Functional segregation of the human cingulate cortex is confirmed by functional connectivity based neuroanatomical parcellation

The four-region model with 7 specified subregions represents a theoretical construct of functionally segregated divisions of the cingulate cortex based on integrated neurobiological assessments. Under this framework, we aimed to investigate the functional specialization of the human cingulate cortex by analyzing the resting-state functional connectivity (FC) of each subregion from a network perspective. In 20 healthy subjects we systematically investigated the FC patterns of the bilateral subgenual (sACC) and pregenual (pACC) anterior cingulate cortices, anterior (aMCC) and posterior (pMCC) midcingulate cortices, dorsal (dPCC) and ventral (vPCC) posterior cingulate cortices and retrosplenial cortices (RSC). We found that each cingulate subregion was specifically integrated in the predescribed functional networks and showed anti-correlated resting-state fluctuations. The sACC and pACC were involved in an affective network and anti-correlated with the sensorimotor and cognitive networks, while the pACC also correlated with the default-mode network and anti-correlated with the visual network. In the midcingulate cortex, however, the aMCC was correlated with the cognitive and sensorimotor networks and anti-correlated with the visual, affective and default-mode networks, whereas the pMCC only correlated with the sensorimotor network and anti-correlated with the cognitive and visual networks. The dPCC and vPCC involved in the default-mode network and anti-correlated with the sensorimotor, cognitive and visual networks, in contrast, the RSC was mainly correlated with the PCC and thalamus. Based on a strong hypothesis driven approach of anatomical partitions of the cingulate cortex, we could confirm their segregation in terms of functional neuroanatomy, as suggested earlier by task studies or exploratory multi-seed investigations.

[1]  E. Kandel,et al.  Resolving Emotional Conflict: A Role for the Rostral Anterior Cingulate Cortex in Modulating Activity in the Amygdala , 2006, Neuron.

[2]  Irene Tracey,et al.  Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal , 2004, NeuroImage.

[3]  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.

[4]  P. Strick,et al.  Imaging the premotor areas , 2001, Current Opinion in Neurobiology.

[5]  G. Northoff,et al.  Is Our Self Nothing but Reward? Neuronal Overlap and Distinction between Reward and Personal Relevance and Its Relation to Human Personality , 2009, PloS one.

[6]  M Forsting,et al.  Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study , 2009, Gut.

[7]  K. Zilles,et al.  Mind Reading: Neural Mechanisms of Theory of Mind and Self-Perspective , 2001, NeuroImage.

[8]  Ethan Kross,et al.  Coping with Emotions Past: The Neural Bases of Regulating Affect Associated with Negative Autobiographical Memories , 2009, Biological Psychiatry.

[9]  Roland Peyron,et al.  Motor cortex stimulation in neuropathic pain. Correlations between analgesic effect and hemodynamic changes in the brain. A PET study , 2007, NeuroImage.

[10]  C. Asanuma,et al.  Neurobiology of Cingulate Cortex and Limbic Thalamus edited by B. A. Vogt and M. Gabriel, Birkha¨user, 1993. $199.00 (639 pages) ISBN 0 8176 3568 8 , 1994, Trends in Neurosciences.

[11]  D. Hassabis,et al.  From Threat to Fear: The Neural Organization of Defensive Fear Systems in Humans , 2009, The Journal of Neuroscience.

[12]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  P. Fox,et al.  Differential limbic–cortical correlates of sadness and anxiety in healthy subjects: implications for affective disorders , 2000, Biological Psychiatry.

[14]  E. Rolls,et al.  From affective value to decision‐making in the prefrontal cortex , 2008, The European journal of neuroscience.

[15]  Derek G. V. Mitchell,et al.  Common regions of dorsal anterior cingulate and prefrontal–parietal cortices provide attentional control of distracters varying in emotionality and visibility , 2007, NeuroImage.

[16]  Michael W. Cole,et al.  Conflict over Cingulate Cortex: Between-Species Differences in Cingulate May Support Enhanced Cognitive Flexibility in Humans , 2010, Brain, Behavior and Evolution.

[17]  F. Bermpohl,et al.  Cortical midline structures and the self , 2004, Trends in Cognitive Sciences.

[18]  Bruce R. Rosen,et al.  Motion detection and correction in functional MR imaging , 1995 .

[19]  Lutz Jäncke,et al.  Structural neuroplasticity in the sensorimotor network of professional female ballet dancers , 2009, Human brain mapping.

[20]  Edmund T. Rolls,et al.  Warm pleasant feelings in the brain , 2008, NeuroImage.

[21]  RP Dum,et al.  The origin of corticospinal projections from the premotor areas in the frontal lobe , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  Steven Laureys,et al.  Cytology and functionally correlated circuits of human posterior cingulate areas , 2006, NeuroImage.

