Biomedical Engineering Reference
In-Depth Information
spike component, and decreases in neuronal activity during the
wave
(92)
. It is possible that some brain regions may have sub-
tle changes in intensity of firing during the spike or changes
in duration of neuronal silence during the wave, which could
lead to a mean
decrease
in neuronal activity during SWD, as dis-
cussed previously
(2, 93)
.
(3) Altered neuro-vascular coupling
.
In this mechanism, unlike those above, the primary event is
an
increase
in neuronal activity during seizures. However, this
increase in neuronal activity is met by an inadequate increase in
blood flow to match metabolic demands, leading to a BOLD
fMRI decrease (
Fig. 9.2D
). Note that in this mechanism, blood
flow can increase (unlike
Fig. 9.2D
); the main point is that the
blood flow increase is inadequate. An example of this mecha-
nism has recently been observed in a rodent model, where BOLD
decreases in the hippocampus accompany intense seizure activ-
ity in the same region
(61)
. There are two main possibilities to
explain abnormal neurovascular coupling during seizures: (3A)
Intense neuronal activity could overwhelm neurovascular coupling
.
In this mechanism, sudden extreme increases in neuronal energy
consumption could exceed the capacity of neurovascular coupling
mechanisms to deliver adequate oxygen. (3B)
Dysregulation of
the neurovascular coupling cascade
. In this mechanism, the inher-
ent signaling cascade underlying neurovascular coupling could be
altered acutely or chronically by seizures (or other causes), leading
to an abnormal, blunted response to neuronal activity changes.
Which of the above mechanisms are involved in BOLD
fMRI decreases during SWD in both humans and animal mod-
els remains to be determined by further investigations.
8. Discussion and
Future Directions
We have seen that fMRI during SWD in both human and ani-
mal models can provide important information about abnor-
mal network behavior during generalized seizures. Studies so far,
have revealed focal bilateral increases in the frontoparietal cor-
tex and thalamus, decreases in other specific cortical regions,
and decreases in the basal ganglia. These investigations support
the concept that “generalized” spike-wave seizures, in fact, arise
from focal network dysfunction in specific regions of cortical-
subcortical networks.
Many important questions remain which should be addressed
by future studies. For example, do seizures in which consciousness
is impaired differ from those in which consciousness is spared?
Is the difference based on the brain regions involved? Are there
different molecular mechanisms causing specific regions but not
others to be involved during seizures? How do the circuit mech-
anisms differ for regions involved or spared by seizures? Is the
