Isoflurane disrupts anterio-posterior phase synchronization of flash-induced field potentials in the rat

Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, USA.
Neuroscience Letters (Impact Factor: 2.03). 08/2006; 402(3):216-21. DOI: 10.1016/j.neulet.2006.04.003
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Consciousness presumes a set of integrated functions such as sensory processing, attention, and interpretation, and may depend upon both local and long-range phase synchronization of neuronal activity in cerebral cortex. Here we investigated whether volatile anesthetic isoflurane at concentrations that produce loss of consciousness (LOC) disrupts long-range anterio-posterior and local anterior synchronization of neuronal activity in the rat. In six rats, deep electrodes were chronically implanted in the primary visual cortex (V1) and in two areas of the motor cortex (M1 and M2) for recording of intracortical event-related potentials (ERP). Thirty discrete flashes were presented at random interstimulus intervals of 15-45 s, and ERPs were recorded at stepwise increasing isoflurane concentrations of 0-1.1%. Neuronal synchronization was estimated using wavelet coherence computed from the ERP data band-pass filtered at 5-50 Hz. We found that (1) in the waking state, long-range anterio-posterior coherence in 5-25 Hz and 25-50 Hz frequency bands was significantly higher than local anterior coherence; (2) anterio-posterior coherence in both 5-25 Hz and 26-50 Hz bands was significantly reduced by isoflurane in a concentration-dependent manner; (3) local anterior coherence was not affected by isoflurane at any of the concentrations studied. These findings suggest that a disruption of long-range anterio-posterior rather than local anterior synchronization of neuronal activity precedes the anesthetic-induced loss of consciousness.

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Available from: Anthony G Hudetz, Sep 30, 2015
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    • "Beyond the implications for the mechanisms underlying propofol-induced sedation, our results may provide further evidence for a key role of backward connections in the maintenance of consciousness. Backward connections seem to be impaired in the vegetative state (Boly et al., 2011) and under isoflurane sedation (Imas et al., 2006). They are also thought to play a role in normal conscious access (Fahrenfort et al., 2007). "
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    ABSTRACT: The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 05/2012; 32(20):7082-90. DOI:10.1523/JNEUROSCI.3769-11.2012 · 6.34 Impact Factor
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    • "Since the separation of the two baseline states (e.g., as reflected by ΔCMR O2 ) in the Smith et al. and Maandag et al. studies differed significantly, these early results about the relevance of baseline for fMRI studies suggest that careful consideration about an absolute measure of resting state is necessary. These results from Maandag et al. also find support from other studies in the literature (Antognini et al., 1997; Disbrow et al., 1999, 2000; Dueck et al., 2005; Erchova et al., 2002; Heinke et al., 2004; Imas et al., 2006; Sperling et al., 2002). Most of these studies, which used either an anesthetic or a sedative to alter the baseline state, suggest that evoked activity is more localized under levels of deep anesthesia or higher sedation (i.e., low baseline state), whereas the response patterns expand beyond the primary area under levels of light anesthesia or lower sedation (i.e., high baseline state). "
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    ABSTRACT: The discovery of functional magnetic resonance imaging (fMRI) has greatly impacted neuroscience. The blood oxygenation level-dependent (BOLD) signal, using deoxyhemoglobin as an endogenous paramagnetic contrast agent, exposes regions of interest in task-based and resting-state paradigms. However the BOLD contrast is at best a partial measure of neuronal activity, because the functional maps obtained by differencing or correlations ignore the total neuronal activity in the baseline state. Here we describe how studies of brain energy metabolism at Yale, especially with (13)C magnetic resonance spectroscopy and related techniques, contributed to development of quantitative functional brain imaging with fMRI by providing a reliable measurement of baseline energy. This narrative takes us on a journey, from molecules to mind, with illuminating insights about neuronal-glial activities in relation to energy demand of synaptic activity. These results, along with key contributions from laboratories worldwide, comprise the energetic basis for quantitative interpretation of fMRI data.
    NeuroImage 04/2012; 62(2):985-94. DOI:10.1016/j.neuroimage.2012.04.027 · 6.36 Impact Factor
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    • "A number of experimental observations are in agreement with this concept. In rats stimulated with light flashes, volatile anesthetics disrupted anterior-posterior phase synchronization of field responses [6] and depressed long-latency spike responses in visual cortex, thought to arise from cortico-cortical interactions [7]. In humans, during the transition from waking to loss of consciousness, various general anesthetics decoupled gamma rhythms between anterior and posterior cortical areas as well as between homologous areas in different hemispheres [8]. "
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    ABSTRACT: Anesthetics dose-dependently shift electroencephalographic (EEG) activity towards high-amplitude, slow rhythms, indicative of a synchronization of neuronal activity in thalamocortical networks. Additionally, they uncouple brain areas in higher (gamma) frequency ranges possibly underlying conscious perception. It is currently thought that both effects may impair brain function by impeding proper information exchange between cortical areas. But what happens at the local network level? Local networks with strong excitatory interconnections may be more resilient towards global changes in brain rhythms, but depend heavily on locally projecting, inhibitory interneurons. As anesthetics bias cortical networks towards inhibition, we hypothesized that they may cause excessive synchrony and compromise information processing already on a small spatial scale. Using a recently introduced measure of signal independence, cross-approximate entropy (XApEn), we investigated to what degree anesthetics synchronized local cortical network activity. We recorded local field potentials (LFP) from the somatosensory cortex of three rats chronically implanted with multielectrode arrays and compared activity patterns under control (awake state) with those at increasing concentrations of isoflurane, enflurane and halothane. Cortical LFP signals were more synchronous, as expressed by XApEn, in the presence of anesthetics. Specifically, XApEn was a monotonously declining function of anesthetic concentration. Isoflurane and enflurane were indistinguishable; at a concentration of 1 MAC (the minimum alveolar concentration required to suppress movement in response to noxious stimuli in 50% of subjects) both volatile agents reduced XApEn by about 70%, whereas halothane was less potent (50% reduction). The results suggest that anesthetics strongly diminish the independence of operation of local cortical neuronal populations, and that the quantification of these effects in terms of XApEn has a similar discriminatory power as changes of spontaneous action potential rates. Thus, XApEn of field potentials recorded from local cortical networks provides valuable information on the anesthetic state of the brain.
    BMC Neuroscience 09/2010; 11(122):122. DOI:10.1186/1471-2202-11-122 · 2.67 Impact Factor
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