Background Recent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating connectivity is an intrinsic phenomenon of brain dynamics that persists during anesthesia. Lately, point process analysis applied on functional data has revealed that much of the information regarding brain connectivity is contained in a fraction of critical time points of a resting state dataset. In the present study we want to extend this methodology for the investigation of resting state fMRI spatial pattern changes during propofol-induced modulation of consciousness, with the aim of extracting new insights on brain networks consciousness-dependent fluctuations. Methods Resting-state fMRI volumes on 18 healthy subjects were acquired in four clinical states during propofol injection: wakefulness, sedation, unconsciousness, and recovery. The dataset was reduced to a spatio-temporal point process by selecting time points in the Posterior Cingulate Cortex (PCC) at which the signal is higher than a given threshold (i.e., BOLD intensity above 1 standard deviation). Spatial clustering on the PCC time frames extracted was then performed (number of clusters = 8), to obtain 8 different PCC co-activation patterns (CAPs) for each level of consciousness. Results The current analysis shows that the core of the PCC-CAPs throughout consciousness modulation seems to be preserved. Nonetheless, this methodology enables to differentiate region-specific propofol-induced reductions in PCC-CAPs, some of them already present in the functional connectivity literature (e.g., disconnections of the prefrontal cortex, thalamus, auditory cortex), some others new (e.g., reduced co-activation in motor cortex and visual area). Conclusion In conclusion, our results indicate that the employed methodology can help in improving and refining the characterization of local functional changes in the brain associated to propofol-induced modulation of consciousness.
References
[1]
Greicius MD, Krasnow B, Reiss AL, Menon V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences 100: 253–258. doi: 10.1073/pnas.0135058100
[2]
Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, et al. (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the United States of America 102: 9673–9678. doi: 10.1073/pnas.0504136102
[3]
Fox MD, Raichle ME (2007) Spontaneous uctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews Neuroscience 8: 700–711. doi: 10.1038/nrn2201
[4]
Fox MD, Greicius M (2010) Clinical applications of resting state functional connectivity. Frontiers in systems neuroscience 4: 19–24. doi: 10.3389/fnsys.2010.00019
[5]
Boly M, Tshibanda L, Vanhaudenhuyse A, Noirhomme Q, Schnakers C, et al. (2009) Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient. Human brain mapping 30: 2393–2400. doi: 10.1002/hbm.20672
[6]
Vanhaudenhuyse A, Noirhomme Q, Tshibanda LJF, Bruno MA, Boveroux P, et al. (2010) Default network connectivity reects the level of consciousness in non-communicative brain-damaged patients. Brain 133: 161–171. doi: 10.1093/brain/awp313
[7]
Boveroux P, Vanhaudenhuyse A, Bruno MA, Noirhomme Q, Lauwick S, et al. (2010) Breakdown of within-and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness. Anesthesiology 113: 1038–1053. doi: 10.1097/aln.0b013e3181f697f5
[8]
Schrouff J, Perlbarg V, Boly M, Marrelec G, Boveroux P, et al. (2011) Brain functional integration decreases during propofol-induced loss of consciousness. Neuroimage 57: 198–205. doi: 10.1016/j.neuroimage.2011.04.020
[9]
Martuzzi R, Ramani R, Qiu M, Rajeevan N, Constable RT (2010) Functional connectivity and alterations in baseline brain state in humans. NeuroImage 49: 823–834. doi: 10.1016/j.neuroimage.2009.07.028
[10]
Deshpande G, Kerssens C, Sebel PS, Hu X (2010) Altered local coherence in the default mode network due to sevourane anesthesia. Brain research 1318: 110–121. doi: 10.1016/j.brainres.2009.12.075
[11]
Hutchison RM, Womelsdorf T, Allen EA, Bandettini PA, Calhoun VD, et al. (2013) Dynamic functional connectivity: Promises, issues, and interpretations. NeuroImage 80: 360–368. doi: 10.1016/j.neuroimage.2013.05.079
[12]
Allen EA, Damaraju E, Plis SM, Erhardt EB, Eichele T, et al. (2012) Tracking whole-brain connectivity dynamics in the resting state. Cerebral Cortex bhs352. doi: 10.1093/cercor/bhs352
[13]
Chang C, Glover GH (2010) Time–frequency dynamics of resting-state brain connectivity measured with fmri. Neuroimage 50: 81–98. doi: 10.1016/j.neuroimage.2009.12.011
[14]
Hutchison RM, Womelsdorf T, Gati JS, Everling S, Menon RS (2012) Resting-state networks show dynamic functional connectivity in awake humans and anesthetized macaques. Human brain mapping 34: 2154–2177. doi: 10.1002/hbm.22058
[15]
Tagliazucchi E, Balenzuela P, Fraiman D, Chialvo DR (2012) Criticality in large-scale brain fmridynamics unveiled by a novel point process analysis. Frontiers in Physiology 3: 15–25. doi: 10.3389/fphys.2012.00015
[16]
Liu X, Duyn JH (2013) Time-varying functional network information extracted from brief instances of spontaneous brain activity. Proceedings of the National Academy of Sciences 110: 4392–4397. doi: 10.1073/pnas.1216856110
[17]
MacLaren R, Plamondon JM, Ramsay KB, Rocker GM, Patrick WD, et al. (2000) A prospective evaluation of empiric versus protocol-based sedation and analgesia. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 20: 662–672. doi: 10.1592/phco.20.7.662.35172
[18]
Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE (2012) Spurious but systematic correlations in functional connectivity mri networks arise from subject motion. Neuroimage 59: 2142–2154. doi: 10.1016/j.neuroimage.2011.10.018
[19]
Fransson P, Marrelec G (2008) The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis. Neuroimage 42: 1178–1184. doi: 10.1016/j.neuroimage.2008.05.059
[20]
Leech R, Kamourieh S, Beckmann CF, Sharp DJ (2011) Fractionating the default mode network: distinct contributions of the ventral and dorsal posterior cingulate cortex to cognitive control. The Journal of Neuroscience 31: 3217–3224. doi: 10.1523/jneurosci.5626-10.2011
[21]
Hastie T, Tibshirani R, Friedman J, Hastie T, Friedman J, et al.. (2009) The elements of statistical learning, volume 2. Springer.
