J. Crow. Rapid changes of cortical oxygen associated with motor and cognitive function in man. In: Blood Flow and Metabolism in the Brain, edited by A. M. Harper, W. B. Jennett, J. D. Miller, and J. O. Rowan. Edinburgh: Churchill Livingstone, 1975, p. 14.8–14.9.
 15. Creasey, H., and S. Rapoport. The aging human brain. Ann. Neurol. 40: 715–719, 1985.
 16. Creutzfeldt, O. D. Neurophysiological correlates of different functional states of the brain. In: Brain Work: The Coupling of Function, Metabolism and Blood Flow in the Brain, edited by D. H. Ingvar and N. A. Lassen. Copenhagen: Munksgaard, 1975, p. 22–47. (Alfred Benzon Symp. 8.)
 17. Crick, F. H. C., D. C. Marr, and T. Poggio. An information‐processing approach to understanding the visual cortex. In: The Organization of the Cerebral Cortex, edited by F. O. Schmidt, F. G. Worden, G. Adelman, and S. G. Dennis. Cambridge, MA: MIT Press, 1981, p. 505–533.
 18. Damasio, H. A computed tomographic guide to the identification of cerebral vascular territories. Arch. Neurol. 40: 138–142, 1983.
 19. Damasio, H., P. Eslinger, A. R. Damasio, M. Rizzo, H. K. Huang, and S. Demeter. Quantitative computed tomographic analysis in the diagnosis of dementia. Arch. Neurol. 40: 715–719, 1983.
 20. Dastur, D. K. Cerebral blood flow and metabolism in normal aging, pathological aging and senile dementia. J. Cereb. Blood Flow Metab. 5: 1–9, 1985.
 21. De Leon, M. J., S. H. Ferris, A. E. George, B. Reisberg, D. R. Christman, I. I. Kricheff, and A. P. Wolf. Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer's disease. J. Cereb. Blood Flow Metab. 3: 391–394, 1983.
 22. DeRusso, P. R., R. J. Roy, and C. M. Close. State Variables for Engineers. New York: Wiley, 1965, p. 7–8.
 23. Deuel, R. K., G. M. Yue, W. R. Sherman, D. J. Schickner, and J. J. H. Ackerman. Monitoring the time course of cerebral deoxyglucose metabolism by 31P nuclear magnetic resonance spectroscopy. Science Wash. DC 228: 1329–1331, 1985.
 24. Dietrich, W. D., D. Durham, O. H. Lowry, and T. A. Woolsey. Quantitative histochemical effects of whisker damage on single identified cortical barrels in the adult mouse. J. Neurosci. 1: 929–935, 1981.
 25. Dietrich, W. D., D. Durham, O. H. Lowry, and T. A. Woolsey. “Increased” sensory stimulation leads to changes in energy‐related enzymes in the brain. J. Neurosci. 2: 1608–1613, 1982.
 26. Dietrich, W. D., M. D. Ginsberg, R. Busto, and D. W. Smith. Metabolic alterations in rat somatosensory cortex following unilateral vibrissal removal. J. Neurosci. 5: 874–880, 1985.
 27. Duara, R., C. Grady, J. Haxley, D. Ingvar, L. Sokoloff, R. A. Margolin, R. G. Manning, N. P. Cutler, and S. I. Rapoport. Human brain glucose utilization and cognitive function in relation to age. Ann. Neurol. 16: 702–713, 1984.
 28. Dumke, P. R., and C. F. Schmidt. Quantitative measurements of cerebral blood flow in the macacque monkey. Am. J. Physiol. 138: 421–431, 1943.
 29. Edvinsson, L., and E. T. Mackenzie. Amine mechanisms in the cerebral circulation. Pharmacol. Rev. 28: 275–348, 1977.
 30. Eklöf, B., N. A. Lassen, L. Nilsson, K. Norberg, B. Siesjö, and P. Torlof. Regional cerebral blood flow in the rat measured by the tissue sampling technique; a critical evaluation using four indicators 14C‐antipyrine, 14C‐ethanol, 3H‐water and 133xenon. Acta Physiol. Scand. 91: 1–10, 1974.
 31. Fick, A. Über die Messung des Blutquantums in den Herzven‐trikeln. Verh. Dtsch. Phys.‐Med. Ges. Wurzburg 2: 16, 1870.
 32. Foit, A., B. Larsen, S. Hattori, E. Skinhøj, and N. A. Lassen. Cortical activation during somatosensory stimulation and voluntary movement in man: a regional cerebral blood flow study. Electroencephalogr. Clin. Neurophysiol. 50: 426–436, 1980.
 33. Fox, P. T., J. M. Fox, M. E. Raichle, and R. M. Burde. The role of cerebral cortex in the generation of voluntary saccades: a positron emission tomographic study. J. Neurophysiol. 54: 348–369, 1985.
 34. Fox, P. T., M. A. Mintun, M. E. Raichle, and P. Herscovitch. A noninvasive approach to quantitative functional mapping of H215O and positron emission tomography. J. Cereb. Blood Flow Metab. 4: 329–333, 1984.
 35. Fox, P. T., M. A. Mintun, M. E. Raichle, F. M. Meizen, J. M. Allman, and D. C. Van Essen. Mapping human visual cortex with positron emission tomography. Nature Lond. 323: 806–809, 1986.
 36. Fox, P. T., J. S. Perlmutter, and M. E. Raichle. A stereotactic method of anatomical localization for positron emission tomography. J. Comput. Assist. Tomogr. 9: 141–153, 1985.
 37. Fox, P. T., and M. E. Raichle. Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography. J. Neurophysiol. 51: 1109–1120, 1984.
 38. Fox, P. T., and M. E. Raichle. Stimulus rate determines regional blood flow in striate cortex. Ann. Neurol. 17: 303–305, 1985.
 39. Fox, P. T., and M. E. Raichle. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc. Natl. Acad. Sci. USA. 83: 1140–1144, 1986.
 40. Fox, P. T., M. E. Raichle, and W. T. Thach. Functional mapping of the human cerebellum with positron emission tomography. Proc. Natl. Acad. Sci. USA 83: 1140–1144, 1986.
 41. Frackowiak, R. S. J., and J. M. Gibbs. The pathophysiology of Alzheimer's disease studied with positron emission tomography. In: Biological Aspects of Alzheimer's Disease, edited by R. Katzman. Cold Spring Harbor, NY: Cold Spring Harbor, 1983, p. 317–324. (Banbury Rep. 15.)
 42. Frackowiak, R. S. J., G.‐L. Lenzi, T. Jones, and J. D. Heather. Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values. J. Comput. Assist. Tomogr. 4: 727–736, 1980.
 43. Fulton, J. F. Observations upon the vascularity of the human occipital lobe during visual activity. Brain 51: 310–320, 1928.
 44. Gado, M., J. Hanaway, and R. Frank. Functional anatomy of the cerebral cortex by computed tomography. J. Comput. Assist. Tomogr. 3: 1–19,1979.
 45. Gado, M., C. P. Hughes, W. Danziger, D. Chi, G. Jost, and L. Berg. Volumetric measurements of cerebrospinal fluid spaces in demented subjects and controls. Radiology 144: 535–538, 1982.
 46. Galaburda, A. M., M. LeMay, T. L. Kemper, and N. Geschwind. Right‐left asymmetries in the brain. Structural differences between the hemispheres may underlie cerebral dominance. Science Wash. DC 199: 852–856, 1978.
