“Resting” CBF in the epileptic baboon: Correlation with ketamine dose and interictal epileptic discharges

Abstract

Background Photosensitive epileptic (SZ) baboons demonstrate different cerebral blood flow (CBF) activation patterns from asymptomatic controls (CTL) during intermittent light stimulation (ILS). This study compares “resting” CBF between PS and CTL animals, and CBF correlations with ketamine dose and interictal epileptic discharges (IEDs) between PS and CTL animals. Methods Continuous intravenous ketamine was administered to eight PS and eight CTL baboons (matched for gender and weight), and maintained at subanesthetic doses (4.8–14.6 mg/kg/hr). Three resting H215O-PET studies were attempted in each animal (CTI/Siemens HR+ scanner). Images were acquired in 3D mode (63 contiguous slices, 2.4 mm thickness). PET images were co-registered with MRI images (3T Siemens Trio, T1-weighted 3D Turboflash sequence, TE/TR/TI = 3.04/2100/785 msec, flip angle=13 degrees). EEG was used to monitor depth of sedation and for quantification of IED rates. Regional CBF was compared between PS and CTL groups and correlations were analyzed for ketamine dose and IED rates. Results When subsets of animals of either group, receiving similar doses of ketamine were compared, PS animals demonstrated relative CBF increases in the occipital lobes and decreases in the frontal lobes. Correlation analyses with ketamine dose confirmed the frontal and occipital lobe changes in the PS animals. The negative correlations of CBF with ketamine dose and IED rate overlapped frontally. While frontal lobe CBF was also negatively correlated with IED rate, positive correlations were found in the parietal lobe. Conclusions “Resting” CBF differs between PS and CTL baboons. Correlation analyses of CBF and ketamine dose reveal that occipital lobe CBF increases and frontal lobe in PS animals are driven by ketamine. While frontal lobe CBF decreases may be related to ketamine’s propensity to activate IEDs, positive CBF correlations with IED rate suggest involvement of the parietal lobes in their generation.

Modeling the effective connectivity of the visual network in healthy and photosensitive, epileptic baboons

“…Furthermore, ketamine was used to lightly sedate the baboons. As mentioned above, ketamine can alter resting CBF in a dose-dependent fashion (Szabó et al 2008), particularly in epileptic baboons. It can also induce IEDs or seizures at low doses (Szabó et al 2005).…”

“…These regions were not included in our model because they did not demonstrate significant CBF changes during the PPR in earlier conditional contrast and covariance studies (Szabó et al 2007; Szabó et al 2011). The thalamus is another structure extensively connected with the frontoparietal cortices, which is typically activated in the setting of prolonged generalized spike-and-wave discharges or absence seizures in humans (Bai et al 2010; Benuzzi et al 2012), and in the setting of sustained repetitive IEDs in the epileptic baboon (Fischer-Williams et al 1968; Szabó et al 2008; Silva-Barrat et al 1986). However, as most of the PPRs were brief and PCRs were restricted to brief myoclonic seizures in the PS baboons, it not surprising that the thalamus was not involved or significantly activated.…”

“…Both in intracranial EEG studies in baboons, and in human EEG-fMRI studies, the thalamus was rarely co-activated in association with discrete PPRs (Moeller et al 2009; Silva-Barrat et al 2008). It is possible, nonetheless, that with a larger sample size, other cortical and subcortical structures that are activated in association with spontaneous IEDs would emerge as nodes of the epileptic network (Szabó et al 2008). …”

Functional neuroimaging of the baboon during concurrent image-guided transcranial magnetic stimulation

“…The use of i.v. ketamine anesthesia may influence the magnitude and distribution of cortical and subcortical CBF changes (Szabó et al 2008). Långsjö et al, 2003 found that ketamine induces a global, concentration-dependent increase in CBF with the largest increases in the anterior cingulate, thalamus, putamen, and frontal cortex.…”

“…The baboon’s large brain size makes them more suitable for magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, increasing its potential as a possible model for functional imaging studies of ischemia and neurological disorders—e.g. stroke (Fukuda & del Zoppo 2003) and epilepsy (Szabó et al, 2008; Szabó et al, 2011). The baboon’s larger brain size also permits the use of standard (human) TMS coils since the induced electric fields (E-fields) will be focally distributed in a larger brain volume than in smaller NHPs—i.e.…”