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How do you feel? Interoception: the sense of the physiological condition of the body

Abstract

As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.

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Figure 1: Pain, visceroceptive and spinothalamocortical pathways.
Figure 2: Hierarchical organization of neural homeostasis involving the sympathetic nervous system.
Figure 3: The organizational chart for interoception.
Figure 4: Activation of the interoceptive cortex in the dorsal posterior insula by various modalities.
Figure 5: Activation of the right (non-dominant) anterior insular cortex associated with different subjective feelings.

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References

  1. Weber, E. H. Handwörterbuch des Physiologie mit Rücksicht auf physiologische Pathologie Bd 3, Abt 2 (ed. Wagner, R.) 481–588 (Biewig und Sohn, Braunschweig, Germany, 1846).

    Google Scholar 

  2. Sherrington, C. S. Text-book of Physiology (ed. Schäfer, E. A.) 920–1001 (Pentland, Edinburgh, UK, 1900).

    Google Scholar 

  3. James, W. The Principles of Psychology [online] 〈http://psychclassics.yorku.ca/James/Principles/index.htm〉 (1890).

    Google Scholar 

  4. Sherrington, C. S. The Integrative Action of the Nervous System (Cambridge Univ. Press, Cambridge, UK, 1948).

    Google Scholar 

  5. Craig, A. D., Chen, K., Bandy, D. & Reiman, E. M. Thermosensory activation of insular cortex. Nature Neurosci. 3, 184–190 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Craig, A. D. Nervous System Plasticity and Chronic Pain (eds Sandkühler, J., Bromm, B. & Gebhart, G. F.) 137–151 (Elsevier, Amsterdam, 2000).

    Book  Google Scholar 

  7. Craig, A. D. The Emotional Motor System (eds Holstege, G., Bandler, R. & Saper, C. B.) 225–242 (Elsevier, Amsterdam, 1996).

    Book  Google Scholar 

  8. Bonica, J. J. The Management of Pain (ed. Bonica, J. J.) 28–95 (Lea & Fibiger, Philadelphia, Pennsylvania, 1990).

    Google Scholar 

  9. Willis, W. D. & Westlund, K. N. Neuroanatomy of the pain system and of the pathways that modulate pain. J. Clin. Neurophysiol. 14, 2–31 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cechetto, D. F. & Saper, C. B. Central Regulation of Autonomic Function (eds Loewy, A. D. & Spyer, K. M.) 208–223 (Oxford Univ. Press, New York, 1990).

    Google Scholar 

  11. Cameron, O. G. Visceral Sensory Neuroscience (Oxford Univ. Press, Oxford, UK, 2002).

    Google Scholar 

  12. Head, H. & Holmes, G. Sensory disturbances from cerebral lesions. Brain 34, 102–254 (1911).

    Article  Google Scholar 

  13. Melzack, R. & Wall, P. D. Pain mechanisms: a new theory. Science 150, 971–979 (1965).

    Article  CAS  PubMed  Google Scholar 

  14. Price, D. D. & Dubner, R. Neurons that subserve the sensory-discriminative aspects of pain. Pain 3, 307–338 (1977).

    Article  CAS  PubMed  Google Scholar 

  15. Cannon, W. B. The Wisdom of the Body (Norton & Co., New York, 1939).

    Book  Google Scholar 

  16. May, W. P. The afferent path. Brain 29, 742–803 (1906).

    Article  Google Scholar 

  17. Bishop, G. H. The relation between nerve fiber size and sensory modality: phylogenetic implications of the afferent innervation of cortex. J. Nerv. Ment. Dis. 128, 89–114 (1959).

    Article  CAS  PubMed  Google Scholar 

  18. Melzack, R. & Casey, K. L. The Skin Senses (ed. Kenshalo, D. R.) 423–443 (Thomas, Springfield, Illinois, 1968).

    Google Scholar 

  19. Cabanac, M. Preferred skin temperature as a function of internal and mean skin temperature. J. Appl. Physiol. 33, 699–703 (1972).

    Article  CAS  PubMed  Google Scholar 

  20. Mower, G. Perceived intensity of peripheral thermal stimuli is independent of internal body temperature. J. Comp. Physiol. Psychol. 90, 1152–1155 (1976).

