Neural top–down control of physiology concerns the direct regulation by the brain of physiological functions (in addition to smooth muscle and glandular ones). Cellular functions include the immune system’s production of T-lymphocytes and antibodies, and nonimmune related homeostatic functions such as liver gluconeogenesis, sodium reabsorption, osmoregulation, and brown adipose tissue nonshivering thermogenesis. This regulation occurs through the sympathetic and parasympathetic system (the autonomic nervous system), and their direct innervation of body organs and tissues that starts in the brainstem. There is also a noninnervation hormonal control through the hypothalamus and pituitary (HPA). These lower brain areas are under control of cerebral cortex ones. Such cortical regulation differs between its left and right sides. Pavlovian conditioning shows that brain control over basic cell level physiological function can be learned.
Higher brain
[edit]Cerebral cortex
[edit]Sympathetic and parasympathetic nervous systems and the hypothalamus are regulated by the higher brain.[1][2][3][4] Through them, the higher cerebral cortex areas can control the immune system, and the body’s homeostatic and stress physiology. Areas doing this include the insular cortex,[5][6][7] the orbital, and the medial prefrontal cortices.[8][9] These cerebral areas also control smooth muscle and glandular physiological processes through the sympathetic and parasympathetic nervous system including blood circulation, urogenital, gastrointestinal[10] functions, pancreatic gut secretions,[11] respiration, coughing, vomiting, piloerection, pupil dilation, lacrimation and salivation.[12]
Lateralization
[edit]The sympathetic nervous system is predominantly controlled by the right side of the brain (focused upon the insular cortex), while the left side predominantly controls the parasympathetic nervous system.[4] The cerebral cortex in rodents shows lateral specialization in its regulation of immunity with immunosuppression being controlled by the right hemisphere, and immunopotention by the left one.[9][13] Humans show similar lateral specialized control of the immune system from the evidence of strokes,[14] surgery to control epilepsy,[15] and the application of TMS.[16]
Brainstem
[edit]The higher brain top down control of physiology is mediated by the sympathetic and parasympathetic nervous systems in the brainstem,[1][2][3][4] and the hypothalamus.[1][17][18] The sympathetic nervous system arises in brainstem nuclei that project down into intermediolateral columns of thoracolumbar spinal cord neurons in spinal segments T1–L2. The parasympathetic nervous system in the motor nuclei of cranial nerves III, VII, IX, (control over the pupil and salivary glands) and X (vagus –many functions including immunity) and sacral spinal segments (gastrointestinal and urogenital systems).[12] Another control occurs through top down control by the medial areas of the prefrontal cortex.[1][17][18] upon the hypothalamus which has a nonnerve control of the body through hormonal secretions of the pituitary.
Immunity
[edit]The brain controls immunity both indirectly through HPA glucocorticoid secretions from the pituitary, and by various direct innervations.[19]
- Antibodies. There is sympathetic innervation of the thymus gland.[20] Sympathetic control exists over antibody production,[21] and the modulation of cytokine concentrations.[22]
- Cellular immunity. An intact sympathetic nervous system is required to maintain full cellular immunoregulation as denervated mice do not produce and activate, for example, splenic suppressor T cells, or thymic NKT cells.[23]
- Organ inflammation. Sympathetic innervation of various organs[19] contacts macrophages and dendritic cells and can increase local inflammation including the kidney[24] gut,[25] the skin,[26] and the synovial joints[27]
- Antiinflammation. The vagus nerve carries a parasympathetic cholinergic antiinflammatory pathway that reduces proinflammatory cytokines such as TNF by spleen macrophages in the red pulp and the marginal zone and so the activation of inflammation.[28][29] This control is in part controlled by direct innervation of body organs such as the spleen.[30] However, the existence of the parasympathetic antiinflammatory nerve pathway is controversial with one reviewer stating: “there is no evidence for an anti-inflammatory role of the efferent vagus nerve that is independent of the sympathetic nervous system.”[31]
Metabolism
[edit]The liver receives both sympathetic and parasympathetic nervous system innervation.[32]