 47. Geschwind, N., and A. M. Galaburda. Cerebral lateralization. Biological mechanisms, associations, and pathology: a hypothesis and a program for research. Arch. Neurol. 42: pt. I, 428–459;
 48. Cerebral lateralization. Biological mechanisms, associations, and pathology: a hypothesis and a program for research. Arch. Neurol. 42: pt. II, 521–552;
 49. Cerebral lateralization. Biological mechanisms, associations, and pathology: a hypothesis and a program for research. Arch. Neurol. 42: pt. III, 634–654, 1985.
 50. Gjedde, A. Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: a re‐examination. Brain Res. Rev. 4: 237–274, 1982.
 51. Gjedde, A. On the measurement of glucose in brain: a comment to Sacks et al. (1983). Neurochem. Res. 9: 1667–1671, 1984.
 52. Godfrey, K. Compartmental Models and Their Application. New York: Academic, 1983.
 53. Goldenson, R. M. Encyclopedia of Human Behavior. New York: Doubleday, 1972, vol. 2, p. 1272–1274.
 54. Greenberg, J., P. Hand, A. Sylvestro, and M. Reivich. Localized metabolic‐flow couple during functional activity. Acta Neurol. Scand. Suppl. 72: 12–13, 1979.
 55. Greenberg, J., M. Reivich, A. Alavi, P. Hand, A. Rosenquist, W. Rintelmann, A. Stein, R. Tusa, R. Dann, D. Christman, J. Fowler, B. MacGregor, and A. Wolf. Metabolic mapping of functional activity in human subjects with the 18F‐fluorodeoxyglucose technique. Science Wash. DC 212: 678–680, 1981.
 56. Greitz, T. A radiologic study of the brain circulation by rapid serial angiography of the carotid artery. Acta Radiol. Suppl. 140: 1–123, 1956.
 57. Grubb, R. L., M. E. Raichle, J. O. Eichling, and M. M. Ter‐Pogossian. The effects of changes in PaCO2 on cerebral blood volume, blood flow and vascular mean transit time. Stroke 5: 630–639,1974.
 58. Grubb, R. L., M. E. Raichle, C. S. Higgins, and J. O. Eichling. Measurement of cerebral blood volume by emission tomography. Ann. Neurol. 4: 322–328, 1978.
 59. Gur, R. C., R. E. Gur, W. D. Obrist, J. P. Hungerbuhler, D. Younkin, A. D. Rosen, B. E. Skolnick, and M. Reivich. Sex and handedness differences in cerebral blood flow during rest and cognitive activity. Science Wash. DC 217: 659–661, 1982.
 60. Gur, R. C., I. K. Packer, J. P. Hungerbuhler, M. Reivich, W. D. Obrist, W. S. Amarnek, and H. A. Sackeim. Differences in the distribution of gray and white matter in human cerebral hemispheres. Science Wash. DC 207: 1226–1228, 1980.
 61. Gur, R. C., and M. Reivich. Cognitive tasks effects on hemispheric blood flow in humans: evidence for individual differences in hemispheric activation. Brain Lang. 9: 78–92, 1980.
 62. Halsey, J. H., V. W. Blauenstein, E. M. Wilson, and E. H. Wills. Regional cerebral blood flow comparison of right and left hand movement. Neurology 29: 21–28, 1979.
 63. Hanaway, J., W. R. Scott, and C. M. Strother. Atlas of the Human Brain and the Orbit for Computed Tomography. St. Louis, MO: Warren Green, 1977.
 64. Hand, P., J. Greenberg, C. Goochee, A. Sylvestro, L. Weller, and M. Reivich. A normal and developmentally‐altered cortical column: a laminar analysis of local glucose utilization with natural stimulation of a single receptor organ. Acta Neurol. Scand. Suppl. 72: 46–47, 1979.
 65. Hawkins, R., W. K. Hass, and J. Ransohoff. Measurement of regional brain glucose utilization in vivo using [2−14C]glucose. Stroke 10: 690–703, 1979.
 66. Hawkins, R. A., A. M. Mans, D. W. Davis, J. R. Vina, and L. S. Hibbard. Cerebral glucose use measured with [14C]‐glucose labeled in the 1, 2, or 6 position. Am. J. Physiol. 248 (Cell Physiol. 17): C170–C176, 1985.
 67. Hawkins, R. A., A. L. Miller, J. E. Cremer, and R. L. Veech. Measurement of the rate of glucose utilization by rat brain in vivo. J. Neurochem. 23: 917–923, 1974.
 68. Heiss, W. D., G. Pawlik, K. Herholz, R. Wagner, and K. Weinhard. Regional cerebral glucose metabolism in man during wakefulness, sleep, and dreaming. Brain Res. 327: 362–366, 1985.
 69. Heistad, D. D., and H. A. Kontos. Cerebral circulation. In: Handbook of Physiology. The Cardiovascular System, edited by J. T. Shepherd and F. M. Abboud. Bethesda, MD: Am. Physiol. Soc., 1983, sect. 2, vol. III, pt. 1, chapt. 5, p. 137–182.
 70. Herscovitch, P., A. Auchus, M. Gado, D. Chi, and M. E. Raichle. Correction of positron emission tomography data for cerebral atrophy. J. Cereb. Blood Flow Metab. 6: 120–124, 1986.
 71. Herscovitch, P., J. Markham, and M. E. Raichle. Brain blood flow measured with intravenous H215O. I. Theory and error analysis. J. Nucl. Med. 24: 782–789, 1983.
 72. Herscovitch, P., M. A. Mintun, and M. E. Raichle. Brain oxygen utilization measured with oxygen‐15 radiotracers and positron emission tomography: generation of metabolic images. J. Nucl. Med. 26: 416–417, 1985.
 73. Herscovitch, P., and M. E. Raichle. Effect of tissue heterogeneity on the measurement of cerebral blood flow with the equilibrium C15O2 inhalation technique. J. Cereb. Blood Flow Metab. 3: 407–415, 1983.
 74. Heuser, D. Local ionic control of cerebral microvessels. In: The Application of Ion‐Selective Microelectrodes, edited by T. Zeuthen. New York: Elsevier, 1981, p. 85–105.
 75. Hill, A. V. The heat production of nerve. J. Pharmacol. Exp. Ther. 29: 161–165, 1926.
 76. Hiroshige, Y., and S. Iwahara. Digital and cephalic vasomotor orientating responses to indifferent, signal and verbal stimuli. Psychophysiology 15: 226–232, 1978.
 77. Hirsch, J. C., A. Pierre‐Kahn, and J. F. Hirsch. Experimental study of intracranial pressure during rapid eye movement sleep in the chronic cat. Neurosci. Lett. 7: 245–249, 1978.
 78. Hoedt‐Rasmussen, K., E. Sveinsdottir, and N. A. Lassen. Regional cerebral blood flow in man determined by intraarterial injection of radioactive inert gas. Circ. Res. 18: 237–247, 1966.
 79. Hoffman, E. J., S.‐C. Huang, and M. E. Phelps. Quantitation in positron emission computed tomography. 1. Effect of object size. J. Comput. Assist. Tomogr. 3: 299–308, 1979.
 80. Hoffman, E. J., S.‐C. Huang, M. E. Phelps, and D. E. Kuhl. Quantitation in positron emission computed tomography. 4. Effect of accidental coincidence. J. Comput. Assist. Tomogr. 5: 391–400, 1981.
 81. Hoffman, E. J., S.‐C. Huang, D. Plummer, and M. E. Phelps. Quantitation in positron emission computed tomography: 6. Effect of nonuniform resolution. J. Comput. Assist. Tomogr. 6: 987–999, 1982.
 82. Holden, J. E., S. J. Gatley, R. D. Hichwa, W. R. Ip, W. J. Shaughnessy, R. J. Nickles, and R. E. Polcyn. Cerebral blood flow using PET measurements of fluoromethane kinetics. J. Nucl. Med. 22: 1084–1088, 1981.