[23]  Rupert Lanzenberger,et al.  Correlations and anticorrelations in resting-state functional connectivity MRI: A quantitative comparison of preprocessing strategies , 2009, NeuroImage.

[24]  B. Vogt,et al.  Human cingulate cortex: Surface features, flat maps, and cytoarchitecture , 1995, The Journal of comparative neurology.

[25]  Brent A. Vogt,et al.  Cytology of human dorsal midcingulate and supplementary motor cortices , 2003, Journal of Chemical Neuroanatomy.

[26]  M. Raichle,et al.  Subgenual prefrontal cortex abnormalities in mood disorders , 1997, Nature.

[27]  A. Schleicher,et al.  Receptor architecture of human cingulate cortex: Evaluation of the four‐region neurobiological model , 2009, Human brain mapping.

[28]  Peter Boesiger,et al.  The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. , 2009, Archives of general psychiatry.

[29]  B. Vogt,et al.  Cytology of human caudomedial cingulate, retrosplenial, and caudal parahippocampal cortices , 2001, The Journal of comparative neurology.

[30]  Edward Awh,et al.  The anterior cingulate cortex lends a hand in response selection , 1999, Nature Neuroscience.

[31]  Karl Zilles,et al.  Cytology and receptor architecture of human anterior cingulate cortex , 2008, The Journal of comparative neurology.

[32]  Chunshui Yu,et al.  Increased neural resources recruitment in the intrinsic organization in major depression. , 2010, Journal of affective disorders.

[33]  M. P. van den Heuvel,et al.  Exploring the brain network: a review on resting-state fMRI functional connectivity. , 2010, European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology.

[34]  D. Amaral,et al.  Macaque monkey retrosplenial cortex: II. Cortical afferents , 2003, The Journal of comparative neurology.

[35]  Mark V. Albert,et al.  Anticipation of conflict monitoring in the anterior cingulate cortex and the prefrontal cortex , 2007, Proceedings of the National Academy of Sciences.

[36]  Yuan Zhou,et al.  The relationship within and between the extrinsic and intrinsic systems indicated by resting state correlational patterns of sensory cortices , 2007, NeuroImage.

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

[38]  E. Maguire.  The retrosplenial contribution to human navigation: a review of lesion and neuroimaging findings. , 2001, Scandinavian journal of psychology.

[39]  M. Lowe,et al.  Functional Connectivity in Single and Multislice Echoplanar Imaging Using Resting-State Fluctuations , 1998, NeuroImage.

[40]  B. Vogt.  Pain and emotion interactions in subregions of the cingulate gyrus , 2005, Nature Reviews Neuroscience.

[41]  T. Paus.  Primate anterior cingulate cortex: Where motor control, drive and cognition interface , 2001, Nature Reviews Neuroscience.

[42]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[43]  B. Biswal,et al.  Functional connectivity of default mode network components: Correlation, anticorrelation, and causality , 2009, Human brain mapping.

[44]  P. Strick,et al.  Motor areas of the medial wall: a review of their location and functional activation. , 1996, Cerebral cortex.

[45]  Gilles Pourtois,et al.  Errors recruit both cognitive and emotional monitoring systems: Simultaneous intracranial recordings in the dorsal anterior cingulate gyrus and amygdala combined with fMRI , 2010, Neuropsychologia.

[46]  Chunshui Yu,et al.  Altered resting-state functional connectivity and anatomical connectivity of hippocampus in schizophrenia , 2008, Schizophrenia Research.

[47]  W. Gehring,et al.  Functions of the Medial Frontal Cortex in the Processing of Conflict and Errors , 2001, The Journal of Neuroscience.

[48]  B. Mensour,et al.  Neural correlates of sad feelings in healthy girls , 2003, Neuroscience.

[49]  C D Frith,et al.  Neural mechanisms involved in the processing of global and local aspects of hierarchically organized visual stimuli. , 1997, Brain : a journal of neurology.

[50]  Armin Blickenstorfer,et al.  Differential representation of dynamic and static power grip force in the sensorimotor network , 2010, The European journal of neuroscience.

[51]  Karl J. Friston,et al.  Detecting Activations in PET and fMRI: Levels of Inference and Power , 1996, NeuroImage.

[52]  Michael W. Cole,et al.  Cingulate cortex: Diverging data from humans and monkeys , 2009, Trends in Neurosciences.

[53]  Hans-Jochen Heinze,et al.  Distinguishing specific sexual and general emotional effects in fMRI—Subcortical and cortical arousal during erotic picture viewing , 2008, NeuroImage.

[54]  Katherine E. Prater,et al.  Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. , 2010, The American journal of psychiatry.

[55]  Naomi Hasegawa,et al.  Thalamocortical and intracortical connections of monkey cingulate motor areas , 2003, The Journal of comparative neurology.