    Article  CAS  PubMed  Google Scholar 

  21. Blatteis, C. M. (ed.) Physiology and Pathophysiology of Temperature Regulation (World Scientific, Singapore, 1998).

    Book  Google Scholar 

  22. Satinoff, E. Neural organization and evolution of thermal regulation in mammals. Science 201, 16–22 (1978).

    Article  CAS  PubMed  Google Scholar 

  23. Altman, J. & Bayer, S. A. The development of the rat spinal cord. Adv. Anat. Embryol. Cell Biol. 85, 1–164 (1984).

    Article  CAS  PubMed  Google Scholar 

  24. Chen, Z. F. et al. The paired homeodomain protein DRG11 is required for the projection of cutaneous sensory afferent fibers to the dorsal spinal cord. Neuron 31, 59–73 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Woodbury, C. J., Ritter, A. M. & Koerber, H. R. Central anatomy of individual rapidly adapting low-threshold mechanoreceptors innervating the 'hairy' skin of newborn mice: early maturation of hair follicle afferents. J. Comp. Neurol. 436, 304–323 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. MacIver, M. B. & Tanelian, D. L. Activation of C fibers by metabolic perturbations associated with tourniquet ischemia. Anesthesiology 76, 617–623 (1992).

    Article  CAS  PubMed  Google Scholar 

  27. Hill, J. M., Pickar, J. G., Parrish, M. D. & Kaufman, M. P. Effects of hypoxia on the discharge of group III and IV muscle afferents in cats. J. Appl. Physiol. 73, 2524–2529 (1992).

    Article  CAS  PubMed  Google Scholar 

  28. Petho, G., Porszasz, R., Peitl, B. & Szolcsanyi, J. Spike generation from dorsal roots and cutaneous afferents by hypoxia or hypercapnia in the rat in vivo. Exp. Physiol. 84, 1–15 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Cook, S. P. & McCleskey, E. W. Cell damage excites nociceptors through release of cytosolic ATP. Pain 95, 41–47 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. Carlton, S. M., Du, J., Zhou, S. & Coggeshall, R. E. Tonic control of peripheral cutaneous nociceptors by somatostatin receptors. J. Neurosci. 21, 4042–4049 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cervero, F. & Janig, W. Visceral nociceptors: a new world order? Trends Neurosci. 15, 374–378 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Perl, E. R. Neurobiology of Nociceptors (eds Belmonte, C. & Cervero, F.) 5–36 (Oxford Univ. Press, Oxford, UK, 1996).

    Google Scholar 

  33. Iggo, A. Cutaneous mechanoreceptors with afferent C fibres. J. Physiol. (Lond.) 152, 337–353 (1960).

    Article  CAS  Google Scholar 

  34. Mense, S. & Meyer, H. Different types of slowly conducting afferent units in cat skeletal muscle and tendon. J. Physiol. (Lond.) 363, 403–417 (1985).

    Article  CAS  Google Scholar 

  35. Gybels, J., Handwerker, H. O. & VanHees, J. A comparison between the discharges of human nociceptive nerve fibres and the subject's ratings of his sensations. J. Physiol. (Lond.) 292, 193–206 (1979).

    Article  CAS  Google Scholar 

  36. Adreani, C. M. & Kaufman, M. P. Effect of arterial occlusion on responses of group III and IV afferents to dynamic exercise. J. Appl. Physiol. 84, 1827–1833 (1998).

    Article  CAS  PubMed  Google Scholar 

  37. Schaible, H. G. & Schmidt, R. F. Activation of groups III and IV sensory units in medial articular nerve by local mechanical stimulation of knee joint. J. Neurophysiol. 49, 35–44 (1983).

    Article  CAS  PubMed  Google Scholar 

  38. Vallbo, A. B., Olausson, H. & Wessberg, J. Unmyelinated afferents constitute a second system coding tactile stimuli of the human hairy skin. J. Neurophysiol. 81, 2753–2763 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Light, A. R. & Willcockson, H. H. Spinal laminae I–II neurons in rat recorded in vivo in whole cell, tight seal configuration: properties and opioid responses. J. Neurophysiol. 82, 3316–3326 (1999).

    Article  CAS  PubMed  Google Scholar 

  40. Craig, A. D. Propriospinal input to thoracolumbar sympathetic nuclei from cervical and lumbar lamina I neurons in the cat and the monkey. J. Comp. Neurol. 331, 517–530 (1993).

    Article  CAS  PubMed  Google Scholar 

  41. Craig, A. D. Distribution of brainstem projections from spinal lamina I neurons in the cat and the monkey. J. Comp. Neurol. 361, 225–248 (1995).