[22]
Genovese CR, Lazar NA, Nichols T (2002) Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15: 870–878. doi: 10.1006/nimg.2001.1037
[23]
Alkire MT, Hudetz AG, Tononi G (2008) Consciousness and anesthesia. Science 322: 876–880. doi: 10.1126/science.1149213
[24]
Fiset P, Paus T, Daloze T, Plourde G, Meuret P, et al. (1999) Brain mechanisms of propofolinduced loss of consciousness in humans: a positron emission tomographic study. The Journal of neuroscience 19: 5506–5513.
[25]
Boveroux P, Bonhomme V, Boly M, Vanhaudenhuyse A, Maquet P, et al. (2008) Brain function in physiologically, pharmacologically, and pathologically altered states of consciousness. International anesthesiology clinics 46: 131–146. doi: 10.1097/aia.0b013e318181a8b3
Wu GR, Liao W, Stramaglia S, Ding JR, Chen H, et al. (2013) A blind deconvolution approach to recover effective connectivity brain networks from resting state fmri data. Medical image analysis 17: 365–374. doi: 10.1016/j.media.2013.01.003
[28]
Peigneux P, Orban P, Balteau E, Degueldre C, Luxen A, et al. (2006) Offline persistence of memoryrelated cerebral activity during active wakefulness. PLoS biology 4: e100. doi: 10.1371/journal.pbio.0040100
[29]
Lee U, Mashour GA, Kim S, Noh GJ, Choi BM (2009) Propofol induction reduces the capacity for neural information integration: implications for the mechanism of consciousness and general anesthesia. Consciousness and cognition 18: 56–64. doi: 10.1016/j.concog.2008.10.005
[30]
John ER, Prichep LS (2005) The anesthetic cascade: a theory of how anesthesia suppresses consciousness. Anesthesiology 102: 447–471. doi: 10.1097/00000542-200502000-00030
[31]
Ying SW, Goldstein PA (2005) Propofol-block of sk channels in reticular thalamic neurons enhances gabaergic inhibition in relay neurons. Journal of neurophysiology 93: 1935–1948. doi: 10.1152/jn.01058.2004
[32]
Guldenmund P, Demertzi A, Boveroux P, Boly M, Vanhaudenhuyse A, et al. (2013) Thalamus, brainstem and salience network connectivity changes during propofol-induced sedation and unconsciousness. Brain connectivity 3: 273–285. doi: 10.1089/brain.2012.0117
[33]
Vijayan S, Ching S, Purdon PL, Brown EN, Kopell NJ (2013) Thalamocortical mechanisms for the anteriorization of alpha rhythms during propofol-induced unconsciousness. The Journal of Neuroscience 33: 11070–11075. doi: 10.1523/jneurosci.5670-12.2013
[34]
Lamme VA, Zipser K, Spekreijse H (1998) Figure-ground activity in primary visual cortex is suppressed by anesthesia. Proceedings of the National Academy of Sciences 95: 3263–3268. doi: 10.1073/pnas.95.6.3263
[35]
Tenenbein PK, Lam AM, Klein M, Lee L (2006) Effects of sevourane and propofol on ash visual evoked potentials. Journal of Neurosurgical Anesthesiology 18: 310. doi: 10.1097/00008506-200610000-00088
[36]
Ziemann U, L？nnecker S, Steinhoff B, Paulus W (1996) Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study. Annals of neurology 40: 367–378. doi: 10.1002/ana.410400306
[37]
Kalkman CJ, Drummond JC, Ribberink AA, Patel PM, Sano T, et al. (1992) Effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial electrical or magnetic stimulation in humans. Anesthesiology 76: 502–509. doi: 10.1097/00000542-199204000-00003
[38]
Gaese BH, Ostwald J (2001) Anesthesia changes frequency tuning of neurons in the rat primary auditory cortex. Journal of neurophysiology 86: 1062–1066.
[39]
Plourde G, Belin P, Chartrand D, Fiset P, Backman SB, et al. (2006) Cortical processing of complex auditory stimuli during alterations of consciousness with the general anesthetic propofol. Anesthesiology 104: 448–457. doi: 10.1097/00000542-200603000-00011
[40]
Dueck M, Petzke F, Gerbershagen H, Paul M, Hesselmann V, et al. (2005) Propofol attenuates responses of the auditory cortex to acoustic stimulation in a dose-dependent manner: A fmri study. Acta anaesthesiologica scandinavica 49: 784–791. doi: 10.1111/j.1399-6576.2005.00703.x
[41]
Untergehrer G, Jordan D, Kochs EF, Ilg R, Schneider G (2014) Fronto-parietal connectivity is a non-static phenomenon with characteristic changes during unconsciousness. PloS one 9: e87498. doi: 10.1371/journal.pone.0087498
