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Chapter 6 - Mapping the Human Emotion Circuits with Positron Emission Tomography

from Section II - Measuring Emotional Processes

Published online by Cambridge University Press:  16 September 2025

Jorge Armony
Affiliation:
McGill University, Montréal
Patrik Vuilleumier
Affiliation:
University of Geneva
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Summary

Positron emission tomography (PET) is the most sensitive technique for imaging of human physiology and molecular pathways in vivo. Here we provide an overview of PET instrumentation and modelling and illustrate how different PET techniques can be used for mapping the molecular basis of the human emotion circuit. We first cover the principles of PET imaging and the most common imaging targets, modelling methods, and experimental designs in brain PET. We then describe how metabolic studies and neuroreceptor mapping of the endogenous dopamine, opioid, serotonin, and cannabinoid systems have contributed to our understanding of the emotional brain. Finally, we review the recent state-of-the art developments in PET-fMRI and total-body PET, and discuss how these techniques can transform the landscape of systems-level biological imaging of the emotion circuits across the brain and periphery.

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Publisher: Cambridge University Press
Print publication year: 2025

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References

Abi-Dargham, A., Gil, R., Krystal, J., Baldwin, R. M., Seibyl, J. P., Bowers, M., … Laruelle, M. (1998). Increased striatal dopamine transmission in schizophrenia: Confirmation in a second cohort. American Journal of Psychiatry, 155, 761–767.CrossRefGoogle ScholarPubMed
Andersson, J. D., Matuskey, D., & Finnema, S. J. (2019). Positron emission tomography imaging of the γ-aminobutyric acid system. Neuroscience Letters, 691, 35–43.CrossRefGoogle ScholarPubMed
Angarita, G. A., Worhunsky, P. D., Naganawa, M., Toyonaga, T., Nabulsi, N. B., Li, C. R., … Malison, R. T. (2022). Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C-UCB-J positron emission tomography study in humans. Addiction Biology, 27, e13123.CrossRefGoogle Scholar
Asch, R. H., Holmes, S. E., Jastreboff, A. M., Potenza, M. N., Baldassarri, S. R., Carson, R. E., … Esterlis, I. (2022). Lower synaptic density is associated with psychiatric and cognitive alterations in obesity. Neuropsychopharmacology, 47, 543–552.CrossRefGoogle ScholarPubMed
Badgaiyan, R. D. (2010). Dopamine is released in the striatum during human emotional processing. Neuroreport, 21, 1172–1176.CrossRefGoogle ScholarPubMed
Badgaiyan, R. D., Fischman, A. J., & Alpert, N. M. (2009). Dopamine release during human emotional processing. NeuroImage, 47, 2041–2045.CrossRefGoogle ScholarPubMed
Bencherif, B., Fuchs, P. N., Sheth, R., Dannals, R. F., Campbell, J. N., & Frost, J. J. (2002). Pain activation of human supraspinal opioid pathways as demonstrated by [11C]-carfentanil and positron emission tomography (PET). Pain, 99, 589–598.CrossRefGoogle ScholarPubMed
Boecker, H., Sprenger, T., Spilker, M. E., Henriksen, G., Koppenhoefer, M., Wagner, K. J., … Tolle, T. R. (2008). The runner’s high: Opioidergic mechanisms in the human brain. Cerebral Cortex, 18, 2523–2531.CrossRefGoogle ScholarPubMed
Brotman, D. J., Golden, S. H., & Wittstein, I. S. (2007). The cardiovascular toll of stress. The Lancet, 370, 1089–1100.CrossRefGoogle ScholarPubMed
Burghardt, P. R., Rothberg, A. E., Dykhuis, K. E., Burant, C. F., & Zubieta, J. K. (2015). Endogenous opioid mechanisms are implicated in obesity and weight loss in humans. Journal of Clinical Endocrinology & Metabolism, 100, 3193–3201.Google ScholarPubMed
Burns, H. D., Van Laere, K., Sanabria-Bohórquez, S., Hamill, T. G., Bormans, G., Eng, W. S., … Hargreaves, R. J. (2007). [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proceedings of the National Academy of Sciences of the United States of America, 104, 9800–9805.Google ScholarPubMed
Cherry, S. R., Badawi, R. D., Karp, J. S., Moses, W. W., Price, P., & Jones, T. (2017). Total-body imaging: Transforming the role of positron emission tomography. Science Translational Medicine, 9, eaaf6169.CrossRefGoogle ScholarPubMed