    Article  CAS  PubMed  Google Scholar 

  42. Miller, A. D. & Ruggiero, D. A. Emetic reflex arc revealed by expression of the immediate-early gene c-fos in the cat. J. Neurosci. 14, 871–888 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sato, A. & Schmidt, R. F. Somatosympathetic reflexes: afferent fibers, central pathways, discharge characteristics. Physiol. Rev. 53, 916–947 (1973).

    Article  CAS  PubMed  Google Scholar 

  44. Buijs, R. M., Chun, S. J., Niijima, A., Romijn, H. J. & Nagai, K. Parasympathetic and sympathetic control of the pancreas: a role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake. J. Comp. Neurol. 431, 405–423 (2001).

    Article  CAS  PubMed  Google Scholar 

  45. Diesel, D. A., Tucker, A. & Robertshaw, D. Cold-induced changes in breathing pattern as a strategy to reduce respiratory heat loss. J. Appl. Physiol. 69, 1946–1952 (1990).

    Article  CAS  PubMed  Google Scholar 

  46. Holstege, G. Direct and indirect pathways to lamina I in the medulla oblongata and spinal cord of the cat. Prog. Brain Res. 77, 47–94 (1988).

    Article  CAS  PubMed  Google Scholar 

  47. Han, Z.-S., Zhang, E.-T. & Craig, A. D. Nociceptive and thermoreceptive lamina I neurons are anatomically distinct. Nature Neurosci. 1, 218–225 (1998).

    Article  CAS  PubMed  Google Scholar 

  48. Craig, A. D., Krout, K. & Andrew, D. Quantitative response characteristics of thermoreceptive and nociceptive lamina I spinothalamic neurons in the cat. J. Neurophysiol. 86, 1459–1480 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Craig, A. D. & Andrew, D. Responses of spinothalamic lamina I neurons to repeated brief contact heat stimulation in the cat. J. Neurophysiol. 87, 1902–1914 (2002).

    Article  CAS  PubMed  Google Scholar 

  50. Andrew, D. & Craig, A. D. Responses of spinothalamic lamina I neurons to maintained noxious mechanical stimulation in the cat. J. Neurophysiol. 87, 1889–1901 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Andrew, D. & Craig, A. D. Spinothalamic lamina I neurones selectively responsive to cutaneous warming in cats. J. Physiol. (Lond.) 537, 489–495 (2001).

    Article  CAS  Google Scholar 

  52. Craig, A. D. & Kniffki, K.-D. Spinothalamic lumbosacral lamina I cells responsive to skin and muscle stimulation in the cat. J. Physiol. (Lond.) 365, 197–221 (1985).

    Article  CAS  Google Scholar 

  53. Light, A. R. The Initial Processing of Pain and Its Descending Control: Spinal and Trigeminal Systems (Karger, Basel, Switzerland, 1992).

    Book  Google Scholar 

  54. Cervero, F. & Tattersall, J. E. Somatic and visceral inputs to the thoracic spinal cord of the cat: marginal zone (lamina I) of the dorsal horn. J. Physiol. (Lond.) 383, 383–395 (1987).

    Article  Google Scholar 

  55. Andrew, D. & Craig, A. D. Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nature Neurosci. 4, 72–77 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Gebhart, G. F. & Ness, T. J. Central mechanisms of visceral pain. Can. J. Physiol. Pharmacol. 69, 627–634 (1991).

    Article  CAS  PubMed  Google Scholar 

  57. Foreman, R. D. Mechanisms of cardiac pain. Annu. Rev. Physiol. 61, 143–167 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Rosas-Arellano, M. P., Solano-Flores, L. P. & Ciriello, J. c-Fos induction in spinal cord neurons after renal arterial or venous occlusion. Am. J. Physiol. 276, R120–R127 (1999).

    Article  CAS  PubMed  Google Scholar 

  59. Wilson, L. B., Andrew, D. & Craig, A. D. Activation of spinobulbar lamina I neurons by static muscle contraction. J. Neurophysiol. 87, 1641–1645 (2002).

    Article  CAS  PubMed  Google Scholar 

  60. Milne, R. J., Foreman, R. D. & Willis, W. D. Responses of primate spinothalamic neurons located in the sacral intermediomedial gray (Stilling's nucleus) to proprioceptive input from the tail. Brain Res. 234, 227–236 (1982).

    Article  CAS  PubMed  Google Scholar 

  61. Carstens, E. Responses of rat spinal dorsal horn neurons to intracutaneous microinjection of histamine, capsaicin, and other irritants. J. Neurophysiol. 77, 2499–2514 (1997).

