Effects of Anesthesia on Effective Connectivity in the Brain

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The brain constitutes a formidably complicated structural network. There are three main types of connectivity used to describe neuronal networks, which reflect three parallel levels of investigation: anatomical connectivity, functional connectivity and effective connectivity. Effective connectivity indicates the direct influence that a node exerts on another, and in the context of neuronal circuits, a causal relationship between the activities of two nodes. Since its definition, effective connectivity analysis has been used to describe causal relationship across multiple spatial scales in PET imaging, fMRI, electroencephalography (EEG) and magnetoencephalography (MEG), single-unit, and local field potential. There are diverse literatures which probe the anesthetized state using effective connectivity analysis over the past two decades. The examination of effective connectivity in the anesthetized state is of relevance to both anesthesiologists and neuroscientists, as it has the potential to elucidate still unclear mechanisms of anesthesia while offering insight into intrinsic functional activity in the brain. The present review attempts to examine, elucidate, and integrate the insight that effective connectivity analysis of the anesthetized state has generated thus far.

Cite this paper

Xu, X. , Wang, G. and Tian, X. (2015) Effects of Anesthesia on Effective Connectivity in the Brain. World Journal of Neuroscience, 5, 99-107. doi: 10.4236/wjns.2015.52012.


[1] Ramón y Cajal, S. (1995) Histology of the Nervous System of Man and Vertebrates. Oxford University Press, Oxford.
[2] Swanson, L.W. (2003) Brain Architecture: Understanding the Basic Plan. Oxford University Press, Oxford.
[3] Bressler, S.L. (1995) Large-Scale Cortical Networks and Cognition. Brain Research Reviews, 20, 288-304. http://dx.doi.org/10.1016/0165-0173(94)00016-I
[4] Buzsáki, G. (2006) Rhythms of the Brain. Oxford University Press, Oxford.
[5] McIntosh, A.R. (2000) Towards a Network Theory of Cognition. Neural Networks, 13, 861-870.
[6] Mesulam, M.M. (1998) From Sensation to Cognition. Brain, 121, 1013-1052.
[7] Feldt, S., Bonifazi, P. and Cossart, R. (2011) Dissecting Functional Connectivity of Neuronal Microcircuits: Experimental and Theoretical Insights. Trends in Neurosciences, 34, 225-236.
[8] Bullmore, E. and Sporns, O. (2009) Complex Brain Networks: Graph Theoretical Analysis of Structural and Functional Systems. Nature Reviews Neuroscience, 10, 186-198.
[9] Friston, K.J., Harrison, L. and Penny, W. (2003) Dynamic Causal Modelling. NeuroImage, 19, 1273-1302. http://dx.doi.org/10.1016/S1053-8119(03)00202-7
[10] Rodrigues, J. and Andrade, A. (2014) Lag-Based Effective Connectivity Applied to fMRI: A Simulation Study Highlighting Dependence on Experimental Parameters and Formulation. NeuroImage, 89, 358-377. http://dx.doi.org/10.1016/j.neuroimage.2013.10.029
[11] Barrett, A.B., Barnett, L. and Seth, A.K. (2010) Multivariate Granger Causality and Generalized Variance. Physical Review E: Statistical, Nonlinear, and Soft Matter Physics, 81, Article ID: 041907. http://dx.doi.org/10.1103/PhysRevE.81.041907
[12] Barrett, A.B., Murphy, M., Bruno, M.A., Noirhomme, Q., Boly, M., Laureys, S., et al. (2012) Granger Causality Analysis of Steady-State Electroencephalographic Signals during Propofol-Induced Anaesthesia. PLoS ONE, 7, e29072. http://dx.doi.org/10.1371/journal.pone.0029072
[13] Lu, Q., Bi, K., Liu, C., Luo, G.P., Tang, H. and Yao, Z.J. (2013) Predicting Depression Based on Dynamic Regional Connectivity: A Windowed Granger Causality Analysis of MEG Recordings. Brain Research, 1535, 52-60. http://dx.doi.org/10.1016/j.brainres.2013.08.033
[14] Zhang, L., Chen, G.F., Niu, R.F., Wei, W., Ma, X.Y., Xu, J.M., et al. (2012) Hippocampal Theta-Driving Cells Revealed by Granger Causality. Hippocampus, 22, 1781-1793.
