Functional atlas of the awake rat brain: A neuroimaging study of rat brain specialization and integration

ABSTRACT Connectivity‐based parcellation approaches present an innovative method to segregate the brain into functionally specialized regions. These approaches have significantly advanced our understanding of the human brain organization. However, parallel progress in animal research is sparse. Using resting‐state fMRI data and a novel, data‐driven parcellation method, we have obtained robust functional parcellations of the rat brain. These functional parcellations reveal the regional specialization of the rat brain, which exhibited high within‐parcel homogeneity and high reproducibility across animals. Graph analysis of the whole‐brain network constructed based on these functional parcels indicates that the rat brain has a topological organization similar to humans, characterized by both segregation and integration. Our study also provides compelling evidence that the cingulate cortex is a functional hub region conserved from rodents to humans. Together, this study has characterized the rat brain specialization and integration, and has significantly advanced our understanding of the rat brain organization. In addition, it is valuable for studies of comparative functional neuroanatomy in mammalian brains.

[1]  Paul M. Thompson,et al.  Heritability of the network architecture of intrinsic brain functional connectivity , 2015, NeuroImage.

[2]  Yang Fan,et al.  Functional Connectivity-Based Parcellation of the Thalamus: An Unsupervised Clustering Method and Its Validity Investigation , 2015, Brain Connect..

[3]  Sheng Zhang,et al.  Functional connectivity mapping of the human precuneus by resting state fMRI , 2012, NeuroImage.

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

[5]  Lianne H. Scholtens,et al.  Topological organization of connectivity strength in the rat connectome , 2015, Brain Structure and Function.

[6]  Alessandro Vespignani,et al.  Detecting rich-club ordering in complex networks , 2006, physics/0602134.

[7]  G. Varoquaux,et al.  Connectivity‐based parcellation: Critique and implications , 2015, Human brain mapping.

[8]  Zhifeng Liang,et al.  Neuroplasticity to a single-episode traumatic stress revealed by resting-state fMRI in awake rats , 2014, NeuroImage.

[9]  M E J Newman,et al.  Fast algorithm for detecting community structure in networks. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[10]  Vince D. Calhoun,et al.  Lateralization of resting state networks and relationship to age and gender , 2015, NeuroImage.

[11]  G. Edelman,et al.  Complexity and coherency: integrating information in the brain , 1998, Trends in Cognitive Sciences.

[12]  Larry W. Swanson,et al.  Brain Maps: Structure of the Rat Brain , 1992 .

[13]  Xiao Liu,et al.  Dynamic resting state functional connectivity in awake and anesthetized rodents , 2015, NeuroImage.

[14]  M. Fox,et al.  Intrinsic functional relations between human cerebral cortex and thalamus. , 2008, Journal of neurophysiology.

[15]  J. Kwon,et al.  Unravelling the Intrinsic Functional Organization of the Human Striatum: A Parcellation and Connectivity Study Based on Resting-State fMRI , 2014, PloS one.

[16]  Zhifeng Liang,et al.  Anticorrelated resting-state functional connectivity in awake rat brain , 2012, NeuroImage.

[17]  Alfred Anwander,et al.  A hierarchical method for whole‐brain connectivity‐based parcellation , 2014, Human brain mapping.

[18]  Alessandro Gozzi,et al.  Large-scale functional connectivity networks in the rodent brain , 2016, NeuroImage.

[19]  Christopher L. Asplund,et al.  The organization of the human cerebellum estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

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

[21]  E. Fombonne,et al.  Structural and functional connectivity of the human brain in autism spectrum disorders and attention‐deficit/hyperactivity disorder: A rich club‐organization study , 2014, Human brain mapping.

[22]  Zhang Nanyin Uncovering intrinsic connectional architecture of functional networks in awake rat brain , 2011 .

[23]  Mark W. Woolrich,et al.  Network modelling methods for FMRI , 2011, NeuroImage.

[24]  Jonas Richiardi,et al.  Graph analysis of functional brain networks: practical issues in translational neuroscience , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[25]  Dustin Scheinost,et al.  Sex differences in normal age trajectories of functional brain networks , 2015, Human brain mapping.

[26]  Zhihao Li,et al.  Dynamic thalamus parcellation from resting‐state fMRI data , 2016, Human brain mapping.

[27]  A. Cavanna,et al.  Functional Connectivity of the Posteromedial Cortex , 2010, PloS one.

[28]  Lei Wang,et al.  Intrinsic connectivity of neural networks in the awake rabbit , 2016, NeuroImage.

[29]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[30]  K. Zilles,et al.  An investigation of the structural, connectional, and functional subspecialization in the human amygdala , 2012, Human brain mapping.

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

[32]  Zhifeng Liang,et al.  Mapping resting-state brain networks in conscious animals , 2010, Journal of Neuroscience Methods.

[33]  Arno Villringer,et al.  Functional connectivity‐based parcellation of the human sensorimotor cortex , 2014, The European journal of neuroscience.

[34]  Thomas Neuberger,et al.  Mapping the functional network of medial prefrontal cortex by combining optogenetics and fMRI in awake rats , 2015, NeuroImage.

