Organization of the intrinsic functional network in the cervical spinal cord: A resting state functional MRI study

Resting state functional magnetic resonance imaging (rsfMRI) has been extensively applied to investigate the organization of functional networks in the brain. As an essential part of the central nervous system (CNS), the spinal cord has not been well explored about its intrinsic functional network. In this study, we aim to thoroughly investigate the characteristics of the intrinsic functional network in the spinal cord using rsfMRI. Functional connectivity and graph theory analysis were employed to evaluate the organization of the functional network, including its topology and network communication properties. Furthermore, the reproducibility of rsfMRI analysis on the spinal cord was also examined by intra-class correlation (ICC). Comprehensive evaluation of the intrinsic functional organization presented a non-uniform distribution of topological characteristics of the functional network, in which the upper levels (C2 and C3 vertebral levels) of the cervical spinal cord showed high levels of connectivity. The present results revealed the significance of the upper cervical cord in the intrinsic functional network of the human cervical spinal cord. In addition, this study demonstrated the efficiency of the cervical spinal cord functional network and the reproducibility of rsfMRI analysis on the spinal cord was also confirmed. As knowledge expansion of intrinsic functional network from the brain to the spinal cord, this study shed light on the organization of the spinal cord functional network in both normal development and clinical disorders.

[1]  P. Stroman,et al.  Measurement and characterization of the human spinal cord SEEP response using event-related spinal fMRI. , 2012, Magnetic resonance imaging.

[2]  Wei Li,et al.  Intrinsic Resting-State Functional Connectivity in the Human Spinal Cord at 3.0 T. , 2016, Radiology.

[3]  E. Kaptanoğlu,et al.  Current and future medical therapeutic strategies for the functional repair of spinal cord injury. , 2015, World journal of orthopedics.

[4]  Wei Liao,et al.  Mapping the Voxel-Wise Effective Connectome in Resting State fMRI , 2013, PloS one.

[5]  Peter A. Bandettini,et al.  Physiological noise effects on the flip angle selection in BOLD fMRI , 2011, NeuroImage.

[6]  Patrick W. Stroman,et al.  Development and validation of retrospective spinal cord motion time-course estimates (RESPITE) for spin-echo spinal fMRI: Improved sensitivity and specificity by means of a motion-compensating general linear model analysis , 2008, NeuroImage.

[7]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[8]  W. Möller-Hartmann,et al.  Interneuronal systems of the cervical spinal cord assessed with BOLD imaging at 1.5 T , 2005, Neuroradiology.

[9]  Alan C. Evans,et al.  Uncovering Intrinsic Modular Organization of Spontaneous Brain Activity in Humans , 2009, PloS one.

[10]  J. Liu,et al.  Alterations of resting-state regional and network-level neural function after acute spinal cord injury , 2014, Neuroscience.

[11]  Randy L. Gollub,et al.  Test–retest study of fMRI signal change evoked by electroacupuncture stimulation , 2007, NeuroImage.

[12]  X. Zuo,et al.  Test-retest reliabilities of resting-state FMRI measurements in human brain functional connectomics: A systems neuroscience perspective , 2014, Neuroscience & Biobehavioral Reviews.

[13]  Gian Domenico Iannetti,et al.  Functional exploration of the human spinal cord during voluntary movement and somatosensory stimulation. , 2010, Magnetic resonance imaging.

[14]  H. Li,et al.  Drift in centrality of different brain regions in an anatomical neural network with Parkinson’s disease: A view from complex network analysis , 2015, Neuroscience.

[15]  Angelo Gemignani,et al.  Singular Spectrum Analysis and Adaptive Filtering Enhance the Functional connectivity Analysis of resting State fMRI Data , 2014, Int. J. Neural Syst..

[16]  O. Sporns,et al.  Organization, development and function of complex brain networks , 2004, Trends in Cognitive Sciences.

[17]  R L Bosma,et al.  Assessment of data acquisition parameters, and analysis techniques for noise reduction in spinal cord fMRI data. , 2014, Magnetic resonance imaging.

[18]  P W Stroman,et al.  BOLD MRI of the human cervical spinal cord at 3 tesla , 1999, Magnetic resonance in medicine.

[19]  R. Müller,et al.  A critical discussion of intraclass correlation coefficients. , 1994, Statistics in medicine.

[20]  Xiaoming Wang,et al.  Altered Structural and Functional Feature of Striato-Cortical Circuit in Benign Epilepsy with Centrotemporal Spikes , 2015, Int. J. Neural Syst..

[21]  John C Gore,et al.  Assessing functional connectivity in the human brain by fMRI. , 2007, Magnetic resonance imaging.

[22]  Robert L Barry,et al.  Resting state functional connectivity in the human spinal cord , 2014, eLife.

[23]  P. Stroman,et al.  Functional MRI of motor and sensory activation in the human spinal cord. , 2001, Magnetic resonance imaging.

[24]  W. Young,et al.  Intraspinal localization of the somatosensory evoked potential. , 1981, Neurosurgery.

[25]  J. Hamada,et al.  Ependymoma and Choroid Plexus Papilloma as Synchronous Multiple Neuroepithelial Tumors in the Same Patient: A Case Report and Review of Literature , 2011, Neurosurgery.

[26]  Patrick W Stroman,et al.  Magnetic resonance imaging of neuronal function in the spinal cord: spinal FMRI. , 2005, Clinical medicine & research.

[27]  D. Mantini,et al.  Functional connectivity and oscillatory neuronal activity in the resting human brain , 2013, Neuroscience.