Cherry, S. R., Jones, T., Karp, J. S., Qi, J., Moses, W. W., & Badawi, R. D. (2018). Total-body PET: Maximizing sensitivity to create new opportunities for clinical research and patient care. Journal of Nuclear Medicine, 59, 3–12.CrossRefGoogle ScholarPubMed
Critchley, H. D., & Harrison, N. A. (2013). Visceral influences on brain and behavior. Neuron, 77, 624–638.CrossRefGoogle ScholarPubMed
Cumming, P. (2014). PET neuroimaging: The white elephant packs his trunk? NeuroImage, 84, 1094–1100.CrossRefGoogle ScholarPubMed
Cumming, P., Abi-Dargham, A., & Gründer, G. (2021). Molecular imaging of schizophrenia: Neurochemical findings in a heterogeneous and evolving disorder. Behavioural Brain Research, 398, 113004.CrossRefGoogle Scholar
D’Esposito, M., Zarahn, E., & Aguirre, G. K. (1999). Event-related functional MRI: Implications for cognitive psychology. Psychological Bulletin, 125, 155–164.Google ScholarPubMed
D’Souza, D. C., Radhakrishnan, R., Naganawa, M., Ganesh, S., Nabulsi, N., Najafzadeh, S., … Skosnik, P. (2021). Preliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder. Molecular Psychiatry, 26, 3192–3200.CrossRefGoogle ScholarPubMed
Damasio, A., & Carvalho, G. B. (2013). The nature of feelings: Evolutionary and neurobiological origins. Nature Reviews Neuroscience, 14, 143–152.CrossRefGoogle ScholarPubMed
Damasio, A. R., Grabowski, T. J., Bechara, A., Damasio, H., Ponto, L. L. B., Parvizi, J., & Hichwa, R. D. (2000). Subcortical and cortical brain activity during the feeling of self-generated emotions. Nature Neuroscience, 3, 1049–1056.CrossRefGoogle ScholarPubMed
de Weijer, B. A., van de Giessen, E., van Amelsvoort, T. A., Boot, E., Braak, B., Janssen, I. M., … Booij, J. (2011). Lower striatal dopamine D2/3 receptor availability in obese compared with non-obese subjects. EJNMMI Research, 1, 37.CrossRefGoogle ScholarPubMed
Drevets, W. C., Frank, E., Price, J. C., Kupfer, D. J., Holt, D., Greer, P. J., … Mathis, C. (1999). Pet imaging of serotonin 1A receptor binding in depression. Biological Psychiatry, 46, 1375–1387.CrossRefGoogle ScholarPubMed
Erritzoe, D., Godlewska, B. R., Rizzo, G., Searle, G. E., Agnorelli, C., Lewis, Y., … Rabiner, E. A. (2023). Brain serotonin release is reduced in patients with depression: A [11C]Cimbi-36 positron emission tomography study with a d-amphetamine challenge. Biological Psychiatry, 93, 1089–1098.CrossRefGoogle ScholarPubMed
Farde, L., Hall, H., Ehrin, E., & Sedvall, G. (1986). Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science, 231, 258–261.CrossRefGoogle ScholarPubMed
Farde, L., Wiesel, F. A., Hall, H., Halldin, C., Stone-Elander, S., & Sedvall, G. (1987). No D2 receptor increase in PET study of schizophrenia. Archives of General Psychiatry, 44, 671–672.CrossRefGoogle ScholarPubMed
Finnema, S. J., Nabulsi, N. B., Eid, T., Detyniecki, K., Lin, S. F., Chen, M. K., … Carson, R. E. (2016). Imaging synaptic density in the living human brain. Science Translational Medicine, 8, 348ra96.CrossRefGoogle ScholarPubMed
Finnema, S. J., Nabulsi, N. B., Mercier, J., Lin, S. F., Chen, M. K., Matuskey, D., … Carson, R. E. (2018). Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. Journal of Cerebral Blood Flow & Metabolism, 38, 2041–2052.CrossRefGoogle ScholarPubMed
Fisher, P. M., Meltzer, C. C., Price, J. C., Coleman, R. L., Ziolko, S. K., Becker, C., … Hariri, A. R. (2009). Medial prefrontal cortex 5-HT2A density is correlated with amygdala reactivity, response habituation, and functional coupling. Cerebral Cortex, 19, 2499–2507.CrossRefGoogle ScholarPubMed
Fisher, P. M., Meltzer, C. C., Ziolko, S. K., Price, J. C., Moses-Kolko, E. L., Berga, S. L., & Hariri, A. R. (2006). Capacity for 5-HT1A-mediated autoregulation predicts amygdala reactivity. Nature Neuroscience, 9, 1362–1363.CrossRefGoogle ScholarPubMed
Fujita, M., Hines, C. S., Zoghbi, S. S., Mallinger, A. G., Dickstein, L. P., Liow, J. S., … Zarate, C. A., Jr. (2012). Downregulation of brain phosphodiesterase type IV measured with 11C-(R)-rolipram positron emission tomography in major depressive disorder. Biology Psychiatry, 72, 548–554.CrossRefGoogle ScholarPubMed
Gilbert, T. M., Zürcher, N. R., Wu, C. J., Bhanot, A., Hightower, B. G., Kim, M., … Hooker, J. M. (2019). PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia. Journal of Clinical Investigation, 129, 364–372.Google ScholarPubMed