    Article  CAS  PubMed  Google Scholar 

  62. Craig, A. D. & Bushnell, M. C. The thermal grill illusion: unmasking the burn of cold pain. Science 265, 252–255 (1994).

    Article  CAS  PubMed  Google Scholar 

  63. Craig, A. D., Reiman, E. M., Evans, A. & Bushnell, M. C. Functional imaging of an illusion of pain. Nature 384, 258–260 (1996).

    Article  CAS  PubMed  Google Scholar 

  64. Yarnitsky, D. & Ochoa, J. L. Release of cold-induced burning pain by block of cold-specific afferent input. Brain 113, 893–902 (1990).

    Article  PubMed  Google Scholar 

  65. Sinoway, L. I., Hill, J. M., Pickar, J. G. & Kaufman, M. P. Effects of contraction and lactic acid on the discharge of group III muscle afferents in cats. J. Neurophysiol. 69, 1053–1059 (1993).

    Article  CAS  PubMed  Google Scholar 

  66. Pickar, J. G., Hill, J. M. & Kaufman, M. P. Dynamic exercise stimulates group III muscle afferents. J. Neurophysiol. 71, 753–760 (1994).

    Article  CAS  PubMed  Google Scholar 

  67. LeDoux, J. F. & Wilson, L. B. Neuronal application of capsaicin modulates somatic pressor reflexes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 281, R868–R877 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Simone, D. A., Marchettini, P., Caputi, G. & Ochoa, J. L. Identification of muscle afferents subserving sensation of deep pain in humans. J. Neurophysiol. 72, 883–889 (1994).

    Article  CAS  PubMed  Google Scholar 

  69. Villanueva, L. & Nathan, P. W. in Proc. 9th World Congr. Pain (eds Devor, M., Rowbotham, M. C. & Wiesenfeld-Hallin, Z.) 371–386 (IASP Press, Seattle, Washington, 2000).

    Google Scholar 

  70. Craig, A. D., Bushnell, M. C., Zhang, E.-T. & Blomqvist, A. A thalamic nucleus specific for pain and temperature sensation. Nature 372, 770–773 (1994).

    Article  CAS  PubMed  Google Scholar 

  71. Blomqvist, A., Zhang, E. T. & Craig, A. D. Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus. Brain 123, 601–619 (2000).

    Article  PubMed  Google Scholar 

  72. Blomqvist, A., Ericson, A. C., Craig, A. D. & Broman, J. Evidence for glutamate as a neurotransmitter in spinothalamic tract terminals in the posterior region of owl monkeys. Exp. Brain Res. 108, 33–44 (1996).

    Article  CAS  PubMed  Google Scholar 

  73. Beckstead, R. M., Morse, J. R. & Norgren, R. The nucleus of the solitary tract in the monkey: projections to the thalamus and brain stem nuclei. J. Comp. Neurol. 190, 259–282 (1980).

    Article  CAS  PubMed  Google Scholar 

  74. Burstein, R. Somatosensory and visceral input to the hypothalamus and limbic system. Prog. Brain Res. 107, 257–267 (1996).

    Article  CAS  PubMed  Google Scholar 

  75. Craig, A. D., Zhang, E. T. & Blomqvist, A. A distinct thermoreceptive subregion of lamina I in nucleus caudalis of the owl monkey. J. Comp. Neurol. 404, 221–234 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Lenz, F. A. et al. Neurons in the area of human thalamic nucleus ventralis caudalis respond to painful heat stimuli. Brain Res. 623, 235–240 (1993).

    Article  CAS  PubMed  Google Scholar 

  77. Davis, K. D. et al. Thalamic relay site for cold perception in humans. J. Neurophysiol. 81, 1970–1973 (1999).

    Article  CAS  PubMed  Google Scholar 

  78. Dostrovsky, J. O., Wells, F. E. B. & Tasker, R. R. in Processing and Inhibition of Nociceptive Information, Int. Congr. Ser. 989 (eds Inoka, R., Shigenaga, Y. & Tohyama, M.) 115–120 (Excerpta Medica, Amsterdam, 1992).

    Google Scholar 

  79. Lenz, F. A. et al. The sensation of angina can be evoked by stimulation of the human thalamus. Pain 59, 119–125 (1994).