[28]  Amanda F. Mejia,et al.  Zen and the Art of Multiple Comparisons , 2015, Psychosomatic medicine.

[29]  W. Backes,et al.  Functional MR imaging of the cervical spinal cord by use of median nerve stimulation and fist clenching. , 2001, AJNR. American journal of neuroradiology.

[30]  Kazuhiko Seki,et al.  Spinal Premotor Interneurons Mediate Dynamic and Static Motor Commands for Precision Grip in Monkeys , 2013, The Journal of Neuroscience.

[31]  W. Möller-Hartmann,et al.  Functional MRI of the Spinal Cord , 2004 .

[32]  Manuel Graña,et al.  Discrimination of Schizophrenia Auditory Hallucinators by Machine Learning of Resting-State Functional MRI , 2015, Int. J. Neural Syst..

[33]  David H. Miller,et al.  Feasibility of grey matter and white matter segmentation of the upper cervical cord in vivo: A pilot study with application to magnetisation transfer measurements , 2012, NeuroImage.

[34]  Patrick W Stroman,et al.  Applying functional MRI to the spinal cord and brainstem. , 2010, Magnetic resonance imaging.

[35]  L. Marstaller,et al.  Aging and large-scale functional networks: White matter integrity, gray matter volume, and functional connectivity in the resting state , 2015, Neuroscience.

[36]  Julien Cohen-Adad,et al.  The current state-of-the-art of spinal cord imaging: Methods , 2014, NeuroImage.

[37]  Christian Büchel,et al.  Intrinsically organized resting state networks in the human spinal cord , 2014, Proceedings of the National Academy of Sciences.

[38]  Andreas Heinz,et al.  Test–retest reliability of resting-state connectivity network characteristics using fMRI and graph theoretical measures , 2012, NeuroImage.

[39]  Leo Grady,et al.  Network, Anatomical, and Non-Imaging Measures for the Prediction of ADHD Diagnosis in Individual Subjects , 2012, Front. Syst. Neurosci..

[40]  Christian Büchel,et al.  Single, slice-specific z-shim gradient pulses improve T2*-weighted imaging of the spinal cord , 2012, NeuroImage.

[41]  Johan Michiels,et al.  Functional MRI of the cervical spinal cord on 1.5 T with fingertapping: to what extent is it feasible? , 2006, Neuroradiology.

[42]  Christine C. Boucard,et al.  Atrophy and structural variability of the upper cervical cord in early multiple sclerosis , 2015, Multiple sclerosis.

[43]  D. Rangaprakash,et al.  Phase Synchronization in Brain Networks derived from Correlation between Probabilities of Recurrences in Functional MRI Data , 2013, Int. J. Neural Syst..

[44]  V. Amassian,et al.  Physiological basis of motor effects of a transient stimulus to cerebral cortex. , 1987, Neurosurgery.

[45]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[46]  Irene Tracey,et al.  Assessment of physiological noise modelling methods for functional imaging of the spinal cord , 2012, NeuroImage.

[47]  Feng Gao,et al.  Resting state networks in human cervical spinal cord observed with fMRI , 2009, European Journal of Applied Physiology.

[48]  Edmund Y. Lam,et al.  Cervical spinal cord BOLD fMRI study: Modulation of functional activation by dexterity of dominant and non-dominant hands , 2008, NeuroImage.

[49]  Frank van der Velde,et al.  The necessity of connection structures in neural models of variable binding , 2015, Cognitive Neurodynamics.

[50]  Han Zhang,et al.  Is resting-state functional connectivity revealed by functional near-infrared spectroscopy test-retest reliable? , 2011, Journal of biomedical optics.

[51]  P. Strick,et al.  Subdivisions of primary motor cortex based on cortico-motoneuronal cells , 2009, Proceedings of the National Academy of Sciences.

[52]  Richard G. Wise,et al.  Physiological noise modelling for spinal functional magnetic resonance imaging studies , 2008, NeuroImage.

[53]  P. Stroman,et al.  Investigation of human cervical and upper thoracic spinal cord motion: Implications for imaging spinal cord structure and function , 2007, Magnetic resonance in medicine.

[54]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[55]  Theo Gasser,et al.  Assessing intrarater, interrater and test–retest reliability of continuous measurements , 2002, Statistics in medicine.

[56]  M. V. D. Heuvel,et al.  Exploring the brain network: A review on resting-state fMRI functional connectivity , 2010, European Neuropsychopharmacology.

[57]  P. W. Stroman,et al.  The current state-of-the-art of spinal cord imaging: Applications , 2014, NeuroImage.

[58]  Keith A. Johnson,et al.  Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease , 2009, The Journal of Neuroscience.

[59]  Giovanni Giulietti,et al.  Issues about the fMRI of the human spinal cord. , 2004, Magnetic resonance imaging.

[60]  V. D. Douglas,et al.  Propriospinal neurons in the C1-C2 spinal segments project to the L5-S1 segments of the rat spinal cord , 1998, Brain Research Bulletin.

[61]  J Nissanov,et al.  Functional MR imaging of the human cervical spinal cord. , 2001, AJNR. American journal of neuroradiology.

[62]  E. Carstens,et al.  Anatomical and physiological properties of ipsilaterally projecting spinothalamic neurons in the second cervical segment of the cat's spinal cord , 1978, The Journal of comparative neurology.

[63]  J. Shimony,et al.  Resting-State fMRI: A Review of Methods and Clinical Applications , 2013, American Journal of Neuroradiology.

[64]  Martin A. Lindquist,et al.  Dynamic connectivity detection: an algorithm for determining functional connectivity change points in fMRI data , 2015, Front. Neurosci..