Biomedical Engineering Reference
In-Depth Information
to control seizure type, frequency and onset, which enable the
collection of the most consistent and reproducible data possible.
Animals may be restrained and/or anesthetized to reduce move-
ment artifact, and animal models make possible the study of fMRI
and its neural correlates by allowing direct study of neural activ-
ity using combined imaging, electrophysiological measurements
with microelectrodes and other techniques
(14, 15, 55, 56, 80)
.
Tissue collected from specific brain regions identified by animal
fMRI studies may uncover the molecular mechanisms giving rise
to seizure susceptibility in those regions.
Of course, animal models of epilepsy are limited in that they
are models. Results from animal models must be analyzed with
the understanding that human and animal physiologies are cru-
cially different. For example, SWD have a faster frequency in
rodent models (7-8 Hz) than in humans (3-4 Hz), and SWD
persist in adulthood in rodents, while they usually disappear in
adolescence in humans. Other difficulties and technical challenges
arise from the high magnetic field strength used to image small
animals, including difficulty in obtaining simultaneous EEG dur-
ing fMRI recordings
(15, 81)
, the sensitivity of imaging signals
to movement artifact, and magnetic susceptibility artifact often
found at air-tissue interfaces.
Anesthesia, if used, must be chosen with care. Anesthetic
agents may suppress seizure activity or alter cerebral hemody-
namics, introducing a confounding factor in fMRI analysis. While
under anesthesia or otherwise, systemic physiology should be
monitored in ventilated animals during fMRI studies. Changes in
blood pressure and
pCO
2
may confound imaging results. Ideally,
SWD seizures should be imaged in animals without anesthesia
(81, 82)
. However, this is a technical challenge due to the exten-
sive animal training required to habituate them to the recording
procedures
(83, 84)
.
Human experiments have left many unanswered questions
about the meaning of SWD-induced fMRI signal increases and
decreases. It is hoped that accurate animal models may answer
these questions by elucidating the relationships between the fMRI
signal changes, underlying neuronal activity, and molecular mech-
anisms
(3)
. The main animal models of SWD studied with fMRI
to date include spontaneous seizures in rat SWD models, and
chemically induced seizures using gamma-butyrolactone (GBL).
Prominent animal models of SWD include spontaneous seizures
seen in Wistar Albino Glaxo rats of Rijswijk (WAG/Rij).
WAG/Rij rats have spontaneous SWD and are an established
model of human absence epilepsy
(85)
. As in human data, there
has been some inconsistency in reported BOLD signal changes
during SWD. Some experimental data of fMRI recordings during
spontaneous SWD activity in WAG/Rij rats have revealed no
6.1. WAG/Rij