[15] David, O., Guillemain, I., Saillet, S., Reyt, S., Deransart, C., Segebarth, C., et al. (2008) Identifying Neural Drivers with Functional MRI: An Electrophysiological Validation. PLoS Biology, 6, 2683-2697. http://dx.doi.org/10.1371/journal.pbio.0060315
[16] Roebroeck, A., Formisano, E. and Goebel, R. (2005) Mapping Directed Influence over the Brain Using Granger Causality and fMRI. NeuroImage, 25, 230-242.
[17] Kaminski, M., Ding, M.Z., Truccolo, W.A. and Bressler, S.L. (2001) Evaluating Causal Relations in Neural Systems: Granger Causality, Directed Transfer Function and Statistical Assessment of Significance. Biological Cybernetics, 85, 145-157. http://dx.doi.org/10.1007/s004220000235
[18] Baccala, L.A. and Sameshima, K. (2001) Partial Directed Coherence: A New Concept in Neural Structure Determination. Biological Cybernetics, 84, 463-474. http://dx.doi.org/10.1007/PL00007990
[19] Eichler, M. (2006) On the Evaluation of Information Flow in Multivariate Systems by the Directed Transfer Function. Biological Cybernetics, 94, 469-482. http://dx.doi.org/10.1007/s00422-006-0062-z
[20] Schelter, B., Winterhalder, M., Eichler, M., Peifer, M., Hellwig, B., Guschlbauer, B., et al. (2006) Testing for Directed Influences among Neural Signals Using Partial Directed Coherence. Journal of Neuroscience Methods, 152, 210-219. http://dx.doi.org/10.1016/j.jneumeth.2005.09.001
[21] Nolte, G., Ziehe, A., Nikulin, V.V., Schl?g, A., Kr?me, N., Brismar, T., et al. (2008) Robustly Estimating the Flow Direction of Information in Complex Physical Systems. Physical Review Letters, 100, Article ID: 234101. http://dx.doi.org/10.1103/PhysRevLett.100.234101
[22] Schreiber, T. (2000) Measuring Information Transfer. Physical Review Letters, 85, 461.
[23] Chávez, M., Le Van Quyen, M., Navarro, V., Baulac, M. and Martinerie, J. (2003) Spatio-Temporal Dynamics Prior to Neocortical Seizures: Amplitude versus Phase Couplings. IEEE Transactions on Biomedical Engineering, 50, 571-583. http://dx.doi.org/10.1109/TBME.2003.810696
[24] Palu?, M. and Stefanovska, A. (2003) Direction of Coupling from Phases of Interacting Oscillators: An Information-Theoretic Approach. Physical Review E: Statistical, Nonlinear, and Soft Matter Physics, 67, Article ID: 055201. http://dx.doi.org/10.1103/PhysRevE.67.055201
[25] Alkire, M.T., Haier, R.J. and Fallon, J.H. (2000) Toward a Unified Theory of Narcosis: Brain Imaging Evidence for a Thalamocortical Switch as the Neurophysiologic Basis of Anesthetic-Induced Unconsciousness. Consciousness and Cognition, 9, 370-386.
[26] Cariani, P. (2000) Anesthesia, Neural Information Processing, and Conscious Awareness. Consciousness and Cognition, 9, 387-395. http://dx.doi.org/10.1006/ccog.1999.0420
[27] Alkire, M.T. and Miller, J. (2005) General Anesthesia and the Neural Correlates of Consciousness. Progress in Brain Research, 150, 229-244, 596-597.
[28] Newman, J. (1995) Thalamic Contributions to Attention and Consciousness. Consciousness and Cognition, 4, 172-193. http://dx.doi.org/10.1006/ccog.1995.1024
[29] Angel, A. (1993) Central Neuronal Pathways and the Process of Anaesthesia. British Journal of Anaesthesia, 71, 148-163. http://dx.doi.org/10.1093/bja/71.1.148
[30] Volkow, N.D., Wang, G.J., Hitzemann, R., Fowler, J.S., Pappas, N., Lowrimore, P., et al. (1995) Depression of Thalamic Metabolism by Lorazepam Is Associated with Sleepiness. Neuropsychopharmacology, 12, 123-132. http://dx.doi.org/10.1016/0893-133X(94)00068-B
[31] Alkire, M.T., Pomfrett, C.J., Haier, R.J., Gianzero, M.V., Chan, C.M., Jacobsen, B.P., et al. (1999) Functional Brain Imaging during Anesthesia in Humans: Effects of Halothane on Global and Regional Cerebral Glucose Metabolism. Anesthesiology, 90, 701-709. http://dx.doi.org/10.1097/00000542-199903000-00011
[32] Fiset, P., Paus, T., Daloze, T., Plourde, G., Meuret, P., Bonhomme, V., et al. (1999) Brain Mechanisms of Propofol-Induced Loss of Consciousness in Humans: A Positron Emission Tomographic Study. The Journal of Neuroscience, 19, 5506-5513.
