| 1. |
- de Manzano, Orjan, et al.
(författare)
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Individual differences in the proneness to have flow experiences are linked to dopamine D2-receptor availability in the dorsal striatum
- 2013
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 67, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Flow is a subjective experience of high but effortless attention, enjoyment, and low self-awareness that can occur during the active performance of challenging tasks. The dispositional proneness to experience flow is associated with personality traits that are known to be influenced by dopaminergic neural systems. Here, for the first time, we investigated relations between flow proneness and dopaminergic function. Specifically, we tested the hypothesis that the availability of dopamine D2-receptors in the striatum is positively associated with flow proneness. Striatal D2-receptor availability was measured in a sample of 25 healthy adults using positron emission tomography and [C-11]raclopride. Flow proneness was measured using the Swedish Flow Proneness Questionnaire. As hypothesized, there was a significant correlation (r = .41) between striatal D2-receptor availability and flow proneness. An exploratory analysis of striatal subregions showed that the relation was mainly driven by the dorsal striatum, with a significantly higher correlation in the putamen than in the ventral striatum. The findings constitute the first demonstration of an association between flow proneness and dopaminergic function. We suggest that the proneness to experience flow is related to personality dimensions that are under dopaminergic control and characterized by low impulsiveness, stable emotion, and positive affect. (C) 2012 Elsevier Inc. All rights reserved.
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| 2. |
- Jucaite, Aurelija
(författare)
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Attention-deficit/hyperactivity disorder : alterations of motor behaviour and dopaminergic transmission
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Altered catecholaminergic neurotransmission in the brain has long been thought to be of importance in the regulation of motor behavior and cognitive performance in children who had symptoms of distractability, impulsivity and clumsiness. The dopamine theory of AD/HD has mainly been substantiated by: i) the effects of psychostimulants, which target the dopamine transporter (DAT), and thereby reduce impulsiveness and inattentiveness, increase the striatal cerebral blood flow and functional activity, and ii) the evidence from linkage studies associating the AD/HD syndrome with allelic variations of genes encoding the dopamine transporter and, possibly, the dopamine D4 receptors. However, the central regulatory mechanisms of dopamine neurotransmission in AD/HD have not been established yet. The main aim of this thesis was to examine the dopaminergic system in vivo in children with AD/HD by using positron emission tomography (PET). Twelve adolescents with AD/HD and ten young adults were investigated applying the double-tracer paradigm. Presynaptic and postsynaptic dopamine markers, DAT and dopamine D2 receptors, were mapped using the radioligands [11C]PE2I and [11C]raclopride. In the group of adolescents with ADHD, we also investigated relationship between the central dopamine markers and behavioral/cognitive performance. A new radioligand [11C]PE2I that has a high affinity and selectivity to the central DAT was used. Its favourable signal-to-background ratio enabled us to quantify the DAT density in the human striatum and midbrain; cross-validation of quatification methods of [11C]PE2I binding permitted its application in the clinical study. The PET measurements showed that the DAT and DRD2 density in the striatum did not differ between adolescents and young adults once a correction had been made for age. Thus, the initial findings of increased DAT in the striatum in AD/HD reported in the literature were not confirmed. The decreased regional density of DAT found in the substantia nigra/ventral tegmentum rather suggests a shift in the focus of the pathophysiology of AD/HD to the midbrain structures. In addition, positive correlations between hyperactivity levels and the density of dopamine markers in the striatum support similar reports by other authors and provide evidence for the involvement of the dopamine system in the pathophysiology of AD/HD. The AD/HD syndrome is a heterogenous diagnostic entity, and it is still a matter of debate whether perception and movement coordination problems are a constituent part of it. We investigated movement coordination problems from the perspective of motor control theories with a load lifting task, providing measurements of manipulative movements and associated postural adjustments. Fifty two children were investigated, including an additional control group of younger children, with the intention of addressing the developmental aspects of motor behavior. The results showed that children with AD/HD and developmental coordination disorder, or both, have a deficit in the programming of their motor behavior that is related to the severity/complexity of the syndrome, but which does not correspond to the motor performance of younger children. The deficient parametric control of the motor output, and lack of temporal coordination between the lifting movement and the postural responses limited the adaptation of the motor behavior to the environment.