    Article  CAS  PubMed  Google Scholar 

  80. Lenz, F. A. et al. Thermal and pain sensations evoked by microstimulation in the area of human ventrocaudal nucleus. J. Neurophysiol. 70, 200–212 (1993).

    Article  CAS  PubMed  Google Scholar 

  81. Pritchard, T. C., Hamilton, R. B., Morse, J. R. & Norgren, R. Projections of thalamic gustatory and lingual areas in the monkey, Macaca fascicularis. J. Comp. Neurol. 244, 213–228 (1986).

    Article  CAS  PubMed  Google Scholar 

  82. Yaxley, S., Rolls, E. T. & Sienkiewicz, Z. J. Gustatory responses of single neurons in the insula of the macaque monkey. J. Neurophysiol. 63, 689–700 (1990).

    Article  CAS  PubMed  Google Scholar 

  83. Schmahmann, J. D. & Leifer, D. Parietal pseudothalamic pain syndrome: clinical features and anatomic correlates. Arch. Neurol. 49, 1032–1037 (1992).

    Article  CAS  PubMed  Google Scholar 

  84. Greenspan, J. D. & Winfield, J. A. Reversible pain and tactile deficits associated with a cerebral tumor compressing the posterior insula and parietal operculum. Pain 50, 29–39 (1992).

    Article  CAS  PubMed  Google Scholar 

  85. Burton, H. & Jones, E. G. The posterior thalamic region and its cortical projection in new world and old world monkeys. J. Comp. Neurol. 168, 249–302 (1976).

    Article  CAS  PubMed  Google Scholar 

  86. Disbrow, E., Roberts, T. & Krubitzer, L. Somatotopic organization of cortical fields in the lateral sulcus of Homo sapiens: evidence for SII and PV. J. Comp. Neurol. 418, 1–21 (2000).

    Article  CAS  PubMed  Google Scholar 

  87. Hofbauer, R. K., Rainville, P., Duncan, G. H. & Bushnell, M. C. Cortical representation of the sensory dimension of pain. J. Neurophysiol. 86, 402–411 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Coghill, R. C., Sang, C. N., Maisog, J. H. & Iadarola, M. J. Pain intensity processing within the human brain: a bilateral, distributed mechanism. J. Neurophysiol. 82, 1934–1943 (1999).

    Article  CAS  PubMed  Google Scholar 

  89. Derbyshire, S. W. G. & Jones, A. K. P. Cerebral responses to a continual tonic pain stimulus measured using positron emission tomography. Pain 76, 127–135 (1998).

    Article  CAS  PubMed  Google Scholar 

  90. Casey, K. L. Forebrain mechanisms of nociception and pain — analysis through imaging. Proc. Natl Acad. Sci. USA 96, 7668–7674 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Brooks, J. C., Nurmikko, T. J., Bimson, W. E., Singh, K. D. & Roberts, N. fMRI of thermal pain: effects of stimulus laterality and attention. Neuroimage 15, 293–301 (2002).

    Article  PubMed  Google Scholar 

  92. Kupers, R. C., Gybels, J. M. & Gjedde, A. Positron emission tomography study of a chronic pain patient successfully treated with somatosensory thalamic stimulation. Pain 87, 295–302 (2000).

    Article  CAS  PubMed  Google Scholar 

  93. Peyron, R. et al. Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case. Pain 84, 77–87 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Drzezga, A. et al. Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies. Pain 92, 295–305 (2001).

    Article  CAS  PubMed  Google Scholar 

  95. King, A. B., Menon, R. S., Hachinski, V. & Cechetto, D. F. Human forebrain activation by visceral stimuli. J. Comp. Neurol. 413, 572–582 (1999).

    Article  CAS  PubMed  Google Scholar 

  96. Williamson, J. W., McColl, R., Mathews, D., Ginsburg, M. & Mitchell, J. H. Activation of the insular cortex is affected by the intensity of exercise. J. Appl. Physiol. 87, 1213–1219 (1999).

    Article  CAS  PubMed  Google Scholar 

  97. Banzett, R. B. et al. Breathlessness in humans activates insular cortex. Neuroreport 11, 2117–2120 (2000).

    Article  CAS  PubMed  Google Scholar 

  98. Tataranni, P. A. et al. Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. Proc. Natl Acad. Sci. USA 96, 4569–4574 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Denton, D. et al. Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness. Proc. Natl Acad. Sci. USA 96, 5304–5309 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kinomura, S. et al. Functional anatomy of taste perception in the human brain studied with positron emission tomography. Brain Res. 659, 263–266 (1994).

