214 results on '"Nummenmaa, L."'
Search Results
2. Alterations in type 2 dopamine receptors across neuropsychiatric conditions: A large-scale PET cohort
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Malén, T., primary, Santavirta, S., additional, De Maeyer, S., additional, Tuisku, J., additional, Kaasinen, V., additional, Kankare, T., additional, Isojärvi, J., additional, Rinne, J., additional, Hietala, J., additional, Nuutila, P., additional, and Nummenmaa, L., additional
- Published
- 2023
- Full Text
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3. Cerebral Topographies of Perceived and Felt Emotions
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Saarimäki, H, primary, Nummenmaa, L, additional, Volynets, S, additional, Santavirta, S, additional, Aksiuto, A, additional, Sams, M, additional, Jääskeläinen, IP, additional, and Lahnakoski, JM, additional
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- 2023
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4. Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity
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Karlsson, H K, Tuulari, J J, Tuominen, L, Hirvonen, J, Honka, H, Parkkola, R, Helin, S, Salminen, P, Nuutila, P, and Nummenmaa, L
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- 2016
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5. Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort
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Rebelos, E., Bucci, M., Karjalainen, T., Oikonen, V., Bertoldo, A., Hannukainen, J. C., Virtanen, K. A., Latva-Rasku, A., Hirvonen, J., Heinonen, I., Parkkola, R., Laakso, M., Ferrannini, E., Iozzo, P., Nummenmaa, L., and Nuutila, P.
- Subjects
Blood Glucose ,Glucose ,Diabetes Mellitus, Type 2 ,Hyperinsulinism ,Positron-Emission Tomography ,Glucose Clamp Technique ,Brain ,Humans ,Insulin ,Bayes Theorem ,Insulin Resistance ,Pathophysiology/Complications - Abstract
Objective Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of subjects across a wide range of age and insulin sensitivity. Research Design and Methods [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 subjects scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex, M value from the clamp, steady-state insulin and free fatty acids levels, C-reactive protein, HbA1c, and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling. Results Insulin sensitivity, indexed by the M value, was associated negatively with BGU in all brain regions, confirming that in insulin resistant subjects BGU is enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with a further increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein, free fatty acids, sex, and HbA1c were not associated with BGU. Conclusions In this large cohort of subjects of either sex across a wide range of age and insulin sensitivity, insulin sensitivity is the best predictor of brain glucose uptake.
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- 2021
6. Patients with complex regional pain syndrome overestimate applied force in observed hand actions
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Hotta, J., Harno, H., Nummenmaa, L., Kalso, E., Hari, R., and Forss, N.
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- 2015
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7. Adult attachment system links with brain mu opioid receptor availability in vivo
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Turtonen, O. (Otto), Saarinen, A. (Aino), Nummenmaa, L. (Lauri), Tuominen, L. (Lauri), Tikka, M. (Maria), Armio, R.-L. (Reetta-Liina), Hautamäki, A. (Airi), Laurikainen, H. (Heikki), Raitakari, O. (Olli), Keltikangas-Järvinen, L. (Liisa), Hietala, J. A. (Jarmo A.), Turtonen, O. (Otto), Saarinen, A. (Aino), Nummenmaa, L. (Lauri), Tuominen, L. (Lauri), Tikka, M. (Maria), Armio, R.-L. (Reetta-Liina), Hautamäki, A. (Airi), Laurikainen, H. (Heikki), Raitakari, O. (Olli), Keltikangas-Järvinen, L. (Liisa), and Hietala, J. A. (Jarmo A.)
- Abstract
Background: Secure attachment is important in maintaining an individual’s health and well-being. Attachment disturbances increase the risk for developing psychiatric disorders such as affective disorders. Yet, the neurobiological correlates of human attachment are poorly understood at the neurotransmitter level. We investigated whether adult attachment style is linked to functioning of the opioid and serotonergic systems in the human brain. Methods: We used positron emission tomography with radioligands [¹¹C]carfentanil and [¹¹C]MADAM to quantify mu opioid receptor (n = 39) and serotonin transporter (n = 37) availability in volunteers with no current psychiatric disorders. Attachment style was determined according to the Dynamic-Maturational Model of Attachment and Adaptation with the structured Adult Attachment Interview. Results: Secure attachment was associated with higher mu opioid receptor availability in the hippocampus, amygdala, thalamus, and prefrontal cortex when compared with insecure (i.e., avoidant or ambivalent groups combined) attachment. In contrast, attachment style was not associated with serotonin transporter availability. Conclusions: Our results provide preliminary in vivo evidence that the opioid system may be involved in the neurocircuits associated with individual differences in adult attachment behavior. The results suggest that variation in mu opioid receptor availability may be linked with the individuals’ social relationships and psychosocial well-being and thus contributes to risk for psychiatric morbidity.
- Published
- 2021
8. Bariatric surgery normalizes brain opioid receptors
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Karlsson, H K, Tuulari, J J, Tuominen, L, Hirvonen, J, Honka, H, Parkkola, R, Helin, S, Salminen, P, Nuutila, P, and Nummenmaa, L
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- 2016
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9. A partial loss-of-function variant in AKT2 is associated with reduced insulin-mediated glucose uptake in multiple insulin-sensitive tissues: A genotype-based callback positron emission tomography study
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Mohlke, K.L., Karjalainen, T., Kuusisto, J., Boehnke, M., Scott, L.J., Latva-Rasku, A., Stringham, H., Gloyn, A.L., Nuutila, P., Manning, A.K., Guan, L., Stanc��kov��, A., Nummenmaa, L., Lindgren, C.M., Honka, M.-J., Laakso, M., and Koistinen, H.A.
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hormones, hormone substitutes, and hormone antagonists - Abstract
Rare fully penetrant mutations in AKT2 are an established cause of monogenic disorders of glucose metabolism. Recently, a novel partial loss-of-function AKT2 coding variant (p.Pro50Thr) was identified that is nearly specific to Finns (frequency 1.1%), with the low-frequency allele associated with an increase in fasting plasma insulin level and risk of type 2 diabetes. The effects of the p.Pro50Thr AKT2 variant (p.P50T/AKT2) on insulin-stimulated glucose uptake (GU) in the whole body and in different tissues have not previously been investigated. We identified carriers (N = 20) and matched noncarriers (N = 25) for this allele in the population-based Metabolic Syndrome in Men (METSIM) study and invited these individuals back for positron emission tomography study with [18F]-fluorodeoxyglucose during euglycemic hyperinsulinemia. When we compared p.P50T/AKT2 carriers to noncarriers, we found a 39.4% reduction in whole-body GU (P = 0.006) and a 55.6% increase in the rate of endogenous glucose production (P = 0.038). We found significant reductions in GU in multiple tissues���skeletal muscle (36.4%), liver (16.1%), brown adipose (29.7%), and bone marrow (32.9%)���and increases of 16.8���19.1% in seven tested brain regions. These data demonstrate that the p.P50T substitution of AKT2 influences insulin-mediated GU in multiple insulin-sensitive tissues and may explain, at least in part, the increased risk of type 2 diabetes in p.P50T/AKT2 carriers.
