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Identifying Functional Specialization
in the Human Brain
Center for Magnetic Resonance Research
Historically, the most compelling argument for the existence of regional
specialization of human brain function was presented by Parisian physician
named Pierre Paul Broca in the middle 19th century [1].
Broca examined a patient who, as a result of a stroke, presented with the
problem of inability to speak or aphasia but was otherwise normal. Based
on an autopsy performed subsequent to the patient's death, Broca concluded
that the seat of the damage was an egg size lesion located in the frontal
lobe in the left hemisphere; this general area is now commonly referred
to as Broca's area although its precise topographical extent remains somewhat
ambiguous. Such lesion studies and, later intraoperative mapping efforts
with electrodes have been until recently the primary source of our current
understanding of functional compartmentation and specialization in the
human brain.
Mapping Regions of Increased Activity in the Human Brain Using Water
Nuclear Spins
A significant recent development, accomplished in part by funding from
National Research Resources funding by NIH to Center for Magnetic Resonance
Research, University of Minnesota, permits the acquisition of such information
much more rapidly and with greater spatial accuracy, fueling explosive
developments in our investigation of human brain function (Also see mitpress).
For example, the language area first identified by Broca can now be visualized
with unprecedented spatial resolution using functional magnetic resonance
imaging (fMRI), in data collection times that last only a few minutes.
The Figure below displays the three-dimensional (3D) result of such a study
[2]. The gray scale picture is the anatomical image of
a single human brain as viewed from the left and right sides; in color
is the functional map generated during a covert task where the subjects
were shown pictures of an objects and were asked to name them. Normally,
we see only the activation on the outer cortical surface that is visible
to an external viewer. When the anatomical image is rendered translucent,
activation in the interior of the brain and within its numerous folds (sulci)
are also visible albeit with diminished intensity.
(Click on image to view full scale)
These images are obtained with magnetic resonance imaging based on BOLD
or blood oxygen level dependent contrast [3-6],
first used to generate functional images in human brain independently and
at about the same time by three groups in the United States [7-9].
BOLD relies on the magnetic field inhomogeneity generated when blood
contains deoxyhemoglobin [10, 3-6].
Hemoglobin is the primary oxygen carrier in the blood. When the oxygen
is used by cells in the body, deoxyhemoglobin is generated. Deoxyhemoglobin
is paramagnetic; as such it has strong magnetic properties that differ
from the magnetic properties of tissue surrounding the blood vessels containing
deoxyhemoglobin.
Differences in magnetic properties between the deoxyhemoglobin containing
blood vessels versus the surrounding space devoid of this strongly
paramagnetic molecule generates magnetic field gradients across and near
the boundaries of these blood vessels. Consequently, magnetic resonance
(MR) images that are sensitized to these gradients have signal intensities
that can be altered if the regional deoxyhemoglobin content is perturbed.
This occurs in the brain during increased neuronal activation.
References
1. Broca, P. and C.E. Brown-Sequard, Proprietes et
fonctions de la moelle epiniere: Rapport quelques experiences de M. Borwn-Sequard:
lu a loa Soceite de biologies le 21 Juillet, Bonaventure et Ducessois.
1855.
2. Erhard, p., T. Kato, J.P. Strupp, P. Andersen, G.
Adriany, P.L. Strick, and K. Ugurbil, Functional mapping of motor in
and near Broca's area. NeuroImaging, 1996. 3: p. S367.
3. Ogawa, S., T.-M. Lee, A.R. Kay, and D.W. Tank, Brain
Magnetic Resonance Imaging with Contrast Dependent on Blood Oxygenation.
Proc Natl Acad Sci USA, 1990. 87: p. 9868- 9872.
4. Ogawa, S., T.-M. Lee, A.S. Nayak, and P. Glynn,
Oxygenation-sensitive contrast in magnetic resonance image of rodent
brain at high magnetic fields. Magn Reson Med, 1990. 14: p. 68-78.
5. Ogawa, S. and T.M. Lee, Magnetic Resonance Imaging
of Blood Vessels at High Fields: in Vivo and in Vitro Measurments and Image
Simulation. Magn Reson Med, 1990. 16: p. 9- 18.
6. Ogawa, S., T.M. Lee, and B. Barrere, Sensitivity
of magnetic resonance image signals of a rat brain to changes in the cerebral
venous blood oxygenation. Magn Reson Med, 1993. 29: p. 205-210.
7. Bandettini, P.A., E.C. Wang, R.S. Hinks, R.S. Rikofsky,
and J.S. Hyde, Time course EPI of human brain function during task activation.
Magn Reson Med, 1992. 25: p. 390-397.
8. Kwong, K.K., J.W. Belliveau, D.A. Chesler, I.E.
Goldberg, R.M. Weisskoff, et al., Dynamic Magnetic Resonance Imaging
of Human Brain Activity during Primary Sensory Stimulation. Proc Natl
Acad Sci USA, 1992(89): p. 5675-5679.
9. Ogawa, S., D.W. Tank, R. Menon, J.M. Ellermann,
S.-G. Kim, H. Merkle, and K. Ugurbil, Intrinsic Signal Changes Accompanying
Sensory Stimulation: Functional Brain Mapping with Magnetic Resonance Imaging.
Proc Natl Acad Sci USA, 1992. 89: p. 5951-5955.
10. Thulborn, K.R., J.C. Waterton, P.M. Mattews, and
G.K. Radda, Oxygenation Dependence of the Transverse Relaxation Time
of Water Protons in Whole Blood at High Field. Biochem Biophys Acta,
1982. 714: p. 265-270.
11. Richter, W., S. Lee, W.S. Warren, and Q. He, Imaging
with intermolecular multiple- quantum coherences in solution nuclear magnetic
resonance. Science, 1995. 267(5198): p. 654-7.
12. Vathyam, S., S. Lee, and W.S. Warren, Homogeneous
NMR spectra in inhomogeneous fields [published erratum appears in Science
1996 Aug 2;273(5275):564]. Science, 1996. 272(5258): p. 92-6.
13. Warren, W.S., S. Ahn, M. Mescher, M. Garwood,
K. Ugurbil, W. Richter, R.R. Rizi, J. Hopkins, and J.S. Leigh, MR imaging
contrast enhancement based on intermolecular zero quantum coherences [In
Process Citation]. Science, 1998. 281(5374): p. 247-51.
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