Fine-Grained Topography and Modularity of the Macaque Frontal Pole Cortex Revealed by Anatomical Connectivity Profiles

The frontal pole cortex (FPC) plays key roles in various higher-order functions and is highly developed in non-human primates. An essential missing piece of information is the detailed anatomical connections for finer parcellation of the macaque FPC than provided by the previous tracer results. This is important for understanding the functional architecture of the cerebral cortex. Here, combining cross-validation and principal component analysis, we formed a tractography-based parcellation scheme that applied a machine learning algorithm to divide the macaque FPC (2 males and 6 females) into eight subareas using high-resolution diffusion magnetic resonance imaging with the 9.4T Bruker system, and then revealed their subregional connections. Furthermore, we applied improved hierarchical clustering to the obtained parcels to probe the modular structure of the subregions, and found that the dorsolateral FPC, which contains an extension to the medial FPC, was mainly connected to regions of the default-mode network. The ventral FPC was mainly involved in the social-interaction network and the dorsal FPC in the metacognitive network. These results enhance our understanding of the anatomy and circuitry of the macaque brain, and contribute to FPC-related clinical research. Electronic supplementary material The online version of this article (10.1007/s12264-020-00589-1) contains supplementary material, which is available to authorized users.

[1]  J. Price,et al.  Architectonic subdivision of the human orbital and medial prefrontal cortex , 2003, The Journal of comparative neurology.

[2]  J. Rilling,et al.  Comparison of diffusion tractography and tract‐tracing measures of connectivity strength in rhesus macaque connectome , 2015, Human brain mapping.

[3]  Helen Barbas,et al.  Anterior Cingulate Synapses in Prefrontal Areas 10 and 46 Suggest Differential Influence in Cognitive Control , 2010, The Journal of Neuroscience.

[4]  Chunshui Yu,et al.  Connectivity-Based Parcellation of the Human Frontal Pole with Diffusion Tensor Imaging , 2013, The Journal of Neuroscience.

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

[6]  D. Pandya,et al.  Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns , 1999, The European journal of neuroscience.

[7]  Christophe Lenglet,et al.  Advances in computational and statistical diffusion MRI , 2019, NMR in biomedicine.

[8]  Saad Jbabdi,et al.  Connectivity Fingerprints: From Areal Descriptions to Abstract Spaces , 2018, Trends in Cognitive Sciences.

[9]  Timothy Edward John Behrens,et al.  Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Guido Gerig,et al.  User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability , 2006, NeuroImage.

[11]  David R. Haynor,et al.  Anatomically Informed Metrics for Connectivity-Based Cortical Parcellation From Diffusion MRI , 2015, IEEE Journal of Biomedical and Health Informatics.

[12]  A. H. Bell,et al.  Frontopolar cortex is a mediator of network modularity in the primate brain , 2019, bioRxiv.

[13]  Adam W. Anderson,et al.  Validation of DTI Tractography-Based Measures of Primary Motor Area Connectivity in the Squirrel Monkey Brain , 2013, PloS one.

[14]  Simon B Eickhoff,et al.  Imaging-based parcellations of the human brain , 2018, Nature Reviews Neuroscience.

[15]  T. Jiang Recent Progress in Basic and Clinical Research on Disorders of Consciousness , 2018, Neuroscience Bulletin.

[16]  Stephen V. Shepherd,et al.  Functional Networks for Social Communication in the Macaque Monkey , 2018, Neuron.

[17]  Helen Barbas,et al.  Synaptic distinction of laminar-specific prefrontal-temporal pathways in primates. , 2006, Cerebral cortex.

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

[19]  M P Young,et al.  Anatomical connectivity defines the organization of clusters of cortical areas in the macaque monkey and the cat. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[20]  Dante Mantini,et al.  Emerging Roles of the Brain’s Default Network , 2013, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[21]  J. Price,et al.  Prefrontal cortical projections to the hypothalamus in Macaque monkeys , 1998, The Journal of comparative neurology.