[33] Alkire, M.T., Hudetz, A.G. and Tononi, G. (2008) Consciousness and Anesthesia. Science, 322, 876-880. http://dx.doi.org/10.1126/science.1149213
[34] Ward, L.M. (2011) The Thalamic Dynamic Core Theory of Conscious Experience. Consciousness and Cognition, 20, 464-486. http://dx.doi.org/10.1016/j.concog.2011.01.007
[35] Andrada, J., Livingston, P., Lee, B.J. and Antognini, J. (2012) Propofol and Etomidate Depress Cortical, Thalamic, and Reticular Formation Neurons during Anesthetic-Induced Unconsciousness. Anesthesia and Analgesia, 114, 661-669. http://dx.doi.org/10.1213/ANE.0b013e3182405228
[36] Kim, S.P., Hwang, E., Kang, J.H., Kim, S. and Choi, J.H. (2012) Changes in the Thalamocortical Connectivity during Anesthesia-Induced Transitions in Consciousness. Neuroreport, 23, 294-298. http://dx.doi.org/10.1097/WNR.0b013e3283509ba0
[37] Velly, L.J., Rey, M.F., Bruder, N.J., Gouvitsos, F.A., Witjas, T., Regis, J.M., et al. (2007) Differential Dynamic of Action on Cortical and Subcortical Structures of Anesthetic Agents during Induction of Anesthesia. Anesthesiology, 107, 202-212.
[38] Naghavi, H.R. and Nyberg, L. (2005) Common Fronto-Parietal Activity in Attention, Memory, and Consciousness: Shared Demands on Integration? Consciousness and Cognition, 14, 390-425. http://dx.doi.org/10.1016/j.concog.2004.10.003
[39] Rees, G., Kreiman, G. and Koch, C. (2002) Neural Correlates of Consciousness in Humans. Nature Reviews Neuroscience, 3, 261-270. http://dx.doi.org/10.1038/nrn783
[40] Sarter, M., Givens, B. and Bruno, J.P. (2001) The Cognitive Neuroscience of Sustained Attention: Where Top-Down Meets Bottom-Up. Brain Research Brain Research Reviews, 35, 146-160.
[41] Imas, O.A., Ropella, K.M., Ward, B.D., Wood, J.D. and Hudetz, A.G. (2005) Volatile Anesthetics Disrupt Frontal-Posterior Recurrent Information Transfer at Gamma Frequencies in Rat. Neuroscience Letters, 387, 145-150. http://dx.doi.org/10.1016/j.neulet.2005.06.018
[42] Lee, U.C., Kim, S., Noh, G.J., Choi, B.M., Hwang, E. and Mashour, G.A. (2009) The Directionality and Functional Organization of Frontoparietal Connectivity during Consciousness and Anesthesia in Humans. Consciousness and Cognition, 18, 1069-1078.
[43] Lee, U.C., Ku, S.W., Noh, G., Baek, S., Choi, B. and Mashour, G.A. (2013) Disruption of Frontal-Parietal Communication by Ketamine, Propofol, and Sevoflurane. Anesthesiology, 118, 1264-1275.
[44] Ku, S.W., Lee, U.C., Noh, G.J., Jun, I.G. and Mashour, G.A. (2011) Preferential Inhibition of Frontal-to-Parietal Feedback Connectivity Is a Neurophysiologic Correlate of General Anesthesia in Surgical Patients. PLoS ONE, 6, e25155. http://dx.doi.org/10.1371/journal.pone.0025155
[45] Jordan, D., Ilg, R., Riedl, V., Schorer, A., Grimberg, S., Neufang, S., et al. (2013) Simultaneous Electroencephalographic and Functional Magnetic Resonance Imaging Indicate Impaired Cortical Top-Down Processing in Association with Anesthetic-Induced Unconsciousness. Anesthesiology, 119, 1031-1042. http://dx.doi.org/10.1097/ALN.0b013e3182a7ca92
[46] Laureys, S., Goldman, S., Phillips, C., Van Bogaert, P., Aerts, J., Luxen, A., et al. (1999) Impaired Effective Cortical Connectivity in Vegetative State: Preliminary Investigation Using PET. NeuroImage, 9, 377-382. http://dx.doi.org/10.1006/nimg.1998.0414
[47] Stamatakis, E.A., Adapa, R.M., Absalom, A.R. and Menon, D.K. (2010) Changes in Resting Neural Connectivity during Propofol Sedation. PLoS ONE, 5, e14224.