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- 2018
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10. Simplified Automated Segmentation of Acute Ischemic Stroke Lesions from Multimodal MRI: A knowledge-based learning approach
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Nazari-Farsani, S., primary, Nyman, M., additional, Karjalainen, T., additional, Bucci, M., additional, Isojarvi, J., additional, and Nummenmaa, L., additional
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- 2019
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11. Dissociable Roles of Cerebral μ-Opioid and Type 2 Dopamine Receptors in Vicarious Pain: A Combined PET-fMRI Study
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Karjalainen, T., Karlsson, H., Lahnakoski, J., Glerean, E., Nuutila, P., Jaaskelainen, I., Hari, R., Sams, M., and Nummenmaa, L.
- Abstract
Neuroimaging studies have shown that seeing others in pain activates brain regions that are involved in first-hand pain, suggesting that shared neuromolecular pathways support processing of first-hand and vicarious pain. We tested whether the dopamine and opioid neurotransmitter systems involved in nociceptive processing also contribute to vicarious pain experience. We used in vivo positron emission tomography to quantify type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities in brains of 35 subjects. During functional magnetic resonance imaging, the subjects watched short movie clips depicting persons in painful and painless situations. Painful scenes activated pain-responsive brain regions including anterior insulae, thalamus and secondary somatosensory cortices, as well as posterior superior temporal sulci. MOR availability correlated negatively with the haemodynamic responses during painful scenes in anterior and posterior insulae, thalamus, secondary and primary somatosensory cortices, primary motor cortex, and superior temporal sulci. MOR availability correlated positively with orbitofrontal haemodynamic responses during painful scenes. D2R availability was not correlated with the haemodynamic responses in any brain region. These results suggest that the opioid system contributes to neural processing of vicarious pain, and that interindividual differences in opioidergic system could explain why some individuals react more strongly than others to seeing pain.
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- 2017
12. Adult attachment style is associated with cerebral μ‐opioid receptor availability in humans
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Nummenmaa, L, Manninen, S, Tuominen, L, Hirvonen, J, Kalliokoski, K, Nuutila, P, Jääskeläinen, I, Hari, R, Dunbar, R, and Sams, M
- Subjects
Adult ,Male ,Brain Mapping ,Psychological Tests ,Individuality ,Receptors, Opioid, mu ,Brain ,Middle Aged ,Object Attachment ,Fentanyl ,Young Adult ,nervous system ,Positron-Emission Tomography ,Surveys and Questionnaires ,Humans ,Female ,Carbon Radioisotopes ,Radiopharmaceuticals ,Research Articles - Abstract
Human attachment behavior mediates establishment and maintenance of social relationships. Adult attachment characteristically varies on anxiety and avoidance dimensions, reflecting the tendencies to worry about the partner breaking the social bond (anxiety) and feeling uncomfortable about depending on others (avoidance). In primates and other mammals, the endogenous μ‐opioid system is linked to long‐term social bonding, but evidence of its role in human adult attachment remains more limited. We used in vivo positron emission tomography to reveal how variability in μ‐opioid receptor (MOR) availability is associated with adult attachment in humans. We scanned 49 healthy subjects using a MOR‐specific ligand [(11)C]carfentanil and measured their attachment avoidance and anxiety with the Experiences in Close Relationships‐Revised scale. The avoidance dimension of attachment correlated negatively with MOR availability in the thalamus and anterior cingulate cortex, as well as the frontal cortex, amygdala, and insula. No associations were observed between MOR availability and the anxiety dimension of attachment. Our results suggest that the endogenous opioid system may underlie interindividual differences in avoidant attachment style in human adults, and that differences in MOR availability are associated with the individuals’ social relationships and psychosocial well‐being. Hum Brain Mapp 36:3621–3628, 2015. © 2015 Wiley Periodicals, Inc.
- Published
- 2015
13. One-week administration of escitalopram decreases neural responses to self-referential processing in major depression
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Komulainen, E., primary, Heikkilä, R., additional, Meskanen, K., additional, Nummenmaa, L., additional, Raij, T.T., additional, Isometsä, E., additional, and Ekelund, J., additional
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- 2016
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14. Just watching the game ain\u2019t enough: striatal fMRI reward responses to successes versus failures in a video game during active versus vicarious playing
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Kxe4tsyri, J, Hari, R, Ravaja, N, and Nummenmaa, L
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- 2013
15. Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity
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Karlsson, H K, primary, Tuulari, J J, additional, Tuominen, L, additional, Hirvonen, J, additional, Honka, H, additional, Parkkola, R, additional, Helin, S, additional, Salminen, P, additional, Nuutila, P, additional, and Nummenmaa, L, additional
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- 2015
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16. Connectivity Analysis Reveals a Cortical Network for Eye Gaze Perception
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Nummenmaa L, Passamonti L, Rowe J, Engell AD, and Calder AJ.
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- 2009
17. Cortical network for eye gaze perception
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Nummenmaa L, Passamonti L, Engell A, Rowe JB, and Calder AJ
- Published
- 2008
18. P.2.b.023 A single dose of mirtazapine modulates neuronal responses to spoken emotional narratives in healthy volunteers
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Komulainen, E., primary, Meskanen, K., additional, Heikkilä, R., additional, Nummenmaa, L., additional, Raij, T., additional, Isometsä, E., additional, and Ekelund, J., additional
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- 2014
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19. P.2.f.020 - One-week administration of escitalopram decreases neural responses to self-referential processing in major depression
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Komulainen, E., Heikkilä, R., Meskanen, K., Nummenmaa, L., Raij, T.T., Isometsä, E., and Ekelund, J.
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- 2016
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20. The brains of high functioning autistic individuals do not synchronize with those of others
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Salmi, J., primary, Roine, U., additional, Glerean, E., additional, Lahnakoski, J., additional, Nieminen-von Wendt, T., additional, Tani, P., additional, Leppämäki, S., additional, Nummenmaa, L., additional, Jääskeläinen, I.P., additional, Carlson, S., additional, Rintahaka, P., additional, and Sams, M., additional
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- 2013
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21. Connectivity Analysis Reveals a Cortical Network for Eye Gaze Perception
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Nummenmaa, L., primary, Passamonti, L., additional, Rowe, J., additional, Engell, A. D., additional, and Calder, A. J., additional
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- 2009
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22. Automatic activation of adolescents' peer-relational schemas: evidence from priming with facial identity.
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Nummenmaa L, Peets K, and Salmivalli C
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- 2008
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23. Maternal BMI and exercise have interactive effects on brain's white and grey matter composition in elderly women
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Marco Bucci, Tuulari, J. J., Raiko, J., Huovinen, V., Lipponen, H., Koskinen, S., Sandboge, S., Eriksson, J., Iozzo, P., Nummenmaa, L., and Nuutila, P.
