High Field fMRI Reveals Thalamocortical Integration of Segregated Cognitive and Emotional Processing in Mediodorsal and Intralaminar Thalamic Nuclei

Thalamocortical loops, connecting functionally segregated, higher order cortical regions, and basal ganglia, have been proposed not only for well described motor and sensory regions, but also for limbic and prefrontal areas relevant for affective and cognitive processes. These functions are, however, more specific to humans, rendering most invasive neuroanatomical approaches impossible and interspecies translations difficult. In contrast, non-invasive imaging of functional neuroanatomy using fMRI allows for the development of elaborate task paradigms capable of testing the specific functionalities proposed for these circuits. Until recently, spatial resolution largely limited the anatomical definition of functional clusters at the level of distinct thalamic nuclei. Since their anatomical distinction seems crucial not only for the segregation of cognitive and limbic loops but also for the detection of their functional interaction during cognitive–emotional integration, we applied high resolution fMRI on 7 Tesla. Using an event-related design, we could isolate thalamic effects for preceding attention as well as experience of erotic stimuli. We could demonstrate specific thalamic effects of general emotional arousal in mediodorsal nucleus and effects specific to preceding attention and expectancy in intralaminar centromedian/parafascicular complex. These thalamic effects were paralleled by specific coactivations in the head of caudate nucleus as well as segregated portions of rostral or caudal cingulate cortex and anterior insula supporting distinct thalamo–striato–cortical loops. In addition to predescribed effects of sexual arousal in hypothalamus and ventral striatum, high resolution fMRI could extent this network to paraventricular thalamus encompassing laterodorsal and parataenial nuclei. We could lend evidence to segregated subcortical loops which integrate cognitive and emotional aspects of basic human behavior such as sexual processing.

[1]  Nikolaus R. McFarland,et al.  Thalamic Relay Nuclei of the Basal Ganglia Form Both Reciprocal and Nonreciprocal Cortical Connections, Linking Multiple Frontal Cortical Areas , 2002, The Journal of Neuroscience.

[2]  P. Read Montague,et al.  Human Neuroscience , 2022 .

[3]  O. Hikosaka,et al.  Representation of negative motivational value in the primate lateral habenula , 2009, Nature Neuroscience.

[4]  Oliver Speck,et al.  High resolution fMRI of subcortical regions during visual erotic stimulation at 7 T , 2008, Magnetic Resonance Materials in Physics, Biology and Medicine.

[5]  M. Lowe,et al.  Activity and Connectivity of Brain Mood Regulating Circuit in Depression: A Functional Magnetic Resonance Study , 2005, Biological Psychiatry.

[6]  B. Chozick.  The behavioral effects of lesions of the corpus striatum: a review. , 1983, The International journal of neuroscience.

[7]  J. Yelnik,et al.  Topographic distribution of the neurons of the central complex (centre médian-parafascicular complex) and of other thalamic neurons projecting to the striatum in macaques , 1991, Neuroscience.

[8]  P. Fox,et al.  Mapping context and content: the BrainMap model , 2002, Nature Reviews Neuroscience.

[9]  Sven Joubert,et al.  Areas of brain activation in males and females during viewing of erotic film excerpts , 2002, Human brain mapping.

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

[11]  H. Groenewegen,et al.  Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat , 1991, Neuroscience.

[12]  Peter Kirsch,et al.  Remission of Major Depression Under Deep Brain Stimulation of the Lateral Habenula in a Therapy-Refractory Patient , 2010, Biological Psychiatry.

[13]  J. Desmond,et al.  Brain activation and sexual arousal in healthy, heterosexual males. , 2002, Brain : a journal of neurology.

[14]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[15]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[16]  Hans-Jochen Heinze,et al.  Self-related processing in the sexual domain: A parametric event-related fMRI study reveals neural activity in ventral cortical midline structures , 2006, Social neuroscience.

[17]  S. Hamann,et al.  Men and women differ in amygdala response to visual sexual stimuli , 2004, Nature Neuroscience.

[18]  L. Coolen,et al.  Distribution of Fos immunoreactivity following mating versus anogenital investigation in the male rat brain , 1997, Neuroscience.