 83. Horowicz, P., and M. G. Larrabee. Glucose consumption and lactate production in a mammalian sympathetic ganglion at rest and in activity. J. Neurochem. 2: 102–118, 1958.
 84. Horowicz, P., and M. G. Larrabee. Oxidation of glucose in a mammalian sympathetic ganglion at rest and in activity. J. Neurochem. 9: 1–21, 1962.
 85. Horowicz, P., and M. G. Larrabee. Metabolic partitioning of carbon from glucose by a mammalian sympathetic ganglion. J. Neurochem. 9: 407–420, 1962.
 86. Howarth, J. V., R. D. Keynes, and J. M. Ritchie. The origin of the initial heat associated with a single impulse in mammalian non‐myelinated nerve fibers. J. Physiol. Lond. 194: 745–793, 1968.
 87. Howse, D. C., J. J. Caronna, T. E. Duffy, and F. Plum. Cerebral energy metabolism, pH, and blood flow during seizures in the cat. Am. J. Physiol. 227: 1444–1451, 1974.
 88. Huang, M.‐T., and R. L. Veech. The quantitative determination of the in vivo dephosphorylation of glucose 6‐phosphate in rat brain. J. Biol. Chem. 257: 1358–1363, 1982.
 89. Huang, M.‐T., and R. L. Veech. Metabolic fluxes between [14C]2‐deoxy‐D‐glucose and [14C]2‐deoxy‐D‐glucose‐6‐phosphate in brain in vivo. J. Neurochem. 44: 567–573, 1985.
 90. Huang, S.‐C., R. E. Carlson, E. J. Hoffman, J. Carson, N. MacDonald, J. R. Barrio, and M. E. Phelps. Quantitative measurement of local cerebral blood flow in humans by positron emission tomography and 15O‐water. J. Cereb. Blood Flow Metab. 3: 141–153, 1983.
 91. Huang, S.‐C., R. E. Carlson, and M. E. Phelps. Measurement of local blood flow and distribution volume with shortlived isotopes: a general input model. J. Cereb. Blood Flow Metab. 2: 99–108, 1982.
 92. Huang, S.‐C., E. J. Hoffman, M. E. Phelps, and D. E. Kuhl. Quantitation in positron emission computed tomography: 2. Effects of inaccurate attenuation correction. J. Comput. Assist. Tomogr. 3: 804–814, 1979.
 93. Huang, S.‐C., E. J. Hoffman, M. E. Phelps, and D. E. Kuhl. Quantitation in positron emission computed tomography: 3. Effect of sampling. J. Comput. Assist. Tomogr. 4: 819–826, 1980.
 94. Huang, S.‐C., M. E. Phelps, E. J. Hoffman, and D. E. Kuhl. Error sensitivity of fluorodeoxyglucose method for measurement of cerebral metabolic rate of glucose. J. Cereb. Blood Flow Metab. 1: 391–401, 1981.
 95. Huang, S.‐C., M. E. Phelps, E. J. Hoffman, K. Sideris, C. J. Selin, and D. E. Kuhl. Noninvasive determination of local cerebral metabolic rate of glucose in man. Am. J. Physiol. 238 (Endocrinol. Metab. 1): E69–E82, 1980.
 96. Iadecola, C., S. Mraovitch, M. P. Meeley, and D. J. Reis. Lesions of the basal forebrain in rat selectively impair the cortical vasodilation elicited from cerebellar fastigial nucleus. Brain Res. 279: 41–52, 1983.
 97. Iadecola, C., M. Nakai, S. Mraovitch, D. A. Ruggiero, L. W. Tucker, and D. Reis. Glucose increase in cerebral metabolism and blood flow produced by focal electrical stimulation of dorsal medullary reticular formation in rat. Brain Res. 272: 101–114, 1983.
 98. Ingvar, D. H. Pattern of brain activity revealed by measurement of regional cerebral blood flow. In: Brain Work, edited by D. H. Ingvar and N. A. Lassen. Copenhagen: Munksgaard, 1975, p. 397–413.
 99. Ingvar, D. H. Functional landscapes of the dominant hemisphere. Brain Res. 107: 181–197, 1976.
 100. Ingvar, D. H. “Hyperfrontal” distribution of the cerebral grey matter flow in resting wakefulness; on the functional anatomy of the conscious state. Acta Neurol. Scand. 60: 12–25, 1979.
 101. Ingvar, D. H. Serial aspects of language and speech related to prefrontal cortical activity. A selective review. Hum. Neurobiol. 2: 177–189, 1983.
 102. Ingvar, D. H., and L. Philipson. Distribution of cerebral blood flow in the dominant hemisphere during motor ideation and motor performance. Ann. Neurol. 2: 230–237, 1977.
 103. Ingvar, D. H., and J. Risberg. Increase of regional cerebral blood flow during mental effort in normals and in patients with focal brain disorders. Exp. Brain Res. 3: 195–211, 1967.
 104. Ingvar, D. H., and M. S. Schwartz. Blood flow patterns induced in the dominant hemisphere by speech and reading. Brain 97: 273–288, 1974.
 105. Jacquez, J. A. Compartmental Analysis in Biology and Medicine. New York: Elsevier, 1972.
 106. Jensen, K. B., K. Hoedt‐Rasmussen, E. Sveinsdottir, B. M. Stewart, and N. A. Lassen. Cerebral blood flow evaluated by inhalation of 133‐xenon and extracranial recording: a methodological study. Clin. Sci. 30: 485–494, 1966.
 107. Jones, S. C., J. H. Greenberg, and M. Reivich. Error analysis for the determination of cerebral blood flow with the continuous inhalation of 15O‐labeled carbon dioxide and positron emission tomography. J. Comput. Assist. Tomogr. 6: 116–124, 1982.
 108. Jones, T., D. A. Chesler, and M. M. Ter‐Pogossian. The continuous inhalation of oxygen‐15 for assessing regional oxygen extraction in the brain of man. Br. J. Radiol. 49: 339–343, 1976.
 109. Kanno, I., A. A. Lammertsma, J. D. Heather, J. M. Gibbs, C. G. Rhodes, J. C. Clark, and T. Jones. Measurement of cerebral blood flow using bolus inhalation of C15O2 and positron emission tomography: description of the method and its comparison with the C15O2 continuous inhalation method. J. Cereb. Blood Flow Metab. 4: 224–234, 1984.
 110. Kanno, I., and N. A. Lassen. Two methods for calculating regional cerebral blood flow from emission computed tomography of inert gas concentrations. J. Comput. Assist. Tomogr. 3: 71–76, 1979.
 111. Karnovsky, M. L., B. L. Burrows, and M. A. Zoccoli. Cerebral glucose‐6‐phosphatase and the movement of 2‐deoxyglucose during slow wave sleep. In: Cerebral Metabolism and Neural Function, edited by J. V. Passonneau, R. A. Hawkins, W. D. Lust, and F. A. Welsch. Baltimore, MD: Williams & Wilkins, 1980, p. 359–366.
 112. Kearfott, K. J., D. A. Rottenberg, and B. T. Volpe. Design of steady‐state positron emission tomography protocols for neurobehavioral studies: CO15O and 19Ne. J. Comput. Assist. Tomogr. 7: 361–369, 1983.
 113. Kennedy, C., J. C. Gillin, W. Mendelson, S. Suda, M. Miyaoka, M. Ito, R. K. Nakamura, W. Storch, J. Pettigrew, M. Mishkin, and L. Sokoloff. Local cerebral glucose utilization in non‐rapid eye movement sleep. Nature Lond. 297: 325–327, 1982.