24. Emotional experiences and psychological well-being in 51 countries during the COVID-19 pandemic.
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Sun, R., Balabanova, A., Bajada, C. J., Liu, Y., Kriuchok, M., Voolma, S-R., Đurić, M., Mayer, C-H., Constantinou, M., Chichua, M., Li, C., Foster-Estwick, A., Borg, K., Hill, C., Kaushal, R., Diwan, K., Vitale, V., Engels, T., Aminudin, R., Ursu, I., Fadhlia, T. N., Wu, Y-J., Sekaja, L., Hadchity, M., Deak, A., Sharaf, S., Figueras, P., Kaziboni, A., Whiston, A., Ioumpa, K., Montelongo, A., Pauw, L., Pavarini, G., Vedernikova, E., Vu, T. V., Nummenmaa, L., Cong, Y-Q., Nikolic, M., Olguin, A., Hou, W. K., Israelashvili, J., Koo, H. J., Khademi, S., Ukachukwu, C. G., Juma, D. O., Kamiloğlu, R. G., Makhmud, A., Lunga, P. S., Rieble, C., Rizwan, M., Helmy, M., Vuillier, Laura, Manokara, K., Quezada, E. C., Tserendamba, D., Yoshie, M., Du, A. H., Philip-Joe, K., Kúld, P. B., Damani, K., Osei-Tutu, A., Sauter, D., Sun, R., Balabanova, A., Bajada, C. J., Liu, Y., Kriuchok, M., Voolma, S-R., Đurić, M., Mayer, C-H., Constantinou, M., Chichua, M., Li, C., Foster-Estwick, A., Borg, K., Hill, C., Kaushal, R., Diwan, K., Vitale, V., Engels, T., Aminudin, R., Ursu, I., Fadhlia, T. N., Wu, Y-J., Sekaja, L., Hadchity, M., Deak, A., Sharaf, S., Figueras, P., Kaziboni, A., Whiston, A., Ioumpa, K., Montelongo, A., Pauw, L., Pavarini, G., Vedernikova, E., Vu, T. V., Nummenmaa, L., Cong, Y-Q., Nikolic, M., Olguin, A., Hou, W. K., Israelashvili, J., Koo, H. J., Khademi, S., Ukachukwu, C. G., Juma, D. O., Kamiloğlu, R. G., Makhmud, A., Lunga, P. S., Rieble, C., Rizwan, M., Helmy, M., Vuillier, Laura, Manokara, K., Quezada, E. C., Tserendamba, D., Yoshie, M., Du, A. H., Philip-Joe, K., Kúld, P. B., Damani, K., Osei-Tutu, A., and Sauter, D.
- Abstract
The COVID-19 pandemic presents challenges to psychological well-being, but how can we predict when people suffer or cope during sustained stress? Here, we test the prediction that specific types of momentary emotional experiences are differently linked to psychological well-being during the pandemic. Study 1 used survey data collected from 24,221 participants in 51 countries during the COVID-19 outbreak. We show that, across countries, well-being is linked to individuals' recent emotional experiences, including calm, hope, anxiety, loneliness, and sadness. Consistent results are found in two age, sex, and ethnicity-representative samples in the United Kingdom (n = 971) and the United States (n = 961) with preregistered analyses (Study 2). A prospective 30-day daily diary study conducted in the United Kingdom (n = 110) confirms the key role of these five emotions and demonstrates that emotional experiences precede changes in well-being (Study 3). Our findings highlight differential relationships between specific types of momentary emotional experiences and well-being and point to the cultivation of calm and hope as candidate routes for well-being interventions during periods of sustained stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
25. Glucose metabolism and radiodensity of abdominal adipose tissue: A 5-year longitudinal study in a large PET cohort.
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Pak K, Santavirta S, Shin S, Nam HY, De Maeyer S, and Nummenmaa L
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- Humans, Male, Adult, Longitudinal Studies, Middle Aged, Retrospective Studies, Intra-Abdominal Fat diagnostic imaging, Intra-Abdominal Fat metabolism, Blood Glucose metabolism, Positron Emission Tomography Computed Tomography, Abdominal Fat diagnostic imaging, Abdominal Fat metabolism, Fluorodeoxyglucose F18, Glucose metabolism
- Abstract
Objective:
18 F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) allows noninvasive assessment of glucose metabolism and radiodensity in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). We aimed to address the effects of ageing and metabolic factors on abdominal adipose tissue., Design, Patients and Measurements: We retrospectively analyzed data from 435 healthy men (mean 42.8 years) who underwent a health check-up programme twice, at baseline and the 5-year follow-up. The mean standardized uptake value (SUV) was measured using SAT and VAT and divided by the liver SUV. The mean Hounsfield units (HU) of the SAT and VAT were measured from the CT scans. The effects of clinical variable clusters on SUVR were investigated using Bayesian hierarchical modelling; metabolic cluster (BMI, waist-to-hip ratio, fat percentage, muscle percentage*-1, HOMA-IR), blood pressure (systolic, diastolic), glucose (fasting plasma glucose level, HbA1c) and C-reactive protein., Results: All the clinical variables changed during the 5-year follow-up period. The SUVR and HU of the VAT increased during follow-up; however, those of the SAT did not change. SUVR and HU were positively correlated with both VAT and SAT. SAT and VAT SUVR were negatively associated with metabolic clusters., Conclusions: Ageing led to increased glucose metabolism and radiodensity in VAT, but not in SAT. VAT may reflect the ageing process more directly than SAT. Glucose metabolism was higher and radiodensity was lower in VAT than in SAT, probably owing to differences in gene expression and lipid density. Both glucose metabolism and radiodensity of VAT and SAT reflect metabolic status., (© 2024 John Wiley & Sons Ltd.)- Published
- 2024
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26. Endogenous opioid receptor system mediates costly altruism in the human brain.
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Chen J, Putkinen V, Seppälä K, Hirvonen J, Ioumpa K, Gazzola V, Keysers C, and Nummenmaa L
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- Humans, Male, Female, Adult, Young Adult, Receptors, Opioid, mu metabolism, Fentanyl analogs & derivatives, Fentanyl pharmacology, Pain physiopathology, Pain metabolism, Analgesics, Opioid pharmacology, Analgesics, Opioid metabolism, Altruism, Brain physiology, Brain metabolism, Brain diagnostic imaging, Magnetic Resonance Imaging
- Abstract
Functional neuroimaging studies suggest that a large-scale brain network transforms others' pain into its vicarious representation in the observer, potentially modulating helping behavior. However, the neuromolecular basis of individual differences in vicarious pain and helping is poorly understood. We investigated the role of the endogenous μ-opioid receptor (MOR) system in altruistic costly helping. MOR density was measured using [
11 C]carfentanil. In a separate fMRI experiment, participants could donate money to reduce a confederate's pain from electric shocks. Participants were generally willing to help, and brain activity was observed in amygdala, anterior insula, anterior cingulate cortex (ACC), striatum, primary motor cortex, primary somatosensory cortex and thalamus when witnessing others' pain. Haemodynamic responses were negatively associated with MOR availability in emotion circuits. However, MOR availability positively associated with the ACC and hippocampus during helping. These findings suggest that the endogenous MOR system modulates altruism in the human brain., (© 2024. The Author(s).)- Published
- 2024
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27. A taxonomy for human social perception: Data-driven modeling with cinematic stimuli.
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Santavirta S, Malén T, Erdemli A, and Nummenmaa L
- Abstract
Every day, humans encounter complex social situations that need to be encoded effectively to allow interaction with others. Yet, principles for organizing the perception of social features from the external world remain poorly characterized. In this large-scale study, we investigated the principles of social perception in dynamic scenes. In the primary data set, we presented 234 movie clips (41 min) containing various social situations to 1,140 participants and asked them to evaluate the presence of 138 social features in each clip. Analyses of the social feature ratings revealed that some features are perceived categorically (present or absent) and others continuously (intensity) and simple social features requiring immediate response are perceived most consistently across participants. To establish the low-dimensional perceptual organization for social features based on movies, we used principal coordinate analysis and consensus clustering for the feature ratings. These dimension reduction analyses revealed that the social perceptual structure can be modeled with eight main dimensions and that behaviorally relevant perceptual categories emerge from these main dimensions. This social perceptual structure generalized from the perception of unrelated Hollywood movie clips to the perception of a full Finnish movie (70 min) and to the perception of static images ( n = 468) and across three independent sets of participants ( n = 2,254). Based on the results, we propose eight basic dimensions of social perception as a model for rapid social perception where social situations are perceived along eight orthogonal perceptual dimensions (most importantly emotional valence, empathy vs. dominance, and cognitive vs. physical behavior). (PsycInfo Database Record (c) 2024 APA, all rights reserved).
