Despite their widespread use, the effect of anesthetic agents on the brain's functional architecture remains poorly understood. This is particularly true of alterations that occur beyond the point of induced unconsciousness. Here, we examined the distributed intrinsic connectivity of macaques across six isoflurane levels using resting-state functional MRI (fMRI) following the loss of consciousness. The results from multiple analysis strategies showed stable functional connectivity (FC) patterns between 1.00% and 1.50% suggesting this as a suitable range for anesthetized nonhuman primate resting-state investigations. Dose-dependent effects were evident at moderate to high dosages showing substantial alteration of the functional topology and a decrease or complete loss of interhemispheric cortical FC strength including that of contralateral homologues. The assessment of dynamic FC patterns revealed that the functional repertoire of brain states is related to anesthesia depth and most strikingly, that the number of state transitions linearly decreases with increased isoflurane dosage. Taken together, the results indicate dose-specific spatial and temporal alterations of FC that occur beyond the typically defined endpoint of consciousness. Future work will be necessary to determine how these findings generalize across anesthetic types and extend to the transition between consciousness and unconsciousness.

Recent Papers from the lab

Laboratory for Neural Circuits and Cognitive Control

Cognitive control requires the selection and maintenance of task-relevant stimulus-response associations, or rules. The dorsolateral prefrontal cortex (DLPFC) has been implicated by lesion, functional imaging, and neurophysiological studies to be involved in encoding rules, but the mechanisms by which it modulates other brain areas are poorly understood. Here, the functional relationship of the DLPFC with the superior colliculus (SC) was investigated by bilaterally deactivating the DLPFC while recording local field potentials (LFPs) in the SC in monkeys performing an interleaved pro- and antisaccade task. Event-related LFPs showed differences between pro- and antisaccades and responded prominently to stimulus presentation. LFP power after stimulus onset was higher for correct saccades than erroneous saccades. Deactivation of the DLPFC did not affect stimulus onset related LFP activity, but reduced high beta (20-30 Hz) and high gamma (60-150 Hz) power during the preparatory period for both pro- and antisaccades. Spike rate during the preparatory period was positively correlated with gamma power and this relationship was attenuated by DLPFC deactivation. These results suggest that top-down control of the SC by the DLPFC may be mediated by beta oscillations.

Based upon cytoarchitectonic properties, the primate prefrontal cortex has been partitioned into different subregions that show unique structural connectivity patterns, with ongoing efforts to provide more fine-grained divisions. While meaningful divisions may be found within the sub-millimeter range, the subdivisions exist within an overall hierarchical architecture and at higher levels likely share similar activity patterns and functionality. Here, we used resting-state fMRI in lightly anesthetized macaque monkeys to measure the intrinsic functional connectivity of the prefrontal cortex. At a gross anatomical level, the data driven approach revealed five broad clusters that showed distinct brain-wide functional connectivity. Although each cluster encompasses several cytoarchitectonic subregions, the clusters overlap with the intrinsic structural connectivity of the prefrontal cortex and each cluster may subserve common functions.

PI: Stefan EverlinG


Isoflurane induces dose-dependent alterations in the cortical connectivity profiles and dynamic properties of the brain's functional architecture.Hutchison RM, Hutchison M, Manning KY, Menon RS, Everling S.Hum Brain Mapp. 2014 Jul 12. doi: 10.1002/hbm.22583. [Epub ahead of print]PMID: 25044934 [PubMed - as supplied by publisher]
Broad intrinsic functional connectivity boundaries of the macaque prefrontal cortex.
Hutchison RM, Everling S.Neuroimage. 2013 Nov 21;88C:202-211. doi: 10.1016/j.neuroimage. 2013.11.024. [Epub ahead of print]PMID: 24269571 [PubMed - as supplied by publisher]
Dorsolateral Prefrontal Cortex Deactivation in Monkeys Reduces Preparatory Beta and Gamma Power in the Superior Colliculus.
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Chan JL, Koval MJ, Womelsdorf T, Lomber SG, Everling S.Cereb Cortex. 2014 Jul 17. pii: bhu154. [Epub ahead of print]PMID: 25037923 [PubMed - as supplied by publisher]

Last updated: 25.10.2014