 114. Kety, S. S. Circulation and metabolism of the human brain in health and disease. Am. J. Med. 8: 205–217, 1950.
 115. Kety, S. S. The theory and applications of the exchange of inert gas at the lungs and tissues. Pharmacol. Rev. 3: 1–41, 1951.
 116. Kety, S. S. The cerebral circulation. In: Handbook of Physiology. Neurophysiology, edited by J. Field and H. W. Magoun. Washington, DC: Am. Physiol. Soc., 1960, sect. 1, vol. III, chapt. 71, p. 1751–1760.
 117. Kety, S. S. Measurement of local blood flow by the exchange of an inert, diffusible substance. Methods Med. Res. 8: 228–236, 1960.
 118. Kety, S. S., and C. F. Schmidt. The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am. J. Physiol. 143: 53–66, 1945.
 119. Kety, S. S., and C. F. Schmidt. The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure, and normal values. J. Clin. Invest. 27: 107–119, 1948.
 120. Knopman, D. S., A. B. Rubens, A. C. Klassen, and M. W. Meyer. Regional cerebral blood flow correlates of auditory processing. Arch. Neurol. 39: 487–493, 1982.
 121. Kuhl, D. E., E. J. Metter, W. H. Riege, and M. E. Phelps. Effects of human aging on patterns of local cerebral glucose utilization determined by the [18F]fluorodeoxyglucose method. J. Cereb. Blood Flow Metab. 2: 163–171, 1982.
 122. Kuschinsky, W., and M. Wahl. Local chemical and neurogenic regulation of cerebral vascular resistance. Physiol. Rev. 58: 656–689, 1978.
 123. Lahti, B. P. Signals, Systems and Communication. New York: Wiley, 1965, p. 437–441.
 124. Lammertsma, A. A., J. D. Heather, T. Jones, R. S. J. Frackowiak, and G. L. Lenzi. A statistical study of the steady state technique for measuring regional cerebral blood flow and oxygen utilisation using 15O. J. Comput. Assist. Tomogr. 6: 566–573, 1982.
 125. Lammertsma, A. A., and T. Jones. Correction for the presence of intravascular oxygen‐15 in the steady state technique for measuring regional oxygen extraction ratio in the brain: 1. Description of the method. J. Cereb. Blood Flow Metab. 3: 416–424, 1983.
 126. Lammertsma, A. A., T. Jones, R. S. J. Frackowiak, and G. L. Lenzi. A theoretical study of the steady state model for measuring regional cerebral blood flow and oxygen utilisation using oxygen‐15. J. Comput. Assist. Tomogr. 5: 544–550, 1981.
 127. Lammertsma, A. A., R. J. S. Wise, J. D. Heather, J. M. Gibbs, K. L. Leenders, R. S. J. Frackowiak, C. G. Rhodes, and T. Jones. Correction for the presence of intravascular oxygen‐15 in the steady state technique for measuring regional oxygen extraction ratio in the brain: 2. Results in normal subjects and brain tumour and stroke patients. J. Cereb. Blood Flow Metab. 3: 425–431, 1983.
 128. Landau, W. M., W. H. J. Freygang, L. P. Roland, L. Sokoloff, and S. S. Kety. The local circulation of the living brain: values in the unanesthetized and anesthetized cat. Trans. Am. Neurol. Assoc. 80: 125–129, 1955.
 129. Larrabee, M. G. Oxygen consumption of excised sympathetic ganglia at rest and in activity. J. Neurochem. 2: 81–101, 1958.
 130. Larsen, B., E. Skinhøj, and N. A. Lassen. Variation in regional cortical blood flow in the right and left hemispheres during automatic speech. Brain 101: 193–209, 1978.
 131. Larson, K. B., and M. E. Raichle. Compartmental models: limitation for measurement of CBF with PET. J. Cereb. Blood Flow Metab. 5: 5649–5650, 1985.
 132. Lassen, N. A. Cerebral blood flow and oxygen consumption in man. Physiol. Rev. 39: 183–238, 1959.
 133. Lassen, N. A., O. Henriksen, and P. Sejrsen. Indicator methods for measurement of organ and tissue blood flow. In: Handbook of Physiology. The Cardiovascular System, edited by J. T. Shepherd and F. M. Abboud. Bethesda, MD: Am. Physiol. Soc., 1983, sect. 2, vol. III, pt. 1, chapt. 2, p. 21–63.
 134. Lassen, N. A., K. Hoedt‐Rasmussen, S. C. Sorensen, E. Skinhøj, S. Cronquist, B. Bodforss, E. Eng, and D. H. Ingvar. Regional cerebral blood flow in man determined by krypton‐85. Neurology 13: 719–727, 1963.
 135. Lassen, N. A., and D. H. Ingvar. Radioisotope assessment of regional cerel” blood flow. Prog. Nucl. Med. 1: 376–409, 1972.
 136. Lassen, N. A., D. H. Ingvar, and E. Skinhøj. Brain function and blood flow. Sci. Am. 239: 62–71, 1978.
 137. Lassen, N. A., and A. Klee. Cerebral blood flow determined by saturation and desaturation with krypton‐85: an evaluation of the validity of the inert gas method of Kety and Schmidt. Circ. Res. 16: 26–32, 1965.
 138. Lassen, N. A., and B. Larsen. Cortical activity in the right and left hemispheres during language‐related brain functions. Phonetica 37: 27–37, 1980.
 139. Lassen, N. A., and W. Perl. Tracer Kinetic Methods in Medical Physiology. New York: Raven, 1979.
 140. Lauter, J. L., P. Herscovitch, C. Formby, and M. E. Raichle. Tonotopic organization in human auditory cortex revealed by positron emission tomography. Hear. Res. 20: 199–205, 1985.
 141. Leenders, K. L., J. M. Gibbs, R. S. J. Frackowiak, A. A. Lammertsma, and T. Jones. Positron emission tomography of the brain: new possibilities for the investigation of human cerebral pathophysiology. Prog. Neurobiol. Oxf. 23: 1–38, 1984.
 142. Leniger‐Follert, E. Mechanisms of regulation of cerebral microflow during bicuculline‐induced seizures in anaesthetized cats. J. Cereb. Blood Flow Metab. 4: 150–165, 1984.
 143. Leniger‐Follert, E., and C. Danz. The role of extracellular potassium and hydrogen activities in the brain cortex for regulation of cerebral microcirculation in the cat during generalized seizures and specific sensory stimulation. In: Progress in Enzyme and Ion‐Selective Electrodes, edited by D. W. Lübbers, H. Acker, R. P. Buck, G. Eisenman, M. Kessler, and W. Simon. Berlin: Springer‐Verlag, 1981, p. 100–105.
 144. Leniger‐Follert, E., and K.‐A. Hossmann. Simultaneous measurements of microflow and evoked potentials in the somatomotor cortex of the cat brain during specific sensory activation. Pfluegers Arch. 380: 85–89, 1979.
 145. Leniger‐Follert, E., and D. W. Lübbers. Behavior of microflow and local Po2 of the brain cortex during and after direct electrical stimulation. Pfluegers Arch. 366: 39–44, 1976.
 146. Lenzi, G. L., R. S. J. Frackowiak, T. Jones, J. D. Heather, A. A. Lammertsma, C. G. Rhodes, and C. Pozzilli. CMRO2 and CBF by the oxygen‐15 inhalation technique. Eur. Neurol. 20: 285–290, 1981.
 147. Lenzi, G. L., T. Jones, C. G. McKenzie, P. D. Buckingham, J. C. Clark, and S. Moss. Study of regional cerebral metabolism and blood flow relationships in man using the method of continuously inhaling oxygen‐15 and oxygen‐15 labeled carbon dioxide. J. Neurol. Neurosurg. Psychiatry 41: 1–10, 1978.