[48] Moller, J.T., Cluitmans, P., Rasmussen, L.S., Houx, P., Rasmussen, H., Canet, J., et al. (1998) Long-Term Postoperative Cognitive Dysfunction in the Elderly ISPOCD1 Study. The Lancet, 351, 857-861. http://dx.doi.org/10.1016/S0140-6736(97)07382-0
[49] Mrak, R.E., Griffin, S.T. and Graham, D.I. (1997) Aging-Associated Changes in Human Brain. Journal of Neuropathology and Experimental Neurology, 56, 1269-1275. http://dx.doi.org/10.1097/00005072-199712000-00001
[50] Seymour, D.G. and Severn, A.M. (2009) Cognitive Dysfunction after Surgery and Anaesthesia: What Can We Tell the Grandparents? Age and Ageing, 38, 147-150.
[51] Butterfield, N.N., Graf, P., Ries, C.R. and MacLeod, B.A. (2004) The Effect of Repeated Isoflurane Anesthesia on Spatial and Psychomotor Performance in Young and Aged Mice. Anesthesia and Analgesia, 98, 1305-1311. http://dx.doi.org/10.1213/01.ANE.0000108484.91089.13
[52] Raja, P.V., Blumenthal, J.A. and Doraiswamy, P.M. (2004) Cognitive Deficits Following Coronary Artery Bypass Grafting: Prevalence, Prognosis, and Therapeutic Strategies. CNS Spectrums, 9, 763-772.
[53] Baddeley, A. (1992) Working Memory. Science, 255, 556-559.
[54] Baddeley, A. (2003) Working Memory: Looking Back and Looking Forward. Nature Reviews Neuroscience, 4, 829-839. http://dx.doi.org/10.1038/nrn1201
[55] Hyafil, A., Summerfield, C. and Koechlin, E. (2009) Two Mechanisms for Task Switching in the Prefrontal Cortex. The Journal of Neuroscience, 29, 5135-5142.
[56] Rossi, A.F., Pessoa, L., Desimone, R. and Ungerleider, L.G. (2009) The Prefrontal Cortex and the Executive Control of Attention. Experimental Brain Research, 192, 489-497.
[57] Xu, X.Y., Tian, Y., Li, S.Y., Li, Y.Z., Wang, G.L. and Tian, X. (2013) Inhibition of Propofol Anesthesia on Functional Connectivity between LFPs in PFC during Rat Working Memory Task. PLoS ONE, 8, e83653. http://dx.doi.org/10.1371/journal.pone.0083653
[58] Chi, H.D., Kawano, T., Tamura, T., Iwata, H., Takahashi, Y., Eguchi, S., et al. (2013) Postoperative Pain Impairs Subsequent Performance on a Spatial Memory Task via Effects on N-methyl-D-Aspartate Receptor in Aged Rats. Life Sciences, 93, 986-993. http://dx.doi.org/10.1016/j.lfs.2013.10.028
[59] Zhang, X.Q., Xin, X., Dong, Y.L., Zhang, Y.Y., Yu, B.W., Mao, J.R., et al. (2013) Surgical Incision-Induced Nociception Causes Cognitive Impairment and Reduction in Synaptic NMDA Receptor 2B in Mice. The Journal of Neuroscience, 33, 17737-17748. http://dx.doi.org/10.1523/JNEUROSCI.2049-13.2013
[60] Cardoso-Cruz, H., Lima, D. and Galhardo, V. (2013) Impaired Spatial Memory Performance in a Rat Model of Neuropathic Pain Is Associated with Reduced Hippocampus-Prefrontal Cortex Connectivity. The Journal of Neuroscience, 33, 2465-2480. http://dx.doi.org/10.1523/JNEUROSCI.5197-12.2013
[61] Cardoso-Cruz, H., Sousa, M., Vieira, J.B., Lima, D. and Galhardo, V. (2013) Prefrontal Cortex and Mediodorsal Thalamus Reduced Connectivity Is Associated with Spatial Working Memory Impairment in Rats with Inflammatory Pain. Pain, 154, 2397-2406. http://dx.doi.org/10.1016/j.pain.2013.07.020
[62] Laroche, S., Davis, S. and Jay, T.M. (2000) Plasticity at Hippocampal to Prefrontal Cortex Synapses: Dual Roles in Working Memory and Consolidation. Hippocampus, 10, 438-446.