- Published
- 2024
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28. Seasonal variation in D2/3 dopamine receptor availability in the human brain.
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Sun L, Malén T, Tuisku J, Kaasinen V, Hietala JA, Rinne J, Nuutila P, and Nummenmaa L
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- Humans, Male, Female, Adult, Middle Aged, Raclopride metabolism, Aged, Young Adult, Receptors, Dopamine D2 metabolism, Seasons, Receptors, Dopamine D3 metabolism, Brain metabolism, Brain diagnostic imaging, Positron-Emission Tomography
- Abstract
Purpose: Brain functional and physiological plasticity is essential to combat dynamic environmental challenges. The rhythmic dopamine signaling pathway, which regulates emotion, reward and learning, shows seasonal patterns with higher capacity of dopamine synthesis and lower number of dopamine transporters during dark seasons. However, seasonal variation of the dopamine receptor signaling remains to be characterized., Methods: Based on a historical database of healthy human brain [
11 C]raclopride PET scans (n = 291, 224 males and 67 females), we investigated the seasonal patterns of D2/3 dopamine receptor signaling. Daylength at the time of scanning was used as a predictor for brain regional non-displaceable binding of the radiotracer, while controlling for age and sex., Results: Daylength was negatively correlated with availability of D2/3 dopamine receptors in the striatum. The largest effect was found in the left caudate, and based on the primary sample, every 4.26 h (i.e., one standard deviation) increase of daylength was associated with a mean 2.8% drop (95% CI -0.042 to -0.014) of the receptor availability., Conclusions: Seasonally varying D2/3 receptor signaling may also underlie the seasonality of mood, feeding, and motivational processes. Our finding suggests that in future studies of brain dopamine signaling, especially in high-latitude regions, the effect of seasonality should be considered., (© 2024. The Author(s).)- Published
- 2024
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29. SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study.
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Latva-Rasku A, Rebelos E, Tuisku J, Aarnio R, Bhowmik A, Keskinen H, Laurila S, Lahesmaa-Hatting M, Pekkarinen L, Isackson H, Kirjavainen AK, Koffert J, Heurling K, Nummenmaa L, Ferrannini E, Oldgren J, Oscarsson J, and Nuutila P
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- Humans, Male, Female, Double-Blind Method, Middle Aged, Aged, Adult, Benzhydryl Compounds therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Glucosides therapeutic use, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Fatty Acids metabolism, Brain metabolism, Brain diagnostic imaging, Brain drug effects, Muscle, Skeletal metabolism, Muscle, Skeletal drug effects, Muscle, Skeletal diagnostic imaging, Positron-Emission Tomography
- Abstract
Objective: The aim of this study was to investigate the impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET)., Research Design and Methods: In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups., Results: A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] μmol ⋅ 100 g-1 ⋅ min-1; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] μmol ⋅ 100 g-1 ⋅ min-1; P = 0.01), an effect observed in both gray and white matter regions., Conclusions: Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain., (© 2024 by the American Diabetes Association.)
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- 2024
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30. Aberrant type 2 dopamine receptor availability in violent offenders with psychopathy.
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Lukkarinen L, Tuisku J, Sun L, Helin S, Karlsson HK, Venetjoki N, Salomaa M, Rautio P, Hirvonen J, Lauerma H, Tiihonen J, and Nummenmaa L
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- Humans, Male, Adult, Receptors, Opioid, mu metabolism, Raclopride pharmacokinetics, Young Adult, Brain metabolism, Brain diagnostic imaging, Fentanyl analogs & derivatives, Receptors, Dopamine D2 metabolism, Antisocial Personality Disorder diagnostic imaging, Antisocial Personality Disorder metabolism, Positron-Emission Tomography methods, Criminals, Violence
- Abstract
Psychopathy is characterized by antisocial behavior, poor behavioral control and lacking empathy, and structural alterations in the corresponding neural circuits. Molecular brain basis of psychopathy remains poorly characterized. Here we studied type 2 dopamine receptor (D2R) and mu-opioid receptor (MOR) availability in convicted violent offenders with high psychopathic traits (n = 11) and healthy matched controls (n = 17) using positron emission tomography (PET). D2R were measured with radioligand [
11 C]raclopride and MORs with radioligand [11 C]carfentanil. Psychopathic subjects had lowered D2R availability in caudate and putamen, and striatal D2R availability was also associated with degree of psychopathic traits in this prisoner sample. No group differences were found in MOR availability, although in the prisoner sample, psychopathic traits were negatively correlated with MOR availability in the amygdala and nucleus accumbens. We conclude that D2R signaling could be the putative neuromolecular pathway for psychopathy, whereas evidence for alterations in the MOR system is more limited., Competing Interests: Declaration of competing interest The authors disclose no conflict of interest, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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31. Bodily Maps of Symptoms and Emotions in Parkinson's Disease.
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Niemi KJ, Huovinen A, Jaakkola E, Glerean E, Nummenmaa L, and Joutsa J
- Subjects
- Case-Control Studies, Humans, Male, Female, Middle Aged, Aged, Random Forest, Body Image, Parkinson Disease pathology, Parkinson Disease psychology, Sensation physiology, Emotions physiology
- Abstract
Background: Emotions are reflected in bodily sensations, and these reflections are abnormal in psychiatric conditions. However, emotion-related bodily sensations have not been studied in neurological disorders., Objective: The aim of this study was to investigate whether Parkinson's disease (PD) is associated with altered bodily representations of emotions., Methods: Symptoms and emotion-related sensations were investigated in 380 patients with PD and 79 control subjects, using a topographical self-report method, termed body sensation mapping. The bodily mapping data were analyzed with pixelwise generalized linear models and principal component analyses., Results: Bodily maps of symptoms showed characteristic patterns of PD motor symptom distributions. Compared with control subjects, PD patients showed decreased parasternal sensation of anger, and longer PD symptom duration was associated with increased abdominal sensation of anger (P
FWE < 0.05). The PD-related sensation patterns were abnormal across all basic emotions (P < 0.05)., Conclusions: The results demonstrate altered bodily maps of emotions in PD, providing novel insight into the nonmotor effects of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)- Published
- 2024
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32. Emotional experiences and psychological well-being in 51 countries during the COVID-19 pandemic.