    Article  CAS  PubMed  Google Scholar 

  101. Olausson, H. et al. Unmyelinated tactile afferents in humans: functional role and cortical projections. Nature Neurosci. (doi:10.1038/nn896).

  102. White, J. C. & Sweet, W. H. Pain and the Neurosurgeon: a Forty-Year Experience (Thomas, Springfield, Illinois, 1969).

    Google Scholar 

  103. Sanchez, M. M., Young, L. J., Plotsky, P. M. & Insel, T. R. Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain. J. Comp. Neurol. 408, 365–377 (1999).

    Article  CAS  PubMed  Google Scholar 

  104. Appenzeller, O. & Oribe, E. The Autonomic Nervous System: an Introduction to Basic and Clinical Concepts (Elsevier, Amsterdam, 1997).

    Google Scholar 

  105. Norrsell, U. & Craig, A. D. Behavioral thermosensitivity after lesions of thalamic target areas of a thermosensory spinothalamic pathway in the cat. J. Neurophysiol. 82, 611–625 (1999).

    Article  CAS  PubMed  Google Scholar 

  106. Craig, A. D. A new version of the thalamic disinhibition hypothesis of central pain. Pain Forum 7, 1–14 (1998).

    Article  Google Scholar 

  107. Mesulam, M.-M. & Mufson, E. J. Insula of the old world monkey. III. Efferent cortical output and comments on function. J. Comp. Neurol. 212, 38–52 (1982).

    Article  CAS  PubMed  Google Scholar 

  108. Devinsky, O., Morrell, M. J. & Vogt, B. A. Contributions of anterior cingulate cortex to behaviour. Brain 118, 279–306 (1995).

    Article  PubMed  Google Scholar 

  109. Yasui, Y., Breder, C. D., Saper, C. B. & Cechetto, D. F. Autonomic responses and efferent pathways from the insular cortex in the rat. J. Comp. Neurol. 303, 355–374 (1991).

    Article  CAS  PubMed  Google Scholar 

  110. Floyd, N. S., Price, J. L., Ferry, A. T., Keay, K. A. & Bandler, R. Orbitomedial prefrontal cortical projections to distinct longitudinal columns of the periaqueductal gray in the rat. J. Comp. Neurol. 422, 556–578 (2000).

    Article  CAS  PubMed  Google Scholar 

  111. Frith, C. D. & Frith, U. Interacting minds — a biological basis. Science 286, 1692–1695 (1999).

    Article  CAS  PubMed  Google Scholar 

  112. Paus, T. Primate anterior cingulate cortex: where motor control, drive and cognition interface. Nature Rev. Neurosci. 2, 417–424 (2001).

    Article  CAS  Google Scholar 

  113. Johnson, S. C. et al. Neural correlates of self-reflection. Brain (in the press).

  114. Talbot, J. D. et al. Multiple representations of pain in human cerebral cortex. Science 251, 1355–1358 (1991).

    Article  CAS  PubMed  Google Scholar 

  115. Rainville, P., Duncan, G. H., Price, D. D., Carrier, B. & Bushnell, M. C. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 277, 968–971 (1997).

    Article  CAS  PubMed  Google Scholar 

  116. Krout, K. E. & Loewy, A. D. Parabrachial nucleus projections to midline and intralaminar thalamic nuclei of the rat. J. Comp. Neurol. 428, 475–494 (2000).

    Article  CAS  PubMed  Google Scholar 

  117. Johansen, J. P., Fields, H. L. & Manning, B. H. The affective component of pain in rodents: direct evidence for a contribution of the anterior cingulate cortex. Proc. Natl Acad. Sci. USA 98, 8077–8082 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Gabriel, M., Kubota, Y., Sparenborg, S., Straube, K. & Vogt, B. A. Effects of cingulate cortical lesions on avoidance learning and training-induced unit activity in rabbits. Exp. Brain Res. 86, 585–600 (1991).

    Article  CAS  PubMed  Google Scholar 

  119. Pritchard, T. C., Macaluso, D. A. & Eslinger, P. J. Taste perception in patients with insular cortex lesions. Behav. Neurosci. 113, 663–671 (1999).

    Article  CAS  PubMed  Google Scholar 

  120. de Araujo, I. E. T., Kringelbach, M. L. & Rolls, E. T. Orbitofrontal cortex responses to the synergistic combination of umami stimuli. Neuroimage 13, S967 (2002).

