Abstract
The spontaneous cerebral hemodynamic fluctuations observed during the resting state have been frequently visualized using functional magnetic resonance imaging (rsfMRI). However, the neuronal populations and neuroelectric characteristics underlying the functional connectivity of cerebrohemodynamic activities are poorly understood. We investigated the characteristics of bi-hemispheric functional connectivity via electrophysiology and rsfMRI in the primary sensory cortex of rats anesthetized by α-chloralose. Unlike the evoked responses, the spontaneous electrophysiological activity was concentrated in the infragranular layers and could be classified into subtypes with distinctive current sources and sinks. Both neuroelectric and rsfMRI signals were interhemispherically correlated in a layer-specific manner, suggesting that there are independent neural inputs to infragranular and granular/supragranular layers. The majority of spontaneous electrophysiological activities were bilaterally paired with delays of up to ~50 ms between each pair. The variable interhemispheric delay implies the involvement of indirect, multi-neural pathways. Our findings demonstrated the diverse activity patterns of layer-specific electrophysiological substrates and suggest the recruitment of multiple, non-specific brain regions in construction of interhemispheric functional connectivity.
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References
Bannister AP (2005) Inter-and intra-laminar connections of pyramidal cells in the neocortex. Neurosci Res 53(2):95–103
Biswal B, Yetkin F, Haughton V, Hyde J (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34(4):537–541
Buxton RB, Uludağ K, Dubowitz DJ, Liu TT (2004) Modeling the hemodynamic response to brain activation. Neuroimage 23:S220–S233
Chapman C, Trepel C, Ivanco T, Froc D, Wilson K, Racine R (1998) Changes in field potentials and membrane currents in rat sensorimotor cortex following repeated tetanization of the corpus callosum in vivo. Cereb Cortex 8(8):730
Crochet S, Petersen CCH (2009) Cortical dynamics by layers. Neuron 64(3):298–300
Csercsa R, Dombovari B, Fabo D, Wittner L, Erss L, Entz L, Solyom A, Rasonyi G, Szcs A, Kelemen A (2010) Laminar analysis of slow wave activity in humans. Brain 133(9):2814
Douglas RJ, Martin KAC (2004) Neuronal circuits of the neocortex. Annu Rev Neurosci 27:419–451
Einevoll G, Pettersen K, Devor A, Ulbert I, Halgren E, Dale A (2007) Laminar population analysis: estimating firing rates and evoked synaptic activity from multielectrode recordings in rat barrel cortex. J Neurophysiol 97(3):2174
Fox M, Raichle M (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8(9):700–711
Fox M, Snyder A, Zacks J, Raichle M (2005) Coherent spontaneous activity accounts for trial-to-trial variability in human evoked brain responses. Nat Neurosci 9(1):23–25
Friston K (1994) Functional and effective connectivity in neuroimaging: a synthesis. Hum Brain Mapp 2(1–2):56–78
Goense J, Merkle H, Logothetis NK (2012) High-resolution fMRI reveals laminar differences in neurovascular coupling between positive and negative BOLD responses. Neuron 76(3):629–639
Harel N, Lin J, Moeller S, Ugurbil K, Yacoub E (2006) Combined imaging-histological study of cortical laminar specificity of fMRI signals. Neuroimage 29(3):879–887
Haslinger R, Ulbert I, Moore CI, Brown EN, Devor A (2006) Analysis of LFP phase predicts sensory response of barrel cortex. J Neurophysiol 96(3):1658
Hayama T, Ogawa H (1997) Regional differences of callosal connections in the granular zones of the primary somatosensory cortex in rats. Brain Res Bull 43(3):341–347
Hyvarinen A, Oja E (1997) A fast fixed-point algorithm for independent component analysis. Neural Comput 9(7):1483–1492
Isseroff A, Schwartz M, Dekker J, Goldman-Rakic P (1984) Columnar organization of callosal and associational projections from rat frontal cortex. Brain Res 293(2):213–223