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Sun R, Balabanova A, Bajada CJ, Liu Y, Kriuchok M, Voolma SR, Đurić M, Mayer CH, Constantinou M, Chichua M, Li C, Foster-Estwick A, Borg K, Hill C, Kaushal R, Diwan K, Vitale V, Engels T, Aminudin R, Ursu I, Fadhlia TN, Wu YJ, Sekaja L, Hadchity M, Deak A, Sharaf S, Figueras P, Kaziboni A, Whiston A, Ioumpa K, Montelongo A, Pauw L, Pavarini G, Vedernikova E, Vu T, Nummenmaa L, Cong YQ, Nikolic M, Olguin A, Hou WK, Israelashvili J, Koo HJ, Khademi S, Ukachukwu CG, Juma DO, Kamiloğlu RG, Makhmud A, Lunga PS, Rieble C, Rizwan M, Helmy M, Vuillier L, Manokara K, Quezada EC, Tserendamba D, Yoshie M, Du AH, Philip-Joe K, Kúld PB, Damani K, Osei-Tutu A, and Sauter D
- Subjects
- Humans, Psychological Well-Being, Prospective Studies, Emotions, Pandemics, COVID-19
- Abstract
The COVID-19 pandemic presents challenges to psychological well-being, but how can we predict when people suffer or cope during sustained stress? Here, we test the prediction that specific types of momentary emotional experiences are differently linked to psychological well-being during the pandemic. Study 1 used survey data collected from 24,221 participants in 51 countries during the COVID-19 outbreak. We show that, across countries, well-being is linked to individuals' recent emotional experiences, including calm, hope, anxiety, loneliness, and sadness. Consistent results are found in two age, sex, and ethnicity-representative samples in the United Kingdom ( n = 971) and the United States ( n = 961) with preregistered analyses (Study 2). A prospective 30-day daily diary study conducted in the United Kingdom ( n = 110) confirms the key role of these five emotions and demonstrates that emotional experiences precede changes in well-being (Study 3). Our findings highlight differential relationships between specific types of momentary emotional experiences and well-being and point to the cultivation of calm and hope as candidate routes for well-being interventions during periods of sustained stress. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
- Published
- 2024
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33. Insulin-stimulated brain glucose uptake correlates with brain metabolites in severe obesity: A combined neuroimaging study.
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Rebelos E, Latva-Rasku A, Koskensalo K, Pekkarinen L, Saukko E, Ihalainen J, Honka MJ, Tuisku J, Bucci M, Laurila S, Rajander J, Salminen P, Nummenmaa L, Jansen JF, Ferrannini E, and Nuutila P
- Subjects
- Humans, Insulin, Fluorodeoxyglucose F18 metabolism, Creatine metabolism, Brain diagnostic imaging, Brain metabolism, Obesity diagnostic imaging, Obesity metabolism, Weight Loss physiology, Neuroimaging, Glucose metabolism, Choline metabolism, Obesity, Morbid metabolism
- Abstract
The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (
1 H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET)) was also performed in a subset of subjects during clamp. In dataset A, 48 participants were studied during fasting with brain1 H-MRS, while in dataset B 21 participants underwent paired brain1 H-MRS acquisitions under fasting and clamp conditions. In dataset C 16 subjects underwent brain18 F-FDG-PET and1 H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.- Published
- 2024
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34. Kinetic Modeling of Brain [ 18- F]FDG Positron Emission Tomography Time Activity Curves with Input Function Recovery (IR) Method.
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Bucci M, Rebelos E, Oikonen V, Rinne J, Nummenmaa L, Iozzo P, and Nuutila P
- Abstract
Accurate positron emission tomography (PET) data quantification relies on high-quality input plasma curves, but venous blood sampling may yield poor-quality data, jeopardizing modeling outcomes. In this study, we aimed to recover sub-optimal input functions by using information from the tail (5th-100th min) of curves obtained through the frequent sampling protocol and an input recovery (IR) model trained with reference curves of optimal shape. Initially, we included 170 plasma input curves from eight published studies with clamp [
18 F]-fluorodeoxyglucose PET exams. Model validation involved 78 brain PET studies for which compartmental model (CM) analysis was feasible (reference (ref) + training sets). Recovered curves were compared with original curves using area under curve (AUC), max peak standardized uptake value (maxSUV). CM parameters (ref + training sets) and fractional uptake rate (FUR) (all sets) were computed. Original and recovered curves from the ref set had comparable AUC (d = 0.02, not significant (NS)), maxSUV (d = 0.05, NS) and comparable brain CM results (NS). Recovered curves from the training set were different from the original according to maxSUV (d = 3) and biologically plausible according to the max theoretical K1 (53//56). Brain CM results were different in the training set ( p < 0.05 for all CM parameters and brain regions) but not in the ref set. FUR showed reductions similarly in the recovered curves of the training and test sets compared to the original curves ( p < 0.05 for all regions for both sets). The IR method successfully recovered the plasma inputs of poor quality, rescuing cases otherwise excluded from the kinetic modeling results. The validation approach proved useful and can be applied to different tracers and metabolic conditions.- Published
- 2024
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35. Bodily maps of musical sensations across cultures.
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Putkinen V, Zhou X, Gan X, Yang L, Becker B, Sams M, and Nummenmaa L
- Subjects
- Humans, Sensation, Cross-Cultural Comparison, Acoustics, Emotions, Auditory Perception, Music psychology
- Abstract
Emotions, bodily sensations and movement are integral parts of musical experiences. Yet, it remains unknown i) whether emotional connotations and structural features of music elicit discrete bodily sensations and ii) whether these sensations are culturally consistent. We addressed these questions in a cross-cultural study with Western (European and North American, n = 903) and East Asian (Chinese, n = 1035). We precented participants with silhouettes of human bodies and asked them to indicate the bodily regions whose activity they felt changing while listening to Western and Asian musical pieces with varying emotional and acoustic qualities. The resulting bodily sensation maps (BSMs) varied as a function of the emotional qualities of the songs, particularly in the limb, chest, and head regions. Music-induced emotions and corresponding BSMs were replicable across Western and East Asian subjects. The BSMs clustered similarly across cultures, and cluster structures were similar for BSMs and self-reports of emotional experience. The acoustic and structural features of music were consistently associated with the emotion ratings and music-induced bodily sensations across cultures. These results highlight the importance of subjective bodily experience in music-induced emotions and demonstrate consistent associations between musical features, music-induced emotions, and bodily sensations across distant cultures., Competing Interests: Competing interests statement:The authors declare no competing interest.
- Published
- 2024
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36. Brain dopamine receptor system is not altered in obesity: Bayesian and frequentist meta-analyses.
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Pak K and Nummenmaa L
- Subjects
- Humans, Raclopride pharmacology, Bayes Theorem, Receptors, Dopamine D2 metabolism, Obesity diagnostic imaging, Brain metabolism, Dopamine, Body Mass Index, Overweight, Radiopharmaceuticals
- Abstract
Feeding induces dopamine release in the striatum, and a dysfunction of the dopaminergic reward system can lead to overeating, and obesity. Studies have reported inconsistent findings of dopamine receptor (DR) positron emission tomography scans in obesity. Here we investigated the association between DR availability and overweight/obesity using Bayesian and frequentist meta-analysis. We performed a systematic search of Embase, Medline, Scopus and Web of Science for studies that compared striatal DR availability between lean subjects and overweight/obese subjects. The standardized mean difference (Hedge's g) of DR availability was calculated after extraction of data from each study. Studies were divided into two groups according to the definition of overweight/obese subjects (body mass index [BMI] cutoff of 25 and 30 kg/m
2 ). Both Bayesian and frequentist meta-analysis was done in R Statistical Software version 4.2.2 (The R Foundation for Statistical Computing). Nine studies were eligible for inclusion in this study. Three studies with C11-raclopride, one with C11-PNHO, two with F18-fallypride, one with I123-IBZM, one with C11-NMB and one with both C11-raclopride and C11-PNHO were included. In Bayesian meta-analysis, the standardized mean difference of DR availability between lean and overweight/obese subjects markedly overlapped with zero regardless of BMI cutoff for obesity. In frequentist meta-analysis, the pooled standardized mean difference of DR availability did not show the significant difference between lean and overweight/obese subjects. There was an effect of the radiopharmaceutical on the standardized mean difference of DR availability in meta-analysis of BMI cutoff of 25 kg/m2 . In conclusion, brain DR availability is not different between lean and overweight/obese subjects. However, the effect is dependent on the radiopharmaceutical and the degree of obesity. Further studies with multi-radiopharmaceutical in the same individuals are needed to understand the association between DR and obesity., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)- Published
- 2023
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37. Bodily maps of emotions and pain: tactile and hedonic sensitivity in healthy controls and patients experiencing chronic pain.