    Article  Google Scholar 

  121. Reiman, E. M. The application of positron emission tomography to the study of normal and pathological emotions. J. Clin. Psychiatry 58, 4–12 (1997).

    PubMed  Google Scholar 

  122. Mayberg, H. S. et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am. J. Psychiatry 156, 675–682 (1999).

    CAS  PubMed  Google Scholar 

  123. Damasio, A. R. et al. Subcortical and cortical brain activity during the feeling of self-generated emotions. Nature Neurosci. 3, 1049–1056 (2000).

    Article  CAS  PubMed  Google Scholar 

  124. Phillips, M. L. et al. A specific neural substrate for perceiving facial expressions of disgust. Nature 389, 495–498 (1997).

    Article  CAS  PubMed  Google Scholar 

  125. Benkelfat, C. et al. Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers. Am. J. Psychiatry 152, 1180–1184 (1995).

    Article  CAS  PubMed  Google Scholar 

  126. Ploghaus, A. et al. Dissociating pain from its anticipation in the human brain. Science 284, 1979–1981 (1999).

    Article  CAS  PubMed  Google Scholar 

  127. Blood, A. J. & Zatorre, R. J. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc. Natl Acad. Sci. USA 98, 11818–11823 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Stoleru, S. et al. Neuroanatomical correlates of visually evoked sexual arousal in human males. Arch. Sex. Behav. 28, 1–21 (1999).

    Article  CAS  PubMed  Google Scholar 

  129. Winston, J. S., Strange, B. A., O'Doherty, J. & Dolan, R. J. Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nature Neurosci. 5, 277–283 (2002).

    Article  CAS  PubMed  Google Scholar 

  130. Adolphs, R. Trust in the brain. Nature Neurosci. 5, 192–193 (2002).

    Article  CAS  PubMed  Google Scholar 

  131. Damasio, A. R. Descartes' Error: Emotion, Reason, and the Human Brain (Putnam, New York, 1993).

    Google Scholar 

  132. Farrer, C. & Frith, C. D. Experiencing oneself vs another person as being the cause of an action: the neural correlates of the experience of agency. Neuroimage 15, 596–603 (2002).

    Article  CAS  PubMed  Google Scholar 

  133. Carmichael, S. T. & Price, J. L. Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys. J. Comp. Neurol. 363, 642–664 (1995).

    Article  CAS  PubMed  Google Scholar 

  134. Chikama, M., McFarland, N. R., Amaral, D. G. & Haber, S. N. Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. J. Neurosci. 17, 9686–9705 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Becerra, L., Breiter, H. C., Wise, R., Gonzalez, R. G. & Borsook, D. Reward circuitry activation by noxious thermal stimuli. Neuron 32, 927–946 (2001).

    Article  CAS  PubMed  Google Scholar 

  136. O'Doherty, J., Rolls, E. T., Francis, S., Bowtell, R. & McGlone, F. Representation of pleasant and aversive taste in the human brain. J. Neurophysiol. 85, 1315–1321 (2001).

    Article  CAS  PubMed  Google Scholar 

  137. Bartels, A. & Zeki, S. The neural basis of romantic love. Neuroreport 11, 3829–3834 (2000).

    Article  CAS  PubMed  Google Scholar 

  138. Petrovic, P., Kalso, E., Petersson, K. M. & Ingvar, M. Placebo and opioid analgesia — imaging a shared neuronal network. Science 295, 1737–1740 (2002).

    Article  CAS  PubMed  Google Scholar 

  139. Carmichael, S. T. & Price, J. L. Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys. J. Comp. Neurol. 371, 179–207 (1996).

    Article  CAS  PubMed  Google Scholar 

  140. Ongur, D. & Price, J. L. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb. Cortex 10, 206–219 (2000).

    Article  CAS  PubMed  Google Scholar 

  141. Francis, S. et al. The representation of pleasant touch in the brain and its relationship with taste and olfactory areas. Neuroreport 10, 453–459 (1999).

    Article  CAS  PubMed  Google Scholar 

  142. Royet, J. P. et al. Emotional responses to pleasant and unpleasant olfactory, visual, and auditory stimuli: a positron emission tomography study. J. Neurosci. 20, 7752–7759 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Rolls, E. T. The Brain and Emotion (Oxford Univ. Press, Oxford, UK, 1999).

    Google Scholar 

  144. Janig, W. Neurobiology of visceral afferent neurons: neuroanatomy, functions, organ regulations and sensations. Biol. Psychol. 42, 29–51 (1996).

