Lateral–Medial Dissociation in Orbitofrontal Cortex–Hypothalamus Connectivity

The orbitofrontal cortex (OFC) is involved in cognitive functions, and is also closely related to autonomic functions. The OFC is densely connected with the hypothalamus, a heterogeneous structure controlling autonomic functions that can be divided into two major parts: the lateral and the medial. Resting-state functional connectivity has allowed us to parcellate the cerebral cortex into putative functional areas based on the changes in the spatial pattern of connectivity in the cerebral cortex when a seed point is moved from one voxel to another. In the present high spatial-resolution fMRI study, we investigate the connectivity-based organization of the OFC with reference to the hypothalamus. The OFC was parcellated using resting-state functional connectivity in an individual subject approach, and then the functional connectivity was examined between the parcellated areas in the OFC and the lateral/medial hypothalamus. We found a functional double dissociation in the OFC: the lateral OFC (the lateral orbital gyrus) was more likely connected with the lateral hypothalamus, whereas the medial OFC (the medial orbital and rectal gyri) was more likely connected with the medial hypothalamus. These results demonstrate the fundamental heterogeneity of the OFC, and suggest a potential neural basis of the OFC–hypothalamic functional interaction.

[1]  Daniel S. Margulies,et al.  Mapping the functional connectivity of anterior cingulate cortex , 2007, NeuroImage.

[2]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited—Again , 1995, NeuroImage.

[3]  Robert Turner,et al.  Development and Evaluation of an Algorithm for the Computer-Assisted Segmentation of the Human Hypothalamus on 7-Tesla Magnetic Resonance Images , 2013, PloS one.

[4]  F. Bell.  Hypothalamic control of food intake , 1971, Proceedings of the Nutrition Society.

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

[6]  K H PRIBRAM,et al.  Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report. , 1949, Journal of neurophysiology.

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

[8]  O Sporns,et al.  Predicting human resting-state functional connectivity from structural connectivity , 2009, Proceedings of the National Academy of Sciences.

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

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

[11]  J. Price,et al.  The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. , 2000, Cerebral cortex.

[12]  Shenmin Zhang,et al.  Resting-State Functional Connectivity of the Locus Coeruleus in Humans: In Comparison with the Ventral Tegmental Area/Substantia Nigra Pars Compacta and the Effects of Age. , 2016, Cerebral cortex.

[13]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[14]  Timothy O. Laumann,et al.  Methods to detect, characterize, and remove motion artifact in resting state fMRI , 2014, NeuroImage.

[15]  Robert Turner,et al.  Diffusion imaging-based subdivision of the human hypothalamus: a magnetic resonance study with clinical implications , 2013, European Archives of Psychiatry and Clinical Neuroscience.

[16]  B. Biswal.  Resting-State Functional Connectivity , 2015 .

[17]  Sheng Zhang,et al.  Resting state functional connectivity of the basal nucleus of Meynert in humans: In comparison to the ventral striatum and the effects of age , 2014, NeuroImage.

[18]  Desmond J. Higham,et al.  Connectivity-based parcellation of human cortex using diffusion MRI: Establishing reproducibility, validity and observer independence in BA 44/45 and SMA/pre-SMA , 2007, NeuroImage.

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

[20]  S. Petersen,et al.  Development of distinct control networks through segregation and integration , 2007, Proceedings of the National Academy of Sciences.

[21]  Evan M. Gordon,et al.  Functional System and Areal Organization of a Highly Sampled Individual Human Brain , 2015, Neuron.

[22]  J. O'Doherty,et al.  Reward representations and reward-related learning in the human brain: insights from neuroimaging , 2004, Current Opinion in Neurobiology.

[23]  Marcel van Gerven,et al.  Probabilistic model-based functional parcellation reveals a robust, fine-grained subdivision of the striatum , 2015, NeuroImage.

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

[25]  Stefan Everling,et al.  Functional subdivisions of medial parieto-occipital cortex in humans and nonhuman primates using resting-state fMRI , 2015, NeuroImage.

[26]  Edmund T. Rolls,et al.  Implementation of a new parcellation of the orbitofrontal cortex in the automated anatomical labeling atlas , 2015, NeuroImage.

[27]  Charles M. Butter,et al.  Perseveration in extinction and in discrimination reversal tasks following selective frontal ablations in Macaca mulatta , 1969 .

[28]  E. Rolls,et al.  The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology , 2004, Progress in Neurobiology.

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

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

[31]  G. Egan,et al.  Volumetric Analysis of the Hypothalamus in Huntington Disease Using 3T MRI: The IMAGE-HD Study , 2015, PloS one.

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

[33]  Evan M. Gordon,et al.  Long-term neural and physiological phenotyping of a single human , 2015, Nature Communications.

[34]  J. Delgado,et al.  Increase of food intake induced by electrical stimulation of the lateral hypothalamus. , 1952, The American journal of physiology.

[35]  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 .

[36]  D. Margulies,et al.  Regional Variation in Interhemispheric Coordination of Intrinsic Hemodynamic Fluctuations , 2008, The Journal of Neuroscience.

[37]  Sheng Zhang,et al.  Cerebral correlates of skin conductance responses in a cognitive task , 2012, NeuroImage.