Johnston J, Vaishnavi S, Smyth M, Zhang D, He B, Zempel J, Shimony J, Snyder A, Raichle M (2008) Loss of resting interhemispheric functional connectivity after complete section of the corpus callosum. J Neurosci 28(25):6453
Kim YR, Biswal BB, Rosen BR (2008) Comparison of spontaneous electrophysiological and fMRI fluctuations during rest in rat brain cortex. In: 16th Annual Meeting of International Society of Magnetic Resonance in Medicine, Toronto, Canada, 2008. Toronto, Canada
Kiviniemi V, Kantola J-H, Jauhiainen J, Hyvärinen A, Tervonen O (2003) Independent component analysis of nondeterministic fMRI signal sources. Neuroimage 19(2):253–260
Lefort S, Tomm C, Floyd Sarria J, Petersen CCH (2009) The excitatory neuronal network of the C2 barrel column in mouse primary somatosensory cortex. Neuron 61(2):301
Leopold DA, Maier A (2012) Ongoing physiological processes in the cerebral cortex. Neuroimage 62(4):2190–2200
Leopold DA, Murayama Y, Logothetis NK (2003) Very slow activity fluctuations in monkey visual cortex: implications for functional brain imaging. Cereb Cortex 13(4):422–433
Liu X, Zhu X-H, Zhang Y, Chen W (2011) Neural origin of spontaneous hemodynamic fluctuations in rats under Burst-Suppression anesthesia condition. Cereb Cortex 21(2):374–384
Lowe M, Mock B, Sorenson J (1998) Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations. Neuroimage 7(2):119–132
Lu H, Zuo Y, Gu H, Waltz JA, Zhan W, Scholl CA, Rea W, Yang Y, Stein EA (2007) Synchronized delta oscillations correlate with the resting-state functional MRI signal. Proc Natl Acad Sci 104(46):18265
Lubke J, Feldmeyer D (2007) Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex. Brain Struct Funct 212(1):3–17
Lumer ED, Edelman GM, Tononi G (1997) Neural dynamics in a model of the thalamocortical system. II. The role of neural synchrony tested through perturbations of spike timing. Cereb Cortex 7(3):228–236
Magnuson ME, Thompson GJ, Pan W-J, Keilholz SD (2014) Effects of severing the corpus callosum on electrical and BOLD functional connectivity and spontaneous dynamic activity in the rat brain. Brain Connectivity 4(1):15–29
Magri C, Schridde U, Murayama Y, Panzeri S, Logothetis NK (2012) The amplitude and timing of the BOLD signal reflects the relationship between local field potential power at different frequencies. J Neurosci 32(4):1395–1407
Maier A, Adams GK, Aura C, Leopold DA (2010) Distinct superficial and deep laminar domains of activity in the visual cortex during rest and stimulation. Front Syst Neurosci 4:31
Majeed W, Magnuson M, Keilholz SD (2009) Spatiotemporal dynamics of low frequency fluctuations in BOLD fMRI of the rat. J Magn Reson Imaging 30(2):384–393
Mandeville JB, Jenkins BG, Kosofsky BE, Moskowitz MA, Rosen BR, Marota JJA (2001) Regional sensitivity and coupling of BOLD and CBV changes during stimulation of rat brain. Magn Reson Med 45(3):443–447
Mohajerani M, McVea D, Fingas M, Murphy T (2010) Mirrored bilateral slow-wave cortical activity within local circuits revealed by fast bihemispheric voltage-sensitive dye imaging in anesthetized and awake mice. J Neurosci 30(10):3745
Nir Y, Fisch L, Mukamel R, Gelbard-Sagiv H, Arieli A, Fried I, Malach R (2007) Coupling between neuronal firing rate, gamma LFP, and BOLD fMRI is related to interneuronal correlations. Curr Biol 17(15):1275–1285
Nir Y, Mukamel R, Dinstein I, Privman E, Harel M, Fisch L, Gelbard-Sagiv H, Kipervasser S, Andelman F, Neufeld MY (2008) Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex. Nat Neurosci 11(9):1100–1108
Pan W-J, Thompson G, Magnuson M, Majeed W, Jaeger D, Keilholz S (2010) Simultaneous FMRI and electrophysiology in the rodent brain. J Vis Exp 42:1901
Pan W-J, Thompson G, Magnuson M, Majeed W, Jaeger D, Keilholz S (2011) Broadband local field potentials correlate with spontaneous fluctuations in functional magnetic resonance imaging signals in the rat somatosensory cortex under isoflurane anesthesia. Brain Connectivity 1(2):119–131