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Ojala J, Suvilehto JT, Nummenmaa L, and Kalso E
- Subjects
- Humans, Touch, Emotions physiology, Culture, Chronic Pain, Touch Perception
- Abstract
Abstract: Pain is an unpleasant sensory and emotional experience. Both pain and emotions are warning signals against outside harm. Interoception, bodily sensations of emotions can be assessed with the emBODY tool where participants colour the body parts where they feel different emotions. Bodily maps of emotions (BMoE) have been shown to be similar between healthy individuals independent of age, sex, cultural background, and language. We used this tool to analyze how these body maps may differ between healthy controls and patients with persistent pain. We recruited 118 patients with chronic pain. An algorithm-selected matched controls from 2348 individuals who were recruited through social media, message boards, and student mailing lists. After providing background information, the participants completed the bodily topography colouring tasks with the emBODY tool using tablets (patients) and online using their own devices (controls), for pain, sensitivity for tactile, nociceptive and hedonic stimuli, and for the 6 basic emotions and a neutral state. Patients with pain coloured significantly larger areas for pain and more negative emotions. On the whole, their BMoEs were dampened compared with healthy controls. They also coloured more areas for nociceptive but not for tactile or hedonic sensitivity. Patients and controls marked different body areas as sensitive to nociceptive and tactile stimulation, but there was no difference in sensitivity to hedonic touch. Our findings suggest that emotional processing changes when pain persists, and this can be assessed with these colouring tasks. BMoEs may offer a new approach to assessing pain., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)
- Published
- 2023
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38. Quantitative Perfusion Imaging with Total-Body PET.
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Knuuti J, Tuisku J, Kärpijoki H, Iida H, Maaniitty T, Latva-Rasku A, Oikonen V, Nesterov SV, Teuho J, Jaakkola MK, Klén R, Louhi H, Saunavaara V, Nuutila P, Saraste A, Rinne J, and Nummenmaa L
- Subjects
- Positron-Emission Tomography methods, Perfusion Imaging methods, Water
- Abstract
Recently, PET systems with a long axial field of view have become the current state of the art. Total-body PET scanners enable unique possibilities for scientific research and clinical diagnostics, but this new technology also raises numerous challenges. A key advantage of total-body imaging is that having all the organs in the field of view allows studying biologic interaction of all organs simultaneously. One of the new, promising imaging techniques is total-body quantitative perfusion imaging. Currently,
15 O-labeled water provides a feasible option for quantitation of tissue perfusion at the total-body level. This review summarizes the status of the methodology and the analysis and provides examples of preliminary findings on applications of quantitative parametric perfusion images for research and clinical work. We also describe the opportunities and challenges arising from moving from single-organ studies to modeling of a multisystem approach with total-body PET, and we discuss future directions for total-body imaging., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
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39. Mapping Lesion-Related Epilepsy to a Human Brain Network.
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Schaper FLWVJ, Nordberg J, Cohen AL, Lin C, Hsu J, Horn A, Ferguson MA, Siddiqi SH, Drew W, Soussand L, Winkler AM, Simó M, Bruna J, Rheims S, Guenot M, Bucci M, Nummenmaa L, Staals J, Colon AJ, Ackermans L, Bubrick EJ, Peters JM, Wu O, Rost NS, Grafman J, Blumenfeld H, Temel Y, Rouhl RPW, Joutsa J, and Fox MD
- Subjects
- Humans, Male, Middle Aged, Adult, Female, Case-Control Studies, Brain pathology, Seizures physiopathology, Epilepsy etiology, Epilepsy pathology, Stroke physiopathology
- Abstract
Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions., Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and networks., Design, Setting, and Participants: This case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded., Main Outcomes and Measures: Epilepsy or no epilepsy., Results: Lesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P < .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P < .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P < .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months)., Conclusions and Relevance: The findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.
- Published
- 2023
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40. Endogenous Opioid Release After Orgasm in Man: A Combined PET/Functional MRI Study.
- Author
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Jern P, Chen J, Tuisku J, Saanijoki T, Hirvonen J, Lukkarinen L, Manninen S, Helin S, Putkinen V, and Nummenmaa L
- Subjects
- Humans, Brain physiology, Positron-Emission Tomography, Magnetic Resonance Imaging, Orgasm physiology, Analgesics, Opioid
- Abstract
The endogenous μ-opioid receptor (MOR) system plays a key role in the mammalian reward circuit. Human and animal experiments suggest the involvement of MORs in human sexual pleasure, yet this hypothesis currently lacks in vivo support. Methods: We used PET with the radioligand [
11 C]carfentanil, which has high affinity for MORs, to quantify endogenous opioid release after orgasm in man. Participants were scanned once immediately after orgasm and once in a baseline state. Hemodynamic activity was measured with functional MRI during penile stimulation. Results: The PET data revealed significant opioid release in the hippocampus. Hemodynamic activity in the somatosensory and motor cortices and in the hippocampus and thalamus increased during penile stimulation, and thalamic activation was linearly dependent on self-reported sexual arousal. Conclusion: Our data show that endogenous opioidergic activation in the medial temporal lobe is centrally involved in sexual arousal, and this circuit may be implicated in orgasmic disorders., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
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41. Lower abdominal adipose tissue cannabinoid type 1 receptor availability in young men with overweight.
- Author
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Pekkarinen L, Kantonen T, Oikonen V, Haaparanta-Solin M, Aarnio R, Dickens AM, von Eyken A, Latva-Rasku A, Dadson P, Kirjavainen AK, Rajander J, Kalliokoski K, Rönnemaa T, Nummenmaa L, and Nuutila P
- Subjects
- Male, Humans, Overweight, Receptors, Cannabinoid, Obesity, Abdominal Fat diagnostic imaging, Endocannabinoids, Adipose Tissue, Insulin Resistance physiology, Diabetes Mellitus, Type 2, Cannabinoids
- Abstract
Objective: Cannabinoid type 1 receptors (CB1R) modulate feeding behavior and energy homeostasis, and the CB1R tone is dysgulated in obesity. This study aimed to investigate CB1R availability in peripheral tissue and brain in young men with overweight versus lean men., Methods: Healthy males with high (HR, n = 16) or low (LR, n = 20) obesity risk were studied with fluoride 18-labeled FMPEP-d
2 positron emission tomography to quantify CB1R availability in abdominal adipose tissue, brown adipose tissue, muscle, and brain. Obesity risk was assessed by BMI, physical exercise habits, and familial obesity risk, including parental overweight, obesity, and type 2 diabetes. To assess insulin sensitivity, fluoro-[18 F]-deoxy-2-D-glucose positron emission tomography during hyperinsulinemic-euglycemic clamp was performed. Serum endocannabinoids were analyzed., Results: CB1R availability in abdominal adipose tissue was lower in the HR than in the LR group, whereas no difference was found in other tissues. CB1R availability of abdominal adipose tissue and brain correlated positively with insulin sensitivity and negatively with unfavorable lipid profile, BMI, body adiposity, and inflammatory markers. Serum arachidonoyl glycerol concentration was associated with lower CB1R availability of the whole brain, unfavorable lipid profile, and higher serum inflammatory markers., Conclusions: The results suggest endocannabinoid dysregulation already in the preobesity state., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)- Published
- 2023
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42. Decoding brain basis of laughter and crying in natural scenes.