 148. Lightman, S. L., S. P. Hunt, and L. L. Iversen. Effects of opiates and osmotic stimuli on rat neurohypophyseal metabolic activity monitored with [3H]‐2‐deoxyglucose. Neuroen‐docrinology 35: 104–110, 1982.
 149. Livingstone, M. S., and D. H. Hubel. Effects of sleep and arousal on the processing of visual information in the cat. Nature Lond. 291: 554–561, 1981.
 150. London, E. D. Metabolism of the brain: a measure of cellular function in aging. In: Aging and Cell Function, edited by J. E. Johnson, New York: Plenum, 1984, p. 187–212.
 151. Lu, D. M., D. W. Davis, A. M. Mans, and R. A. Hawkins. Regional cerebral glucose utilization measured with [14C]glucose in brief experiments. Am. J. Physiol. 245 (Cell Physiol. 14): C428–C438, 1983.
 152. Lübbers, D. W., and E. Leniger‐Follert. Capillary flow in brain cortex during changes in oxygen supply and state of activation. In: Cerebral Vascular Smooth Muscle and Its Control. Amsterdam: Elsevier/North‐Holland, 1978, p. 21–42. (Ciba Found. Symp. 56.)
 153. Luzzatti, C., G. Scotti, and A. Gattoni. Further suggestions for cerebral CT‐localization. Cortex 15: 483–490, 1979.
 154. Mallett, B. L., and N. Veall. The measurement of regional cerebral clearance rates in man using xenon‐133 inhalation and extracranial recording. Clin. Sci. 29: 179–191, 1965.
 155. Mamo, H., J. Seylaz, J. P. Caron, and R. Houdart. Mesure du début saguin du cortex de l'homme par une méthode semi‐quantitative continue et focale (technique, données physiologiques et physio‐pathologiques). Rev. Neurol. Paris 117: 689–713, 1967.
 156. Mangold, R., L. Sokoloff, E. Conner, J. Kleinerman, P. O. G. Therman, and S. Kety. The effects of sleep and lack of sleep on the cerebral circulation and metabolism of normal young men. J. Clin. Invest. 34: 1092–1100, 1955.
 157. Martin, W. R. W., and M. E. Raichle. Cerebellar blood flow and metabolism in cerebral hemisphere infarction. Ann. Neurol. 14: 168–176, 1983.
 158. Mata, M., D. J. Fink, H. Gainer, C. B. Smith, L. Davidsen, H. Savaki, W. J. Schwartz, and L. Sokoloff. Activity‐dependent energy metabolism in rat posterior pituitary primarily reflects sodium pump activity. J. Neurochem. 34: 213–215, 1980.
 159. Matsui, T., and A. Hirano. An Atlas of the Human Brain for Computerized Tomography. New York: Igaku Shoin, 1978.
 160. Maximilian, V. A. Cortical blood flow asymmetries during monaural verbal stimulation. Brain Lang. 15: 1–11, 1982.
 161. Maximilian, V. A., I. Prohovnik, J. Risberg, and K. Håkansson. Regional blood flow changes in the left cerebral hemisphere during word pair learning and recall. Brain Lang. 6: 22–31, 1978.
 162. Mazziotta, J. C., M. E. Phelps, R. E. Carson, and D. E. Kuhl. Tomographic mapping of human cerebral metabolism: auditory stimulation. Neurology 32: 921–937, 1982.
 163. Mazziotta, J. C., M. E. Phelps, R. E. Carson, and D. E. Kuhl. Tomographic mapping of human cerebral metabolism: sensory deprivation. Ann. Neurol. 12: 435–444, 1982.
 164. Mazziotta, J. C., M. E. Phelps, A. K. Meadors, A. Ricci, K. Winter, and J. R. Bentson. Anatomical localization schemes for use in positron computed tomography using a specially designed headholder. J. Comput. Assist. Tomogr. 6: 848–853, 1982.
 165. Mazziotta, J. C., M. E. Phelps, J. Miller, and D. E. Kuhl. Tomographic mapping of human cerebral metabolism: normal unstimulated state. Neurology 31: 506–516, 1981.
 166. Mazziotta, J. C., M. E. Phelps, D. Plummer, and D. E. Kuhl. Quantitation in positron emission computed tomography: 5. Physical‐anatomical effects. J. Comput. Assist. Tomogr. 5: 734–743, 1981.
 167. Mazzocchi, F., and L. A. Vignolo. Computer assisted tomography in neuropsychological research: a simple procedure for lesion mapping. Cortex 14: 136–144, 1978.
 168. Melamed, E. Cortical activation pattern during saccadic eye movements in humans: localization by focal cerebral blood flow increases. Ann. Neurol. 5: 79–88, 1979.
 169. Meldrum, B. S., and B. Nilsson. Cerebral blood flow and metabolic rate early and late in prolonged epileptic seizures induced in rats by bicuculline. Brain 99: 523–542, 1976.
 170. Meyer, J. S., F. Nomura, K. Sakamoto, and A. Kondo. Effect of stimulation of the brain‐stem reticular formation on cerebral blood flow and oxygen consumption. Electroencephalogr. Clin. Neurophysiol. 26: 125–132, 1969.
 171. Meyer, J. S., and M. Toyoda. Studies of rapid changes in cerebral circulation and metabolism during arousal and rapid eye movement sleep in human subjects with cerebrovascular disease. In: Cerebral Circulation and Stroke, edited by K. J. Zulch. New York: Springer‐Verlag, 1971, p. 156–163.
 172. Mintun, M. A., M. E. Raichle, W. R. W. Martin, and P. Herscovitch. Brain oxygen utilization measured with 15O radiotracers and positron emission tomography. J. Nucl. Med. 25: 177–187, 1984.
 173. Miyazaki, M. Effect of undesirable sound (noise) on cerebral circulation. Jpn. Circ. J. 35: 931–936, 1971.
 174. Miyazaki, M. Circulatory effect of jet noise with special reference to the cerebral circulation. Jpn. Circ. J. 42: 1019–1024, 1978.
 175. Naeser, M. A., and R. W. Hayward. Lesion localization in aphasia with cranial computed tomography and the Boston Diagnostic Aphasia Exam. Neurology 28: 545–551, 1978.
 176. Nakai, M., C. Iadecola, and D. J. Reis. Global cerebral vasodilation by stimulation of rat fastigial cerebellar nucleus. Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H226–H235, 1982.
 177. Nakai, M., C. Iadecola, D. A. Ruggiero, L. W. Tucker, and D. J. Reis. Electrical stimulation of cerebellar fastigial nucleus increases cerebral cortical blood flow without change in local metabolism: evidence for an intrinsic system in brain for primary vasodilation. Brain Res. 269: 35–49, 1983.
 178. Nakamura, R. K., C. Kennedy, J. C. Dillin, S. Suda, M. Ito, F. I. Storch, W. Mendelson, L. Sokoloff, and M. Mishkin. Hypnogenic center theory of sleep: no support from metabolic mapping in monkeys. Brain Res. 268: 372–376, 1983.
 179. Nelson, T., G. Lucignani, S. Atlas, A. M. Crane, G. A. Dienel, and L. Sokoloff. Re‐examination of glucose‐6‐phosphatase activity in brain in vivo: no evidence for a futile cycle. Science Wash. DC 229: 60–62, 1985.
 180. Nishizawa, Y., T. S. Olsen, B. Larsen, and N. A. Lassen. Left‐right cortical asymmetries of regional cerebral blood flow during listening to words. J. Neurophysiol. 48: 458–466, 1982.
 181. Obrist, W. A., H. K. Thompson, C. H. King, and H. S. Wang. Determination of regional cerebral blood flow by inhalation of 133Xenon. Circ. Res. 20: 124–135, 1967.
