Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves

Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.

[1]  N. Logothetis,et al.  Very slow activity fluctuations in monkey visual cortex: implications for functional brain imaging. , 2003, Cerebral cortex.

[2]  Erkki Oja,et al.  Independent component analysis: algorithms and applications , 2000, Neural Networks.

[3]  J. Born,et al.  Grouping of Spindle Activity during Slow Oscillations in Human Non-Rapid Eye Movement Sleep , 2002, The Journal of Neuroscience.

[4]  M. Raichle,et al.  Rat brains also have a default mode network , 2012, Proceedings of the National Academy of Sciences.

[5]  M. Furey,et al.  In vivo evaluation of the effect of stimulus distribution on FIR statistical efficiency in event-related fMRI , 2013, Journal of Neuroscience Methods.

[6]  Zhongming Liu,et al.  Broadband Electrophysiological Dynamics Contribute to Global Resting-State fMRI Signal , 2016, The Journal of Neuroscience.

[7]  R N Henson,et al.  Repetition effects for words and nonwords as indexed by event-related fMRI: a preliminary study. , 2001, Scandinavian journal of psychology.

[8]  M. Verhoye,et al.  Functional Connectivity fMRI of the Rodent Brain: Comparison of Functional Connectivity Networks in Rat and Mouse , 2011, PloS one.

[9]  Randy M. Bruno,et al.  Effects and Mechanisms of Wakefulness on Local Cortical Networks , 2011, Neuron.

[10]  C. Stosiek,et al.  In vivo two-photon calcium imaging of neuronal networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Nathalie L Rochefort,et al.  Reactivation of the same synapses during spontaneous up states and sensory stimuli. , 2013, Cell reports.

[12]  Dara S. Manoach,et al.  Aberrant error processing in relation to symptom severity in obsessive–compulsive disorder: A multimodal neuroimaging study , 2014, NeuroImage: Clinical.

[13]  L. Shah,et al.  Functional magnetic resonance imaging. , 2010, Seminars in roentgenology.

[14]  Andrea Kronfeld,et al.  Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains. , 2015, Medical physics.

[15]  Enzo Tagliazucchi,et al.  Dynamic BOLD functional connectivity in humans and its electrophysiological correlates , 2012, Front. Hum. Neurosci..

[16]  K. Ohki,et al.  Transient neuronal coactivations embedded in globally propagating waves underlie resting-state functional connectivity , 2016, Proceedings of the National Academy of Sciences.

[17]  Christian F. Doeller,et al.  Evidence for grid cells in a human memory network , 2010, Nature.

[18]  M. Schölvinck,et al.  Neural basis of global resting-state fMRI activity , 2010, Proceedings of the National Academy of Sciences.

[19]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[20]  Marcello Massimini,et al.  Shaping the Default Activity Pattern of the Cortical Network , 2017, Neuron.

[21]  Ying-Shing Chan,et al.  Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile , 2016, Proceedings of the National Academy of Sciences.

[22]  G. Glover Deconvolution of Impulse Response in Event-Related BOLD fMRI1 , 1999, NeuroImage.

[23]  T. Sejnowski,et al.  Origin of slow cortical oscillations in deafferented cortical slabs. , 2000, Cerebral cortex.

[24]  M. Mattia,et al.  Slow wave activity as the default mode of the cerebral cortex. , 2014, Archives italiennes de biologie.

[25]  Hellmut Merkle,et al.  Sensory and optogenetically driven single-vessel fMRI , 2016, Nature Methods.

[26]  Hanbing Lu,et al.  Constituents and functional implications of the rat default mode network , 2016, Proceedings of the National Academy of Sciences.

[27]  A M Dale,et al.  Optimal experimental design for event‐related fMRI , 1999, Human brain mapping.

[28]  Takeshi Ogawa,et al.  An in vivo MRI Template Set for Morphometry, Tissue Segmentation, and fMRI Localization in Rats , 2011, Front. Neuroinform..

[29]  M. Raichle,et al.  Human cortical–hippocampal dialogue in wake and slow-wave sleep , 2016, Proceedings of the National Academy of Sciences.

[30]  Dieter Jaeger,et al.  Infraslow LFP correlates to resting-state fMRI BOLD signals , 2013, NeuroImage.