- Plasma glucose levels. A vagus brain-liver axis exists that detects lipids produced by the gut and acts to regulate glucose homeostasis.[10][33]
- Glycogenesis. Vagal activation also controls glycogen synthesis in the liver.[34]
- lipogenesis. Vagal activation also controls the generation of lipids in brown adipose tissue.[34]
- Insulin. Vagal innervation of the pancreas controls the release of insulin release from its beta cells (and this is inhibited by norepinephrine released under sympathetic control from the splanchnic nerve).[35]
- Thyroid hormones can control glucose production via the hypothalamus and its sympathetic and parasympathetic innervation of the liver.[36]
Other
[edit]- Thermogenesis – this is controlled by the sympathetic nervous system starting in the dorsolateral preoptic area of the anterior hypothalamus via projections from the rostral raphe pallidus to the spinal intermediolateral nucleus nonshivering thermogenesis by brown adipose tissue.[37]
- Stress – norepinephrine and epinephrine, the stress hormones, are released from nerve terminals in the adrenal medulla in the kidney innervated from the sympathetic nervous system’s splanchnic nerve.[38][39]
- Kidney function – the sympathetic nervous system projects to the kidney and controls glomerular filtration rate and so fluid balance, sodium reabsorption, and osmoregulation.[40][41]
Conditioning
[edit]The brains of animals can anticipatorily learn to control cell level physiology such as immunity through Pavlovian conditioning. In this conditioning, a neutral stimulus saccharin is paired in a drink with an agent, cyclophosphamide, that produces an unconditioned response (immunosuppression). After learning this pairing, the taste of saccharin by itself through neural top down control created immunosuppression, as a new conditioned response.[42] This work was originally done on rats, however, the same conditioning can also occur in humans.[43] The conditioned response happens in the brain with the ventromedial nucleus of the hypothalamus providing the output pathway to the immune system, the amygdala, the input of visceral information, and the insular cortex acquires and creates the conditioned response.[5] The production of different components of the immune system can be controlled as conditioned responses:
- Antibodies[43][44][45]
- IL-2[46][47]
- B, CD8+ T cells and CD4+ naive and memory T cells, and granulocytes.[48] Such conditioning in rats can last a year.[49]
Nonimmune functions can also be conditioned:
- Serum iron levels[50]
- The level of oxidative DNA damage[51]
- Insulin secretion[52][53]
- Blood glucose levels[53][54]
See also
[edit]- Autonomic nervous system
- Homeostasis
- Homeostatic emotion
- Neurogastroenterology
- Neuroendocrinology
- Neuroimmunology
- Parasympathetic nervous system
- Peripheral nervous system
- Psychoneuroimmunology
- Sympathetic nervous system
- Vis medicatrix naturae
References
[edit]- ^ a b c d Cerqueira, J. O. J.; Almeida, O. F. X.; Sousa, N. (2008). "The stressed prefrontal cortex. Left? Right!". Brain, Behavior, and Immunity. 22 (5): 630–638. doi:10.1016/j.bbi.2008.01.005. hdl:1822/61458. PMID 18281193. S2CID 9876327.
- ^ a b Critchley, H. D. (2005). "Neural mechanisms of autonomic, affective, and cognitive integration". The Journal of Comparative Neurology. 493 (1): 154–166. doi:10.1002/cne.20749. PMID 16254997. S2CID 32616395.
- ^ a b Van Eden, C. G.; Buijs, R. M. (2000). "Functional neuroanatomy of the prefrontal cortex: autonomic interactions". Cognition, emotion and autonomic responses: The integrative role of the prefrontal cortex and limbic structures. Progress in Brain Research. Vol. 126. pp. 49–62. doi:10.1016/S0079-6123(00)26006-8. ISBN 9780444503329. PMID 11105639.
- ^ a b c Craig, A. D. (B. (2005). "Forebrain emotional asymmetry: A neuroanatomical basis?". Trends in Cognitive Sciences. 9 (12): 566–571. doi:10.1016/j.tics.2005.10.005. PMID 16275155. S2CID 16892662.
- ^ a b Pacheco-Lopez, G.; Niemi, M. B.; Kou, W.; Härting, M.; Fandrey, J.; Schedlowski, M. (2005). "Neural Substrates for Behaviorally Conditioned Immunosuppression in the Rat". Journal of Neuroscience. 25 (9): 2330–2337. doi:10.1523/JNEUROSCI.4230-04.2005. PMC 6726099. PMID 15745959.
- ^ Ramírez-Amaya, V.; Alvarez-Borda, B.; Ormsby, C. E.; Martínez, R. D.; Pérez-Montfort, R.; Bermúdez-Rattoni, F. (1996). "Insular cortex lesions impair the acquisition of conditioned immunosuppression". Brain, Behavior, and Immunity. 10 (2): 103–114. doi:10.1006/brbi.1996.0011. PMID 8811934. S2CID 24813018.
