Interindividual variability and lateralization of μ-opioid receptors in the human brain

Kantonen, Tatu; Karjalainen, Tomi; Isojärvi, Janne; Nuutila, Pirjo; Tuisku, Jouni; Rinne, Juha O.; Hietala, Jarmo; Kaasinen, Valtteri; Kalliokoski, Kari K.; Scheinin, Harry; Hirvonen, Jussi; Vehtari, Aki; Nummenmaa, Lauri

doi:10.1016/j.neuroimage.2020.116922

Cited by 63 publications

(55 citation statements)

References 67 publications

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“…PET images were preprocessed similarly using automated processing pipeline Magia (Karjalainen et al, 2020). [ 11 C]carfentanil data preprocessing has been described previously (Kantonen et al, 2020). MOR availability was expressed as [ 11 C]carfentanil binding potential ( BP ND ), which is the ratio of specifically bound radioligand to that of nondisplaceable radioligand in tissue (Innis et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

“…[ 11 C]carfentanil data preprocessing has been described previously (24). MOR availability was expressed as [ 11 C]carfentanil binding potential (BP ND ), which is the ratio of specifically bound radioligand to that of nondisplaceable radioligand in tissue (41).…”

Section: Image Processing and Modelingmentioning

confidence: 99%

“…Human positron emission tomography (PET) studies have revealed that obesity associates with decrease of MORs in appetite regulating brain areas (Burghardt et al, 2015; Karlsson et al, 2015), and insular MORs are lowered in patients with bulimia nervosa proportionally to fasting behavior (Bencherif et al, 2005). Central MOR system function varies considerably also in healthy humans (Kantonen et al, 2020), and traits linked with feeding control such as impulsivity are associated with MOR availability (Love et al, 2009). Nevertheless, the association between the MOR system and specific patterns of eating behavior remains elusive.…”

Section: Introductionmentioning

confidence: 99%

“…We created distinct models for Total DEBQ score and all the subscale scores. Because age influences [ 11 C]carfentanil binding(24,45) and different PET scanners may yield slightly different BP ND estimates (46), both age and PET scanner were added as nuisance covariates to [ 11 C]carfentanil models. Only age was added as a covariate in [ 18 F]FMPEP-d 2 V T models, since all [ 18 F]FMPEP-d 2 scans were acquired with the same PET scanner.…”

mentioning

confidence: 99%

“…The Bayesian models were both tracers, we created models separately for the Total DEBQ score as well as its subscales, adjusting for age. [ 11 C]carfentanil BP ND and [ 18 F]FMPEP-d 2 V T were log-transformed to improve model fit(24). For both tracers, we estimated varying (random) intercepts for the subjects and ROIs, and varying (random) slopes across ROIs for the predictor of interest (e.g.…”

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confidence: 99%

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Cerebral μ-opioid and CB₁-receptor systems have distinct roles in human feeding behavior

Kantonen

Karjalainen

Pekkarinen

et al. 2020

Preprint

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Eating behavior varies greatly between healthy individuals, but the neurobiological basis of these trait-like differences in feeding remains unknown. Central μ-opioid receptors (MOR) and cannabinoid CB1-receptors (CB1R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brain's opioid and endocannabinoid signaling, the variation in MOR and CB1R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [11C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [18F]FMPEP-d2 scans of CB1Rs from 35 subjects (all males, all also included in the [11C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating - individuals with low MORs reported being more likely to eat in response to environment's palatable food cues. CB1R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB1Rs overlap anatomically and functionally in the brain, they have distinct roles in mediating individual feeding patterns.

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Section: Methodsmentioning

confidence: 99%

Section: Image Processing and Modelingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Cerebral μ-opioid and CB₁-receptor systems have distinct roles in human feeding behavior

Kantonen

Karjalainen

Pekkarinen

et al. 2020

Preprint

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Progressive Voxel‐Wise Homotopic Connectivity from childhood to adulthood: Age‐related functional asymmetry in resting‐state functional magnetic resonance imaging

Tarchi

Damiani

Vittori

et al. 2023

Developmental Psychobiology

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Homotopic connectivity during resting state has been proposed as a risk marker for neurologic and psychiatric conditions, but a precise characterization of its trajectory through development is currently lacking. Voxel-Mirrored Homotopic Connectivity (VMHC) was evaluated in a sample of 85 neurotypical individuals aged 7-18 years.VMHC associations with age, handedness, sex, and motion were explored at the voxel-wise level. VMHC correlates were also explored within 14 functional networks.Primary and secondary outcomes were repeated in a sample of 107 adults aged 21-50 years. In adults, VMHC was negatively correlated with age only in the posterior insula (false discovery rate p < .05, >30-voxel clusters), while a distributed effect among the medial axis was observed in minors. Four out of 14 considered networks showed significant negative correlations between VMHC and age in minors (basal ganglia r = -.280, p = .010; anterior salience r = -.245, p = .024; language r = -.222, p = .041; primary visual r = -.257, p = .017), but not adults. In minors, a positive effect of motion on VMHC was observed only in the putamen. Sex did not significantly influence age effects on VMHC. The current study showed a specific decrease in VMHC for minors as a function of age, but not adults, supporting the notion that interhemispheric interactions can shape late neurodevelopment.

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Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice

et al. 2022

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The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 μm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence.

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Interindividual variability and lateralization of μ-opioid receptors in the human brain

Cited by 63 publications

References 67 publications

Cerebral μ-opioid and CB₁-receptor systems have distinct roles in human feeding behavior

Cerebral μ-opioid and CB₁-receptor systems have distinct roles in human feeding behavior

Progressive Voxel‐Wise Homotopic Connectivity from childhood to adulthood: Age‐related functional asymmetry in resting‐state functional magnetic resonance imaging

Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice

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Interindividual variability and lateralization of μ-opioid receptors in the human brain

Cited by 63 publications

References 67 publications

Cerebral μ-opioid and CB1-receptor systems have distinct roles in human feeding behavior

Cerebral μ-opioid and CB1-receptor systems have distinct roles in human feeding behavior

Progressive Voxel‐Wise Homotopic Connectivity from childhood to adulthood: Age‐related functional asymmetry in resting‐state functional magnetic resonance imaging

Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice

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Cerebral μ-opioid and CB₁-receptor systems have distinct roles in human feeding behavior

Cerebral μ-opioid and CB₁-receptor systems have distinct roles in human feeding behavior