Biomedical Engineering Reference
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hemispheres of the cerebral cortex existed for at least five
different frequencies, which get augmented during exsanguina-
tion ( Fig. 12.4 ). While this is unlikely due to aliasing effects in
the low frequency range, it is possible that connected neuronal
networks may be oscillating at multiple frequencies which is more
consistent with neuronal than myogenic origin of the BOLD sig-
nal fluctuation.
4.4. Implication
for Anesthesia
Studies in Humans
The increase in the very low frequency below 0.01 Hz in the
BOLD signal fluctuations during exsanguination, which remained
after replacement of withdrawn blood ( Fig. 12.1b and c ), may
indicate an alteration in autoregulatory equilibrium. Though
the reasons behind the loss of CBF autoregulation are still
controversial, anesthesia can have a major influence on autoreg-
ulation (43, 50) . The increase in the gain of the fluctuating feed-
back system that led to an increase in BOLD signal fluctuations
during exsanguination may indeed be a result of an alteration
of autoregulatory equilibrium (43, 51, 52) . These results are in
concurrence with studies on anesthetized children undergoing
fMRI which have shown significantly altered baseline BOLD sig-
nal fluctuations in the very low frequency range 0.02-0.04 Hz
(53) when compared to BOLD signal fluctuations at 0.1 Hz in
awake human subjects (26) . Prominent, very low frequency fluc-
tuations (0.02-0.04 Hz) are suggested to occur in the absence
of autoregulation (18) . A complete physiological monitoring and
biophysical characterization of physiological fluctuations using
the anesthetized rat model can be very useful in translation studies
using anesthesia and fMRI in humans where invasive physiologi-
cal monitoring can be a problem due to ethical reasons (53) .
5. Conclusions
Exsanguination significantly enhances the amplitude and spatial
spread of the low frequency BOLD fluctuations to most of the
cortical, sub-cortical and deeper brain structures in the isoflurane-
anesthetized rat brain. The behavior of the resting state BOLD
signal fluctuations similar to CBF fluctuations during exsanguina-
tion indicates a myogenic dependence. On the other hand, a high
intra-hemispheric symmetry in the BOLD fluctuations with sim-
ilar phase characteristics in most other regions except the hip-
pocampus suggests that the fMRI-BOLD signal fluctuations in
anesthetized rats may carry information from distinct functional
networks. Hypotension near the autoregulatory limits in anes-
thetized rats can be used to improve the detection of distinct
resting state neural networks despite the myogenic artefact.
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