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This is an excellent review article. Lauritzen reports on the relationship between neural activity and hemodynamic responses, using the rat cerebellar cortex as a model. Spike activity does not affect the hemodynamic response (see his Fig. 4), whereas synaptic activity predominantly induces cerebral blood flow changes. The magnitudes of CBF change and synaptic field potentials have a monotonic relationship (see Figures 5, 6, 8) and a linear relationship in some cases. This observation is consistent with studies in the monkey visual cortex [13••].
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Lauritzen M. Relationship of spikes, synaptic activity, and local changes of cerebral blood flow. J Cereb Blood Flow Metab. 21:2001;1367-1383. This is an excellent review article. Lauritzen reports on the relationship between neural activity and hemodynamic responses, using the rat cerebellar cortex as a model. Spike activity does not affect the hemodynamic response (see his Fig. 4 ), whereas synaptic activity predominantly induces cerebral blood flow changes. The magnitudes of CBF change and synaptic field potentials have a monotonic relationship (see Figures 5, 6, 8) and a linear relationship in some cases. This observation is consistent with studies in the monkey visual cortex [13••] .
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This is a good review article, describing our current understanding of and the controversies surrounding the neurophysiological source of BOLD fMRI.
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Arthurs O.J., Boniface S. How well do we understand the neural origin of the fMRI BOLD signal? Trends Neurosci. 25:2002;27-31. This is a good review article, describing our current understanding of and the controversies surrounding the neurophysiological source of BOLD fMRI.
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Arthurs, O.J.1
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Here the spatial specificity of CBF regulation is investigated using a cat orientation column as a model. The authors used arterial spin labeling MRI technique in cat area 18 during single orientation stimulation. They find that functional maps obtained using this new approach are immune to large draining vessels and specific to parenchyma. Further, functionally active areas appear like columnar structures based on the average distance of patchy clusters. The most important finding is that the hemodynamic response is regulated at a submillimeter columnar level, suggesting that columnar structures can be obtained without using differential imaging methods if large vessel contributions are minimized (see also [11•,18••,20•]).
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Duong T.Q., Kim D.-S., Ugurbil K., Kim S.-G. Localized cerebral blood flow response at submillimeter columnar resolution. Proc Natl Acad Sci USA. 98:2001;10904-10909. Here the spatial specificity of CBF regulation is investigated using a cat orientation column as a model. The authors used arterial spin labeling MRI technique in cat area 18 during single orientation stimulation. They find that functional maps obtained using this new approach are immune to large draining vessels and specific to parenchyma. Further, functionally active areas appear like columnar structures based on the average distance of patchy clusters. The most important finding is that the hemodynamic response is regulated at a submillimeter columnar level, suggesting that columnar structures can be obtained without using differential imaging methods if large vessel contributions are minimized (see also [11•,18••,20•] ).
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Harrison et al. compare the spatial distribution of the auditory stimulus response from intrinsic optical images in the auditory cortex to the distribution of blood vessels, visualized in the same animal by corrosion casts. They find that intrinsic signals are well correlated with capillary densities. Further, blood-controlling sphincters are located at capillary branching points in the arterioles (see their Figure 7), suggesting that each capillary controls flow independently. Thus, the ultimate spatial resolution of the hemodynamic response is the spatial extent of a single capillary (see their Figure 8). This is consistent with the observation of Duong et al. [10••].
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Harrison R.V., Harel N., Panesar J., Mount R. Blood capillary distribution correlates with hemodynamic-based functional imaging in cerebral cortex. Cereb Cortex. 12:2002;225-233. Harrison et al. compare the spatial distribution of the auditory stimulus response from intrinsic optical images in the auditory cortex to the distribution of blood vessels, visualized in the same animal by corrosion casts. They find that intrinsic signals are well correlated with capillary densities. Further, blood-controlling sphincters are located at capillary branching points in the arterioles (see their Figure 7), suggesting that each capillary controls flow independently. Thus, the ultimate spatial resolution of the hemodynamic response is the spatial extent of a single capillary (see their Figure 8). This is consistent with the observation of Duong et al. [10••] .