[63] Vertes, R.P., Hoover, W.B., Szigeti-Buck, K. and Leranth, C. (2007) Nucleus Reuniens of the Midline Thalamus: Link between the Medial Prefrontal Cortex and the Hippocampus. Brain Research Bulletin, 71, 601-609. http://dx.doi.org/10.1016/j.brainresbull.2006.12.002
[64] Fell, J., Klaver, P., Lehnertz, K., Grunwald, T., Schaller, C., Elger, C.E., et al. (2001) Human Memory Formation Is Accompanied by Rhinal-Hippocampal Coupling and Decoupling. Nature Neuroscience, 4, 1259-1264. http://dx.doi.org/10.1038/nn759
[65] Jones, M.W. and Wilson, M.A. (2005) Theta Rhythms Coordinate Hippocampal-Prefrontal Interactions in a Spatial Memory Task. PLoS Biology, 3, e402. http://dx.doi.org/10.1371/journal.pbio.0030402
[66] Baeg, E.H., Kim, Y.B., Kim, J., Ghim, J.W., Kim, J.J. and Jung, M.W. (2007) Learning-Induced Enduring Changes in Functional Connectivity among Prefrontal Cortical Neurons. The Journal of Neuroscience, 27, 909-918. http://dx.doi.org/10.1523/JNEUROSCI.4759-06.2007
[67] Adhikari, A., Sigurdsson, T., Topiwala, M.A. and Gordon, J.A. (2010) Cross-Correlation of Instantaneous Amplitudes of Field Potential Oscillations: A Straightforward Method to Estimate the Directionality and Lag between Brain Areas. Journal of Neuroscience Methods, 191, 191-200. http://dx.doi.org/10.1016/j.jneumeth.2010.06.019
[68] Taxidis, J., Coomber, B., Mason, R. and Owen, M. (2010) Assessing Cortico-Hippocampal Functional Connectivity under Anesthesia and Kainic Acid Using Generalized Partial Directed Coherence. Biological Cybernetics, 102, 327-340. http://dx.doi.org/10.1007/s00422-010-0370-1
[69] Brockmann, M.D., P?schel, B., Cichon, N. and Hanganu-Opatz, I.L. (2011) Coupled Oscillations Mediate Directed Interactions between Prefrontal Cortex and Hippocampus of the Neonatal Rat. Neuron, 71, 332-347. http://dx.doi.org/10.1016/j.neuron.2011.05.041
[70] Hentschke, H., Schwarz, C. and Antkowiak, B. (2005) Neocortex Is the Major Target of Sedative Concentrations of Volatile Anaesthetics: Strong Depression of Firing Rates and Increase of GABAA Receptor-Mediated Inhibition. The European Journal of Neuroscience, 21, 93-102.
[71] Kaisti, K.K., Metsahonkala, L., Teras, M., Oikonen, V., Aalto, S., Jaaskelainen, S., et al. (2002) Effects of Surgical Levels of Propofol and Sevoflurane Anesthesia on Cerebral Blood Flow in Healthy Subjects Studied with Positron Emission Tomography. Anesthesiology, 96, 1358-1370.
[72] Solt, K. and Forman, S.A. (2007) Correlating the Clinical Actions and Molecular Mechanisms of General Anesthetics. Current Opinion in Anaesthesiology, 20, 300-306.
[73] Nakhnikian, A., Rebec, G.V., Grasse, L.M., Dwiel, L.L., Shimono, M. and Beggs, J.M. (2014) Behavior Modulates Effective Connectivity between Cortex and Striatum. PLoS ONE, 9, e89443.
[74] Sharott, A., Magill, P.J., Bolam, J.P. and Brown, P. (2005) Directional Analysis of Coherent Oscillatory Field Potentials in the Cerebral Cortex and Basal Ganglia of the Rat. The Journal of Physiology, 562, 951-963. http://dx.doi.org/10.1113/jphysiol.2004.073189
[75] Alkire, M.T., Gruver, R., Miller, J., McReynolds, J.R., Hahn, E.L. and Cahill, L. (2008) Neuroimaging Analysis of an Anesthetic Gas That Blocks Human Emotional Memory. Proceedings of the National Academy of Sciences of the United States of America, 105, 1722-1727.


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