- ^ Ramı́Rez-Amaya, V.; Bermudez-Rattoni, F. (1999). "Conditioned Enhancement of Antibody Production is Disrupted by Insular Cortex and Amygdala but Not Hippocampal Lesions". Brain, Behavior, and Immunity. 13 (1): 46–60. doi:10.1006/brbi.1998.0547. PMID 10371677. S2CID 20527835.
- ^ Ohira, H.; Isowa, T.; Nomura, M.; Ichikawa, N.; Kimura, K.; Miyakoshi, M.; Iidaka, T.; Fukuyama, S.; Nakajima, T.; Yamada, J. (2008). "Imaging brain and immune association accompanying cognitive appraisal of an acute stressor". NeuroImage. 39 (1): 500–514. doi:10.1016/j.neuroimage.2007.08.017. PMID 17913515. S2CID 26357564.
- ^ a b Vlajković, S.; Nikolić, V.; Nikolić, A.; Milanović, S.; Janković, B. D. (1994). "Asymmetrical modulation of immune reactivity in left- and right-biased rats after ipsilateral ablation of the prefrontal, parietal and occipital brain neocortex". The International Journal of Neuroscience. 78 (1–2): 123–134. doi:10.3109/00207459408986051. PMID 7829286.
- ^ a b Pocai, A.; Obici, S.; Schwartz, G. J.; Rossetti, L. (2005). "A brain-liver circuit regulates glucose homeostasis". Cell Metabolism. 1 (1): 53–61. doi:10.1016/j.cmet.2004.11.001. PMID 16054044.
- ^ Love, J. A.; Yi, E.; Smith, T. G. (2007). "Autonomic pathways regulating pancreatic exocrine secretion". Autonomic Neuroscience. 133 (1): 19–34. doi:10.1016/j.autneu.2006.10.001. PMID 17113358. S2CID 24929003.
- ^ a b Brading, A. (1999). The autonomic nervous system and its effectors. Oxford: Blackwell Science. ISBN 978-0-632-02624-1.
- ^ Barnéoud, P.; Neveu, P. J.; Vitiello, S.; Mormède, P.; Le Moal, M. (1988). "Brain neocortex immunomodulation in rats". Brain Research. 474 (2): 394–398. doi:10.1016/0006-8993(88)90458-1. PMID 3145098. S2CID 23658789.
- ^ Koch, H. J.; Uyanik, G.; Bogdahn, U.; Ickenstein, G. W. (2006). "Relation between Laterality and Immune Response after Acute Cerebral Ischemia". Neuroimmunomodulation. 13 (1): 8–12. doi:10.1159/000092108. PMID 16612132. S2CID 21581127.
- ^ Meador, K. J.; Loring, D. W.; Ray, P. G.; Helman, S. W.; Vazquez, B. R.; Neveu, P. J. (2004). "Role of cerebral lateralization in control of immune processes in humans". Annals of Neurology. 55 (6): 840–844. doi:10.1002/ana.20105. PMID 15174018. S2CID 25106845.
- ^ Clow, A.; Lambert, S.; Evans, P.; Hucklebridge, F.; Higuchi, K. (2003). "An investigation into asymmetrical cortical regulation of salivary S-IgA in conscious man using transcranial magnetic stimulation". International Journal of Psychophysiology. 47 (1): 57–64. doi:10.1016/S0167-8760(02)00093-4. PMID 12543446.
- ^ a b Radley, J. J.; Arias, C. M.; Sawchenko, P. E. (2006). "Regional Differentiation of the Medial Prefrontal Cortex in Regulating Adaptive Responses to Acute Emotional Stress". Journal of Neuroscience. 26 (50): 12967–12976. doi:10.1523/JNEUROSCI.4297-06.2006. PMC 6674963. PMID 17167086.
- ^ a b Kern, S.; Oakes, T. R.; Stone, C. K.; McAuliff, E. M.; Kirschbaum, C.; Davidson, R. J. (2008). "Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor". Psychoneuroendocrinology. 33 (4): 517–529. doi:10.1016/j.psyneuen.2008.01.010. PMC 2601562. PMID 18337016.