- Author
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Nummenmaa L, Malèn T, Nazari-Farsani S, Seppälä K, Sun L, Santavirta S, Karlsson HK, Hudson M, Hirvonen J, Sams M, Scott S, and Putkinen V
- Subjects
- Humans, Brain physiology, Brain Mapping, Gyrus Cinguli physiology, Crying physiology, Laughter
- Abstract
Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 min of a full-length feature film, and iii) listened to 13.5 min of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66-77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others' bonding and distress signals., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
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43. Brain lesion locations associated with secondary seizure generalization in tumors and strokes.
- Author
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Nordberg J, Schaper FLWVJ, Bucci M, Nummenmaa L, and Joutsa J
- Subjects
- Adult, Humans, Seizures diagnostic imaging, Seizures etiology, Brain diagnostic imaging, Cerebral Cortex diagnostic imaging, Electroencephalography, Epilepsy diagnostic imaging, Epilepsy etiology, Stroke complications, Stroke diagnostic imaging, Neoplasms
- Abstract
Structural brain lesions are the most common cause of adult-onset epilepsy. The lesion location may contribute to the risk for epileptogenesis, but whether specific lesion locations are associated with a risk for secondary seizure generalization from focal to bilateral tonic-clonic seizures, is unknown. We identified patients with a diagnosis of adult-onset epilepsy caused by an ischemic stroke or a tumor diagnosed at the Turku University Hospital in 2004-2017. Lesion locations were segmented on patient-specific MR imaging and transformed to a common brain atlas (MNI space). Both region-of-interest analyses (intersection with the cortex, hemisphere, and lobes) and voxel-wise analyses were conducted to identify the lesion locations associated with focal to bilateral tonic-clonic compared to focal seizures. We included 170 patients with lesion-induced epilepsy (94 tumors, 76 strokes). Lesions predominantly localized in the cerebral cortex (OR 2.50, 95% C.I. 1.21-5.15, p = .01) and right hemisphere (OR 2.22, 95% C.I. 1.17-4.20, p = .01) were independently associated with focal to bilateral tonic-clonic seizures. At the lobar-level, focal to bilateral tonic-clonic seizures were associated with lesions in the right frontal cortex (OR 4.41, 95% C.I. 1.44-13.5, p = .009). No single voxels were significantly associated with seizure type. These effects were independent of lesion etiology. Our results demonstrate that lesion location is associated with the risk for secondary generalization of epileptic seizures. These findings may contribute to identifying patients at risk for focal to bilateral tonic-clonic seizures., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
- Published
- 2023
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44. Functional organization of social perception networks in the human brain.
- Author
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Santavirta S, Karjalainen T, Nazari-Farsani S, Hudson M, Putkinen V, Seppälä K, Sun L, Glerean E, Hirvonen J, Karlsson HK, and Nummenmaa L
- Subjects
- Humans, Occipital Lobe physiology, Magnetic Resonance Imaging, Social Perception, Brain Mapping methods, Brain diagnostic imaging, Brain physiology
- Abstract
Humans rapidly extract diverse and complex information from ongoing social interactions, but the perceptual and neural organization of the different aspects of social perception remains unresolved. We showed short movie clips with rich social content to 97 healthy participants while their haemodynamic brain activity was measured with fMRI. The clips were annotated moment-to-moment for a large set of social features and 45 of the features were evaluated reliably between annotators. Cluster analysis of the social features revealed that 13 dimensions were sufficient for describing the social perceptual space. Three different analysis methods were used to map the social perceptual processes in the human brain. Regression analysis mapped regional neural response profiles for different social dimensions. Multivariate pattern analysis then established the spatial specificity of the responses and intersubject correlation analysis connected social perceptual processing with neural synchronization. The results revealed a gradient in the processing of social information in the brain. Posterior temporal and occipital regions were broadly tuned to most social dimensions and the classifier revealed that these responses showed spatial specificity for social dimensions; in contrast Heschl gyri and parietal areas were also broadly associated with different social signals, yet the spatial patterns of responses did not differentiate social dimensions. Frontal and subcortical regions responded only to a limited number of social dimensions and the spatial response patterns did not differentiate social dimension. Altogether these results highlight the distributed nature of social processing in the brain., Competing Interests: Declaration of Competing Interest The authors declare no competing financial or non-financial interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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45. Secretin modulates appetite via brown adipose tissue-brain axis.
- Author
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Sun L, Laurila S, Lahesmaa M, Rebelos E, Virtanen KA, Schnabl K, Klingenspor M, Nummenmaa L, and Nuutila P
- Subjects
- Single-Blind Method, Magnetic Resonance Imaging, Positron-Emission Tomography, Glucose metabolism, Reward, Signal Transduction drug effects, Humans, Food, Adipose Tissue, Brown drug effects, Adipose Tissue, Brown metabolism, Adipose Tissue, Brown physiology, Appetite drug effects, Appetite physiology, Brain drug effects, Brain metabolism, Brain physiology, Secretin metabolism, Secretin pharmacology, Satiety Response drug effects, Satiety Response physiology, Brain-Gut Axis drug effects, Brain-Gut Axis physiology, Functional Neuroimaging, Feeding Behavior drug effects
- Abstract
Purpose: Secretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is largely unknown., Methods and Results: In this placebo-controlled, single-blinded neuroimaging study, firstly using [
18 F]-fluorodeoxyglucose (FDG) PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis. Predominantly, we found that BAT and caudate glucose uptake levels were negatively correlated (r = -0.54, p = 0.037) during secretin but not placebo condition. Then, using functional magnetic resonance imaging (fMRI; n = 14), we found that secretin improved inhibitory control and downregulated the brain response to appetizing food images. Finally, in a PET-fMRI fusion analysis (n = 10), we disclosed the patterned correspondence between caudate glucose uptake and neuroactivity to reward and inhibition, showing that the secretin-induced neurometabolic coupling patterns promoted satiation., Conclusion: These findings suggest that secretin may modulate the BAT-brain metabolic crosstalk and subsequently the neurometabolic coupling to induce satiation. The study advances our understanding of the secretin signaling in motivated eating behavior and highlights the potential role of secretin in treating eating disorders and obesity., Trial Registration: EudraCT no. 2016-002373-35, registered 2 June 2016; Clinical Trials no. NCT03290846, registered 25 September 2017., (© 2023. The Author(s).)- Published
- 2023
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46. Bodily feelings and aesthetic experience of art.
