The data obtained by electrophysiological measurements of neuron ensembles has been complemented by recordings of whole-brain activity using functional magnetic resonance imaging (fMRI). With collaborators at the Medical College of Wisconsin, Milwaukee, WI we made significant advances in the development of high-field functional resonance imaging of the entire rodent brain at unprecedented spatial resolution. We found that the anesthetic propofol at a dose that produces unconsciousness exerted dose-dependent, multiphasic modifications of intrinsic functional connectivity of the rat brain. This result highlighted the complexity of network interactions in the brain at different depths of anesthesia. For the first time, we also tested the effect of propofol on the temporal dynamics of brain states and found that both the state repertoire and the complexity of global brain states were substantially reduced during unconsciousness suggesting reduced global information integration in the brain. Brainstem stimulation partially restored the functional connectivity of subcortical networks in anesthetized rats.



Liu X, Pillay S, Li R, Vizuete JA, Pechman KR, Schmainda KM, Hudetz AG. Multiphasic modification of intrinsic functional connectivity of the rat brain during increasing levels of propofol. Neuroimage. 2013;83:581-92. PubMed PMID: 23851326; PMCID: 3815996.

Hudetz AG, Liu X, Pillay S. Dynamic repertoire of intrinsic brain states is reduced in propofol-induced unconsciousness. Brain Connect. 2015;5(1):10-22. PubMed PMID: 24702200; PMCID: 4313411.

Hudetz AG, Liu X, Pillay S, Boly M, Tononi G. Propofol anesthesia reduces Lempel-Ziv complexity of spontaneous brain activity in rats. Neurosci Lett. 2016 Aug 15;628:132-5. PubMed PMID: 27291459; PubMed Central PMCID: PMC5086801.

Pillay S, Liu X, Baracskay P, Hudetz AG. Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats. Brain Connect. 2014;4(7):523-34. PubMed PMID: 25090190; PMCID: 4146494.





Neuroimaging of consciousness in humans.

For nearly a decade, we have been investigating the effect of propofol on thalamocortical and corticocortical functional connectivity in human volunteers. Intriguingly, we found that cortical activation in response to auditory stimuli persists during loss of consciousness but the connectivity of higher-order cortical regions with primary sensory reception areas is interrupted. This finding supported our ‚Äúdisintegration hypothesis‚ÄĚ of anesthetic unconsciousness. To better understand the role of thalamocortical connectivity changes in anesthesia we investigated the specific and nonspecific systems during auditory stimulation. Previous fMRI connectivity analyses did not differentiate among the various thalamic nuclei. We showed for the first time that during propofol sedation to the point of unconsciousness, functional connectivity was reduced substantially more in the nonspecific than in the specific thalamocortical system. Because the nonspecific system plays a modulatory role, its preferential suppression may reflect the loss cortical integrative function in spite of the partially preserved specific stimulus transmission during anesthesia. We also compared the functional connectivity of brain networks in two types of unconscious states, healthy anesthetized participants and patients diagnosed with unresponsive wakefulness (UWS). Intriguingly, we found that the scale-free hierarchical organization of the brain was maintained in anesthetized healthy participants but not in UWS patients. This finding suggests a potentially important neuronal correlate of the irreversibility of unconsciousness in UWS patients. Our current research focuses on the relationship between resting state connectivity and task-response in order to determine how dynamic state changes influence the residual processing of sensory stimuli and in the anesthetized brain.



Liu X, Lauer KK, Ward BD, Rao SM, Li SJ, Hudetz AG. Propofol disrupts functional interactions between sensory and high-order processing of auditory verbal memory. Hum Brain Mapp. 2012;33(10):2487-98. PubMed PMID: 21932265; PMCID: 3244539.

Liu X, Lauer KK, Ward BD, Li SJ, Hudetz AG. Differential effects of deep sedation with propofol on the specific and nonspecific thalamocortical systems: a functional magnetic resonance imaging study. Anesthesiology. 2013;118(1):59-69. PubMed PMID: 23221862; PMCID: 4080838.*

*Highlighted by an editorial view (Anesthesiology 2013; 118:13-5).

Liu X, Li SJ, Hudetz AG. Increased precuneus connectivity during propofol sedation. Neurosci Lett. 2014;561:18-23. PubMed PMID: 24373986; PMCID: 3959727.

Liu X, Ward BD, Binder JR, Li SJ, Hudetz AG. Scale-free functional connectivity of the brain is maintained in anesthetized healthy participants but not in patients with unresponsive wakefulness syndrome. PLoS One. 2014;9(3):e92182. PubMed PMID: 24647227; PMCID: 3960221.

Liu X, Lauer KK, Douglas Ward B, Roberts C, Liu S, Gollapudy S, Rohloff R, Gross W, Chen G, Xu Z, Binder JR, Li SJ, Hudetz AG. Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness. Neuroimage. 2017 Feb 15;147:295-301. PubMed PMID: 27993673; PubMed Central PMCID: PMC5303656.

Liu X, Lauer KK, Ward D, Roberts C, Liu S, Suneeta G, Rohloff R, Gross W, Xu Z, Chen G, Binder J, Li SJ, Hudetz AG. Fine-grained parcellation of brain connectivity improves differentiation of states of consciousness during graded propofol sedation. Brain Connect. 2017 May 25. PubMed PMID: 28540741.