Pan W-J, Thompson GJ, Magnuson ME, Jaeger D, Keilholz S (2013) Infraslow LFP correlates to resting-state fMRI BOLD signals. Neuroimage 74:288–297
Peeters R, Tindemans I, De Schutter E, Van der Linden A (2001) Comparing BOLD fMRI signal changes in the awake and anesthetized rat during electrical forepaw stimulation. Magn Reson Imaging 19(6):821–826
Quigley M, Cordes D, Turski P, Moritz C, Haughton V, Seth R, Meyerand M (2003) Role of the corpus callosum in functional connectivity. Am J Neuroradiol 24(2):208
Raichle M, Mintun M (2006) Brain work and brain imaging. Annu Rev Neurosci 29:449–476
Scholvinck ML, Maier A, Ye FQ, Duyn JH, Leopold DA (2010) Neural basis of global resting-state fMRI activity. Proc Natl Acad Sci 107(22):10238
Seggie J, Berry M (1972) Ontogeny of interhemispheric evoked potentials in the rat: significance of myelination of the corpus callosum. Exp Neurol 35(2):215–232
Shmuel A, Leopold DA (2008) Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: implications for functional connectivity at rest. Hum Brain Mapp 29(7):751–761
Shmueli K, van Gelderen P, de Zwart JA, Horovitz SG, Fukunaga M, Jansma JM, Duyn JH (2007) Low frequency fluctuations in the cardiac rate as a source of variance in the resting-state fMRI BOLD signal. Neuroimage 38(2):306
Shulman R, Rothman D, Behar K, Hyder F (2004) Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci 27(8):489–495
Silva AC, Koretsky AP (2002) Laminar specificity of functional MRI onset times during somatosensory stimulation in rat. Proc Natl Acad Sci 99(23):15182
Silva AC, Koretsky AP, Duyn JH (2007) Functional MRI impulse response for BOLD and CBV contrast in rat somatosensory cortex. Magn Reson Med 57(23):1110–1118
Thompson GJ, Merritt MD, Pan W-J, Magnuson ME, Grooms JK, Jaeger D, Keilholz SD (2013) Neural correlates of time-varying functional connectivity in the rat. Neuroimage 83:826–836
Tian P, Teng IC, May LD, Kurz R, Lu K, Scadeng M, Hillman E, De Crespigny AJ, D’Arceuil HE, Mandeville JB (2010) Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal. Proc Natl Acad Sci 107(34):15246
Uddin LQ, Mooshagian E, Zaidel E, Scheres A, Margulies DS, Kelly AC, Shehzad Z, Adelstein JS, Castellanos FX, Biswal BB (2008) Residual functional connectivity in the split-brain revealed with resting-state fMRI. Neuroreport 19(7):703
Vizuete J, Pillay S, Ropella K, Hudetz A (2014) Graded defragmentation of cortical neuronal firing during recovery of consciousness in rats. Neuroscience 275:340–351
Williams KA, Magnuson M, Majeed W, LaConte SM, Peltier SJ, Hu X, Keilholz SD (2010) Comparison of α-chloralose, medetomidine and isoflurane anesthesia for functional connectivity mapping in the rat. Magn Reson Imaging 28(7):995–1003
Wise SP (1975) The laminar organization of certain afferent and efferent fiber systems in the rat somatosensory cortex. Brain Res 90(1):139
Acknowledgments
The authors thank Drs. Jitendra Sharma and Robert Haslinger for their valuable comments on this manuscript. This work was supported by grants from the National Institutes of Health (Grant Number 5R01EB002066, R01 EB001954) and a Korea Science and Engineering Foundation (KOSEF) grant that was funded by the Korean government (Grant number NRF-2006-2005399, M10644000028-06N4400-02810).
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K. Baek and W. H. Shim contributed equally to this study.
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Baek, K., Shim, W.H., Jeong, J. et al. Layer-specific interhemispheric functional connectivity in the somatosensory cortex of rats: resting state electrophysiology and fMRI studies. Brain Struct Funct 221, 2801–2815 (2016). https://doi.org/10.1007/s00429-015-1073-0
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DOI: https://doi.org/10.1007/s00429-015-1073-0