- Author
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Nummenmaa L and Hari R
- Subjects
- Humans, Esthetics, Databases, Factual, Emotions physiology
- Abstract
Humans all around the world are drawn to creating and consuming art due to its capability to evoke emotions, but the mechanisms underlying art-evoked feelings remain poorly characterised. Here we show how embodiement contributes to emotions evoked by a large database of visual art pieces (n = 336). In four experiments, we mapped the subjective feeling space of art-evoked emotions (n = 244), quantified "bodily fingerprints" of these emotions (n = 615), and recorded the subjects' interest annotations (n = 306) and eye movements (n = 21) while viewing the art. We show that art evokes a wide spectrum of feelings, and that the bodily fingerprints triggered by art are central to these feelings, especially in artworks where human figures are salient. Altogether these results support the model that bodily sensations are central to the aesthetic experience.
- Published
- 2023
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47. Pattern recognition reveals sex-dependent neural substrates of sexual perception.
- Author
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Putkinen V, Nazari-Farsani S, Karjalainen T, Santavirta S, Hudson M, Seppälä K, Sun L, Karlsson HK, Hirvonen J, and Nummenmaa L
- Subjects
- Humans, Female, Male, Sex Characteristics, Pleasure, Perception, Arousal physiology, Sexual Behavior physiology
- Abstract
Sex differences in brain activity evoked by sexual stimuli remain elusive despite robust evidence for stronger enjoyment of and interest toward sexual stimuli in men than in women. To test whether visual sexual stimuli evoke different brain activity patterns in men and women, we measured hemodynamic brain activity induced by visual sexual stimuli in two experiments with 91 subjects (46 males). In one experiment, the subjects viewed sexual and nonsexual film clips, and dynamic annotations for nudity in the clips were used to predict hemodynamic activity. In the second experiment, the subjects viewed sexual and nonsexual pictures in an event-related design. Men showed stronger activation than women in the visual and prefrontal cortices and dorsal attention network in both experiments. Furthermore, using multivariate pattern classification we could accurately predict the sex of the subject on the basis of the brain activity elicited by the sexual stimuli. The classification generalized across the experiments indicating that the sex differences were task-independent. Eye tracking data obtained from an independent sample of subjects (N = 110) showed that men looked longer than women at the chest area of the nude female actors in the film clips. These results indicate that visual sexual stimuli evoke discernible brain activity patterns in men and women which may reflect stronger attentional engagement with sexual stimuli in men., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
- Published
- 2023
- Full Text
- View/download PDF
48. Resistance Training Increases White Matter Density in Frail Elderly Women.
- Author
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Bucci M, Iozzo P, Merisaari H, Huovinen V, Lipponen H, Räikkönen K, Parkkola R, Salonen M, Sandboge S, Eriksson JG, Nummenmaa L, and Nuutila P
- Abstract
We aimed to investigate the effects of maternal obesity on brain structure and metabolism in frail women, and their reversibility in response to exercise. We recruited 37 frail elderly women (20 offspring of lean/normal-weight mothers (OLM) and 17 offspring of obese/overweight mothers (OOM)) and nine non-frail controls to undergo magnetic resonance and diffusion tensor imaging (DTI), positron emission tomography with Fluorine-18-fluorodeoxyglucose (PET), and cognitive function tests (CERAD). Frail women were studied before and after a 4-month resistance training, and controls were studied once. White matter (WM) density (voxel-based morphometry) was higher in OLM than in OOM subjects. Exercise increased WM density in both OLM and OOM in the cerebellum in superior parietal regions in OLM and in cuneal and precuneal regions in OOM. OLM gained more WM density than OOM in response to intervention. No significant results were found from the Freesurfer analysis, nor from PET or DTI images. Exercise has an impact on brain morphology and cognition in elderly frail women.
- Published
- 2023
- Full Text
- View/download PDF
49. Neural responses to biological motion distinguish autistic and schizotypal traits.
- Author
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Hudson M, Santavirta S, Putkinen V, Seppälä K, Sun L, Karjalainen T, Karlsson HK, Hirvonen J, and Nummenmaa L
- Subjects
- Adult, Female, Humans, Male, Young Adult, Hemodynamics, Magnetic Resonance Imaging, Finland, Autistic Disorder diagnostic imaging, Autistic Disorder psychology, Brain blood supply, Brain diagnostic imaging, Brain physiopathology, Schizophrenia diagnostic imaging, Schizophrenia physiopathology, Schizophrenic Psychology, Social Interaction, Social Perception
- Abstract
Difficulties in social interactions characterize both autism and schizophrenia and are correlated in the neurotypical population. It is unknown whether this represents a shared etiology or superficial phenotypic overlap. Both conditions exhibit atypical neural activity in response to the perception of social stimuli and decreased neural synchronization between individuals. This study investigated if neural activity and neural synchronization associated with biological motion perception are differentially associated with autistic and schizotypal traits in the neurotypical population. Participants viewed naturalistic social interactions while hemodynamic brain activity was measured with fMRI, which was modeled against a continuous measure of the extent of biological motion. General linear model analysis revealed that biological motion perception was associated with neural activity across the action observation network. However, intersubject phase synchronization analysis revealed neural activity to be synchronized between individuals in occipital and parietal areas but desynchronized in temporal and frontal regions. Autistic traits were associated with decreased neural activity (precuneus and middle cingulate gyrus), and schizotypal traits were associated with decreased neural synchronization (middle and inferior frontal gyri). Biological motion perception elicits divergent patterns of neural activity and synchronization, which dissociate autistic and schizotypal traits in the general population, suggesting that they originate from different neural mechanisms., (© The Author(s) 2023. Published by Oxford University Press.)
- Published
- 2023
- Full Text
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50. Thermogenic Capacity of Human Supraclavicular Brown Fat and Cold-Stimulated Brain Glucose Metabolism.
- Author
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U-Din M, Rebelos E, Saari T, Niemi T, Kuellmer K, Eskola O, Fromme T, Rajander J, Taittonen M, Klingenspor M, Nuutila P, Nummenmaa L, and Virtanen KA
- Abstract
Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of UCP-1 , which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress. Ten healthy human participants underwent
18 F-FDG PET scanning of the brain under cold stimulus to determine brain glucose uptake (BGU). On a separate day, an excision biopsy of the supraclavicular fat-the fat proximal to the carotid arteries supplying the brain with warm blood-was performed to determine the mRNA expression of the thermogenic protein UCP-1 . Expression of UCP-1 in supraclavicular BAT was directly related to the whole brain glucose uptake rate determined under cold stimulation ( rho = 0.71, p = 0.03). In sub-compartmental brain analysis, UCP-1 expression in supraclavicular BAT was directly related to cold-stimulated glucose uptake rates in the hypothalamus, medulla, midbrain, limbic system, frontal lobe, occipital lobe, and parietal lobe (all rho ≥ 0.67, p < 0.05). These relationships were independent of body mass index and age. When analysing gene expressions of BAT secretome, we found a positive correlation between cold-stimulated BGU and DIO2 . These findings provide evidence of functional links between brain metabolism under cold stimulation and UCP-1 and DIO2 expressions in BAT in humans. More research is needed to evaluate the importance of these findings in clinical outcomes, for instance, in examining the supporting role of BAT in cognitive functions under cold stress.- Published
- 2023
- Full Text
- View/download PDF
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