- ^ a b Sternberg, E. M. (2006). "Neural regulation of innate immunity: A coordinated nonspecific host response to pathogens". Nature Reviews Immunology. 6 (4): 318–328. doi:10.1038/nri1810. PMC 1783839. PMID 16557263.
- ^ Trotter, R. N.; Stornetta, R. L.; Guyenet, P. G.; Roberts, M. R. (2007). "Transneuronal mapping of the CNS network controlling sympathetic outflow to the rat thymus". Autonomic Neuroscience. 131 (1–2): 9–20. doi:10.1016/j.autneu.2006.06.001. PMID 16843070. S2CID 25595673.
- ^ Besedovsky, H. O.; Del Rey, A.; Sorkin, E.; Da Prada, M.; Keller, H. H. (1979). "Immunoregulation mediated by the sympathetic nervous system". Cellular Immunology. 48 (2): 346–355. doi:10.1016/0008-8749(79)90129-1. PMID 389444.
- ^ Kin, N. W.; Sanders, V. M. (2006). "It takes nerve to tell T and B cells what to do". Journal of Leukocyte Biology. 79 (6): 1093–1104. doi:10.1189/jlb.1105625. PMID 16531560. S2CID 20491482.
- ^ Li, X.; Taylor, S.; Zegarelli, B.; Shen, S.; O'Rourke, J.; Cone, R. E. (2004). "The induction of splenic suppressor T cells through an immune-privileged site requires an intact sympathetic nervous system". Journal of Neuroimmunology. 153 (1–2): 40–49. doi:10.1016/j.jneuroim.2004.04.008. PMID 15265662. S2CID 41872803.
- ^ Veelken, R.; Vogel, E. -M.; Hilgers, K.; Amann, K.; Hartner, A.; Sass, G.; Neuhuber, W.; Tiegs, G. (2008). "Autonomic Renal Denervation Ameliorates Experimental Glomerulonephritis". Journal of the American Society of Nephrology. 19 (7): 1371–1378. doi:10.1681/ASN.2007050552. PMC 2440306. PMID 18400940.
- ^ Straub, R. H.; Grum, F.; Strauch, U.; Capellino, S.; Bataille, F.; Bleich, A.; Falk, W.; Schölmerich, J.; Obermeier, F. (2008). "Anti-inflammatory role of sympathetic nerves in chronic intestinal inflammation". Gut. 57 (7): 911–921. doi:10.1136/gut.2007.125401. PMID 18308830. S2CID 25930381.
- ^ Pavlovic, S.; Daniltchenko, M.; Tobin, D. J.; Hagen, E.; Hunt, S. P.; Klapp, B. F.; Arck, P. C.; Peters, E. M. J. (2007). "Further Exploring the Brain–Skin Connection: Stress Worsens Dermatitis via Substance P-dependent Neurogenic Inflammation in Mice". Journal of Investigative Dermatology. 128 (2): 434–446. doi:10.1038/sj.jid.5701079. PMID 17914449.
- ^ Miller, L. E.; Jüsten, H. P.; Schölmerich, J.; Straub, R. H. (2000). "The loss of sympathetic nerve fibers in the synovial tissue of patients with rheumatoid arthritis is accompanied by increased norepinephrine release from synovial macrophages". The FASEB Journal. 14 (13): 2097–2107. doi:10.1096/fj.99-1082com. PMID 11023994. S2CID 6610938.
- ^ Huston, J. M.; Ochani, M.; Rosas-Ballina, M.; Liao, H.; Ochani, K.; Pavlov, V. A.; Gallowitsch-Puerta, M.; Ashok, M.; Czura, C. J.; Foxwell, B.; Tracey, K. J.; Ulloa, L. (2006). "Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis". Journal of Experimental Medicine. 203 (7): 1623–1628. doi:10.1084/jem.20052362. PMC 2118357. PMID 16785311.
- ^ Rosas-Ballina, M.; Ochani, M.; Parrish, W. R.; Ochani, K.; Harris, Y. T.; Huston, J. M.; Chavan, S.; Tracey, K. J. (2008). "Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia". Proceedings of the National Academy of Sciences. 105 (31): 11008–11013. Bibcode:2008PNAS..10511008R. doi:10.1073/pnas.0803237105. PMC 2504833. PMID 18669662.
- ^ Exton, M. S.; Schult, M.; Donath, S.; Strubel, T.; Bode, U.; Del Rey, A.; Westermann, J.; Schedlowski, M. (1999). "Conditioned immunosuppression makes subtherapeutic cyclosporin effective via splenic innervation". The American Journal of Physiology. 276 (6 Pt 2): R1710–R1717. doi:10.1152/ajpregu.1999.276.6.R1710. PMID 10362751.
