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

Abstract

The epileptic baboon represents a natural model for genetic generalized epilepsy (GGE), closely resembling juvenile myoclonic epilepsy (JME). Due to functional neuroimaging and pathological differences between epileptic (SZ+) and asymptomatic control (CTL) baboons, we expected structural differences in gray matter concentration (GMC) using voxel-based morphometry (VBM). Standard anatomical (MP-RAGE) MRI scans using a 3T Siemens TIM Trio (Siemens, Erlangen, Germany) were available in 107 baboons (67 females; mean age 16 ± 6 years) with documented clinical histories and scalp-electroencephalography (EEG) results. For neuroimaging, baboons were anesthetized with isoflurane 1% (1-1.5 MAC) and paralyzed with vecuronium (0.1-0.3 mg/kg). Data processing and analysis were performed using FSL’s VBM toolbox. GMC was compared between CTL and SZ+ baboons, epileptic baboons with interictal epileptic discharges on scalp EEG (SZ+/IED+), asymptomatic baboons with abnormal EEGs (SZ−/IED+), and IED+ baboons with (IED+/PS+) and without (IED+/PS−) photosensitivity, and the subgroups amongst themselves. Age and gender related changes in gray matter volumes were also included as confound regressors in the VBM analyses of each animal group. Significant increases in GMC were noted in the SZ+/IED+ subgroup compared to the CTL group, including bilaterally in the frontopolar, orbitofrontal and anterolateral temporal cortices, while decreases in GMC were noted in the right more than left primary visual cortices and in the specific nuclei of the thalamus, including reticular, anterior and medial dorsal nuclei. No significant differences were noted otherwise, except that SZ+/IED+ baboons demonstrated increased GMC in the globus pallidae bilaterally compared to the SZ−/IED+ group. Similar to human studies of JME, the epileptic baboons demonstrated GMC decreases in the thalami and occipital cortices, suggesting secondary injury due to chronic epilepsy. Cortical GMC, on the other hand, was increased in the anterior frontal and temporal lobes, also consistent with human JME studies. This VBM study may indicate a combination of developmental and acquired structural changes in the epileptic baboon.

Photosensitivity and epilepsy: Current concepts and perspectives—A narrative review

“…In the photosensitive group of B-PP they also found a major decrease in the right primary visual cortices and in the reticular, anterior and medial dorsal nuclei of the thalamus. The authors considered that such results may indicate a combination of developmental and acquired structural changes in the epileptic baboon [39].…”

Neuroimaging in the Epileptic Baboon

“…GMC changes were also documented with VBM in epileptic baboons [ Figures 2A,B ; ( 38 )]. GMC increases were noted in the frontopolar, orbitofrontal and anterolateral temporal cortices bilaterally.…”

“…(A,B) demonstrate increases (blue) and decreases (red) in gray matter concentration in epileptic baboons compared to controls. (C) Demonstrate significant decreases (red) and marginally significant decreases (yellow) in sulcal areas of baboons with IEDs on scalp EEG compared to healthy controls [adapted from Epilepsy Research , references ( 35 , 38 ), respectively].…”

Ontogeny and programming of the fetal temporal cortical endocannabinoid system by moderate maternal nutrient reduction in baboons ( Papio spp.)

“…)), autism spectrum disorder and epilepsy (Di Marzo ). Based on the facts that epilepsy occurs naturally in baboons (Szabo and Salinas ) and these NHP express all components of the ECS (Brocato et al. ; Rodriguez‐Sanchez et al.…”