Biomedical Engineering Reference
In-Depth Information
within and across hemispheres in primary sensorimotor cortex
during rest. We defined resting-state connectivity (RSC) as
significant correlation signal between functionally related brain
regions in the absence of any stimulus or task. This result has been
validated by a number of groups using different models
(1, 2)
and
is a subject which has been recently reviewed by Fox and Raichle
(3)
. This correlated signal arises from spontaneous low-frequency
signal fluctuations (SLFs). These low-frequency spontaneous fluc-
tuations have also been observed by several investigators using
animal models and a variety of measurement techniques, includ-
ing polarographic technique of tissue oxygenation
(4, 5)
, laser
Doppler flowmetry (LDF)
(6)
, fluororeflectometry of NADH
and cytochrome-aa3
(7)
.
Testing hypotheses of the role of SLFs has involved attempts
to determine their physiological origins. Cooper et al.
(8)
hypothesized that these fluctuations represent cellular mainte-
nance of an optimum balance between cerebral blood flow
(CBF) and oxidative metabolic rate (
CMR
O
2
). Testing this
hypothesis has involved manipulation of cerebral metabolism
with anesthesia. These studies have involved comparison of
activity during waking and anesthetized states in animals using
various techniques including LDF
(6)
and fMRI in humans
(9, 10)
. Signal oscillations in the rodent brain vary with dif-
fering levels of halothane anesthesia, carbon dioxide level and
nitric oxide synthase (NOS) blockade
(11)
. These results sug-
gest support for the biophysical-origin hypothesis that affects
the cerebral vasculature, either directly or indirectly. The neu-
ral mechanisms of slow rhythmic fluctuations have not yet
been clearly defined, though with recent evidence indicating
an active role for glia in neurovascular coupling
(12-15)
,the
slow rhythmic fluctuations may have both neuronal and glial
origins.
In spectrophotometric studies of the intramitochondrial
redox state of enzyme cytochrome aa
3
(CYTox) and cerebral
blood volume (CBV), continuous slow oscillations and inter-
hemispheric synchrony has been observed between these variables
(16)
. The relationship between CYTox and CBV oscillations
seem to be independent of the physiological state as they have
been observed during both awake state and sleep
(6, 16, 17)
,
anesthesia
(5, 18, 19)
and during cerebral ischemia
(20, 21)
.
Though there have been studies indicating the presence of
metabolic oscillations in the absence of CBF oscillations - indi-
cating that metabolic oscillations may be primary in origin -
there is no concrete evidence to indicate so. On the contrary,
flow oscillations can be linked to metabolic oscillations by the
evidence indicating that NADH and/or cytochrome aa
3
oscil-
lations lagged behind CBV oscillations
(16, 17)
. These results
indicate that spontaneous oscillations in the intra-mitochondrial