Gorelick, D. A., Kim, Y. K., Bencherif, B., Boyd, S. J., Nelson, R., Copersino, M., … Frost, J. J. (2005). Imaging brain mu-opioid receptors in abstinent cocaine users: Time course and relation to cocaine craving. Biological Psychiatry, 57, 1573–1582.CrossRefGoogle ScholarPubMed
Gryglewski, G., Lanzenberger, R., Kranz, G. S., & Cumming, P. (2014). Meta-analysis of molecular imaging of serotonin transporters in major depression. Journal of Cerebral Blood Flow and Metabolism, 34, 1096–1103.CrossRefGoogle ScholarPubMed
Gunn, R. N., Lammertsma, A. A., Hume, S. P., & Cunningham, V. J. (1997). Parametric imaging of ligand-receptor binding in PET using a simplified reference region model. NeuroImage, 6, 279–287.CrossRefGoogle ScholarPubMed
Gunn, R. N., & Rabiner, E. A. (2014). PET neuroimaging: The elephant unpacks his trunk: Comment on Cumming: ‘PET neuroimaging: The white elephant packs his trunk?’. NeuroImage, 94, 408–410.CrossRefGoogle ScholarPubMed
Hahn, A., Gryglewski, G., Nics, L., Hienert, M., Rischka, L., Vraka, C., … Lanzenberger, R. (2016). Quantification of task-specific glucose metabolism with constant infusion of 18F-FDG. Journal of Nuclear Medicine, 57, 1933–1940.CrossRefGoogle ScholarPubMed
Haltia, L. T., Rinne, J. O., Helin, S., Parkkola, R., Nagren, K., & Kaasinen, V. (2008). Effects of intravenous placebo with glucose expectation on human basal ganglia dopaminergic function. Synapse, 62, 682–688.CrossRefGoogle ScholarPubMed
Haltia, L. T., Rinne, J. O., Merisaari, H., Maguire, R. P., Savontaus, E., Helin, S., … Kaasinen, V. (2007). Effects of intravenous glucose on dopaminergic function in the human brain in vivo. Synapse, 61, 748–756.CrossRefGoogle ScholarPubMed
Hanssen, T. A., Nordrehaug, J. E., Eide, G. E., Bjelland, I., & Rokne, B. (2009). Anxiety and depression after acute myocardial infarction: An 18-month follow-up study with repeated measures and comparison with a reference population. European Journal of Cardiovascular Prevention Rehabilitation, 16, 651–659.CrossRefGoogle ScholarPubMed
Heinz, A., Reimold, M., Wrase, J., Hermann, D., Croissant, B., Mundle, G., … Mann, K. (2005). Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: A positron emission tomography study using carbon 11-labeled carfentanil. Archives of General Psychiatry, 62, 57–64.CrossRefGoogle ScholarPubMed
Henriksen, G., & Willoch, F. (2008). Imaging of opioid receptors in the central nervous system. Brain, 131, 1171–1196.CrossRefGoogle ScholarPubMed
Hillman, E. M. C. (2014). Coupling mechanism and significance of the BOLD signal: A status report. Annual Review of Neuroscience, 37, 161–181.CrossRefGoogle Scholar
Hirvonen, J. (2015). In vivo imaging of the cannabinoid CB1 receptor with positron emission tomography. Clinical Pharmacology & Therapeutics, 97, 565–567.CrossRefGoogle ScholarPubMed
Hirvonen, J., Goodwin, R. S., Li, C. T., Terry, G. E., Zoghbi, S. S., Morse, C., … Innis, R. B. (2012). Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Molecular Psychiatry, 17, 642–649.CrossRefGoogle ScholarPubMed
Hirvonen, J., Karlsson, H., Kajander, J., Lepola, A., Markkula, J., Rasi-Hakala, H., … Hietala, J. (2008). Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: An in-vivo imaging study using PET and [carbonyl-11C]WAY-100635. International Journal of Neuropsychopharmacology, 11, 465–476.CrossRefGoogle ScholarPubMed
Hirvonen, J., Virtanen, K. A., Nummenmaa, L., Hannukainen, J. C., Honka, M.-J., Bucci, M., … Nuutila, P. (2011). Effects of insulin on brain glucose metabolism in impaired glucose tolerance. Diabetes, 60, 443–447.CrossRefGoogle ScholarPubMed
Hirvonen, J., Zanotti-Fregonara, P., Gorelick, D. A., Lyoo, C. H., Rallis-Frutos, D., Morse, C., … Innis, R. B. (2018). Decreased cannabinoid CB1 receptors in male tobacco smokers examined with positron emission tomography. Biological Psychiatry, 84, 715–721.CrossRefGoogle ScholarPubMed
Hirvonen, J., Zanotti-Fregonara, P., Umhau, J. C., George, D. T., Rallis-Frutos, D., Lyoo, C. H., … Heilig, M. (2013). Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography. Molecular Psychiatry, 18, 916–921.CrossRefGoogle ScholarPubMed