[38]  Sheng Zhang,et al.  Ventromedial prefrontal cortex and the regulation of physiological arousal. , 2014, Social cognitive and affective neuroscience.

[39]  R. Buckner,et al.  Parcellating Cortical Functional Networks in Individuals , 2015, Nature Neuroscience.

[40]  N. Miller.  Motivational effects of brain stimulation and drugs. , 1960, Federation proceedings.

[41]  A. Anwander,et al.  Connectivity-Based Parcellation of Broca's Area. , 2006, Cerebral cortex.

[42]  Shenmin Zhang,et al.  Barratt Impulsivity and Neural Regulation of Physiological Arousal , 2015, PloS one.

[43]  Timothy Edward John Behrens,et al.  Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging , 2003, Nature Neuroscience.

[44]  J. Brobeck,et al.  Hypothalamic Control of Food Intake in Rats and Cats * , 1951, The Yale journal of biology and medicine.

[45]  M. Cole.  The Frontal Granular Cortex and Behavior. , 1964 .

[46]  Michael Petrides,et al.  Three-Dimensional Probabilistic Atlas of the Human Orbitofrontal Sulci in Standardized Stereotaxic Space , 2001, NeuroImage.

[47]  M. Milham.  Open Neuroscience Solutions for the Connectome-wide Association Era , 2012, Neuron.

[48]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[49]  Keiichi Onoda,et al.  Small-worldness and modularity of the resting-state functional brain network decrease with aging , 2013, Neuroscience Letters.

[50]  S. W. Ranson,et al.  Hypothalamic lesions and adiposity in the rat , 1940 .

[51]  Ravi S. Menon,et al.  Resting‐state networks show dynamic functional connectivity in awake humans and anesthetized macaques , 2013, Human brain mapping.

[52]  Anders M. Dale,et al.  Cortical Surface-Based Analysis I. Segmentation and Surface Reconstruction , 1999, NeuroImage.

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

[54]  A. Damasio,et al.  Emotion, decision making and the orbitofrontal cortex. , 2000, Cerebral cortex.

[55]  Hubert Preissl,et al.  Resting‐state functional connectivity of the human hypothalamus , 2014, Human brain mapping.

[56]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited , 1995, NeuroImage.

[57]  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..

[58]  M. Petrides,et al.  Orbitofrontal sulci of the human and macaque monkey brain , 2000, The Journal of comparative neurology.

[59]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[60]  Shenmin Zhang,et al.  Resting-state functional connectivity of the medial superior frontal cortex. , 2012, Cerebral cortex.

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

[62]  Timothy Edward John Behrens,et al.  Diffusion-Weighted Imaging Tractography-Based Parcellation of the Human Parietal Cortex and Comparison with Human and Macaque Resting-State Functional Connectivity , 2011, The Journal of Neuroscience.

[63]  John F. Canny,et al.  A Computational Approach to Edge Detection , 1986, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[64]  M. Chun,et al.  Functional connectome fingerprinting: Identifying individuals based on patterns of brain connectivity , 2015, Nature Neuroscience.

[65]  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.

[66]  O. Sporns,et al.  Functional connectivity between anatomically unconnected areas is shaped by collective network-level effects in the macaque cortex. , 2012, Cerebral cortex.

[67]  Osamu Abe,et al.  Local Signal Time-Series during Rest Used for Areal Boundary Mapping in Individual Human Brains , 2012, PloS one.

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

[69]  Timothy O. Laumann,et al.  Parcellating an Individual Subject's Cortical and Subcortical Brain Structures Using Snowball Sampling of Resting-State Correlations , 2013, Cerebral cortex.

[70]  Simon B. Eickhoff,et al.  A cross-modal, cross-species comparison of connectivity measures in the primate brain , 2016, NeuroImage.

[71]  M. Roesch,et al.  A new perspective on the role of the orbitofrontal cortex in adaptive behaviour , 2009, Nature Reviews Neuroscience.

[72]  Damien A. Fair,et al.  Defining functional areas in individual human brains using resting functional connectivity MRI , 2008, NeuroImage.

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

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

[75]  T. Robbins.  Dissociating executive functions of the prefrontal cortex. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[76]  Yasushi Miyashita,et al.  Functional relevance of micromodules in the human association cortex delineated with high-resolution FMRI. , 2013, Cerebral cortex.

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

[78]  S. W. Ranson,et al.  Hypothalamic lesions and adiposity in the rat , 1940 .

[79]  H. Barbas.  Flow of information for emotions through temporal and orbitofrontal pathways , 2007, Journal of anatomy.

[80]  A. Dale,et al.  Cortical Surface-Based Analysis II: Inflation, Flattening, and a Surface-Based Coordinate System , 1999, NeuroImage.

[81]  Katrin Amunts,et al.  Cortical Folding Patterns and Predicting Cytoarchitecture , 2007, Cerebral cortex.

[82]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[83]  E. Bullmore,et al.  Undirected graphs of frequency-dependent functional connectivity in whole brain networks , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[84]  S. Petersen,et al.  Characterizing the Hemodynamic Response: Effects of Presentation Rate, Sampling Procedure, and the Possibility of Ordering Brain Activity Based on Relative Timing , 2000, NeuroImage.