    Article  CAS  PubMed  Google Scholar 

  145. Loewy, A. D. & Spyer, K. M. Central Regulation of Autonomic Functions (Oxford, New York, 1990).

    Google Scholar 

  146. Sawchenko, P. E. et al. in The Emotional Motor System (eds Holstege, G., Bandler, R. & Saper, C. B.) 201–224 (Elsevier, Amsterdam, 1996).

    Book  Google Scholar 

  147. Swanson, L. W. Cerebral hemisphere regulation of motivated behavior. Brain Res. 886, 113–164 (2000).

    Article  CAS  PubMed  Google Scholar 

  148. Critchley, H. D., Mathias, C. J. & Dolan, R. J. Neuroanatomical basis for first- and second-order representations of bodily states. Nature Neurosci. 4, 207–212 (2001).

    Article  CAS  PubMed  Google Scholar 

  149. Potts, J. T. Exercise and sensory integration. Role of the nucleus tractus solitarius. Ann. NY Acad. Sci. 940, 221–236 (2001).

    Article  CAS  PubMed  Google Scholar 

  150. Zagon, A. Does the vagus nerve mediate the sixth sense? Trends Neurosci. 24, 671–673 (2001).

    Article  CAS  PubMed  Google Scholar 

  151. Ness, T. J., Fillingim, R. B., Randich, A., Backensto, E. M. & Faught, E. Low intensity vagal nerve stimulation lowers human thermal pain thresholds. Pain 86, 81–85 (2000).

    Article  CAS  PubMed  Google Scholar 

  152. Chandler, M. J., Zhang, J., Qin, C. & Foreman, R. D. Spinal inhibitory effects of cardiopulmonary afferent inputs in monkeys: neuronal processing in high cervical segments. J. Neurophysiol. 87, 1290–1302 (2002).

    Article  PubMed  Google Scholar 

  153. Oppenheimer, S. The anatomy and physiology of cortical mechanisms of cardiac control. Stroke 24, I3–I5 (1993).

    CAS  PubMed  Google Scholar 

  154. Blok, B. F. M., Willemsen, A. T. M. & Holstege, G. A PET study on brain control of micturition in humans. Brain 120, 111–121 (1997).

    Article  PubMed  Google Scholar 

  155. Saper, C. B. Pain as a visceral sensation. Prog. Brain Res. 122, 237–243 (2000).

    Article  CAS  PubMed  Google Scholar 

  156. Macphail, E. M. The Evolution of Consciousness (Oxford Univ. Press, Oxford, UK, 1998).

    Book  Google Scholar 

  157. Nimchinsky, E. A. et al. A neuronal morphologic type unique to humans and great apes. Proc. Natl Acad. Sci. USA 96, 5268–5273 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Pagni, C. A. Central Pain: a Neurosurgical Challenge (Ediziona Minerva Medica S. P. A., Turin, 1998).

    Google Scholar 

  159. Churchland, P. S. Self-representation in nervous systems. Science 296, 308–310 (2002).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

I thank E. Rolls and L. Watkins for their comments on the manuscript, and many collaborators and friends for constructive discussions. Work in the author's laboratory is supported by the National Institutes of Health and the Barrow Neurological Foundation.

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FURTHER INFORMATION

Encyclopedia of Life Sciences

sensory system organization

sensory systems in vertebrates: general overview

somatosensory systems

MIT Encyclopedia of Cognitive Sciences

emotion and the human brain

Glossary

AIR HUNGER

Hypercapnia with mechanically restricted ventilation.

ERGORECEPTION

Afferent activity relating tissue energy and metabolic needs.

EXERCISE PRESSOR REFLEX

Increased blood pressure and heart rate caused by activity in small-diameter afferents from muscle.

FIRST PAIN

Sharp, pricking pain associated with rapidly conducting Aδ-fibres.

LABELLED LINES

Anatomically and physiologically distinct neurons that are specifically associated with particular sensations.

NEUROPATHIC PAIN

Intractable pain associated with damage to the peripheral or central nervous system.

SECOND PAIN

Dull, burning pain associated with slowly conducting C-fibres.

TRIADIC ARRANGEMENT

Ultrastructural contacts between an afferent terminal, a relay cell dendrite and a GABA-containing presynaptic dendrite that is characteristic of high-fidelity transmission in sensory relay nuclei.

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Craig, A. How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci 3, 655–666 (2002). https://doi.org/10.1038/nrn894

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