 182. Obrist, W. A., H. K. Thompson, H. S. Wang, and W. E. Wilkinson. Regional cerebral blood flow estimated by 133‐xenon inhalation. Stroke 6: 245–256, 1975.
 183. Olesen, J. Contralateral focal increase of cerebral blood flow in man during arm work. Brain 94: 635–646, 1971.
 184. Orgogozo, J. M., and B. Larsen. Activation of the supplementary motor area during voluntary movement in man suggests it works as a supramotor area. Science Wash. DC 206: 847–850, 1979.
 185. Pantano, P., J. C. Baron, P. Lebrun‐Grandie, N. Duquesnoy, M. G. Bousser, and D. Comar. Regional cerebral blood flow and oxygen consumption in human aging. Stroke 15: 635–641, 1984.
 186. Paulson, O. B., S. Cronqvist, J. Risberg, and F. I. Jeppesen. Regional cerebral blood flow: a comparison of 8‐detector and 16‐detector instrumentation. J. Nucl. Med. 10: 164–173, 1969.
 187. Perlmutter, J. S., P. Herscovitch, W. J. Powers, P. T. Fox, and M. E. Raichle. Standardized mean regional method for calculating global positron emission tomographic measurements. J. Cereb. Blood Flow Metab. 5: 476–480, 1985.
 188. Perlmutter, J. S., W. J. Powers, P. Herscovitch, P. T. Fox, and M. E. Raichle. Regional asymmetries of cerebral blood flow, blood volume and oxygen utilization and extraction in normal subjects. J. Cereb. Blood Flow Metab. 7: 64–67, 1987.
 189. Perlmutter, J. S., and M. E. Raichle. Pure hemidystonia with basal ganglion abnormalities on positron emission tomography. Ann. Neurol. 15: 228–233, 1984.
 190. Phelps, M. E., E. J. Hoffman, S.‐C. Huang, and M. M. Pogossian. Effect of positron range on spatial resolution. J. Nucl. Med. 16: 649–652, 1975.
 191. Phelps, M. E., S.‐C. Huang, E. J. Hoffman, and D. E. Kuhl. Validation of tomographic measurement of cerebral blood volume with 11C‐labeled carboxyhemoglobin. J. Nucl. Med. 20: 328–334, 1979.
 192. Phelps, M. E., S.‐C. Huang, E. J. Hoffman, C. Selin, L. Sokoloff, and D. E. Kuhl. Tomographic measurement of local cerebral glucose metabolic rate in humans with [18F]2‐fluoro‐2‐deoxy‐D‐glucose: validation of method. Ann. Neurol. 6: 371–388, 1979.
 193. Phelps, M. E., D. E. Kuhl, and J. C. Mazziotta. Metabolic mapping of the brain's response to visual stimulation: studies in humans. Science Wash. DC 211: 1445–1448, 1981.
 194. Phelps, M. E., and J. C. Mazziotta. Positron emission tomography: human brain function and biochemistry. Science Wash. DC 228: 799–809, 1985.
 195. Phelps, M. E., J. C. Mazziotta, and S.‐C. Huang. Study of cerebral function with positron computed tomography. J. Cereb. Blood Flow Metab. 2: 113–162, 1982.
 196. Phelps, M. E., J. C. Mazziotta, D. E. Kuhl, M. Nuwer, J. Packwood, J. Metter, and J. Engel. Tomographic mapping of human cerebral metabolism: visual stimulation and deprivation. Neurology 31: 517–529, 1981.
 197. Plum, F., J. B. Posner, and B. Troy. Cerebral metabolic and circulatory responses to induced convulsions in animals. Arch. Neurol. 18: 1–13, 1968.
 198. Posner, J. B., F. Plum, and A. Van Poznak. Cerebral metabolism during electrically induced seizures in man. Arch. Neurol. 20: 388–395, 1969.
 199. Powers, W. J., and M. E. Raichle. Positron emission tomography and its application to the study of cerebrovascular disease in man. Stroke 16: 361–376, 1985.
 200. Prohovnik, I., K. Håkansson, and J. Risberg. Observations on the functional significance of regional cerebral blood flow in “resting” normal subjects. Neuropsychologia 18: 203–217, 1980.
 201. Raichle, M. E. Quantitative in vivo autoradiography with positron emission tomography. Brain Res. Rev. 1: 47–68, 1979.
 202. Raichle, M. E. Positron emission tomography. Ann. Rev. Neurosci. 6: 249–267, 1983.
 203. Raichle, M. E., R. L. Grubb, Jr., J. O. Eichling, and M. M. Ter‐Pogossian. Measurement of brain oxygen utilization with radioactive oxygen‐15: experimental verification. J. Appl. Physiol. 40: 638–640, 1976.
 204. Raichle, M. E., R. L. Grubb, Jr., M. L. Gado, J. O. Eichling, and M. M. Ter‐Pogossian. Correlation between regional cerebral blood flow and oxidative metabolism. Arch. Neurol. 33: 523–526, 1976.
 205. Raichle, M. E., K. B. Larson, M. E. Phelps, R. L. Grubb, Jr., M. J. Welch, and M. M. Ter‐Pogossian. In vivo measurement of brain glucose transport and metabolism employing glucose‐11C. Am. J. Physiol. 228: 1936–1948, 1975.
 206. Raichle, M. E., W. R. W. Martin, P. Herscovitch, M. A. Mintun, and J. Markham. Brain blood flow measured with intravenous H215O. II. Implementation and validation. J. Nucl. Med. 24: 790–798, 1983.
 207. Raichle, M. E., J. B. Posner, and F. Plum. Cerebral blood flow during and after hyperventilation. Arch. Neurol. 23: 394–403, 1970.
 208. Ramm, P., and B. J. Frost. Regional metabolic activity in the rat brain during sleep‐wake activity. Sleep Basel 6: 196–216, 1983.
 209. Rang, H. P., and J. M. Ritchie. On the electrogenic sodium pump in mammalian non‐myelinated nerve fibres and its activation by various external cations. J. Physiol. Lond. 196: 183–221, 1968.
 210. Rang, H. P., and J. W. Ritchie. The ionic content of mammalian non‐myelinated nerve fibres and its alteration as a result of electrical activity. J. Physiol. Lond. 196: 223–236, 1968.
 211. Reiman, E. M., M. E. Raichle, F. K. Butler, P. Herscovitch, and E. Robins. A focal brain abnormality in panic disorder, a severe form of anxiety. Nature Lond. 310: 683–685, 1984.
 212. Reis, D. J. Central neural control of cerebral circulation and metabolism. In: Neurotransmitters and the Cerebral Circulation, edited by E. T. MacKenzie, J. Seylaz, and A. Bes. New York: Raven, 1984, p. 91–120.
 213. Reivich, M. Blood flow metabolism couple in brain. Res. Publ. Assoc. Res. Nerv. Ment. Dis. 53: 125–140, 1974.
 214. Reivich, M., A. Alavi, A. Wolf, J. Fowler, J. Russell, C. Arnett, R. R. MacGregor, C. Y. Shive, H. Atkins, A. Anand, R. Dann, and J. Greenberg. Glucose metabolic rate kinetic model parameters determination in humans: the lumped constants and rate constants for (18F)fluorodeoxyglucose and (11C)deoxyglucose. J. Cereb. Blood Flow Metab. 5: 179–192, 1985.
 215. Reivich, M., A. Alavi, A. Wolf, J. H. Greenberg, J. Fowler, D. Christman, R. MacGregor, S. C. Jones, J. London, C. Shive, and Y. Yonekura. Use of 2‐deoxy‐D[1‐11C] glucose for the determination of local cerebral glucose metabolism in humans: variation within and between subjects. J. Cereb. Blood Flow Metab. 2: 307–319, 1982.
