Dataset Information

Brain Map of Intrinsic Functional Flexibility in Anesthetized Monkeys and Awake Humans.

ABSTRACT: Emerging neuroimaging studies emphasize the dynamic organization of spontaneous brain activity in both human and non-human primates, even under anesthesia. In a recent study, we were able to characterize the heterogeneous architecture of intrinsic functional flexibility in the awake, resting human brain using time-resolved analysis and a probabilistic model. However, it is unknown whether this organizational principle is preserved in the anesthetized monkey brain, and how anesthesia affects dynamic and static measurements of spontaneous brain activity. To investigate these issues, we collected resting-state functional magnetic resonance imaging (fMRI) datasets from 178 awake humans and 11 anesthetized monkeys (all healthy). Our recently established method, a complexity measurement (i.e., Shannon entropy) of dynamic functional connectivity patterns of each brain region, was used to map the intrinsic functional flexibility across the cerebral cortex. To further explore the potential effects of anesthesia, we performed time series analysis and correlation analysis between dynamic and static measurements within awake human and anesthetized monkey brains, respectively. We observed a heterogeneous profile of intrinsic functional flexibility in the anesthetized monkey brain, which showed some similarities to that of awake humans (r = 0.30, p = 0.007). However, we found that brain activity in anesthetized monkeys generally shifted toward random fluctuations. Moreover, there is a negative correlation between nodal entropy for the distribution of dynamic functional connectivity patterns and static functional connectivity strength in anesthetized monkeys, but not in awake humans. Our findings indicate that the heterogeneous architecture of intrinsic functional flexibility across cortex probably reflects an evolutionarily conserved aspect of functional brain organization, which persists across levels of cognitive processing (states of consciousness). The coupling between nodal entropy for the distribution of dynamic functional connectivity patterns and static functional connectivity strength may serve as a potential signature of anesthesia. This study not only offers fresh insight into the evolution of brain functional architecture, but also advances our understanding of the dynamics of spontaneous brain activity.

SUBMITTER: Yin D

PROVIDER: S-EPMC6403192 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Brain Map of Intrinsic Functional Flexibility in Anesthetized Monkeys and Awake Humans.

Yin Dazhi D Zhang Zhao Z Wang Zhiwei Z Zeljic Kristina K Lv Qian Q Cai Danchao D Wang Yingwei Y Wang Zheng Z

Frontiers in neuroscience 20190228

Emerging neuroimaging studies emphasize the dynamic organization of spontaneous brain activity in both human and non-human primates, even under anesthesia. In a recent study, we were able to characterize the heterogeneous architecture of intrinsic functional flexibility in the awake, resting human brain using time-resolved analysis and a probabilistic model. However, it is unknown whether this organizational principle is preserved in the anesthetized monkey brain, and how anesthesia affects dyna ...[more]

PMID: 30873000

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Project description:The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009-0.08Hz), intermediate (0.08-0.4Hz), and high (0.4-4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6-1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4-4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke.

Project description:Neuroreceptor imaging in the nonhuman primate (NHP) is valuable for translational research approaches in humans. However, most NHP studies are conducted under anesthesia, which affects the interpretability of receptor binding measures. The aims of this study were to develop awake NHP imaging with minimal head restraint and to compare in vivo binding of the ?-aminobutyric acid type A (GABAA)-benzodiazepine radiotracer (11)C-flumazenil under anesthetized and awake conditions. We hypothesized that (11)C-flumazenil binding potential (BPND) would be higher in isoflurane-anesthetized monkeys.The small animal PET scanner was fitted to a mechanical device that raised and tilted the scanner 45° while the awake NHP was tilted back 35° in a custom chair for optimal brain positioning, which required acclimation of the animals to the chair, touch-screen tasks, intravenous catheter insertion, and tilting. For PET studies, the bolus-plus-constant infusion method was used for (11)C-flumazenil administration. Two rhesus monkeys were scanned under the awake (n = 6 scans) and isoflurane-anesthetized (n = 4 scans) conditions. An infrared camera was used to track head motion during PET scans. Under the awake condition, emission and head motion-tracking data were acquired for 40-75 min after injection. Anesthetized monkeys were scanned for 90 min. Cortisol measurements were acquired during awake and anesthetized scans. Equilibrium analysis was used for both the anesthetized (n = 4) and the awake (n = 5) datasets to compute mean BPND images in NHP template space, using the pons as a reference region. The percentage change per minute in radioactivity concentration was calculated in high- and low-binding regions to assess the quality of equilibrium.The monkeys acclimated to procedures in the NHP chair necessary to perform awake PET imaging. Image quality was comparable between awake and anesthetized conditions. The relationship between awake and anesthetized values was BPND (awake) = 0.94 BPND (anesthetized) + 0.36 (r(2) = 0.95). Cortisol levels were significantly higher under the awake condition (P < 0.05).We successfully performed awake NHP imaging with minimal head restraint. There was close agreement in (11)C-flumazenil BPND values between awake and anesthetized conditions.

Dataset Information

Brain Map of Intrinsic Functional Flexibility in Anesthetized Monkeys and Awake Humans.

Publications

Brain Map of Intrinsic Functional Flexibility in Anesthetized Monkeys and Awake Humans.

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