[56]  Anthony K. P. Jones,et al.  Pain processing during three levels of noxious stimulation produces differential patterns of central activity , 1997, Pain.

[57]  Michelle Hampson,et al.  Functional connectivity between task-positive and task-negative brain areas and its relation to working memory performance. , 2010, Magnetic resonance imaging.

[58]  Kevin Murphy,et al.  The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? , 2009, NeuroImage.

[59]  P. Fransson.  Spontaneous low‐frequency BOLD signal fluctuations: An fMRI investigation of the resting‐state default mode of brain function hypothesis , 2005, Human brain mapping.

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

[61]  Vinod Menon,et al.  Where and When the Anterior Cingulate Cortex Modulates Attentional Response: Combined fMRI and ERP Evidence , 2006, Journal of Cognitive Neuroscience.

[62]  P. Strick,et al.  The Spinothalamic System Targets Motor and Sensory Areas in the Cerebral Cortex of Monkeys , 2009, The Journal of Neuroscience.

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

[64]  D. Amaral,et al.  Macaque monkey retrosplenial cortex: III. Cortical efferents , 2003, The Journal of comparative neurology.

[65]  B. Mensour,et al.  Separate neural circuits for primary emotions? Brain activity during self-induced sadness and happiness in professional actors , 2003, Neuroreport.

[66]  Peter Falkai,et al.  Dynamic interactions between neural systems underlying different components of verbal working memory , 2007, Journal of Neural Transmission.

[67]  Thomas E. Nichols,et al.  Placebo Effects Mediated by Endogenous Opioid Activity on μ-Opioid Receptors , 2005, The Journal of Neuroscience.

[68]  M. Phillips,et al.  A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder , 2008, Molecular Psychiatry.

[69]  Cameron S. Carter,et al.  Conflict-related activity in the caudal anterior cingulate cortex in the absence of awareness , 2009, Biological Psychology.

[70]  Christophe Habas,et al.  Functional connectivity of the human rostral and caudal cingulate motor areas in the brain resting state at 3T , 2009, Neuroradiology.

[71]  M. Gabriel,et al.  Neurobiology of Cingulate Cortex and Limbic Thalamus , 1993 .

[72]  P. Goldman-Rakic,et al.  Prefrontal connections of medial motor areas in the rhesus monkey , 1993, The Journal of comparative neurology.

[73]  Patrick Dupont,et al.  Abnormal Regional Brain Activity During Rest and (Anticipated) Gastric Distension in Functional Dyspepsia and the Role of Anxiety: A H215O-PET Study , 2010, The American Journal of Gastroenterology.

[74]  E. Rolls,et al.  How the brain represents the reward value of fat in the mouth. , 2010, Cerebral cortex.

[75]  Thomas Weiss,et al.  Dynamic activation of the anterior cingulate cortex during anticipatory anxiety , 2009, NeuroImage.

[76]  Marcus E Raichle,et al.  Volumetric reduction in left subgenual prefrontal cortex in early onset depression , 2002, Biological Psychiatry.

[77]  G. Glover,et al.  Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus , 2007, Biological Psychiatry.

[78]  S. Matsuura,et al.  Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study. , 2002, The Journal of urology.

[79]  M. Bushnell,et al.  Differentiation of visceral and cutaneous pain in the human brain. , 2003, Journal of neurophysiology.

[80]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[81]  N. Ramnani,et al.  Distinct portions of anterior cingulate cortex and medial prefrontal cortex are activated by reward processing in separable phases of decision-making cognition , 2004, Biological Psychiatry.

[82]  B. Horwitz,et al.  Brain activity during transient sadness and happiness in healthy women. , 1995, The American journal of psychiatry.

[83]  E. Maguire,et al.  What does the retrosplenial cortex do? , 2009, Nature Reviews Neuroscience.

[84]  Edward Awh,et al.  The anterior cingulate cortex lends a hand in response , 1999 .

[85]  Peter A. Bandettini,et al.  Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI , 2006, NeuroImage.

[86]  K. Davis,et al.  Two systems of resting state connectivity between the insula and cingulate cortex , 2009, Human brain mapping.

[87]  H. Critchley.  Neural mechanisms of autonomic, affective, and cognitive integration , 2005, The Journal of comparative neurology.

[88]  D. Pandya,et al.  Cingulate cortex of the rhesus monkey: II. Cortical afferents , 1987, The Journal of comparative neurology.

[89]  J. Downar,et al.  A cortical network sensitive to stimulus salience in a neutral behavioral context across multiple sensory modalities. , 2002, Journal of neurophysiology.

[90]  C. N. Macrae,et al.  Finding the Self? An Event-Related fMRI Study , 2002, Journal of Cognitive Neuroscience.

[91]  M. Rushworth,et al.  Behavioral / Systems / Cognitive Connectivity-Based Parcellation of Human Cingulate Cortex and Its Relation to Functional Specialization , 2008 .