 216. Reivich, M., R. Gur, and A. Alavi. Positron emission tomographic studies of sensory stimuli, cognitive processes and anxiety. Hum. Neurobiol. 2: 25–33, 1983.
 217. Reivich, M., G. Isaacs, E. Evarti, and S. Kety. The effect of slow wave sleep and REM sleep on cerebral blood flow in cats. J. Neurochem. 15: 301–306, 1968.
 218. Reivich, M., J. Jehle, L. Sokoloff, and S. S. Kety. Measurement of regional cerebral blood flow with antipyrine‐14C in awake cats. J. Appl. Physiol. 27: 296–300, 1969.
 219. Reivich, M., D. Kuhl, A. Wolf, J. Greenberg, M. Phelps, T. Ido, V. Casella, J. Fowler, E. Hoffman, A. Alavi, P. Som, and L. Sokoloff. The [18F]fluorodeoxyglucose method for the measurement of local glucose utilization in man. Circ. Res. 44: 127–137, 1979.
 220. Reppert, S. M., and W. J. Schwartz. The suprachiasmatic nuclei of the fetal rat: characterization of a functional circadian clock using 14C‐labeled deoxyglucose. J. Neurosci. 4: 1677–1682, 1984.
 221. Risberg, J., J. H. Halsey, E. L. Wills, and E. M. Wilson. Hemispheric specialization in normal man studied by bilateral measurements of the regional cerebral blood flow. Brain 98: 511–524, 1975.
 222. Risberg, J., and D. H. Ingvar. Increase in regional cerebral blood volume during REM sleep in man. In: Sleep: Physiology, Biochemistry, Psychology, Clinical Implications. Basel: Karger, 1972, p. 1–5. (1st Europ. Congr. Sleep Res.)
 223. Risberg, J., and D. H. Ingvar. Multibolus technique for measuring the distribution of cerebral blood flow over short intervals in man. Circ. Res. 31: 889–898, 1972.
 224. Risberg, J., and D. H. Ingvar. Patterns of activation in the gray matter of the dominant hemisphere during memorizing and reasoning. Brain 96: 737–756, 1973.
 225. Risberg, J., V. A. Maximilian, and I. Prohovnik. Changes in cortical activity patterns during habituation to a reasoning test. A study with the 133‐Xe inhalation technique for measurement of regional cerebral blood flow. Neuropsychologia 15: 793–798, 1977.
 226. Risberg, J., and I. Prohovnik. Cortical processing of visual and tactile stimuli studied by non‐invasive rCBF measurements. Hum. Neurobiol. 2: 5–10, 1983.
 227. Ritchie, J. M. The oxygen consumption of mammalian nonmyelinated nerve fibres at rest and during activity. J. Physiol. Lond. 188: 309–329, 1967.
 228. Ritchie, J. M., and R. W. Straub. Oxygen consumption and phosphate efflux in mammalian non‐myelinated nerve fibres. J. Physiol. Lond. 304: 109–121, 1980.
 229. Roland, P. E. Somatotopical tuning of postcentral gyrus during focal attention in man. A regional cerebral blood flow study. J. Neurophysiol. 46: 744–754, 1981.
 230. Roland, P. E. Cortical regulation of selective attention in man. A regional cerebral blood flow study. J. Neurophysiol. 48: 1059–1078, 1982.
 231. Roland, P. E. Organization of motor control by the normal human brain. Hum. Neurobiol. 2: 205–216, 1984.
 232. Roland, P. E., and L. Friberg. Localization of cortical areas activated by thinking. J. Neurophysiol. 53: 1219–1243, 1985.
 233. Roland, P. E., and B. Larsen. Focal increase in cerebral blood flow during stereognostic testing in man. Arch. Neurol. 33: 551–558, 1976.
 234. Roland, P. E., B. Larsen, N. A. Lassen, and E. Skinhøj. Supplementary motor area and other cortical areas in organization of voluntary movements in man. J. Neurophysiol. 43: 118–136, 1980.
 235. Roland, P. E., E. Meyer, T. Shibasaki, Y. L. Yamamoto, and C. J. Thompson. Regional cerebral blood flow changes in cortex and basal ganglia during voluntary movements in normal human volunteers. J. Neurophysiol. 48: 467–480, 1982.
 236. Roland, P. E., and E. Skinhøj. Extrastriate cortical areas activated during visual discrimination in man. Brain Res. 222: 166–171, 1981.
 237. Roland, P. E., E. Skinhøj, and N. A. Lassen. Focal activations of human cerebral cortex during auditory discrimination. J. Neurophysiol. 45: 1139–1151, 1981.
 238. Roland, P. E., E. Skinhøj, N. A. Lassen, and B. Larsen. Different cortical areas in man in organization of voluntary movements in extrapersonal space. J. Neurophysiol. 43: 137–150, 1980.
 239. Roy, C. S., and C. S. Sherrington. On the regulation of the blood supply of the brain. J. Physiol. Lond. 11: 85–108, 1890.
 240. Sacks, W., S. Sacks, and A. Fleischer. A comparison of the cerebral uptake and metabolism of labeled glucose and deoxyglucose in vivo in rats. Neurochem. Res. 8: 661–685, 1983.
 241. Sakurada, O., C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff. Measurement of local cerebral blood flow with iodo[14C]antipyrine. Am. J. Physiol. 234 (Heart Circ. Physiol. 3): H59–H66, 1978.
 242. Sandman, C. A., J. P. O'Halloran, and R. Isenhart. Is there an evoked vascular response? Science Wash. DC 224: 1355–1357, 1984.
 243. Santiago, T. V., E. Guerra, J. A. Neubauer, and N. H. Edelman. Correlation between ventilation and brain blood flow during sleep. J. Clin. Invest. 73: 497–506, 1984.
 244. Schaltenbrand, G., and W. Wahren. Atlas for Stereotaxy of the Human Brain. Chicago, IL: Year Book, 1977.
 245. Schmidt, C. F. Central nervous system circulation, fluids and barriers—introduction. In: Handbook of Physiology. Neurophysiology, edited by J. Field and H. W. Magoun. Washington, DC: Am. Physiol. Soc., 1960, sect. 1, vol. III, chapt. 70, p. 1745–1750.
 246. Schmidt, C. F. The early days of the indifferent gas method for measuring cerebral blood flow. J. Cereb. Blood Flow Metab. 2: 1–2, 1982.
 247. Schmidt, C. F., and J. P. Hendrix. The action of chemical substances on cerebral blood vessels. Res. Publ. Assoc. Res. Nerv. Ment. Dis. 18: 229–276, 1937.
 248. Schwartz, E. L., D. R. Christman, and A. P. Wolf. Human primary visual cortex topography imaged via positron tomography. Brain Res. 294: 225–230, 1984.
 249. Schwartz, M., H. Creasey, C. L. Grady, J. M. De Leo, H. A. Frederickson, N. P. Cutler, and S. I. Rapoport. Computed tomographic analysis of brain morphometrics in 30 healthy men aged 21 to 81 years. Ann. Neurol. 17: 146–157, 1985.
 250. Schwartz, W. J., C. B. Smith, L. Davidsen, H. Savaki, L. Sokoloff, M. Mata, D. J. Fink, and H. Gainer. Metabolic mapping of functional activity in the hypothalamo‐neurohypophysial system of the rat. Science Wash. DC 205: 723–725, 1979.
