Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness

Oluwaseun Akeju,Vitaly Napadow,Shirley Hsu,Marco L Loggia,Patrick L Purdon,Grae Arabasz,Jacob M Hooker,Emery N Brown,Ciprian Catana,David Izquierdo-Garcia,Daniel B Chonde,Kara J Pavone,Kathleen Habeeb,Rafael Vazquez,Violeta Contreras Ramirez,James Rhee

doi:10.7554/elife.04499

Abstract

Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α₂-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness.

Highlights

Understanding the neural mechanisms of consciousness is a fundamental challenge of current neuroscience research
In 10 healthy volunteers, we used EEG recordings, and an auditory task to confirm that dexmedetomidine induced a loss of voluntary responsiveness, and exhibited a neurophysiological profile that was similar to non rapid eye movement (NREM) II sleep (Akeju et al, 2014)
Consistent with a global decrease in glucose metabolism, we found that during the unconscious state, there was a broad reduction in 18F-FDG standardized uptake values in the brain (Figure 2—figure supplement 1A)

Summary

Introduction

Understanding the neural mechanisms of consciousness is a fundamental challenge of current neuroscience research. We note that precise definitions of the words ‘consciousness’ and ‘unconsciousness’ remain ambiguous. Loss of voluntary response in a task is an effective and clinically relevant definition of unconsciousness. Important insights have been gained by using functional magnetic resonance imaging (fMRI) to characterize the brain during sleep, and disorders of consciousness (DOC) such as coma, vegetative states, and minimally conscious states (Greicius et al, 2008; Horovitz et al, 2008; Boly et al, 2009; Cauda et al, 2009; Horovitz et al, 2009; LarsonPrior et al, 2009; Vanhaudenhuyse et al, 2010; Samann et al, 2011; Fernandez-Espejo et al, 2012; Picchioni et al, 2014).

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