Cortical and subcortical connectivity changes during decreasing levels of consciousness in humans: a functional magnetic resonance imaging study using propofol

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Mhuircheartaigh, R. N. ; Rosenorn-Lanng, D. ; Wise, Richard Geoffrey ; Jbabdi, S. ; Rogers, R. ; Tracey, I. (2010)

While ubiquitous, pharmacological manipulation of consciousness remains poorly defined and incompletely understood (Prys-Roberts, 1987). This retards anesthetic drug development, confounds interpretation of animal studies conducted under anesthesia, and limits the sensitivity of clinical monitors of cerebral function to intact perception. Animal and human studies propose a functional “switch” at the level of the thalamus, with inhibition of thalamo-cortical transmission characterizing loss of consciousness (Alkire et al., 2000; Mashour, 2006). We investigated the effects of propofol, widely used for anesthesia and sedation, on spontaneous and evoked cerebral activity using functional magnetic resonance imaging (fMRI). A series of auditory and noxious stimuli was presented to eight healthy volunteers at three behavioral states: awake, “sedated” and “unresponsive.” Performance in a verbal task and the absence of a response to verbal stimulation, rather than propofol concentrations, were used to define these states clinically. Analysis of stimulus-related blood oxygenation level-dependent signal changes identified reductions in cortical and subcortical responses to auditory and noxious stimuli in sedated and unresponsive states. A specific reduction in activity within the putamen was noted and further investigated with functional connectivity analysis. Progressive failure to perceive or respond to auditory or noxious stimuli was associated with a reduction in the functional connectivity between the putamen and other brain regions, while thalamo-cortical connectivity was relatively preserved. This result has not been previously described and suggests that disruption of subcortical thalamo-regulatory systems may occur before, or even precipitate, failure of thalamo-cortical transmission with the induction of unconsciousness.
  • References (60)
    60 references, page 1 of 6

    Abulafia R, Zalkind V, Devor M (2009) Cerebral activity during the anesthesia-like state induced by mesopontine microinjection of pentobarbital. J Neurosci 29: 7053- 64.

    Alkire MT (2008) Loss of effective connectivity during general anesthesia. Int Anesthesiol Clin 46:55-73.

    Alkire MT, Pomfrett CJ, Haier RJ, Gianzero MV, Chan CM, Jacobsen BP, Fallon JH (1999) Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism. Anesthesiology 90:701-709.

    Alkire MT, Haier RJ, Fallon JH (2000) Toward a unified theory of narcosis: brain imaging evidence for a thalamocortical switch as the neurophysiologic basis of anesthetic-induced unconsciousness. Conscious Cogn 9:370 -386.

    Alkire MT, McReynolds JR, Hahn EL, Trivedi AN (2007) Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Anesthesiology 107:264 -272.

    Angel A (1991) The G. L. Brown lecture. Adventures in anesthesia. Exp Physiol 76:1-38.

    Antognini JF, Schwartz K (1993) Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology 79:1244 -1249.

    Antognini JF, Barter L, Carstens E (2005) Overview movement as an index of anesthetic depth in humans and experimental animals. Comp Med 55:413- 418.

    Baars BJ (1995) Tutorial commentary: surprisingly small subcortical structures are needed for the state of waking consciousness, while cortical projection areas seem to provide perceptual contents of consciousness. Conscious Cogn 4:159 -162.

    Barter LS, Mark LO, Jinks SL, Carstens EE, Antognini JF (2008) Immobilizing doses of halothane, isoflurane or propofol, do not preferentially depress noxious heat-evoked responses of rat lumbar dorsal horn neurons with ascending projections. Anesth Analg 106:985-990.

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