[31]  Maria V. Sanchez-Vives,et al.  Cellular and network mechanisms of rhythmic recurrent activity in neocortex , 2000, Nature Neuroscience.

[32]  Sabine Kastner,et al.  Electrophysiological Low-Frequency Coherence and Cross-Frequency Coupling Contribute to BOLD Connectivity , 2012, Neuron.

[33]  M. Lindquist,et al.  Validity and power in hemodynamic response modeling: A comparison study and a new approach , 2007, Human brain mapping.

[34]  F. Helmchen,et al.  Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo , 2004, Nature Methods.

[35]  Maxim Bazhenov,et al.  Thalamocortical oscillations , 2006, Scholarpedia.

[36]  Zhifeng Liang,et al.  Functional atlas of the awake rat brain: A neuroimaging study of rat brain specialization and integration , 2016, NeuroImage.

[37]  G Buzsáki,et al.  The hippocampo-neocortical dialogue. , 1996, Cerebral cortex.

[38]  J. Born,et al.  Elevated Sleep Spindle Density after Learning or after Retrieval in Rats , 2006, The Journal of Neuroscience.

[39]  O. Garaschuk,et al.  Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo , 2006, Nature Protocols.

[40]  Xiao Liu,et al.  EEG correlates of time-varying BOLD functional connectivity , 2013, NeuroImage.

[41]  S. Neufang,et al.  Task Performance Changes the Amplitude and Timing of the BOLD Signal , 2017, Translational neuroscience.

[42]  J. Csicsvari,et al.  Communication between neocortex and hippocampus during sleep in rodents , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[43]  S. Panzeri,et al.  An inhibitory gate for state transition in cortex , 2017, eLife.

[44]  M. Steriade,et al.  Neuronal Plasticity in Thalamocortical Networks during Sleep and Waking Oscillations , 2003, Neuron.

[45]  Rick van der Zwan,et al.  Medication Adherence in Patients with Rheumatoid Arthritis: The Effect of Patient Education, Health Literacy, and Musculoskeletal Ultrasound , 2015, BioMed research international.

[46]  B. Sakmann,et al.  Phase-locking of hippocampal interneurons' membrane potential to neocortical up-down states , 2006, Nature Neuroscience.

[47]  Igor Timofeev,et al.  Global Intracellular Slow-Wave Dynamics of the Thalamocortical System , 2014, The Journal of Neuroscience.

[48]  I. Fried,et al.  Regional Slow Waves and Spindles in Human Sleep , 2011, Neuron.

[49]  E. Stern,et al.  Pathological Tau Disrupts Ongoing Network Activity , 2015, Neuron.

[50]  Mathias Hoehn,et al.  Reliability and spatial specificity of rat brain sensorimotor functional connectivity networks are superior under sedation compared with general anesthesia , 2013, NMR in biomedicine.

[51]  C. Schroeder,et al.  How Local Is the Local Field Potential? , 2011, Neuron.

[52]  G. Buzsáki,et al.  Sequential structure of neocortical spontaneous activity in vivo , 2007, Proceedings of the National Academy of Sciences.

[53]  Esther Pogatzki-Zahn,et al.  Characterization of incisional and inflammatory pain in rats using functional tools of MRI , 2016, NeuroImage.

[54]  Xi-Nian Zuo,et al.  REST: A Toolkit for Resting-State Functional Magnetic Resonance Imaging Data Processing , 2011, PloS one.

[55]  D. Leopold,et al.  Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: Implications for functional connectivity at rest , 2008, Human brain mapping.

[56]  Stephen V. David,et al.  Cortical Membrane Potential Signature of Optimal States for Sensory Signal Detection , 2015, Neuron.

[57]  A. Konnerth,et al.  Making Waves: Initiation and Propagation of Corticothalamic Ca2+ Waves In Vivo , 2013, Neuron.

[58]  A. Oeltermann,et al.  Hippocampal–cortical interaction during periods of subcortical silence , 2012, Nature.

[59]  Hans Förstl,et al.  Rescue of long-range circuit dysfunction in Alzheimer's disease models , 2015, Nature Neuroscience.

[60]  Maria V. Sanchez-Vives,et al.  Temperature modulation of slow and fast cortical rhythms. , 2010, Journal of neurophysiology.