Holmes, S. E., Scheinost, D., Finnema, S. J., Naganawa, M., Davis, M. T., DellaGioia, N., … Esterlis, I. (2019). Lower synaptic density is associated with depression severity and network alterations. Nature Communications, 10, 1529.CrossRefGoogle ScholarPubMed
Horwitz, B., & Simonyan, K. (2014). PET neuroimaging: Plenty of studies still need to be performed: Comment on Cumming: ‘PET neuroimaging: The white elephant packs his trunk?’. NeuroImage, 84, 1101–1103.CrossRefGoogle ScholarPubMed
Hsu, D. T., Sanford, B. J., Meyers, K. K., Love, T. M., Hazlett, K. E., Walker, S. J., … Zubieta, J. K. (2015). It still hurts: Altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder. Molecular Psychiatry, 20, 193–200.CrossRefGoogle ScholarPubMed
James, W. (1884). What is an emotion? Mind, 9, 188–205.Google Scholar
Jern, P., Chen, J., Tuisku, J., Saanijoki, T., Hirvonen, J., Lukkarinen, L., … Nummenmaa, L. (2023). Endogenous opioid release following orgasm in man: A combined PET–fMRI study. Journal of Nuclear Medicine, 64, 1310–1313.CrossRefGoogle Scholar
Johnson, P. M., & Kenny, P. J. (2010). Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature Neuroscience, 13, 635–641.Google ScholarPubMed
Jonasson, L. S., Axelsson, J., Riklund, K., Braver, T. S., Ogren, M., Backman, L., & Nyberg, L. (2014). Dopamine release in nucleus accumbens during rewarded task switching measured by [11C]raclopride. NeuroImage, 99, 357–364.CrossRefGoogle ScholarPubMed
Joseph, A. T. (2004). Understanding the standardized uptake value, its methods, and implications for usage. Journal of Nuclear Medicine, 45, 1431.Google Scholar
Joutsa, J., Johansson, J., Niemela, S., Ollikainen, A., Hirvonen, M. M., Piepponen, P., … Kaasinen, V. (2012). Mesolimbic dopamine release is linked to symptom severity in pathological gambling. NeuroImage, 60, 1992–1999.CrossRefGoogle ScholarPubMed
Kajander, S., Joutsiniemi, E., Saraste, M., Pietilä, M., Ukkonen, H., Saraste, A., … Knuuti, J. (2010). Cardiac positron emission tomography/computed tomography imaging accurately detects anatomically and functionally significant coronary artery disease. Circulation, 122, 603–613.CrossRefGoogle ScholarPubMed
Kantonen, T., Karjalainen, T., Isojärvi, J., Nuutila, P., Tuisku, J., Rinne, J., … Nummenmaa, L. (2020). Interindividual variability and lateralization of µ-opioid receptors in the human brain. NeuroImage, 217, 116922.CrossRefGoogle ScholarPubMed
Kantonen, T., Karjalainen, T., Pekkarinen, L., Isojärvi, J., Kalliokoski, K., Kaasinen, V., … Nummenmaa, L. (2021). Cerebral μ-opioid and CB1 receptor systems have distinct roles in human feeding behavior. Translational Psychiatry, 11, 442.CrossRefGoogle ScholarPubMed
Kantonen, T., Pekkarinen, L., Karjalainen, T., Bucci, M., Kalliokoski, K., Haaparanta-Solin, M., … Nummenmaa, L. (2021). Obesity risk is associated with altered cerebral glucose metabolism and decreased µ-opioid and CB1-receptor availability. International Journal of Obesity, 46, 400–407.Google Scholar
Karjalainen, T., Karlsson, H. K., Lahnakoski, J. M., Glerean, E., Nuutila, P., Jaaskelainen, I. P., … Nummenmaa, L. (2017). Dissociable roles of cerebral µ-opioid and type 2 dopamine receptors in vicarious pain: A combined PET–fMRI study. Cerebral Cortex, 27, 4257–4266.CrossRefGoogle Scholar
Karjalainen, T., Seppala, K., Glerean, E., Karlsson, H. K., Lahnakoski, J. M., Nuutila, P., … Nummenmaa, L. (2019). Opioidergic regulation of emotional arousal: A combined PET–fMRI study. Cereb Cortex, 29, 4006–4016.CrossRefGoogle ScholarPubMed
Karlsson, H. K., Tuominen, L., Tuulari, J. J., Hirvonen, J., Honka, H., Parkkola, R., … Nummenmaa, L. (2016). Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity. Molecular Psychiatry, 21, 1057–1062.Google ScholarPubMed
Karlsson, H. K., Tuominen, L., Tuulari, J. J., Hirvonen, J., Parkkola, R., Helin, S., … Nummenmaa, L. (2015). Obesity is associated with decreased µ-opioid but unaltered dopamine D2 receptor availability in the brain. Journal of Neuroscience, 35, 3959–3965.CrossRefGoogle ScholarPubMed
Kennedy, S. E., Koeppe, R. A., Young, E. A., & Zubieta, J. K. (2006). Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Archives of General Psychiatry, 63, 1199–1208.CrossRefGoogle ScholarPubMed
Kirkham, T. C., Williams, C. M., Fezza, F., & Di Marzo, V. (2002). Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: Stimulation of eating by 2-arachidonoyl glycerol. British Journal of Pharmacology, 136, 550–557.CrossRefGoogle ScholarPubMed
