Functional PET Evaluation of the Photosensitive Baboon

Abstract

The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes.

Epileptic baboons have lower numbers of neurons in specific areas of cortex

“…9 and 10). Cortical cell and neuron numbers were determined using the flow fractionator method (37,38) in epileptic baboon tissue obtained from the Texas Biomedical Research Institute, where a number of individuals develop generalized epilepsy within a pedigreed baboon colony (31)(32)(33)(34)(35)(36). Our results reveal a regionally specific neuron reduction in the cortex of baboons with naturally occurring, generalized seizures.…”

“…Selected strains of baboons have been studied as a natural primate model of generalized epilepsy (30)(31)(32)(33)(34)(35)(36) that is analogous to juvenile myoclonic epilepsy in humans. The baboons demonstrate generalized myoclonic and tonic-clonic seizures, and they have generalized interictal and ictal epileptic discharges on scalp EEG.…”

The average baboon brain: MRI templates and tissue probability maps from 89 individuals

“…After the anthropoid apes, Old World monkeys are the next closest relatives to humans (Stewart and Disotell, 1998). As well as being an excellent natural model for epilepsy (Killam, 1979;Szabo et al, 2011aSzabo et al, , 2011b) baboons (Papio), an Old World monkey, possess several features that make them a particularly fruitful model for understanding human brain structure and function (Black et al, 2009). A baboon brain, for example, is on average two times larger than the brain of a rhesus macaque (Macaca mulatta, Leigh, 2004) -one of the most common Old World monkeys found in laboratories.…”

“…The baboon brain also has a larger degree of gyrification (folding) than other Old World monkeys and contains all the primary cortical structures found in humans (Rogers et al, 2010). Accordingly, the baboon model has been used in numerous structural and functional neuroimaging experiments (e.g., Kochunov et al, 2010aKochunov et al, , 2010bKroenke et al, 2005Kroenke et al, , 2007Liu et al, 2008;Miller et al, 2013;Phillips and Kochunov, 2011;Phillips et al, 2012;Rogers et al, 2007;Salinas et al, 2011;Szabo et al, 2007Szabo et al, , 2011aSzabo et al, , 2011bWey et al, 2013).…”

Voxel-based morphometry in epileptic baboons: Parallels to human juvenile myoclonic epilepsy

“…Based upon these electroclinical features, the epilepsy of the baboon closely resembles JME. Earlier morphometric studies evaluating sulcal areas did not demonstrate significant differences between baboons with interictal epileptic discharges (IED+) on scalp EEG, some of which also had a history of witnessed seizure, compared to asymptomatic baboons without interictal epileptic discharges (IED−) (Szabó et al, 2011). Nonetheless, post-hoc comparisons demonstrated significant decreases in sulcal areas in central, intraparietal and cingulate sulci in the IED+ baboons.…”