- ^ Nance, D. M.; Sanders, V. M. (2007). "Autonomic innervation and regulation of the immune system (1987–2007)". Brain, Behavior, and Immunity. 21 (6): 736–745. doi:10.1016/j.bbi.2007.03.008. PMC 1986730. PMID 17467231. p. 741
- ^ Uyama, N.; Geerts, A.; Reynaert, H. (2004). "Neural connections between the hypothalamus and the liver". The Anatomical Record. 280A (1): 808–820. doi:10.1002/ar.a.20086. PMID 15382020.
- ^ Wang, P. Y. T.; Caspi, L.; Lam, C. K. L.; Chari, M.; Li, X.; Light, P. E.; Gutierrez-Juarez, R.; Ang, M.; Schwartz, G. J.; Lam, T. K. T. (2008). "Upper intestinal lipids trigger a gut–brain–liver axis to regulate glucose production". Nature. 452 (7190): 1012–1016. Bibcode:2008Natur.452.1012W. doi:10.1038/nature06852. PMID 18401341. S2CID 4425358.
- ^ a b Shimazu, T. (1981). "Central nervous system regulation of liver and adipose tissue metabolism". Diabetologia. 20 Suppl (3): 343–356. doi:10.1007/BF00254502. PMID 7014330. S2CID 10191299.
- ^ Brunicardi, F. C.; Shavelle, D. M.; Andersen, D. K. (1995). "Neural regulation of the endocrine pancreas". International Journal of Pancreatology. 18 (3): 177–195. doi:10.1007/BF02784941. PMID 8708389. S2CID 20558942.
- ^ Klieverik, L. P.; Janssen, S. F.; Riel, A. V.; Foppen, E.; Bisschop, P. H.; Serlie, M. J.; Boelen, A.; Ackermans, M. T.; Sauerwein, H. P.; Fliers, E.; Kalsbeek, A. (2009). "Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver". Proceedings of the National Academy of Sciences. 106 (14): 5966–5971. Bibcode:2009PNAS..106.5966K. doi:10.1073/pnas.0805355106. PMC 2660059. PMID 19321430.
- ^ Nakamura, K.; Morrison, S. F. (2006). "Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue". AJP: Regulatory, Integrative and Comparative Physiology. 292 (1): R127–R136. doi:10.1152/ajpregu.00427.2006. PMC 2441894. PMID 16931649.
- ^ Edwards, A. V.; Jones, C. T. (1993). "Autonomic control of adrenal function". Journal of Anatomy. 183 (Pt 2): 291–307. PMC 1259909. PMID 8300417.
- ^ Engeland, W. (2007). "Functional Innervation of the Adrenal Cortex by the Splanchnic Nerve". Hormone and Metabolic Research. 30 (6/07): 311–314. doi:10.1055/s-2007-978890. PMID 9694555.
- ^ Dibona, G. F. (2000). "Neural control of the kidney: Functionally specific renal sympathetic nerve fibers". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 279 (5): R1517–R1524. doi:10.1152/ajpregu.2000.279.5.r1517. PMID 11049831. S2CID 8795875.
- ^ Denton, K. M.; Luff, S. E.; Shweta, A.; Anderson, W. P. (2004). "Differential Neural Control of Glomerular Ultrafiltration". Clinical and Experimental Pharmacology and Physiology. 31 (5–6): 380–386. doi:10.1111/j.1440-1681.2004.04002.x. PMID 15191417. S2CID 31128522.
- ^ Ader, R.; Cohen, N. (1975). "Behaviorally conditioned immunosuppression". Psychosomatic Medicine. 37 (4): 333–340. doi:10.1097/00006842-197507000-00007. PMID 1162023.
- ^ a b Goebel, M. U.; Trebst, A. E.; Steiner, J.; Xie, Y. F.; Exton, M. S.; Frede, S.; Canbay, A. E.; Michel, M. C.; Heemann, U.; Schedlowski, M. (2002). "Behavioral conditioning of immunosuppression is possible in humans". The FASEB Journal. 16 (14): 1869–1873. doi:10.1096/fj.02-0389com. PMID 12468450. S2CID 1135858.