Knuuti, J., Tuisku, J., Kärpijoki, H., Iida, H., Maaniitty, T., Latva-Rasku, A., … Nummenmaa, L. (2023). Quantitative perfusion imaging with total-body PET. Journal of Nuclear Medicine, 64, 11S–19S.CrossRefGoogle ScholarPubMed
Koch, T., & Hollt, V. (2008). Role of receptor internalization in opioid tolerance and dependence. Pharmacology & Therapeutics, 117, 199–206.CrossRefGoogle ScholarPubMed
Koepp, M. J., Gunn, R. N., Lawrence, A. D., Cunningham, V. J., Dagher, A., Jones, T., … Grasby, P. M. (1998). Evidence for striatal dopamine release during a video game. Nature, 393, 266–268.CrossRefGoogle ScholarPubMed
Koepp, M. J., Hammers, A., Lawrence, A. D., Asselin, M. C., Grasby, P. M., & Bench, C. J. (2009). Evidence for endogenous opioid release in the amygdala during positive emotion. NeuroImage, 44, 252–256.CrossRefGoogle ScholarPubMed
Köhler-Forsberg, K., Dam, V. H., Ozenne, B., Sankar, A., Beliveau, V., Landman, E. B., … Knudsen, G. M. (2023). Serotonin 4 receptor brain binding in major depressive disorder and association with memory dysfunction. JAMA Psychiatry, 80, 296–304.CrossRefGoogle Scholar
Laaksonen, L., Kallioinen, M., Långsjö, J., Laitio, T., Scheinin, A., Scheinin, J., … Scheinin, H. (2018). Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: A positron emission tomography study. British Journal of Anaesthesia, 121, 281–290.CrossRefGoogle ScholarPubMed
Lammertsma, A. A., & Hume, S. P. (1996). Simplified reference tissue model for PET receptor studies. NeuroImage, 4, 153–158.CrossRefGoogle ScholarPubMed
Lan, M. J., Zanderigo, F., Pantazatos, S. P., Sublette, M. E., Miller, J., Ogden, R. T., & Mann, J. J. (2022). Serotonin 1A receptor binding of [11C]CUMI-101 in bipolar depression quantified using positron emission tomography: Relationship to psychopathology and antidepressant response. International Journal of Neuropsychopharmacology, 25, 534–544.CrossRefGoogle ScholarPubMed
Logothetis, N. K., & Wandell, B. A. (2004). Interpreting the BOLD signal. Annual Review of Physiology, 66, 735–769.CrossRefGoogle ScholarPubMed
Majo, V. J., Prabhakaran, J., Mann, J. J., & Kumar, J. S. D. (2013). PET and SPECT tracers for glutamate receptors. Drug Discovery Today, 18, 173–184.CrossRefGoogle ScholarPubMed
Majuri, J., Joutsa, J., Johansson, J., Voon, V., Alakurtti, K., Parkkola, R., … Kaasinen, V. (2016). Dopamine and opioid neurotransmission in behavioral addictions: A comparative PET study in pathological gambling and binge eating. Neuropsychopharmacology, 42, 1169–1177.Google ScholarPubMed
Manninen, S., Tuominen, L., Dunbar, R. I. M., Karjalainen, T., Hirvonen, J., Arponen, E., … Nummenmaa, L. (2017). Social laughter triggers endogenous opioid release in humans. The Journal of Neuroscience, 37, 6125–6131.CrossRefGoogle ScholarPubMed
Marek, S., Tervo-Clemmens, B., Calabro, F. J., Montez, D. F., Kay, B. P., Hatoum, A. S., … Dosenbach, N. U. F. (2022). Reproducible brain-wide association studies require thousands of individuals. Nature, 603, 654–660.CrossRefGoogle ScholarPubMed
Martinez, D., Saccone, P. A., Liu, F., Slifstein, M., Orlowska, D., Grassetti, A., … Comer, S. D. (2012). Deficits in dopamine D2 receptors and presynaptic dopamine in heroin dependence: Commonalities and differences with other types of addiction. Biological Psychiatry, 71, 192–198.CrossRefGoogle ScholarPubMed
Mechoulam, R., & Parker, L. A. (2013). The endocannabinoid system and the brain. Annual Review of Psychology, 64, 21–47.CrossRefGoogle ScholarPubMed
Meyer, J. H., Wilson, A. A., Sagrati, S., Hussey, D., Carella, A., Potter, W. Z., … Houle, S. (2004). Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: An [11C]DASB positron emission tomography study. American Journal of Psychiatry, 161, 826–835.CrossRefGoogle ScholarPubMed
Moses, W. W. (2011). Fundamental limits of spatial resolution in PET. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 648, S236–S240.CrossRefGoogle ScholarPubMed
Nummenmaa, L., Glerean, E., Hari, R., & Hietanen, J. K. (2014). Bodily maps of emotions. Proceedings of the National Academy of Sciences of the United States of America, 111, 646–651.Google ScholarPubMed