[22]  K. Brodmann Vergleichende Lokalisationslehre der Großhirnrinde : in ihren Prinzipien dargestellt auf Grund des Zellenbaues , 1985 .

[23]  Heidi Johansen-Berg,et al.  Using diffusion imaging to study human connectional anatomy. , 2009, Annual review of neuroscience.

[24]  Alan C. Evans,et al.  Revealing modular architecture of human brain structural networks by using cortical thickness from MRI. , 2008, Cerebral cortex.

[25]  Aldo Genovesio,et al.  Evaluating self-generated decisions in frontal pole cortex of monkeys , 2009, Nature Neuroscience.

[26]  A. Walker,et al.  A cytoarchitectural study of the prefrontal area of the macaque monkey , 1940 .

[27]  Ming Song,et al.  Brain Network Studies in Chronic Disorders of Consciousness: Advances and Perspectives , 2018, Neuroscience Bulletin.

[28]  Tianzi Jiang,et al.  Mapping Connectional Differences between Humans and Macaques in the Nucleus Accumbens Shell-Core Architecture , 2020, bioRxiv.

[29]  Brian D. Mills,et al.  Bridging the Gap between the Human and Macaque Connectome: A Quantitative Comparison of Global Interspecies Structure-Function Relationships and Network Topology , 2014, The Journal of Neuroscience.

[30]  Mark W. Woolrich,et al.  Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? , 2007, NeuroImage.

[31]  Keiji Tanaka,et al.  Behavioral consequences of selective damage to frontal pole and posterior cingulate cortices , 2015, Proceedings of the National Academy of Sciences.

[32]  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.

[33]  S. Carmichael,et al.  Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys , 1996 .

[34]  J. Price,et al.  Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey , 1994, The Journal of comparative neurology.

[35]  Tianzi Jiang,et al.  Fine-Grained Parcellation of the Macaque Nucleus Accumbens by High-Resolution Diffusion Tensor Tractography , 2019, Front. Neurosci..

[36]  S. Carmichael,et al.  Networks related to the orbital and medial prefrontal cortex; a substrate for emotional behavior? , 1996, Progress in brain research.

[37]  H. Barbas,et al.  Cortical Connections Position Primate Area 25 as a Keystone for Interoception, Emotion, and Memory , 2018, The Journal of Neuroscience.

[38]  Yundi Shi,et al.  A diffusion tensor MRI atlas of the postmortem rhesus macaque brain , 2015, NeuroImage.

[39]  Bevil R. Conway,et al.  Visual stimulus-driven functional organization of macaque prefrontal cortex , 2019, NeuroImage.

[40]  Tianzi Jiang,et al.  Tractography-based Parcellation of the Human Middle Temporal Gyrus , 2015, Scientific Reports.

[41]  D. Pandya,et al.  Architecture and intrinsic connections of the prefrontal cortex in the rhesus monkey , 1989, The Journal of comparative neurology.

[42]  G. V. Van Hoesen,et al.  Neural connections of the posteromedial cortex in the macaque , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Yasushi Miyashita,et al.  Causal neural network of metamemory for retrospection in primates , 2017, Science.

[44]  White Matter Abnormalities in Major Depression Biotypes Identified by Diffusion Tensor Imaging , 2019, Neuroscience Bulletin.

[45]  J. Sliwa,et al.  A dedicated network for social interaction processing in the primate brain , 2017, Science.

[46]  H. Kaiser The Application of Electronic Computers to Factor Analysis , 1960 .

[47]  David C. Van Essen,et al.  Application of Information Technology: An Integrated Software Suite for Surface-based Analyses of Cerebral Cortex , 2001, J. Am. Medical Informatics Assoc..

[48]  Stefan Everling,et al.  Intrinsic functional architecture of the macaque dorsal and ventral lateral frontal cortex , 2016, bioRxiv.

[49]  G. Orban,et al.  Default Mode of Brain Function in Monkeys , 2011, The Journal of Neuroscience.

