title: The effective connectivity of the seizure onset zone and ictal perfusion changes in amygdala kindled rhesus monkeys.
abstract: Epileptic seizures are network-level phenomena. Hence, epilepsy may be regarded as a circuit-level disorder that cannot be understood outside this context. Better insight into the effective connectivity of the seizure onset zone and the manner in which seizure activity spreads could lead to specifically-tailored therapies for epilepsy. We applied the electrical amygdala kindling model in two rhesus monkeys until these animals displayed consistent stage IV seizures. At this stage, we investigated the effective connectivity of the amygdala by means of electrical microstimulation during fMRI (EM-fMRI). In addition, we imaged changes in perfusion during a seizure using ictal SPECT perfusion imaging. The spatial overlap between the connectivity network and the ictal perfusion network was assessed both at the regional level, by calculating Dice coefficients using anatomically defined regions of interest, and at the voxel level. The kindled amygdala was extensively connected to bilateral cortical and subcortical structures, which in many cases were connected multisynaptically to the amygdala. At the regional level, the spatial extents of many of these fMRI activations and deactivations corresponded to the respective increases and decreases in perfusion imaged during a stage IV seizure. At the voxel level, however, some regions showed residual seizure-specific activity (not overlapping with the EM-fMRI activations) or fMRI-specific activation (not overlapping with the ictal SPECT activations), indicating that frequently, only a part of a region anatomically connected to the seizure onset zone participated in seizure propagation. Thus, EM-fMRI in the amygdala of electrically-kindled monkeys reveals widespread areas that are often connected multisynaptically to the seizure focus. Seizure activity appears to spread, to a large extent, via these connected areas.
authors.affiliation: Laboratory for Neuro- and Psychophysiology, KU Leuven, O&N II Herestraat 49 - bus 1021, 3000 Leuven, Belgium; Laboratory for Epilepsy Research, KU Leuven, UZ Herestraat 49 - bus 7003 48, 3000 Leuven, Belgium.
authors.forename: Evy
authors.initials: E
authors.lastname: Cleeren
authors.affiliation: Laboratory for Neuro- and Psychophysiology, KU Leuven, O&N II Herestraat 49 - bus 1021, 3000 Leuven, Belgium.
authors.forename: Elsie
authors.initials: E
authors.lastname: Premereur
authors.affiliation: Nuclear Medicine & Molecular Imaging, Department of Imaging and Pathology, UZ Herestraat 49 - bus 7003 59, 3000 Leuven, Belgium; Molecular Small Animal Imaging Center (MoSAIC), O&N I Herestraat 49 - bus 505, 3000 Leuven, Belgium.
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.affiliation: Nuclear Medicine & Molecular Imaging, Department of Imaging and Pathology, UZ Herestraat 49 - bus 7003 59, 3000 Leuven, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Goffin
authors.affiliation: Laboratory for Neuro- and Psychophysiology, KU Leuven, O&N II Herestraat 49 - bus 1021, 3000 Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Janssen
authors.affiliation: Laboratory for Epilepsy Research, KU Leuven, UZ Herestraat 49 - bus 7003 48, 3000 Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Van Paesschen
mesh_terms: D000679:Amygdala / Q000000981:diagnostic imaging / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001931:Brain Mapping; D003545:Cysteine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography; D007091:Image Processing, Computer-Assisted; D007696:Kindling, Neurologic / Q000502:physiology*; D008253:Macaca mulatta; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010100:Oxygen / Q000097:blood; D012640:Seizures / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015609:Organotechnetium Compounds; C059659:technetium Tc 99m bicisate; D003545:Cysteine; D010100:Oxygen
keywords: 99mTc-ECD, 99m-technetium labeled ethyl cysteinate diethylester; Amygdala kindling; EM-fMRI, electrical microstimulation during functional magnetic resonance imaging; Electrical microstimulation; Functional magnetic resonance imaging; Ictal single photon emission computed tomography; MION, monocrystalline iron oxide nanoparticle; MTLE, mesial temporal lobe epilepsy; Mesial temporal lobe epilepsy; PSC, percent signal change; SISCOM, subtraction Ictal SPECT co-registered to MRI; SPECT, single photon emission computed tomography; VOI, Volume-Of-Interest