Nummenmaa, L., Hari, R., Hietanen, J. K., & Glerean, E. (2018). Maps of subjective feelings. Proceedings of the National Academy of Sciences of the United States of America, 115, 9198–9203.Google ScholarPubMed
Nummenmaa, L., Hirvonen, J., Hannukainen, J. C., Immonen, H., Lindroos, M. M., Salminen, P., & Nuutila, P. (2012). Dorsal striatum and its limbic connectivity mediate abnormal anticipatory reward processing in obesity. PloS ONE, 7, 10.CrossRefGoogle ScholarPubMed
Nummenmaa, L., Karjalainen, T., Isojärvi, J., Kantonen, T., Tuisku, J., Kaasinen, V., … Rinne, J. (2020). Lowered endogenous mu-opioid receptor availability in subclinical depression and anxiety. Neuropsychopharmacology, 45, 1953–1959.CrossRefGoogle ScholarPubMed
Nummenmaa, L., & Saarimäki, H. (2017). Emotions as discrete patterns of systemic activity. Neuroscience Letters, 693, 3–8.Google ScholarPubMed
Nummenmaa, L., & Tuominen, L. J. (2018). Opioid system and human emotions. British Journal of Pharmacology, 175, 2737–2749.CrossRefGoogle ScholarPubMed
Ogawa, S., Lee, T. M., Kay, A. R., & Tank, D. W. (1990). Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proceedings of the National Academy of Sciences of the United States of America, 87, 9868–9872.Google ScholarPubMed
Onwordi, E. C., Halff, E. F., Whitehurst, T., Mansur, A., Cotel, M. C., Wells, L., … Howes, O. D. (2020). Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats. Nature Communications, 11, 246.CrossRefGoogle ScholarPubMed
Pak, K., Malen, T., Santavirta, S., Shin, S., Nam, H.-Y., De Mayer, S., & Nummenmaa, L. (2022). Brain glucose metabolism and ageing: A 5-year longitudinal study in a large PET cohort. Diabetes Care, 46, e64–e66.Google Scholar
Parsey, R. V., Ogden, R. T., Miller, J. M., Tin, A., Hesselgrave, N., Goldstein, E., … Mann, J. J. (2010). Higher serotonin 1A binding in a second major depression cohort: modeling and reference region considerations. Biological Psychiatry, 68, 170–178.CrossRefGoogle Scholar
Pascoal, T. A., Chamoun, M., Lax, E., Wey, H. Y., Shin, M., Ng, K. P., … Rosa-Neto, P. (2022). [11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease. Nature Communications, 13, 4171.Google ScholarPubMed
Raichle, M. E. (2010). Two views of brain function. Trends in Cognitive Sciences, 14, 180–190.CrossRefGoogle ScholarPubMed
Raine, A., Stoddard, J., Bihrle, S., & Buchsbaum, M. (1998). Prefrontal glucose deficits in murderers lacking psychosocial deprivation. Neuropsychiatry Neuropsychology and Behavioral Neurology, 11, 1–7.Google ScholarPubMed
Rebelos, E., Bucci, M., Karjalainen, T., Oikonen, V., Bertoldo, A., Hannukainen, J. C., … Nuutila, P. (2021). Insulin resistance is associated with enhanced brain glucose uptake during euglycemic hyperinsulinemia: A large-scale PET cohort. Diabetes Care, 44, 788–794.CrossRefGoogle ScholarPubMed
Reiman, E. M., Lane, R. D., Ahern, G. L., Schwartz, G. E., Davidson, R. J., Friston, K. J., … Chen, K. (1997). Neuroanatomical correlates of externally and internally generated human emotion. American Journal of Psychiatry, 154, 918–925.Google ScholarPubMed
Rhodes, R. A., Murthy, N. V., Dresner, M. A., Selvaraj, S., Stavrakakis, N., Babar, S., … Grasby, P. M. (2007). Human 5-HT transporter availability predicts amygdala reactivity in vivo. Journal of Neuroscience, 27, 9233–9237.CrossRefGoogle ScholarPubMed
Risch, N., Herrell, R., Lehner, T., Liang, K. Y., Eaves, L., Hoh, J., … Merikangas, K. R. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression a meta-analysis. JAMA, 301, 2462–2471.CrossRefGoogle ScholarPubMed
Rowlett, J. K., Platt, D. M., Lelas, S., Atack, J. R., & Dawson, G. R. (2005). Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates. Proceedings of the National Academy of Sciences, 102, 915–920.CrossRefGoogle ScholarPubMed
Saanijoki, T., Tuominen, L., Tuulari, J. J., Nummenmaa, L., Arponen, E., Kalliokoski, K., & Hirvonen, J. (2017). Opioid release after high-intensity interval training in healthy human subjects. Neuropsychopharmacology, 43, 246–254.Google ScholarPubMed
Salimpoor, V. N., Benovoy, M., Larcher, K., Dagher, A., & Zatorre, R. J. (2011). Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nature Neuroscience, 14, 257–262.CrossRefGoogle Scholar