[50]  Antoine Grigis,et al.  Pypreclin: An automatic pipeline for macaque functional MRI preprocessing , 2019, NeuroImage.

[51]  W. Freiwald,et al.  Functionally defined white matter of the macaque monkey brain reveals a dorso-ventral attention network , 2019, eLife.

[52]  Changsong Zhou,et al.  Features of spatial and functional segregation and integration of the primate connectome revealed by trade-off between wiring cost and efficiency , 2017, PLoS computational biology.

[53]  Romain Valabregue,et al.  Subdivision of the occipital lobes: An anatomical and functional MRI connectivity study , 2014, Cortex.

[54]  K. Saleem,et al.  Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey , 2008, The Journal of comparative neurology.

[55]  Klaas E. Stephan,et al.  The history of CoCoMac , 2013, NeuroImage.

[56]  S. Wold Cross-Validatory Estimation of the Number of Components in Factor and Principal Components Models , 1978 .

[57]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[58]  Richard F. Betzel,et al.  Linking Structure and Function in Macroscale Brain Networks , 2020, Trends in Cognitive Sciences.

[59]  Hai Li,et al.  MonkeyCBP: A Toolbox for Connectivity-Based Parcellation of Monkey Brain , 2020, Frontiers in Neuroinformatics.

[60]  E. Koechlin,et al.  Managing competing goals — a key role for the frontopolar cortex , 2017, Nature Reviews Neuroscience.

[61]  J. Price,et al.  Midline and intralaminar thalamic connections with the orbital and medial prefrontal networks in macaque monkeys , 2007, The Journal of comparative neurology.

[62]  Guy B. Williams,et al.  Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[63]  Jiaojian Wang,et al.  Parcellation of Macaque Cortex with Anatomical Connectivity Profiles , 2018, Brain Topography.

[64]  D. Pandya,et al.  Efferent Association Pathways from the Rostral Prefrontal Cortex in the Macaque Monkey , 2007, The Journal of Neuroscience.

[65]  Heidi Johansen-Berg,et al.  The role of diffusion MRI in neuroscience , 2017, bioRxiv.

[66]  M. Mesulam,et al.  Cortical afferent input to the principals region of the rhesus monkey , 1985, Neuroscience.

[67]  Nikos K. Logothetis,et al.  Validation of High-Resolution Tractography Against In Vivo Tracing in the Macaque Visual Cortex , 2015, Cerebral cortex.

[68]  O. Sporns,et al.  Mapping the Structural Core of Human Cerebral Cortex , 2008, PLoS biology.

[69]  Y. Miyashita,et al.  Reversible Silencing of the Frontopolar Cortex Selectively Impairs Metacognitive Judgment on Non-experience in Primates , 2018, Neuron.

[70]  Claus C. Hilgetag,et al.  Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala , 2007, NeuroImage.

[71]  Tianzi Jiang,et al.  Connectivity-based parcellation of the human temporal pole using diffusion tensor imaging. , 2014, Cerebral cortex.

[72]  D. Leopold,et al.  Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited , 2014, Proceedings of the National Academy of Sciences.

[73]  Ben Jeurissen,et al.  Diffusion MRI fiber tractography of the brain , 2019, NMR in biomedicine.

[74]  H. Barbas,et al.  Medial Prefrontal Cortices Are Unified by Common Connections With Superior Temporal Cortices and Distinguished by Input From Memory‐Related Areas in the Rhesus Monkey , 1999, The Journal of comparative neurology.

[75]  David C. Van Essen,et al.  Windows on the brain: the emerging role of atlases and databases in neuroscience , 2002, Current Opinion in Neurobiology.

[76]  Angela R. Laird,et al.  Subspecialization in the human posterior medial cortex , 2015, NeuroImage.

[77]  E. Spelke,et al.  This Review Comes from a Themed Issue on Biocatalysis and Biotransformation Edited , 2022 .

[78]  M. Feinberg,et al.  Specificity in inhibitory systems associated with prefrontal pathways to temporal cortex in primates. , 2007, Cerebral cortex.