[35]  M. Diamond,et al.  Morphological changes in the young, adult and aging rate cerebral cortex, hippocampus, and diencephalon. , 1975, Behavioral biology.

[36]  E. Tolosa,et al.  Functional brain networks and cognitive deficits in Parkinson's disease , 2014, Human brain mapping.

[37]  Rex E. Jung,et al.  A Baseline for the Multivariate Comparison of Resting-State Networks , 2011, Front. Syst. Neurosci..

[38]  Olaf Sporns,et al.  THE HUMAN CONNECTOME: A COMPLEX NETWORK , 2011, Schizophrenia Research.

[39]  Jonathan D. Power,et al.  A Parcellation Scheme for Human Left Lateral Parietal Cortex , 2010, Neuron.

[40]  Tao Li,et al.  Mapping thalamocortical networks in rat brain using resting-state functional connectivity , 2013, NeuroImage.

[41]  Nanyin Zhang,et al.  Intrinsic Organization of the Anesthetized Brain , 2012, The Journal of Neuroscience.

[42]  Samuel D. Carpenter,et al.  Structural and Functional Rich Club Organization of the Brain in Children and Adults , 2014, PloS one.

[43]  R. Buckner,et al.  The organization of the human striatum estimated by intrinsic functional connectivity. , 2012, Journal of neurophysiology.

[44]  Henry Kennedy,et al.  Cortical High-Density Counterstream Architectures , 2013, Science.

[45]  Timothy O. Laumann,et al.  Generation and Evaluation of a Cortical Area Parcellation from Resting-State Correlations. , 2016, Cerebral cortex.

[46]  L. M. Yager,et al.  The ins and outs of the striatum: Role in drug addiction , 2015, Neuroscience.

[47]  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.

[48]  O. Sporns,et al.  Rich-Club Organization of the Human Connectome , 2011, The Journal of Neuroscience.

[49]  Angelo Bifone,et al.  A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: Application to pharmacological MRI , 2006, NeuroImage.

[50]  Olaf Sporns,et al.  Small worlds inside big brains , 2006, Proceedings of the National Academy of Sciences.

[51]  Angela R. Laird,et al.  Tackling the multifunctional nature of Broca's region meta-analytically: Co-activation-based parcellation of area 44 , 2013, NeuroImage.

[52]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[53]  R Cameron Craddock,et al.  A whole brain fMRI atlas generated via spatially constrained spectral clustering , 2012, Human brain mapping.

[54]  L. Becerra,et al.  Robust Reproducible Resting State Networks in the Awake Rodent Brain , 2011, PloS one.

[55]  Timothy O. Laumann,et al.  An approach for parcellating human cortical areas using resting-state correlations , 2014, NeuroImage.

[56]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[57]  Nikola T. Markov,et al.  A Weighted and Directed Interareal Connectivity Matrix for Macaque Cerebral Cortex , 2012, Cerebral cortex.

[58]  Sang Won Seo,et al.  Defining functional SMA and pre-SMA subregions in human MFC using resting state fMRI: Functional connectivity-based parcellation method , 2010, NeuroImage.

[59]  Xenophon Papademetris,et al.  Groupwise whole-brain parcellation from resting-state fMRI data for network node identification , 2013, NeuroImage.

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

[61]  G. Paxinos The Rat nervous system , 1985 .

[62]  Peter Stiers,et al.  Unravelling the Intrinsic Functional Organization of the Human Lateral Frontal Cortex: A Parcellation Scheme Based on Resting State fMRI , 2012, The Journal of Neuroscience.

[63]  Liang Wang,et al.  Parcellation‐dependent small‐world brain functional networks: A resting‐state fMRI study , 2009, Human brain mapping.

[64]  M. Petrides,et al.  Broca’s region: linking human brain functional connectivity data and non‐human primate tracing anatomy studies , 2010, The European journal of neuroscience.

[65]  Stephen M. Smith,et al.  Spatially constrained hierarchical parcellation of the brain with resting-state fMRI , 2013, NeuroImage.

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

[67]  Lauren L. Cloutman,et al.  Connectivity-based structural and functional parcellation of the human cortex using diffusion imaging and tractography , 2012, Front. Neuroanat..

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

[69]  R. Kahn,et al.  Aberrant Frontal and Temporal Complex Network Structure in Schizophrenia: A Graph Theoretical Analysis , 2010, The Journal of Neuroscience.

[70]  Gemma Navarro,et al.  Adenosine–cannabinoid receptor interactions. Implications for striatal function , 2010, British journal of pharmacology.

[71]  Luke J. Chang,et al.  Connectivity-Based Parcellation of the Human Orbitofrontal Cortex , 2012, The Journal of Neuroscience.

[72]  Sara B. Taylor,et al.  The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans , 2013, Substance abuse and rehabilitation.

[73]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[74]  Christian Windischberger,et al.  Toward discovery science of human brain function , 2010, Proceedings of the National Academy of Sciences.

[75]  Alessandro Gozzi,et al.  Functional connectivity hubs of the mouse brain , 2015, NeuroImage.