Scott, D. J., Stohler, C. S., Koeppe, R. A., & Zubieta, J. K. (2007). Time-course of change in [11C]carfentanil and [11C]raclopride binding potential after a nonpharmacological challenge. Synapse, 61, 707–714.CrossRefGoogle ScholarPubMed
Selvaraj, S., Mouchlianitis, E., Faulkner, P., Turkheimer, F., Cowen, P. J., Roiser, J. P., & Howes, O. (2015). Presynaptic serotoninergic regulation of emotional processing: A multimodal brain imaging study. Biology Psychiatry, 78, 563–571.CrossRefGoogle ScholarPubMed
Shackman, A. J., Fox, A. S., Oler, J. A., Shelton, S. E., Davidson, R. J., & Kalin, N. H. (2013). Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Proceedings of the National Academy of Sciences, 110, 6145–6150.CrossRefGoogle ScholarPubMed
Shrestha, S., Hirvonen, J., Hines, C. S., Henter, I. D., Svenningsson, P., Pike, V. W., & Innis, R. B. (2012). Serotonin-1A receptors in major depression quantified using PET: Controversies, confounds, and recommendations. NeuroImage, 59, 3243–3251.CrossRefGoogle ScholarPubMed
Siegel, E. H., Sands, M. K., Van den Noortgate, W., Condon, P., Chang, Y., Dy, J., … Barrett, L. F. (2018). Emotion fingerprints or emotion populations? A meta-analytic investigation of autonomic features of emotion categories. Psychological Bulletin, 144, 343–393.CrossRefGoogle ScholarPubMed
Small, D. M., Jones-Gotman, M., & Dagher, A. (2003). Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. NeuroImage, 19, 1709–1715.CrossRefGoogle ScholarPubMed
Smith, A. L., Freeman, S. M., Barnhart, T. E., Abbott, D. H., Ahlers, E. O., Kukis, D. L., … Young, L. J. (2016). Initial investigation of three selective and potent small molecule oxytocin receptor PET ligands in New World monkeys. Bioorganic & Medicinal Chemistry Letters, 26, 3370–3375.CrossRefGoogle ScholarPubMed
Sokoloff, L. (1999). Energetics of functional activation in neural tissues. Neurochemical Research, 24, 321–329.CrossRefGoogle ScholarPubMed
Steele, K. E., Prokopowicz, G. P., Schweitzer, M. A., Magunsuon, T. H., Lidor, A. O., Kuwabawa, H., … Wong, D. F. (2010). Alterations of central dopamine receptors before and after gastric bypass surgery. Obesity Surgery, 20, 369–374.CrossRefGoogle ScholarPubMed
Stiernman, L. J., Grill, F., Hahn, A., Rischka, L., Lanzenberger, R., Panes Lundmark, V., … Rieckmann, A. (2021). Dissociations between glucose metabolism and blood oxygenation in the human default mode network revealed by simultaneous PET-fMRI. Proceedings of the National Academy of Sciences, 118, e2021913118.CrossRefGoogle ScholarPubMed
Su, L., Cai, Y., Xu, Y., Dutt, A., Shi, S., & Bramon, E. (2014). Cerebral metabolism in major depressive disorder: A voxel-based meta-analysis of positron emission tomography studies. BMC Psychiatry, 14, 321.CrossRefGoogle ScholarPubMed
Surti, S. (2015). Update on time-of-flight PET imaging. Journal of Nuclear Medicine, 56, 98–105.CrossRefGoogle ScholarPubMed
Taglialatela, J. P., Russell, J. L., Schaeffer, J. A., & Hopkins, W. D. (2008). Communicative signaling activates Broca’s homolog in chimpanzees. Current Biology, 18, 343–348.CrossRefGoogle ScholarPubMed
Tan, H., Gu, Y., Yu, H., Hu, P., Zhang, Y., Mao, W., & Shi, H. (2020). Total-body PET/CT: Current applications and future perspectives. American Journal of Roentgenology, 215, 325–337.CrossRefGoogle ScholarPubMed
Terry, G. E., Hirvonen, J., Liow, J. S., Zoghbi, S. S., Gladding, R., Tauscher, J. T., … Innis, R. B. (2010). Imaging and quantitation of cannabinoid CB1 receptors in human and monkey brains using (18)F-labeled inverse agonist radioligands. Journal of Nuclear Medicine, 51, 112–120.CrossRefGoogle Scholar
Terry, G. E., Liow, J. S., Zoghbi, S. S., Hirvonen, J., Farris, A. G., Lerner, A., … Innis, R. B. (2009). Quantitation of cannabinoid CB1 receptors in healthy human brain using positron emission tomography and an inverse agonist radioligand. NeuroImage, 48, 362–370.CrossRefGoogle Scholar
Tiger, M., Farde, L., Rück, C., Varrone, A., Forsberg, A., Lindefors, N., … Lundberg, J. (2016). Low serotonin1B receptor binding potential in the anterior cingulate cortex in drug-free patients with recurrent major depressive disorder. Psychiatry Research Neuroimaging, 253, 36–42.CrossRefGoogle ScholarPubMed
Tseng, C. J., Gilbert, T. M., Catanese, M. C., Hightower, B. G., Peters, A. T., Parmar, A. J., … Hooker, J. M. (2020). In vivo human brain expression of histone deacetylases in bipolar disorder. Translational Psychiatry, 10, 224.CrossRefGoogle ScholarPubMed