[79]  H. Barbas,et al.  Topographic Organization of Connections between the Hypothalamus and Prefrontal Cortex in the Rhesus Monkey , 2022 .

[80]  Alan Connelly,et al.  MRtrix: Diffusion tractography in crossing fiber regions , 2012, Int. J. Imaging Syst. Technol..

[81]  Helen D'Arceuil,et al.  Connectivity-based parcellation of the macaque frontal cortex, and its relation with the cytoarchitectonic distribution described in current atlases , 2017, Brain Structure and Function.

[82]  Clara Fischer,et al.  A validation dataset for Macaque brain MRI segmentation , 2018, Data in brief.

[83]  J. Fudge,et al.  Cortico–Amygdala–Striatal Circuits Are Organized as Hierarchical Subsystems through the Primate Amygdala , 2013, The Journal of Neuroscience.

[84]  Timothy E. J. Behrens,et al.  The evolution of the arcuate fasciculus revealed with comparative DTI , 2008, Nature Neuroscience.

[85]  Adam G. Thomas,et al.  Comparison of Human Ventral Frontal Cortex Areas for Cognitive Control and Language with Areas in Monkey Frontal Cortex , 2014, Neuron.

[86]  J. Price,et al.  Prefrontal cortical projections to the striatum in macaque monkeys: Evidence for an organization related to prefrontal networks , 2000, The Journal of comparative neurology.

[87]  E. Koechlin,et al.  Anterior Prefrontal Function and the Limits of Human Decision-Making , 2007, Science.

[88]  Tianzi Jiang,et al.  Connectivity Profiles Reveal a Transition Subarea in the Parahippocampal Region That Integrates the Anterior Temporal–Posterior Medial Systems , 2016, The Journal of Neuroscience.

[89]  Yu Zhang,et al.  The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture , 2016, Cerebral cortex.

[90]  Joseph S. Gati,et al.  Exploring the limits of network topology estimation using diffusion-based tractography and tracer studies in the macaque cortex , 2018, NeuroImage.

[91]  S. Wise,et al.  Frontal pole cortex: encoding ends at the end of the endbrain , 2011, Trends in Cognitive Sciences.

[92]  Timothy E. J. Behrens,et al.  Review Frontal Cortex and Reward-guided Learning and Decision-making Figure 1. Frontal Brain Regions in the Macaque Involved in Reward-guided Learning and Decision-making Finer Grained Anatomical Divisions with Frontal Cortical Systems for Reward-guided Behavior , 2022 .

[93]  J. Fuster The Prefrontal Cortex—An Update Time Is of the Essence , 2001, Neuron.

[94]  Paul H. E. Tiesinga,et al.  The Scalable Brain Atlas: Instant Web-Based Access to Public Brain Atlases and Related Content , 2013, Neuroinformatics.

[95]  J. Price,et al.  Prefrontal cortical projections to longitudinal columns in the midbrain periaqueductal gray in Macaque monkeys , 1998, The Journal of comparative neurology.

[96]  M. Buckley,et al.  Essential functions of primate frontopolar cortex in cognition , 2015, Proceedings of the National Academy of Sciences.

[97]  K. Zilles,et al.  Parcellation of the frontal cortex of the New World monkey Callithrix jacchus by eight neurotransmitter-binding sites , 1995, Anatomy and Embryology.

[98]  P S Goldman-Rakic,et al.  Topographic organization of medial pulvinar connections with the prefrontal cortex in the rhesus monkey , 1997, The Journal of comparative neurology.

[99]  S. Sotiropoulos Processing of diffusion MR images of the brain : from crossing fibres to distributed tractography , 2010 .

[100]  Kadharbatcha S Saleem,et al.  Subdivisions and connectional networks of the lateral prefrontal cortex in the macaque monkey , 2014, The Journal of comparative neurology.

[101]  David N. Messina,et al.  Evolutionary and Biomedical Insights from the Rhesus Macaque Genome , 2007, Science.