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This is the first demonstration of simultaneous BOLD and multiunit recordings in the same animal. This paper provides rich information regarding the neurophysiological source of the BOLD signal and shows a great technical achievement. The authors demonstrate that the BOLD fMRI signal is closely related to local field potentials rather than to spike activity, similar to findings from Lauritzen's laboratory and others [2••,14,15•]. However, close examination of Figure 5 in this paper shows that local field potentials and spike activity behave similarly relative to the BOLD signal change, suggesting that the BOLD signal can also be an index of spike activity. Another interesting observation is that the BOLD signal change appears significant even when normalized local field potentials and spike activity approach zero. This observation indicates that a sigmoidal relationship between neural activity and the hemodynamic response is expected (see also [15•]).
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Logothetis N.K., Pauls J., Augath M., Trinath T., Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature. 412:2001;150-157. This is the first demonstration of simultaneous BOLD and multiunit recordings in the same animal. This paper provides rich information regarding the neurophysiological source of the BOLD signal and shows a great technical achievement. The authors demonstrate that the BOLD fMRI signal is closely related to local field potentials rather than to spike activity, similar to findings from Lauritzen's laboratory and others [2••,14,15•] . However, close examination of Figure 5 in this paper shows that local field potentials and spike activity behave similarly relative to the BOLD signal change, suggesting that the BOLD signal can also be an index of spike activity. Another interesting observation is that the BOLD signal change appears significant even when normalized local field potentials and spike activity approach zero. This observation indicates that a sigmoidal relationship between neural activity and the hemodynamic response is expected (see also [15•] ).
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Ogawa S., Lee T.-M., Stepnoski R., Chen W., Zhu X.-H., Ugurbil K. An approach to probe some neural systems interaction by functional MRI at neural time scale down to milliseconds. Proc Natl Acad Sci USA. 97:2000;11026-11031.
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These authors investigate the relationship between neural activity and CBF response in S1 during somatosensory stimulation using laser Doppler flowmetry and field potential measurements. Consistent with their previous cerebellar studies (see [2••]), a monotonic relationship between field potentials and CBF response was observed. Also, layer-specific CBF changes were seen, suggesting that layer-specific functional mapping is possible using hemodynamic-based fMRI techniques.
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Here human ocular dominance columns were mapped using the conventional BOLD technique with post-processing approaches at 4 T. Although not the first paper to map human ocular dominance columns using MRI, the systematic analyses and high reproducibility described in Figure 9 of this paper demonstrate that ocular dominance columns obtained using the differential imaging method are genuine. The discussion section provides an excellent reference for high-resolution fMRI studies. This study, along with studies from Menon's laboratory [20•], shows that high magnetic fields can be used for mapping high-resolution functional images at columnar resolution. However, this technique still relies on the subtraction method (see also [10••,20•]).
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Cheng K., Waggoner R., Tanaka K. Human ocular dominance columns as revealed by high-field functional magnetic resonance imaging. Neuron. 32:2001;359-374. Here human ocular dominance columns were mapped using the conventional BOLD technique with post-processing approaches at 4 T. Although not the first paper to map human ocular dominance columns using MRI, the systematic analyses and high reproducibility described in Figure 9 of this paper demonstrate that ocular dominance columns obtained using the differential imaging method are genuine. The discussion section provides an excellent reference for high-resolution fMRI studies. This study, along with studies from Menon's laboratory [20•], shows that high magnetic fields can be used for mapping high-resolution functional images at columnar resolution. However, this technique still relies on the subtraction method (see also [10••,20•] ).
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Goodyear B., Menon R.S. Brief visual stimulation allows mapping of ocular dominance in visual cortex using fMRI. Hum Brain Mapp. 14:2001;210-217. Goodyear and Menon obtain human ocular dominance columns using conventional BOLD fMRI and post-processing methods at 4 T, similarly to [18••] . They demonstrate that early BOLD responses are more specific than late BOLD responses. See also [10••] .
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Yacoub E., Shmuel A., Pfeuffer J., Van De Moortele P., Adriany G., Andersen P., Vaughan J., Merkle H., Ugurbil K., Hu X. Imaging brain function in humans at 7 Tesla. Magn Reson Med. 45:2001;588-594. Here human fMRI at 7T is reported for the first time. The sensitivity and spatial specificity of the conventional BOLD signal was improved using higher magnetic fields. To take advantage of the high SNR achieved by high fields, signal fluctuations by physiological motions should be corrected because fluctuations also increase proportionally.
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