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utilization as well as glial lactate production; see references 11
and 12 for details). Recent immunohistochemical and molecu-
lar studies (48-51) have identified receptors for a variety of neu-
rotransmitters (including glutamate) on specific cellular compo-
nents of the microvasculature. Furthermore, small increases (in
nM range) in cytosolic Ca 2 + , in both the post-synaptic neuron
and astrocytes mediated respectively by activation of ionotropic
(52,53) and metabotropic (54,55) glutamate receptors, may stim-
ulate enzymes like nitric oxide synthase (and others) to generate
strong vasoactive agents like nitric oxide (and others). Together,
these new findings shed some preliminary (56, 57) but not always
complete (58) understanding about complexities of “neuroglio-
vascular” coupling.
4. Functional
Brain Imaging
The goal of the ideal functional imaging technique is to map task-
induced changes in activity in the brain in vivo. The task may
be sensory or cognitive and the extent of the activated region
may be localized (as generally observed with sensory paradigms
(59) ) or delocalized (as often found with cognitive paradigms
(60) ). To what extent do different methods allow dynamic iden-
tification of task activated brain region(s)? The answer depends
on the spatiotemporal resolution of the method. There are at
least three relevant factors. Spatial coverage of the brain by the
method is a practical limitation. Specificity depends on the phys-
iological basis of the measurement. Sensitivity, if enhanced, can
improve either the spatial or temporal resolution, but rarely both.
Together, these factors describe the spatiotemporal resolution of
the method ( Fig. 1.2 ). Other (e.g., hardware) factors that affect
spatiotemporal resolution of a given method are beyond the scope
of discussion here.
Schematic illustration of spatial and temporal resolution
ranges from a few experimental techniques is shown in
Figure 1.2 Since it is impractical to refer to the several dozen
studies that were used to develop this figure, three reports
(61-63) with similar comparisons are highlighted. But these may
be questioned for several reasons. Techniques which did not
reflect dynamic activity changes in their measurements (i.e., static
or steady-state) were included with methods that were strictly
designed for measuring transient signal changes. Methods specif-
ically designed for use in humans were not separated from those
applied in small animals. Similarly, differences between in vivo
and in vitro methods were not distinguished. Thus the apparent
superiority of one method versus another is debatable. Because
there have also been technological advancements that influence
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