 251. Serota, H. M., and R. W. Gerard. Localized thermal changes in the cat's brain. J. Neurophysiol. 1: 115–124, 1938.
 252. Sharp, F. R. Relative cerebral glucose uptake of neuronal perikarya and neuropil determined with 2‐deoxyglucose in resting and swimming rat. Brain Res. 110: 127–139, 1976.
 253. Shipley, R. A., and R. E. Clark. Tracer Methods for In Vivo Kinetics. New York: Academic, 1972.
 254. Siesjo, B. K. Brain Energy Metabolism. New York: Wiley, 1978.
 255. Smith, C. B., A. M. Crane, M. Kadekard, B. W. Agranoff, and L. Sokoloff. Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy. J. Neurosci. 4: 2489–2496, 1984.
 256. Sokoloff, L. The action of drugs on the cerebral circulation. Pharmacol. Rev. 11: 1–85, 1959.
 257. Sokoloff, L. Metabolism of the central nervous system in vivo. In: Handbook of Physiology. Neurophysiology, edited by J. Field and H. W. Magoun. Washington, DC: Am. Physiol. Soc., 1960, sect. 1, vol. III, chapt. 77, p. 1843–1864.
 258. Sokoloff, L. Effects of normal aging on cerebral circulation and energy metabolism. In: Brain Function In Old Age: Evaluation of Changes and Disorders, edited by F. Hoffmeister and C. Muller. Berlin: Springer‐Verlag, 1979, p. 367–380. (Bayer Symp. Ser., vol. 7.)
 259. Sokoloff, L. Relationships among local functional activity, energy metabolism, and blood flow in the central nervous system. Federation Proc. 40: 2311–2316, 1981.
 260. Sokoloff, L. The radioactive deoxyglucose method: theory, procedure and applications for the measurement of local glucose utilization in the central nervous system. Adv. Neurochem. 4: 1–82, 1982.
 261. Sokoloff, L. Metabolic probes of central nervous system activity in experimental animals and man. Sunderland, MA: Sinauer, 1984, vol. 1, p. 1–2. (Magnes Lecture Series.)
 262. Sokoloff, L., R. Mangold, R. L. Wechsler, and S. S. Kety. The effect of mental arithmetic on cerebral circulation and metabolism. J. Clin. Invest. 34: 1101–1108, 1955.
 263. Sokoloff, L., M. Reivich, C. Kennedy, M. H. Des Rosiers, C. S. Patlak, K. D. Pettigrew, O. Sakurada, and M. Shinohara. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28: 897–916, 1977.
 264. Subramanyam, R., N. M. Alpert, B. Hoop, Jr., G. L. Brownell, and J. M. Taveras. A model for regional cerebral oxygen distribution during continuous inhalation of 15O2, C15O and C15O2. J. Nucl. Med. 19: 48–53, 1978.
 265. Sutherland, R. C., M. J. Martin, J. K. McQueen, and G. Fink. Water deprivation results in increased 2‐deoxyglucose uptake by paraventricular neurones as well as pars nervosa in Wistar and Brattleboro rats. Brain Res. 271: 101–108, 1983.
 266. Sveinsdottir, E., B. Larsen, P. Rommer, and N. A. Lassen. A multidetector scintillation camera with 254 channels. J. Nucl. Med. 18: 168–174, 1977.
 267. Sveinsdottir, E., P. Thorlof, J. Risberg, D. H. Ingvar, and N. A. Lassen. Calculation of regional cerebral blood flow (rCBF) initial‐slope‐index compared to height‐over‐total‐area values. In: Brain and Blood Flow, edited by R. W. R. Russell. London: Pitman, 1971, p. 85–93.
 268. Takase, M., A. Tokunaga, K. Otani, and T. Horie. Atlas of the human brain for computed tomography based on the glabella‐inion line. Neuroradiology 14: 73–79, 1977.
 269. Talairach, J., G. Szikla, P. Tournoux, A. Prossalentis, M. Bordas‐Ferrer, L. Corello, M. Iacob, and E. Mempel. Atlas d'Anatomie Stéréotaxique du Télécéphale. Paris: Masson, 1967.
 270. Ter‐Pogossian, M. M. Basic principles of computed axial tomography. Semin. Nucl. Med. 7: 109–127, 1977.
 271. Ter‐Pogossian, M. M., J. O. Eichling, D. O. Davis, and M. J. Welch. The measure in vivo of regional cerebral oxygen utilization by means of oxyhemoglobin labeled with radioactive oxygen‐15. J. Clin. Invest. 49: 381–391, 1970.
 272. Ter‐Pogossian, M. M., J. O. Eichling, D. O. Davis, M. J. Welch, and J. M. Metzger. The determination of regional cerebral blood flow by means of water labeled with radioactive oxygen‐15. Radiology 93: 31–40, 1969.
 273. Ter‐Pogossian, M. M., D. C. Ficke, M. A. Mintun, P. Herscovitch, P. T. Fox, and M. E. Raichle. Dynamic cerebral positron emission tomographic studies. Ann. Neurol. 15: 46–47, 1984.
 274. Theurich, M., C. M. Muller, and H. Scheich. 2‐Deoxyglucose accumulation parallels extracellularly recorded spike activity in avian auditory neostriatum. Brain Res. 322: 157–161, 1984.
 275. Tokunaga, A., M. Takase, and K. Otani. The glabella‐inion line as a baseline for CT scanning of the brain. Neuroradiology 14: 67–71, 1977.
 276. Townsend, R. E., P. N. Prinz, and W. D. Obrist. Human cerebral blood flow during sleep and waking. J. Appl. Physiol. 35: 620–625, 1973.
 277. Urbanics, R., E. Leniger‐Follert, and D. W. Lübbers. Time course of change of extracellular H+ and K+ activities during and after direct electrical stimulation of the brain cortex. Pfluegers Arch. 378: 47–53, 1978.
 278. Van Essen, D. C. Functional organization of primate visual cortex. In: Cerebral Cortex. Visual Cortex, edited by A. Peters and E. G. Jones. New York: Plenum, 1985, vol. 3, p. 259–329.
 279. Wallenstein, S., C. L. Zucker, and J. L. Fleiss. Some statistical methods useful in circulation research. Circ. Res. 47: 1–9, 1980.
 280. Wechsler, R. L., L. M. Kleiss, and S. S. Kety. The effects of intravenously administered aminophylline on cerebral circulation and metabolism in man. J. Clin. Invest. 29: 28–30, 1950.
 281. Wood, F., B. Taylor, R. Penny, and D. Stump. Regional cerebral blood flow response to recognition memory versus semantic classification tasks. Brain Lang. 9: 113–122, 1980.
 282. Wooten, G. F., and R. C. Collins. Metabolic effects of unilateral lesion of the substantia nigra. J. Neurosci. 1: 285–291, 1981.
 283. Yarowsky, P. J., and D. H. Ingvar. Neuronal activity and energy metabolism. Federation Proc. 40: 2353–2362, 1981.
 284. Yarowsky, P., M. Kadekard, and L. Sokoloff. Frequency‐dependent activation of glucose utilization in the superior cervical ganglion by electrical stimulation of cervical sympathetic trunk. Proc. Natl. Acad. Sci. USA 80: 4179–4183, 1983.
 285. Zatz, L. M., T. L. Jernigan, and A. J. Ahumbra. Changes on computed cranial tomography with aging: intracranial fluid volume. J. Neuroradiol. 3: 1–11, 1982.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Circulatory and Metabolic Correlates of Brain Function in Normal Humans
 

How to Cite

Marcus E. Raichle. Circulatory and Metabolic Correlates of Brain Function in Normal Humans. Compr Physiol 2011, Supplement 5: Handbook of Physiology, The Nervous System, Higher Functions of the Brain: 643-674. First published in print 1987. doi: 10.1002/cphy.cp010516