Developing new neurophysiological signatures of general anesthesia induced loss of consciousness

Cimenser, Aylin; Pierce, Eric T.; Gómez, Andrés Felipe Salazar; Walsh, J.; Harrell, P. Grace; Tavares, Casie L.; Habeeb, Kathleen; Purdon, Patrick L.; Brown, Emery N.

doi:10.1186/1471-2202-10-s1-p79

Cited by 2 publications

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“…Recent data analyses (2,3) suggest that this rhythm, which is spatially distinct from the classic occipital α-rhythm, is highly coherent across electrodes. Moreover, its appearance is well correlated with the anesthetic-induced loss of consciousness.…”

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Thalamocortical model for a propofol-induced α-rhythm associated with loss of consciousness

Ching

Cimenser

Purdon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Recent data reveal that the general anesthetic propofol gives rise to a frontal α-rhythm at dose levels sufficient to induce loss of consciousness. In this work, a computational model is developed that suggests the network mechanisms responsible for such a rhythm. It is shown that propofol can alter the dynamics in thalamocortical loops, leading to persistent and synchronous α-activity. The synchrony that forms in the cortex by virtue of the involvement of the thalamus may impede responsiveness to external stimuli, thus providing a correlate for the unconscious state.general anesthesia | oscillations | global coherence | GABA T he anesthetic agent propofol (2,6-di-isopropylphenol) is known to elicit frontal α-rhythms (10-13 Hz) in the EEG (1). Recent data analyses (2, 3) suggest that this rhythm, which is spatially distinct from the classic occipital α-rhythm, is highly coherent across electrodes. Moreover, its appearance is well correlated with the anesthetic-induced loss of consciousness. Although much is known about the molecular actions of propofol, an understanding of the network mechanisms that lead to such EEG-level phenomena remains absent. The present work uses computational models to elucidate some of these mechanisms. It builds on the work of McCarthy et al. (4), in which a model of cortical networks was used to reveal dynamic changes that may underlie the paradoxical excitation associated with low doses of propofol. Here, these mechanisms are incorporated into a broader thalamocortical model that accounts for the aforementioned EEG features associated with the administration of higher anesthetic doses.The model suggests that propofol, via its potentiation of the GABA A synaptic current, effectively enhances the strength of projections from the cortex to thalamus, resulting in a wellcoordinated thalamocortical α-oscillation. We consider a network of cortical pyramidal (E) cells and interneurons (INs), coupled with thalamocortical relay (TC) and thalamic reticular (RE) neurons. Reciprocal projections between the E and TC cells form an excitatory thalamocortical loop. Propofol enters the model as an increase in the conductance and decay time of the GABA A inhibitory current. At low levels of the drug, the cortical part of the model produces the expected paradoxical excitation, whereas the thalamic part fires at a slower irregular rate. Increasing the inhibition to a level commensurate with a higher dose of the drug causes cortical cell firing to slow into the α-range. Importantly, this also changes the thalamic substrate by increasing the inhibition delivered by the RE neurons to the TC neurons, producing rebound spiking. Thus, the cortical input to the thalamus is effectively enhanced, enabling the latter to be recruited into the same α-frequency. Because the reticular nucleus innervates widely, it has the capacity to synchronize thalamic oscillations. These oscillations then manifest coherently at the cortex through the thalamocortical loop. Thus, the model produces a coherent propofol-induced α-rhyth...

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“…To ascertain the spatiotemporal properties of this activity, a global coherence analysis was performed over all electrodes (2,3) (Fig. 1C).…”

mentioning

confidence: 99%

Thalamocortical model for a propofol-induced α-rhythm associated with loss of consciousness

Ching

Cimenser

Purdon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

340

408

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Robust time-varying multivariate coherence estimation: Application to electroencephalogram recordings during general anesthesia

Wong

Mukamel

Zuluaga

et al. 2011

2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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Coherence analysis characterizes frequency-dependent covariance between signals, and is useful for multivariate oscillatory data often encountered in neuroscience. The global coherence provides a summary of coherent behavior in high-dimensional multivariate data by quantifying the concentration of variance in the first mode of an eigenvalue decomposition of the cross-spectral matrix. Practical application of this useful method is sensitive to noise, and can confound coherent activity in disparate neural populations or spatial locations that have a similar frequency structure. In this paper we describe two methodological enhancements to the global coherence procedure that increase robustness of the technique to noise, and that allow characterization of how power within specific coherent modes change through time.

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Developing new neurophysiological signatures of general anesthesia induced loss of consciousness

Cited by 2 publications

References 5 publications

Thalamocortical model for a propofol-induced α-rhythm associated with loss of consciousness

Thalamocortical model for a propofol-induced α-rhythm associated with loss of consciousness

Robust time-varying multivariate coherence estimation: Application to electroencephalogram recordings during general anesthesia

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