- ^ Alvarez-Borda, B.; Ramírez-Amaya, V.; Pérez-Montfort, R.; Bermúdez-Rattoni, F. (1995). "Enhancement of antibody production by a learning paradigm". Neurobiology of Learning and Memory. 64 (2): 103–105. doi:10.1006/nlme.1995.1048. PMID 7582817. S2CID 36079870.
- ^ Oberbeck, R.; Kromm, A.; Exton, M. S.; Schade, U.; Schedlowski, M. (2003). "Pavlovian conditioning of endotoxin-tolerance in rats". Brain, Behavior, and Immunity. 17 (1): 20–27. doi:10.1016/S0889-1591(02)00031-4. PMID 12615046. S2CID 26029221.
- ^ Pacheco-López, G.; Niemi, M. -B.; Kou, W.; Härting, M.; Del Rey, A.; Besedovsky, H. O.; Schedlowski, M. (2004). "Behavioural endocrine immune-conditioned response is induced by taste and superantigen pairing". Neuroscience. 129 (3): 555–562. doi:10.1016/j.neuroscience.2004.08.033. PMID 15541877. S2CID 25300739.
- ^ Exton, M. S.; Von Hörsten, S.; Schult, M.; Vöge, J.; Strubel, T.; Donath, S.; Steinmüller, C.; Seeliger, H.; Nagel, E.; Westermann, J. R.; Schedlowski, M. (1998). "Behaviorally conditioned immunosuppression using cyclosporine A: Central nervous system reduces IL-2 production via splenic innervation". Journal of Neuroimmunology. 88 (1–2): 182–191. doi:10.1016/S0165-5728(98)00122-2. PMID 9688340. S2CID 20921504.
- ^ Von Hörsten, S.; Exton, M. S.; Schult, M.; Nagel, E.; Stalp, M.; Schweitzer, G.; Vöge, J.; Del Rey, A.; Schedlowski, M.; Westermann, J. R. (1998). "Behaviorally conditioned effects of Cyclosporine a on the immune system of rats: Specific alterations of blood leukocyte numbers and decrease of granulocyte function". Journal of Neuroimmunology. 85 (2): 193–201. doi:10.1016/S0165-5728(98)00011-3. PMID 9630168. S2CID 36315130.
- ^ Exton, M. S.; Von Hörsten, S.; Strubel, T.; Donath, S.; Schedlowski, M.; Westermann, J. (2000). "Conditioned alterations of specific blood leukocyte subsets are reconditionable". Neuroimmunomodulation. 7 (2): 106–114. doi:10.1159/000026428. PMID 10686521. S2CID 44539812.
- ^ Exton, M. S.; Bull, D. F.; King, M. G.; Husband, A. J. (1995). "Behavioral conditioning of endotoxin-induced plasma iron alterations". Pharmacology Biochemistry and Behavior. 50 (4): 675–679. doi:10.1016/0091-3057(94)00353-X. PMID 7617718. S2CID 24150355.
- ^ Irie, M.; Asami, S.; Nagata, S.; Miyata, M.; Kasai, H. (2000). "Classical conditioning of oxidative DNA damage in rats". Neuroscience Letters. 288 (1): 13–16. doi:10.1016/S0304-3940(00)01194-0. PMID 10869804. S2CID 28291041.
- ^ Stockhorst, U.; Steingrüber, H. J.; Scherbaum, W. A. (2000). "Classically conditioned responses following repeated insulin and glucose administration in humans". Behavioural Brain Research. 110 (1–2): 143–159. doi:10.1016/S0166-4328(99)00192-8. PMID 10802311. S2CID 11190637.
- ^ a b Stockhorst, U.; Mahl, N.; Krueger, M.; Huenig, A.; Schottenfeldnaor, Y.; Huebinger, A.; Berresheim, H.; Steingrueber, H.; Scherbaum, W. (2004). "Classical conditioning and conditionability of insulin and glucose effects in healthy humans". Physiology & Behavior. 81 (3): 375–388. doi:10.1016/j.physbeh.2003.12.019. PMID 15135009. S2CID 2498317.
- ^ Fehm-Wolfsdorf, G.; Gnadler, M.; Kern, W.; Klosterhalfen, W.; Kerner, W. (1993). "Classically conditioned changes of blood glucose level in humans". Physiology & Behavior. 54 (1): 155–160. doi:10.1016/0031-9384(93)90058-N. PMID 8327595. S2CID 35578093.