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| 3. |
- Kanegawa, Naoki, et al.
(författare)
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In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects
- 2016
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Ingår i: Brain, behavior, and immunity. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0889-1591 .- 1090-2139. ; 54, s. 149-157
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Tidskriftsartikel (refereegranskat)abstract
- Microglia, the resident macrophages in the central nervous system, are thought to be maintained by a local self-renewal mechanism. Although preclinical and in vitro studies have suggested that the brain may contain immune cells also from peripheral origin, the functional association between immune cells in the periphery and brain at physiological conditions is poorly understood. We examined 32 healthy individuals using positron emission tomography (PET) and [C-11]PBR28, a radioligand for the 18-kDa translocator protein (TSPO) which is expressed both in brain microglia and blood immune cells. In 26 individuals, two measurements were performed with varying time intervals. In a subgroup of 19 individuals, of which 12 had repeat examinations, leukocyte numbers in blood was measured on each day of PET measurements. All individuals were genotyped for TSPO polymorphism and categorized as high, mixed, and low affinity binders. We assessed TSPO binding expressed as total distribution volume of [C-11]PBR28 in brain and in blood cells. TSPO binding in brain was strongly and positively correlated to binding in blood cells both at baseline and when analyzing change between two PET examinations. Furthermore, there was a significant correlation between change of leukocyte numbers and change in TSPO binding in brain, and a trend level correlation to change in TSPO binding in blood cells. These in vivo findings indicate an association between immunological cells in blood and brain via intact BBB, suggesting a functional interaction between these two compartments, such as interchange of peripherally derived cells or a common regulatory mechanism. Measurement of radioligand binding in blood cells may be a way to control for peripheral immune function in PET studies using TSPO as a marker of brain immune activation. (C) 2016 Elsevier Inc. All rights reserved.
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| 4. |
- Laurell, Gjertrud L, et al.
(författare)
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Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies.
- 2021
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:3, s. 412-417
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Tidskriftsartikel (refereegranskat)abstract
- The PET ligand 11C-PBR28 (N-((2-(methoxy-11C)-phenyl)methyl)-N-(6-phenoxy-3-pyridinyl)acetamide) binds to the 18-kDa translocator protein (TSPO), a biomarker of glia. In clinical studies of TSPO, the ligand total distribution volume, VT, is frequently the reported outcome measure. Since VT is the sum of the ligand-specific distribution volume (VS) and the nondisplaceable-binding distribution volume (VND), differences in VND across subjects and groups will have an impact on VTMethods: Here, we used a recently developed method for simultaneous estimation of VND (SIME) to disentangle contributions from VND and VS Data from 4 previously published 11C-PBR28 PET studies were included: before and after a lipopolysaccharide challenge (8 subjects), in alcohol use disorder (14 patients, 15 controls), in first-episode psychosis (16 patients, 16 controls), and in Parkinson disease (16 patients, 16 controls). In each dataset, regional VT estimates were obtained with a standard 2-tissue-compartment model, and brain-wide VND was estimated with SIME. VS was then calculated as VT - VND VND and VS were then compared across groups, within each dataset. Results: A lower VND was found for individuals with alcohol-use disorder (34%, P = 0.00084) and Parkinson disease (34%, P = 0.0032) than in their corresponding controls. We found no difference in VND between first-episode psychosis patients and their controls, and the administration of lipopolysaccharide did not change VNDConclusion: Our findings suggest that in TSPO PET studies, nondisplaceable binding can differ between patient groups and conditions and should therefore be considered.
