Multiphasic modification of intrinsic functional connectivity of the rat brain during increasing levels of propofol

Liu, Xiping; Pillay, Siveshigan; Li, Rupeng; Vizuete, Jeannette A.; Pechman, Kimberly R.; Schmainda, Kathleen M.; Hudetz, Anthony G.

doi:10.1016/j.neuroimage.2013.07.003

Cited by 53 publications

(69 citation statements)

References 106 publications

(154 reference statements)

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“…Experimental evidence shows that the effects of propofol on arterial blood pressure and cerebral blood flow are small [58][59][60][61], ruling out confounding effects related to pressure-dependent changes in BOLD signals. As discussed by Hudetz et al [62], confounding effects owing to alterations in neurovascular coupling are also unlikely given the preservation of functional responses during propofol-induced loss of consciousness [63].…”

Section: Discussionmentioning

confidence: 99%

Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics

Tagliazucchi

Chialvo

Siniatchkin

et al. 2016

J. R. Soc. Interface.

180

187

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Loss of cortical integration and changes in the dynamics of electrophysiological brain signals characterize the transition from wakefulness towards unconsciousness. In this study, we arrive at a basic model explaining these observations based on the theory of phase transitions in complex systems. We studied the link between spatial and temporal correlations of large-scale brain activity recorded with functional magnetic resonance imaging during wakefulness, propofol-induced sedation and loss of consciousness and during the subsequent recovery. We observed that during unconsciousness activity in frontothalamic regions exhibited a reduction of long-range temporal correlations and a departure of functional connectivity from anatomical constraints. A model of a system exhibiting a phase transition reproduced our findings, as well as the diminished sensitivity of the cortex to external perturbations during unconsciousness. This framework unifies different observations about brain activity during unconsciousness and predicts that the principles we identified are universal and independent from its causes.

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Section: Discussionmentioning

confidence: 99%

Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics

Tagliazucchi

Chialvo

Siniatchkin

et al. 2016

J. R. Soc. Interface.

180

187

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“…The initial propofol infusion rate was either 20 or 40 mg/kg/h and reversed in consecutive experiments. These doses were chosen to produce conscious sedated and unconscious anesthetized states, respectively, based on prior studies of behavioral responses and electroencephalogram patterns in animals that did not receive muscle relaxant (Liu et al, 2013d). In the present study, propofol was added to pancuronium bromide (1 mg/kg/h, iv) and administered by a programmable MR-compatible infusion pump.…”

Section: Animal Preparationmentioning

confidence: 99%

Dynamic Repertoire of Intrinsic Brain States Is Reduced in Propofol-Induced Unconsciousness

2015

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The richness of conscious experience is thought to scale with the size of the repertoire of causal brain states, and it may be diminished in anesthesia. We estimated the state repertoire from dynamic analysis of intrinsic functional brain networks in conscious sedated and unconscious anesthetized rats. Functional resonance images were obtained from 30-min whole-brain resting-state blood oxygen level-dependent (BOLD) signals at propofol infusion rates of 20 and 40 mg/kg/h, intravenously. Dynamic brain networks were defined at the voxel level by sliding window analysis of regional homogeneity (ReHo) or coincident threshold crossings (CTC) of the BOLD signal acquired in nine sagittal slices. The state repertoire was characterized by the temporal variance of the number of voxels with significant ReHo or positive CTC. From low to high propofol dose, the temporal variances of ReHo and CTC were reduced by 78% -20% and 76% -20%, respectively. Both baseline and propofol-induced reduction of CTC temporal variance increased from lateral to medial position. Group analysis showed a 20% reduction in the number of unique states at the higher propofol dose. Analysis of temporal variance in 12 anatomically defined regions of interest predicted that the largest changes occurred in visual cortex, parietal cortex, and caudate-putamen. The results suggest that the repertoire of large-scale brain states derived from the spatiotemporal dynamics of intrinsic networks is substantially reduced at an anesthetic dose associated with loss of consciousness.