[19]  N. Costes,et al.  Brain processing of visual sexual stimuli in human males , 2000, Human brain mapping.

[20]  A. Parent,et al.  Topography of the projection from the central complex of the thalamus to the sensorimotor striatal territory in monkeys , 1991, The Journal of comparative neurology.

[21]  Robert P. Vertes,et al.  Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat , 2006, Neuroscience.

[22]  G. J. Royce.  Autoradiographic evidence for a discontinuous projection to the caudate nucleus from the centromedian nucleus in the cat , 1978, Brain Research.

[23]  W. Cowan,et al.  The connexions of the midline and intralaminar nuclei of the thalamus of the rat. , 1954, Journal of anatomy.

[24]  O. Hikosaka,et al.  Lateral habenula as a source of negative reward signals in dopamine neurons , 2007, Nature.

[25]  J. Rosenblatt,et al.  First and second order maternal behavior related afferents of the lateral habenula. , 1999, Neuroreport.

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

[27]  Helen E. Fisher,et al.  Reward, motivation, and emotion systems associated with early-stage intense romantic love. , 2005, Journal of neurophysiology.

[28]  Denis Dooley,et al.  Atlas of the Human Brain. , 1971 .

[29]  P. Yahr,et al.  Anatomical and functional connections among cell groups in the gerbil brain that are activated with ejaculation , 2001, The Journal of comparative neurology.

[30]  I. Divac,et al.  Dissociative effects of selective lesions in the caudate nucleus of cats and rats. , 1975, Acta neurobiologiae experimentalis.

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

[32]  R. Brickenkamp,et al.  D2 Test of Attention , 1998 .

[33]  M. Zaitsev,et al.  High resolution single-shot EPI at 7T , 2008, Magnetic Resonance Materials in Physics, Biology and Medicine.

[34]  G. J. Royce,et al.  Efferent connections of the centromedian and parafascicular thalamic nuclei: An autoradiographic investigation in the cat , 1985, The Journal of comparative neurology.

[35]  S. Haber,et al.  The cortico-basal ganglia integrative network: The role of the thalamus , 2009, Brain Research Bulletin.

[36]  A. Rangel,et al.  Dissociating valuation and saliency signals during decision-making. , 2011, Cerebral cortex.

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

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

[39]  C. Woolsey,et al.  Organization of the mammalian thalamus and its relationships to the cerebral cortex. , 1949, Electroencephalography and clinical neurophysiology.

[40]  V. Visser-Vandewalle,et al.  Thalamus and penile erection , 2004, International Journal of Impotence Research.

[41]  M. Molinari,et al.  The thalamo-caudate versus thalamo-cortical projections as studied in the cat with fluorescent retrograde double labeling , 2004, Experimental Brain Research.

[42]  H Nishijo,et al.  Emotional and Behavioral Correlates of Mediodorsal Thalamic Neurons during Associative Learning in Rats , 1996, The Journal of Neuroscience.

[43]  Okihide Hikosaka,et al.  Habenula: Crossroad between the Basal Ganglia and the Limbic System , 2008, The Journal of Neuroscience.

[44]  C. Koch,et al.  What is the function of the claustrum? , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[45]  A. B. Wells,et al.  Afferent connections of the parvocellular subparafascicular thalamic nucleus in the rat: Evidence for functional subdivisions , 2003, The Journal of comparative neurology.

[46]  David A Lewis,et al.  Cortical connections of the lateral mediodorsal thalamus in cynomolgus monkeys , 2004, The Journal of comparative neurology.

[47]  Chris Rorden,et al.  Improving Lesion-Symptom Mapping , 2007, Journal of Cognitive Neuroscience.

[48]  Timothy Edward John Behrens,et al.  Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus. , 2005, Cerebral cortex.

[49]  B. Gulyás,et al.  Activation by Attention of the Human Reticular Formation and Thalamic Intralaminar Nuclei , 1996, Science.

[50]  M Zaitsev,et al.  Point spread function mapping with parallel imaging techniques and high acceleration factors: Fast, robust, and flexible method for echo‐planar imaging distortion correction , 2004, Magnetic resonance in medicine.