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| 5. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Accuracy and reliability of [C-11]PBR28 specific binding estimated without the use of a reference region
- 2019
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 188, s. 102-110
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Tidskriftsartikel (refereegranskat)abstract
- [C-11]PBR28 is a positron emission tomography radioligand used to examine the expression of the 18 kDa translocator protein (TSPO). TSPO is located in glial cells and can function as a marker for immune activation. Since TSPO is expressed throughout the brain, no true reference region exists. For this reason, an arterial input function is required for accurate quantification of [C-11]PBR28 binding and the most common outcome measure is the total distribution volume (V-T). Notably, V-T reflects both specific binding and non-displaceable binding. Therefore, estimates of specific binding, such as binding potential (e.g. BPND) and specific distribution volume (V-S) should theoretically be more sensitive to underlying differences in TSPO expression. It is unknown, however, if unbiased and accurate estimates of these outcome measures are obtainable for [C-11]PBR28. The Simultaneous Estimation (SIME) method uses time-activity-curves from multiple brain regions with the aim to obtain a brain-wide estimate of the non-displaceable distribution volume (V-ND), which can subsequently be used to improve the estimation of BPND and V-S. In this study we evaluated the accuracy of SIME-derived V-ND, and the reliability of resulting estimates of specific binding for [C-11]PBR28, using a combination of simulation experiments and in vivo studies in healthy humans. The simulation experiments, based on data from 54 unique [C-11]PBR28 examinations, showed that V-ND values estimated using SIME were both precise and accurate. Data from a pharmacological competition challenge (n = 5) showed that SIME provided V-ND values that were on average 19% lower than those obtained using the Lassen plot, but similar to values obtained using the Likelihood-Estimation of Occupancy technique. Test-retest data (n = 11) showed that SIME-derived V-S values exhibited good reliability and precision, while larger variability was observed in SIME-derived BPND values. The results support the use of SIME for quantifying specific binding of [C-11]PBR28, and suggest that V-S can be used in complement to the conventional outcome measure V-T. Additional studies in patient cohorts are warranted.
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| 6. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Test-retest reliability and convergent validity of (R)-[11C]PK11195 outcome measures without arterial input function
- 2018
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The PET radioligand (R)-[C-11]PK11195 is used to quantify the 18-kDa translocator protein (TSPO), a marker for glial activation. Since there is no brain region devoid of TSPO, an arterial input function (AIF) is ideally required for quantification of binding. However, obtaining an AIF is experimentally demanding, is sometimes uncomfortable for participants, and can introduce additional measurement error during quantification. The objective of this study was to perform an evaluation of the test-retest reliability and convergent validity of techniques used for quantifying (R)-[C-11]PK11195 binding without an AIF in clinical studies.Methods: Data from six healthy individuals who participated in two PET examinations, 6weeks apart, were analyzed. Regional non-displaceable binding potential (BPND) values were calculated using the simplified reference tissue model, with either cerebellum as reference region or a reference input derived using supervised cluster analysis (SVCA). Standardized uptake values (SUVs) were estimated for the time interval of 40-60min.Results: Test-retest reliability for BPND estimates were poor (80% of ICCs <0.5). BPND estimates derived without an AIF were not correlated with BPND, total or specific distribution volume from the 2TCM using an AIF (all R-2<12%). SUVs showed moderate reliability but no correlation to any other outcome measure.Conclusions: Caution is warranted when interpreting patient-control comparisons employing (R)-[C-11]PK11195 outcome measures obtained without an AIF.
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| 7. |
- Tuisku, Jouni, et al.
(författare)
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Effects of age, BMI and sex on the glial cell marker TSPO : a multicentre [11C]PBR28 HRRT PET study
- 2019
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 46:11, s. 2329-2338
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C-11]PBR28. Methods [C-11]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V-T) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V-T in the frontal and temporal cortex. BMI showed a significant negative correlation with V-T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V-T. A subgroup analysis revealed a positive correlation between V-T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.
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