Tuominen, L., Salo, J., Hirvonen, J., Nagren, K., Laine, P., Melartin, T., … Hietala, J. (2012). Temperament trait Harm Avoidance associates with µ-opioid receptor availability in frontal cortex: A PET study using [11C] carfentanil. NeuroImage, 61, 670–676.CrossRefGoogle ScholarPubMed
Tuominen, L., Tuulari, J., Karlsson, H., Hirvonen, J., Helina, S., Salminen, P., … Nummenmaa, L. (2015). Aberrant mesolimbic dopamine-opiate interaction in obesity. NeuroImage, 122, 80–86.CrossRefGoogle ScholarPubMed
Tuulari, J. J., Tuominen, L., de Boer, F. E., Hirvonen, J., Helin, S., Nuutila, P., & Nummenmaa, L. (2017). Feeding releases endogenous opioids in humans. Journal of Neuroscience, 37, 8284–8291.CrossRefGoogle ScholarPubMed
Villien, M., Wey, H.-Y., Mandeville, J. B., Catana, C., Polimeni, J. R., Sander, C. Y., … Hooker, J. M. (2014). Dynamic functional imaging of brain glucose utilization using fPET-FDG. NeuroImage, 100, 192–199.CrossRefGoogle ScholarPubMed
Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Ding, Y. S., Sedler, M., … Pappas, N. (2001). Low level of brain dopamine D2 receptors in methamphetamine abusers: Association with metabolism in the orbitofrontal cortex. American Journal of Psychiatry, 158, 2015–2021.CrossRefGoogle ScholarPubMed
Volkow, N. D., Fowler, J. S., Wang, G. J., Baler, R., & Telang, F. (2009). Imaging dopamine’s role in drug abuse and addiction. Neuropharmacology, 56, 3–8.CrossRefGoogle ScholarPubMed
Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Hitzemann, R., Ding, Y. S., … Piscani, K. (1996). Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcoholism: Clinical and Experimental Research, 20, 1594–1598.CrossRefGoogle Scholar
Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Thanos, P. K., Logan, J., … Pradhan, K. (2008). Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors. NeuroImage, 42, 1537–1543.CrossRefGoogle ScholarPubMed
Wadsak, W., & Mitterhauser, M. (2010). Basics and principles of radiopharmaceuticals for PET/CT. European Journal of Radiology, 73, 461–469.CrossRefGoogle ScholarPubMed
Wang, G. J., Volkow, N. D., Logan, J., Pappas, N. R., Wong, C. T., Zhu, W., … Fowler, J. S. (2001). Brain dopamine and obesity. Lancet, 357, 354–357.CrossRefGoogle ScholarPubMed
Weerts, E. M., Wand, G. S., Kuwabara, H., Munro, C. A., Dannals, R. F., Hilton, J., … McCaul, M. E. (2011). Positron emission tomography imaging of mu- and delta-opioid receptor binding in alcohol-dependent and healthy control subjects. Alcoholism: Clinical and Experimental Research, 35, 2162–2173.CrossRefGoogle ScholarPubMed
Wey, H.-Y., Gilbert, T. M., Zürcher, N. R., She, A., Bhanot, A., Taillon, B. D., … Hooker, J. M. (2016). Insights into neuroepigenetics through human histone deacetylase PET imaging. Science Translational Medicine, 8, 351ra106.CrossRefGoogle ScholarPubMed
Whistler, J. L. (2012). Examining the role of mu opioid receptor endocytosis in the beneficial and side-effects of prolonged opioid use: From a symposium on new concepts in mu-opioid pharmacology. Drug and Alcohol Dependence, 121, 189–204.CrossRefGoogle ScholarPubMed
Wong, D. F., Kuwabara, H., Horti, A. G., Raymont, V., Brasic, J., Guevara, M., … Cascella, N. (2010). Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR. NeuroImage, 52, 1505–1513.CrossRefGoogle ScholarPubMed
Wong, D. F., Wagner, H. N., Jr., Tune, L. E., Dannals, R. F., Pearlson, G. D., Links, J. M., … Gjedde, A. (1986). Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science, 234, 1558–1563.CrossRefGoogle ScholarPubMed
Zald, D. H. (2003). The human amygdala and the emotional evaluation of sensory stimuli. Brain Research. Brain Research Reviews, 41, 88–123.CrossRefGoogle ScholarPubMed
Zhang, X., Cherry, S. R., Xie, Z., Shi, H., Badawi, R. D., & Qi, J. (2020). Subsecond total-body imaging using ultrasensitive positron emission tomography. Proceedings of the National Academy of Sciences, 117, 2265–2267.Google ScholarPubMed
Zubieta, J. K., Smith, Y. R., Bueller, J. A., Xu, Y. J., Kilbourn, M. R., Jewett, D. M., … Stohler, C. S. (2001). Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science, 293, 311–315.CrossRefGoogle ScholarPubMed

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