[61]  M Steriade,et al.  Slow sleep oscillation, rhythmic K‐complexes, and their paroxysmal developments , 1998, Journal of sleep research.

[62]  Maria V. Sanchez-Vives,et al.  Slow and fast rhythms generated in the cerebral cortex of the anesthetized mouse. , 2011, Journal of neurophysiology.

[63]  Waqas Majeed,et al.  Robust Data Driven Model Order Estimation for Independent Component Analysis of fMRI Data with Low Contrast to Noise , 2014, PloS one.

[64]  J. Pekar,et al.  A method for making group inferences from functional MRI data using independent component analysis , 2001, Human brain mapping.

[65]  Sean L. Hill,et al.  The Sleep Slow Oscillation as a Traveling Wave , 2004, The Journal of Neuroscience.

[66]  Cornelius Faber,et al.  Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[67]  David F Abbott,et al.  Absence epilepsy subnetworks revealed by event‐related independent components analysis of functional magnetic resonance imaging , 2013, Epilepsia.

[68]  G. Tononi,et al.  Local sleep in awake rats , 2011, Nature.

[69]  Yul-Wan Sung,et al.  Functional magnetic resonance imaging , 2004, Scholarpedia.

[70]  A. Grinvald,et al.  Spatiotemporal Dynamics of Sensory Responses in Layer 2/3 of Rat Barrel Cortex Measured In Vivo by Voltage-Sensitive Dye Imaging Combined with Whole-Cell Voltage Recordings and Neuron Reconstructions , 2003, The Journal of Neuroscience.

[71]  T. Sejnowski,et al.  Thalamocortical oscillations in the sleeping and aroused brain. , 1993, Science.

[72]  M. Wilson,et al.  Coordinated memory replay in the visual cortex and hippocampus during sleep , 2007, Nature Neuroscience.

[73]  Cornelius Faber,et al.  True and apparent optogenetic BOLD fMRI signals , 2017, Magnetic resonance in medicine.

[74]  Karl J. Friston,et al.  Event‐related f MRI , 1997, Human brain mapping.

[75]  P. Achermann,et al.  Low-frequency (<1Hz) oscillations in the human sleep electroencephalogram , 1997, Neuroscience.

[76]  N. Logothetis,et al.  Scaling Brain Size, Keeping Timing: Evolutionary Preservation of Brain Rhythms , 2013, Neuron.

[77]  H. Laufs,et al.  Decoding Wakefulness Levels from Typical fMRI Resting-State Data Reveals Reliable Drifts between Wakefulness and Sleep , 2014, Neuron.

[78]  F. Helmchen,et al.  Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex , 2012, Nature Methods.

[79]  Francisco J. Vico,et al.  Robust Off- and Online Separation of Intracellularly Recorded Up and Down Cortical States , 2007, PloS one.

[80]  Maxim Volgushev,et al.  Origin of Active States in Local Neocortical Networks during Slow Sleep Oscillation , 2010, Cerebral cortex.

[81]  J. Pillai Functional Connectivity. , 2017, Neuroimaging clinics of North America.

[82]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[83]  Mariel G Kozberg,et al.  Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons , 2016, Proceedings of the National Academy of Sciences.

[84]  J. Matias Palva,et al.  Infra-Slow EEG Fluctuations Are Correlated with Resting-State Network Dynamics in fMRI , 2014, The Journal of Neuroscience.

[85]  David S. Greenberg,et al.  Imaging input and output of neocortical networks in vivo. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[86]  M. T. Hasan,et al.  General Anesthetic Conditions Induce Network Synchrony and Disrupt Sensory Processing in the Cortex , 2016, Front. Cell. Neurosci..

[87]  Tülay Adali,et al.  Estimating the number of independent components for functional magnetic resonance imaging data , 2007, Human brain mapping.

[88]  D. Contreras,et al.  The slow (< 1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[89]  J. Poulet,et al.  Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice , 2008, Nature.

[90]  Christine Grienberger,et al.  Imaging Calcium in Neurons , 2012, Neuron.

[91]  R. Turner,et al.  Event-Related fMRI: Characterizing Differential Responses , 1998, NeuroImage.