[51]  M. Witter,et al.  The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness , 2002, Brain Research Reviews.

[52]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

[53]  J. Price,et al.  The cortical projections of the mediodorsal nucleus and adjacent thalamic nuclei in the rat , 1977, The Journal of comparative neurology.

[54]  D. Melchitzky,et al.  Subcortical afferents to the lateral mediodorsal thalamus in cynomolgus monkeys , 2004, Neuroscience.

[55]  Harold Mouras,et al.  Neuroanatomical correlates of penile erection evoked by photographic stimuli in human males , 2006, NeuroImage.

[56]  R. Reep,et al.  Afferent connections of dorsal and ventral agranular insular cortex in the hamsterMesocricetus auratus , 1982, Neuroscience.

[57]  Remco Renken,et al.  Men versus women on sexual brain function: Prominent differences during tactile genital stimulation, but not during orgasm , 2009, Human brain mapping.

[58]  Nikolaus R. McFarland,et al.  The Place of the Thalamus in Frontal Cortical-Basal Ganglia Circuits , 2001, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[59]  S. Petersen,et al.  A dual-networks architecture of top-down control , 2008, Trends in Cognitive Sciences.

[60]  B. Vogt,et al.  Contributions of anterior cingulate cortex to behaviour. , 1995, Brain : a journal of neurology.

[61]  S. Thompson,et al.  Organisation of subcortical pathways for sensory projections to the limbic cortex. II. Afferent projections to the thalamic lateral dorsal nucleus in the rat , 1987, The Journal of comparative neurology.

[62]  Shiro Nakagawa,et al.  Topographical projections from the thalamus, subthalamic nucleus and pedunculopontine tegmental nucleus to the striatum in the Japanese monkey, Macaca fuscata , 1990, Brain Research.

[63]  Harold Mouras,et al.  Brain processing of visual sexual stimuli in healthy men: a functional magnetic resonance imaging study , 2003, NeuroImage.

[64]  O. Phillipson,et al.  Afferent projections to the parafascicular thalamic nucleus of the rat, as shown by the retrograde transport of wheat germ agglutinin , 1988, Brain Research Bulletin.

[65]  M M Mesulam,et al.  Thalamic connections of the insula in the rhesus monkey and comments on the paralimbic connectivity of the medial pulvinar nucleus , 1984, The Journal of comparative neurology.

[66]  J. Price.  Prefrontal Cortical Networks Related to Visceral Function and Mood , 1999, Annals of the New York Academy of Sciences.

[67]  A J Barkovich,et al.  Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T. , 1989, Radiology.

[68]  W. Klemm.  Habenular and interpeduncularis nuclei: shared components in multiple-function networks. , 2004, Medical science monitor : international medical journal of experimental and clinical research.

[69]  A. Graybiel,et al.  Neurons in the thalamic CM-Pf complex supply striatal neurons with information about behaviorally significant sensory events. , 2001, Journal of neurophysiology.

[70]  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.

[71]  G. E. Alexander,et al.  Effects of cooling prefrontal cortex on cell firing in the nucleus medialis dorsalis. , 1973, Brain research.

[72]  B. Knowlton,et al.  Learning and memory functions of the Basal Ganglia. , 2002, Annual review of neuroscience.

[73]  Rainer Goebel,et al.  Analysis of functional image analysis contest (FIAC) data with brainvoyager QX: From single‐subject to cortically aligned group general linear model analysis and self‐organizing group independent component analysis , 2006, Human brain mapping.

[74]  C. Saper,et al.  Organization of visceral and limbic connections in the insular cortex of the rat , 1991, The Journal of comparative neurology.

[75]  L. Coolen,et al.  Neural activation following sexual behavior in the male and female rat brain , 1998, Behavioural Brain Research.

[76]  Ruud Boessen,et al.  Dynamic subcortical blood flow during male sexual activity with ecological validity: A perfusion fMRI study , 2010, NeuroImage.

[77]  S. Thompson,et al.  Organisation of subcortical pathways for sensory projections to the limbic cortex. I. Subcortical projections to the medial limbic cortex in the rat , 1987, The Journal of comparative neurology.

