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significantly negative BOLD changes associated with SWDs (86) .
The same experiment showed widespread increases in the thala-
mus and in the cortex. No significant changes were found in the
hippocampus (86) . A second group utilizing continuous EEG-
fMRI found increased BOLD signal change in several regions
of the cortex and subcortical structures, without major fMRI
decreases ( Fig. 9.4 ) (15) . Increases were seen in the somatosen-
sory cortex, motor cortex, thalamus, basal ganglia, hippocampus,
and brainstem (tectum and tegmental nuclei) and were mostly
bilaterally and symmetrically distributed (15) . More recent stud-
ies with a higher field (9.4T) system detected both fMRI increases
as well as decreases in specific brain regions in the same rodent
model (87) . fMRI decreases were seen mainly in the basal gan-
glia, but were also occasionally present in small regions of the
neocortex (87) .
Although absence epilepsy is considered a generalized seizure
disorder, fMRI and electrical recordings of SWD have found that
focal anterior regions of the brain were most intensively involved,
while other brain regions remained relatively quiet ( Figs. 9.2
and 9.4 ) (13-15) . Studies in rodent models have revealed focal
abnormalities in voltage gated channel expression which may be
related to epileptogenesis in this form of epilepsy (27, 88) .The
ability to non-invasively image focal network involvement may
ultimately lead to a better understanding of mechanisms in spe-
cific brain regions crucial for generation of SWD in both animal
models and human patients.
6.2. GBL Rat Model
GBL is a precursor of
-hydroxybutyrate and produces robust
SWDs in rats, resembling petit mal status epilepticus (82, 89) .
There is evidence that anesthesia limits the BOLD signal change
in GBL-induced SWD (82) but awake animals have yielded
interesting BOLD fMRI data. GBL-induced SWDs showed
widespread negative changes in the cortex while also showing
positive changes in the somatosensory and parietal cortices.
The thalamus showed only significant positive BOLD changes.
While these findings in some ways resemble reported changes
during human SWD, important differences include the frequency
of the discharges (6-7 Hz in GBL rat model vs. 3-4 Hz in
human) and their duration (continuous status epilepticus in
rat GBL model vs. brief episodes in human). The GBL model
has some advantages compared to spontaneous rodent seizure
models, since GBL-induced seizures are robust and long lasting
, however, the spontaneous seizure models have the advantage of
producing brief seizure episodes more similar to typical seizure
durations in humans.
γ
6.3. GBL Monkey
Model
GBL seizures have also been studied in non-human primates.
Advantages of primate models of SWD include SWD activ-
ity more closely resembling human SWD. Marmoset monkeys
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