Biomedical Engineering Reference
In-Depth Information
reviews see
(1, 2)
). Since the 1990s, however, nuclear mag-
netic resonance (NMR) - both imaging (MRI) and spectroscopy
(MRS) - has played a major role in studies of in vivo neuroscience,
both in animals and humans (for reviews see
(3, 4)
). The discov-
ery of functional MRI (fMRI) by Seiji Ogawa in 1990
(5)
fur-
ther reinforced the role of functional imaging studies in neuro-
science. The fMRI method, as originally proposed, depends on
the paramagnetic effect of deoxyhemoglobin (in blood) upon the
NMR transverse relaxation times of nearby water protons (in tis-
sue)
(6)
. Since changes in the oxygen level in the blood determine
the fraction of deoxygenated hemoglobin, the image contrast was
fittingly termed blood oxygenation level dependent (BOLD).
After the initial demonstrations of the BOLD method in map-
ping dynamic brain function in humans during sensory stimula-
tion
(7-10)
, the cognitive neuroscience community immediately
embraced the method
(11)
. Today BOLD fMRI is arguably the
most popular functional mapping tool for human studies, per-
haps, in part, due to its non-invasive nature of application, rela-
tively good spatiotemporal resolution, superior coverage of large
parts of the brain, and the fact that experiments can be conducted
on most clinical MRI scanners by slight adjustments. However,
future utility of fMRI for diagnostic and treatment measures in
humans is largely dependent on a better neurophysiologic inter-
pretation of the BOLD signal change because the conventional
fMRI map reflects changes in blood oxygenation, not the actual
neuronal activity
(12-14)
. This particular goal seems to be best
achieved in animal models
(15-17)
primarily due to the invasive
nature of the non-NMR methods used
(18-20)
and/or pharma-
cological agents applied
(21-23)
to probe different features of
cellular activity coupled to the BOLD signal change.
In the last decade, we have invested considerable research
efforts towards developing various sensory stimulation protocols
in rodents with fMRI
(24-26)
. Over that same period of time,
coupled with state-of-the-art NMR advancements in high mag-
netic field scanners and improvements in other hardware compo-
nents (e.g., gradient, shim, and radio frequency coils)
(27)
,weare
now able to reproducibly
(28, 29)
measure relatively small BOLD
signal changes (in rat or mouse brains) induced by peripheral
stimuli with superior spatiotemporal resolution
(30, 31)
.Herewe
describe tactile (i.e., whisker, forepaw) and non-tactile (i.e., olfac-
tory, visual) sensory paradigms applied to the anesthetized rat. We
discuss features of peripheral stimulus delivery equipment needed
to generate identical stimuli, both inside and outside the mag-
net. The focus is on development and validation of methods for
stimulation of each sensory modality applied independently or in
conjunction with one another. We demonstrate reproducibility of
induced activations, as measured by changes in the BOLD signal
and other non-NMR signals (e.g., electrical activity, laser Doppler