[78]  G. J. Royce.  Cortical neurons with collateral projections to both the caudate nucleus and the centromedian-parafascicular thalamic complex: A fluorescent retrograde double labeling study in the cat , 2004, Experimental Brain Research.

[79]  A. Parent,et al.  Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: A PHA‐L study of subcortical projections , 1992, The Journal of comparative neurology.

[80]  B. Hallgren,et al.  THE EFFECT OF AGE ON THE NON‐HAEMIN IRON IN THE HUMAN BRAIN , 1958, Journal of neurochemistry.

[81]  O. Hikosaka.  The habenula: from stress evasion to value-based decision-making , 2010, Nature Reviews Neuroscience.

[82]  M. J. Showers.  Correlation of medial thalamic nuclear activity with cortical and subcortical neuronal arcs , 1958, The Journal of comparative neurology.

[83]  M. T. Shipley,et al.  Parvocellular subparafascicular thalamic nucleus in the rat: Anatomical and functional compartmentalization , 2003, The Journal of comparative neurology.

[84]  J M Wyss,et al.  Projections from the laterodorsal nucleus of the thalamus to the limbic and visual cortices in the rat , 1992, The Journal of comparative neurology.

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

[86]  M. Fox,et al.  Noninvasive functional and structural connectivity mapping of the human thalamocortical system. , 2010, Cerebral cortex.

[87]  A. Ryszka,et al.  Afferent connections of the laterodorsal thalamic nucleus in the rat , 1979, Neuroscience Letters.

[88]  H. Groenewegen,et al.  Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum , 1990, The Journal of comparative neurology.

[89]  M. Raichle,et al.  A functional anatomical study of unipolar depression , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[90]  J. Price,et al.  The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys , 1993, The Journal of comparative neurology.

[91]  O. Phillipson,et al.  Afferent projections to the dorsal thalamus of the rat as shown by retrograde lectin transport—I. The mediodorsal nucleus , 1988, Neuroscience.

[92]  Alexander Sartorius,et al.  Deep brain stimulation of the lateral habenula in treatment resistant major depression. , 2007, Medical hypotheses.

[93]  Martin Walter,et al.  Pedophilia is Linked to Reduced Activation in Hypothalamus and Lateral Prefrontal Cortex During Visual Erotic Stimulation , 2007, Biological Psychiatry.

[94]  Karl J. Friston.  Functional and effective connectivity in neuroimaging: A synthesis , 1994 .

[95]  L. G. Isaacson,et al.  Cholinergic and non-cholinergic projections from the canine pontomesencephalic tegmentum (Ch5 area) to the caudal intralaminar thalamic nuclei , 2004, Experimental Brain Research.

[96]  H. Shibata.  Organization of retrosplenial cortical projections to the laterodorsal thalamic nucleus in the rat , 2000, Neuroscience Research.

[97]  D L Rosene,et al.  Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents , 1987, The Journal of comparative neurology.

[98]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[99]  P. Yahr,et al.  C-Fos immunoreactivity in the sexually dimorphic area of the hypothalamus and related brain regions of male gerbils after exposure to sex-related stimuli or performance of specific sexual behaviors , 1996, Neuroscience.

[100]  R. L. Reep,et al.  Efferent connections of dorsal and ventral agranular insular cortex in the hamster, Mesocricetus auratus , 1982, Neuroscience.

[101]  Jesper Andersson,et al.  Valid conjunction inference with the minimum statistic , 2005, NeuroImage.

[102]  P. Lang.  International affective picture system (IAPS) : affective ratings of pictures and instruction manual , 2005 .

[103]  J. Price,et al.  The organization of the thalamocortical connections of the mediodorsal thalamic nucleus in the rat, related to the ventral forebrain–prefrontal cortex topography , 1992, The Journal of comparative neurology.

[104]  G. Moruzzi,et al.  Brain stem reticular formation and activation of the EEG. , 1949, Electroencephalography and clinical neurophysiology.

[105]  Timothy Edward John Behrens,et al.  Topography of connections between human prefrontal cortex and mediodorsal thalamus studied with diffusion tractography , 2010, NeuroImage.