Abstract
Animal functional magnetic resonance imaging (fMRI) has provided key insights into the physiological mechanisms underlying healthy and diseased brain states. In non-human primates, resting-state fMRI studies are commonly conducted under isoflurane anesthesia, where anesthetic concentration is used to roughly infer anesthesia depth. However, within the recommended isoflurane concentration range (1.00–1.50%), the brain state can switch from moderate anesthesia characterized by stable slow wave (SW) electroencephalogram (EEG) signals to deep anesthesia characterized by burst suppression (BS), which is electrophysiologically distinct from the resting state. To confirm the occurrence rate of BS activity in common setting of animal fMRI study, we conducted simultaneous resting-state EEG and fMRI experiments on 16 monkeys anesthetized using 0.80–1.30% isoflurane, and detected BS activity in two of them. Datasets either featured with BS or SW activity from these two monkeys were analyzed to investigate the intrinsic functional connectivity (FC) patterns during BS. In datasets with BS activity, we observed robust coupling between the BS pattern (the binary alternation between burst and suppression activity in EEG signal) and filtered BOLD signals in most brain areas, which was associated with a non-specific enhancement in whole brain connectivity. After eliminating the BS coupling effect by regressing out the BS pattern, we detected an overall increase in FC with a few decreased connectivity compared to datasets with SW activity. These affected connections were preferentially distributed within orbitofrontal cortex, between orbitofrontal and prefrontal/cingulate/occipital cortex, and between temporal and parietal cortex. Persistence of the default mode network and recovery of thalamocortical connections were also detected under deep anesthesia with BS activity. Taken together, the observed spatially specific alterations in BS activity induced by isoflurane not only highlight the necessity of EEG monitoring and careful data preprocessing in fMRI studies on anesthetized animals, but also advance our understanding of the underlying multi-phased mechanisms of anesthesia.
Highlights
Functional magnetic resonance imaging has become a commonly used noninvasive technique for brain activity research in both animals and humans
Group analysis results indicated that the blood oxygenation level dependent (BOLD) fluctuations of most neocortex were positively correlated with the EEG BS pattern (Figure 1C, voxel-wise P < 0.001, Family-wise error (FWE) correction), including the prefrontal cortex, temporal cortex, parietal cortex, somatosensory cortex, posterior cingulate cortex (PCC), primary motor and premotor cortex, visural cortex, as well as thalamus
The BS coupling effect on BOLD fluctuations is supported by the physiological basis that synchronization of spontaneous highvoltage burst activity across a large population of neurons can result in the synchronization of hemodynamic fluctuations across different brain regions
Summary
Functional magnetic resonance imaging (fMRI) has become a commonly used noninvasive technique for brain activity research in both animals and humans. Resting-state fMRI (rsfMRI) measures functional connectivity (FC) between different brain regions in the non-stimulus state and is a valuable technique for exploring complex brain networks in different brain states or disease models (Greicius, 2008; Van Den Heuvel and Hulshoff Pol, 2010). Anesthesia is an effective method to prevent head motion and physiological stress when collecting blood oxygenation level dependent (BOLD) fMRI signals, in animal studies. Isoflurane, the most prevalent inhaled anesthetic for monkey fMRI study, has a significant, concentration-dependent influence on FC networks (Vincent et al, 2007; Nallasamy and Tsao, 2011; Grandjean et al, 2014; Hutchison et al, 2014; Bukhari et al, 2018). A limited range of isoflurane concentration (1.00–1.50%) is recommended to obtain stable FC in anesthetized nonhuman primate resting-state experiments (Hutchison et al, 2014)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
