BOLD fMRI of visual and somatosensory–motor stimulations in baboons

Abstract

Baboon, with its large brain size and extensive cortical folding compared to other non-human primates, serves as a good model for neuroscience research. This study reports the implementation of a baboon model for blood oxygenation level-dependent (BOLD) fMRI studies (1.5 × 1.5 × 4 mm resolution) on a clinical 3 T-MRI scanner. BOLD fMRI responses to hypercapnic (5% CO 2 ) challenge, 10 Hz flicker visual, and vibrotactile somatosensory-motor stimulations were investigated in baboons anesthetized sequentially with isoflurane and ketamine. Hypercapnia evoked robust BOLD increases. Paralysis was determined to be necessary to achieve reproducible functional activations within and between subjects under our experimental conditions. With optimized anesthetic doses (0.8-1.0% isoflurane or 6-8 mg/kg/h ketamine) and adequate paralysis (vecuronium, 0.2 mg/kg), robust activations were detected in the visual (V), primary (S1) and secondary (S2) somatosensory, primary motor (M cortices), supplementary motor area (SMA), lateral geniculate nucleus (LGN) and thalamus (Th). Data were tabulated for 11 trials under isoflurane and 10 trials under ketamine on 5 baboons. S1, S2, M, and V activations were detected in essentially all trials (90-100% of the time, except 82% for S2 under isoflurane and 70% for M under ketamine).LGN activations were detected 64-70% of the time under both anesthetics. SMA and Th activations were detected 36-45% of the time under isoflurane and 60% of the time under ketamine. BOLD percent changes among different structures were slightly higher under ketamine than isoflurane (0.75% versus 0.58% averaging all structures), but none was statistically different (P>0.05). This baboon model offers an opportunity to non-invasively image brain functions and dysfunctions in large non-human primates.

MRI Techniques and New Animal Models for Imaging the Brain

“…Conversely, the networks of vision, motor or auditory sensitivity described in the resting state persisted regardless of the depth or type of general anaesthesia (Hutchison et al 2010), and no difference between anaesthetics was found after visual stimulation in dogs (Willis et al 2001). Several MRI paradigms in anaesthetized animals have been developed to map brain activation induced by serotonin infusion in the baboon (Wey et al 2010) and cat (Henderson et al 2002) or brain connectivity in the rat (Pawela et al 2009, Zhao et al 2008). …”

Brain hemodynamic response to somatosensory stimulation in Neuroligin-1 knockout mice

“…Thus, we cannot exclude the possibility that the anesthetic used in the present study could have masked additional between-genotype differences because of NMDAR inhibition by Ketamine. Nevertheless, we believe that the observed genotype differences are valid because high-amplitude cerebrovascular responses were observed under Ketamine/Xylazine anesthesia (Wey et al, 2010;Kim and Jeong, 2013), and the overall magnitude of hemodynamic responses reported here (3-4% change) was similar to previous studies performed with alpha-chloralose (Dubeau et al, 2011). More importantly, the application of NMDAR and AMPAR antagonists blocks the hemodynamic response to somatosensory stimulation under Ketamine/Xylazine anesthesia (Scott and Murphy, 2012), which supports that glutamatergic transmission is preserved under such anesthetic conditions and that our findings of altered cerebrovascular parameters in Nlgn1 KO mice could be linked to modifications in glutamate receptor functions.…”

Multimodal MRI of Nonhuman Primate Stroke

“…The common choices of anesthesia are sevoflurane, isoflurane, ketamine, and propofol. The choice of anesthetics and dosages vary depending on the types of MRI experiments (i.e., anatomical MRI versus functional MRI (fMRI)) and the duration of the MRI exams [4]. It is necessary to monitor the physiological status of anesthetized NHPs during MRI experiments.…”

“…Human scanners are however more widely used for imaging large NHPs (macaque and larger species) [4, 7–9]. The large scanner size and the ease of use for many commonly available MRI protocols make human MRI systems more facile than small-animal imaging systems for translational aspects of NHP imaging research.…”