[92]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[93]  W. K. Simmons,et al.  Circular analysis in systems neuroscience: the dangers of double dipping , 2009, Nature Neuroscience.

[94]  S. L. Wilcox,et al.  Cortico–Cortical Connections of Primary Sensory Areas and Associated Symptoms in Migraine , 2016, eNeuro.

[95]  Jessica A. Cardin,et al.  Waking State: Rapid Variations Modulate Neural and Behavioral Responses , 2015, Neuron.

[96]  Maxim Volgushev,et al.  Properties of Slow Oscillation during Slow-Wave Sleep and Anesthesia in Cats , 2011, The Journal of Neuroscience.

[97]  M Steriade,et al.  Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: an intracellular study. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[98]  G. Tononi,et al.  *Both authors contributed equally to this manuscript. , 2022 .

[99]  M Steriade,et al.  Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[100]  N. Logothetis,et al.  The Amplitude and Timing of the BOLD Signal Reflects the Relationship between Local Field Potential Power at Different Frequencies , 2012, The Journal of Neuroscience.

[101]  C. Petersen,et al.  Cholinergic signals in mouse barrel cortex during active whisker sensing. , 2014, Cell reports.

[102]  B. Nolan Boosting slow oscillations during sleep potentiates memory , 2008 .

[103]  Karl J. Friston,et al.  Behavioral / Systems / Cognitive Connectivity Changes Underlying Spectral EEG Changes during Propofol-Induced Loss of Consciousness , 2012 .

[104]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[105]  H. S. Meyer,et al.  Cellular organization of cortical barrel columns is whisker-specific , 2013, Proceedings of the National Academy of Sciences.

[106]  Miriam Schwalm,et al.  Cortical Temperature Change: A Tool for Modulating Brain States?12 , 2016, eNeuro.

[107]  I. Timofeev,et al.  Moderate Cortical Cooling Eliminates Thalamocortical Silent States during Slow Oscillation , 2015, The Journal of Neuroscience.

[108]  P. Barthó,et al.  UP-DOWN cortical dynamics reflect state transitions in a bistable network , 2017, eLife.

[109]  Mark Shein-Idelson,et al.  Slow waves, sharp waves, ripples, and REM in sleeping dragons , 2016, Science.

[110]  Guy B. Williams,et al.  Voxel-based morphometry with templates and validation in a mouse model of Huntington’s disease , 2013, Magnetic resonance imaging.

[111]  Stefan Everling,et al.  Broad intrinsic functional connectivity boundaries of the macaque prefrontal cortex , 2014, NeuroImage.

[112]  Stefan R. Pulver,et al.  Ultra-sensitive fluorescent proteins for imaging neuronal activity , 2013, Nature.

[113]  Israel Nelken,et al.  Sound‐evoked network calcium transients in mouse auditory cortex in vivo , 2012, The Journal of physiology.

[114]  A. Destexhe,et al.  Are corticothalamic ‘up’ states fragments of wakefulness? , 2007, Trends in Neurosciences.

[115]  Manuel Schabus,et al.  Spontaneous neural activity during human slow wave sleep , 2008, Proceedings of the National Academy of Sciences.

[116]  Christine Grienberger,et al.  In vivo calcium recordings and channelrhodopsin-2 activation through an optical fiber. , 2014, Cold Spring Harbor protocols.

[117]  Jianhua Ma,et al.  Aberrant Functional Connectivity Architecture in Alzheimer's Disease and Mild Cognitive Impairment: A Whole-Brain, Data-Driven Analysis , 2015, BioMed research international.

[118]  O. Garaschuk Imaging microcircuit function in healthy and diseased brain , 2013, Experimental Neurology.

[119]  M. Steriade,et al.  A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[120]  Celia M. Dong,et al.  Low-frequency hippocampal–cortical activity drives brain-wide resting-state functional MRI connectivity , 2017, Proceedings of the National Academy of Sciences.

[121]  M. Steriade,et al.  Natural waking and sleep states: a view from inside neocortical neurons. , 2001, Journal of neurophysiology.

[122]  Dieter Jaeger,et al.  Quasi-periodic patterns (QPP): Large-scale dynamics in resting state fMRI that correlate with local infraslow electrical activity , 2014, NeuroImage.