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“…If high levels of anaesthesia lead to widely synchronized neural activity and urethane does not specifically target a single receptor system, highly retained local synchronization revealed by ReHo within the thalamus may be a plausible outcome. This explanation may be further supported by studies on brain activations of rats under varied anaesthetic levels using rsfMRI and EEG under isoflurane or propofol (Liu et al, 2013b;Liu et al, 2013a).…”

Section: Uncorrected Post Hoc Tests Revealed Significantly Increased mentioning

confidence: 84%

“…EEG and rsfMRI studies in rats under isoflurane and propofol reported a global synchronization in functional connectivity associated with EEG burst suppression as anaesthesia deepened (Austin et al, 2005;Liu et al, 2013b;Liu et al, 2013a). Hence, the merged community may be explained by the cortical synchronization masking more specific submodules in the brain.…”

Section: Anaesthetic Depths Influence Modular Organizationsmentioning

confidence: 99%

“…One study on rats under propofol anaesthesia revealed that thalamocortical FC was suppressed at high surgical dosages (Tu et al, 2011). Another study investigated the dosage-dependent effects of this agent on rats reported complex FC changes in cortical and subcortical areas as anaesthetic level increased (Liu et al, 2013b).…”

Section: General Anaesthesia and Commonly Used Anaesthetic Regimens Fmentioning

confidence: 99%

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Functional network study on the wild type and DISC1 transgenic mice

Wu¹

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Major mental disorders such as schizophrenia (SZ), bipolar disorder and major depression create a heavy social burden and remain poorly treated. Recent reports examining the genetic and molecular structure of brain disorders discovered the gene Disrupted-in-Schizophrenia 1 (DISC1) to be significantly associated with these disorders and plays a substantial role in influencing a range of shared endophenotypes underlying these disorders. This has led to a powerful gateway to explore the underlying pathology and to achieve better diagnosis and treatments of major mental diseases. Characterising the phenotypes of DISC1 in brain functions would provide valuable insights into the mechanism of how this gene influences the brain.Resting-state fMRI (rs-fMRI) is a powerful technique being applied to more than 30 different kinds of brain disorders and different species. Findings from rs-fMRI studies on humans provide ample evidence of abnormal functional patterns in patients with mental illnesses. Specifically, altered functional connectivity (FC) and network topologies are proposed to be plausible imaging endophenotypes of psychotic disorders. However, little is known about the direct effects of gene dysfunction, such as DISC1 mutations, on restingstate brain activations. One aim of this thesis is to investigate the impacts of DISC1 on variations of resting-state functional networks (RSNs) in anaesthetized mouse brains using DISC1 transgenic mice and rs-fMRI.Before characterizing disease phenotypes in mouse models, it is necessary to understand how the mouse brain functions in normal states. Anaesthesia is currently an integrated part of most mouse rs-fMRI experiment. However, it influences blood-oxygenation-leveldependent (BOLD) fMRI signals via modulation of neurovascular coupling and brain metabolism, and therefore alters FC and topologies of RSNs. Investigating FC and its changes associated with genes therefore initially requires an understanding of the anaesthetics. Furthermore, various anaesthetic protocols are adopted by different labs leading to difficulties in result comparisons. The brain is a complex and hierarchical system, whereby its RSN architecture can be characterised from mutiple perspectives at regional or global levels. Previous mouse rs-fMRI studies have focused on long-distance FC, however, given the non-uniform influence of anaesthesia on the brain, mapping functional activations across scales in mice under different anaesthetics remain sparsely explored. Establishing this relationahsip would provide a reliable reference to study mouse brain functions in abnormal states and facilitate comparisons across laboratories. | P a g eIn the first aim of this thesis, I investigated the local connectivity in wide type (WT) mice under six commonly used anaesthetic regimens. I identified that the regional connectivity altered across the brain as a function of the expression density of receptors relative to specific agents. In addition, the depth of anaesthesia influences local synchronization.In the seco...

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Multiphasic modification of intrinsic functional connectivity of the rat brain during increasing levels of propofol

Cited by 53 publications

References 106 publications

Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics

Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics

Dynamic Repertoire of Intrinsic Brain States Is Reduced in Propofol-Induced Unconsciousness

Functional network study on the wild type and DISC1 transgenic mice

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