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Andersson, Micael
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Publications (10 of 27) Show all publications
Karalija, N., Papenberg, G., Wåhlin, A., Johansson, J., Andersson, M., Axelsson, J., . . . Nyberg, L. (2019). C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition. Journal of cognitive neuroscience, 31(2), 314-325
Open this publication in new window or tab >>C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition
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2019 (English)In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 2, p. 314-325Article in journal (Refereed) Published
Abstract [en]

The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.

Place, publisher, year, edition, pages
MIT Press, 2019
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-155630 (URN)10.1162/jocn_a_01354 (DOI)000454429400011 ()30407135 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationRagnar Söderbergs stiftelseTorsten Söderbergs stiftelseThe Swedish Brain FoundationVästerbotten County Council
Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved
Salami, A., Garrett, D. D., Wåhlin, A., Rieckmann, A., Papenberg, G., Karalija, N., . . . Nyberg, L. (2019). Dopamine D2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion.. Journal of Neuroscience, 39(3), 537-547
Open this publication in new window or tab >>Dopamine D2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion.
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2019 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 39, no 3, p. 537-547Article in journal (Refereed) Published
Abstract [en]

Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA (measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA–BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 low-performing) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n-back task along with DA D2/3 PET assessment using [11C]raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D2/3 receptors to BOLD response in the thalamo–striatal–cortical circuit, which supports WM functioning. Critically, the DA–BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA–BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA–BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.

Keywords
PET, aging, dopamine, fMRI, working memory
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-155492 (URN)10.1523/JNEUROSCI.1493-18.2018 (DOI)000455849400013 ()30478031 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseThe Swedish Brain FoundationVästerbotten County Council
Available from: 2019-01-18 Created: 2019-01-18 Last updated: 2019-02-08Bibliographically approved
Papenberg, G., Karalija, N., Salami, A., Andersson, M., Axelsson, J., Riklund, K., . . . Bäckman, L. (2019). The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms. Journal of cognitive neuroscience, 31(9), 1422-1429
Open this publication in new window or tab >>The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms
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2019 (English)In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 9, p. 1422-1429Article in journal (Refereed) Published
Abstract [en]

Episodic memory is a polygenic trait influenced by different molecular mechanisms. We used PET and a candidate gene approach to investigate how individual differences at the molecular level translate into between-person differences in episodic memory performance of elderly persons. Specifically, we examined the interactive effects between hippocampal dopamine D2 receptor (D2DR) availability and candidate genes relevant for hippocampus-related memory functioning. We show that the positive effects of high D2DR availability in the hippocampus on episodic memory are confined to carriers of advantageous genotypes of the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. By contrast, these polymorphisms did not modulate the positive relationship between caudate D2DR availability and episodic memory.

Place, publisher, year, edition, pages
MIT Press, 2019
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-162391 (URN)10.1162/jocn_a_01429 (DOI)000477974100012 ()31112471 (PubMedID)2-s2.0-85070257740 (Scopus ID)
Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2019-08-20Bibliographically approved
Lövdén, M., Karalija, N., Andersson, M., Wåhlin, A., Axelsson, J., Köhncke, Y., . . . Lindenberger, U. (2018). Latent-profile analysis reveals behavioral and brain correlates of dopamine-cognition associations. Cerebral Cortex, 28(11), 3894-3907
Open this publication in new window or tab >>Latent-profile analysis reveals behavioral and brain correlates of dopamine-cognition associations
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2018 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 11, p. 3894-3907Article in journal (Refereed) Published
Abstract [en]

Evidence suggests that associations between the neurotransmitter dopamine and cognition are nonmonotonic and open to modulation by various other factors. The functional implications of a given level of dopamine may therefore differ from person to person. By applying latent-profile analysis to a large (n = 181) sample of adults aged 64-68 years, we probabilistically identified 3 subgroups that explain the multivariate associations between dopamine D2/3R availability (probed with C-11-raclopride-PET, in cortical, striatal, and hippocampal regions) and cognitive performance (episodic memory, working memory, and perceptual speed). Generally, greater receptor availability was associated with better cognitive performance. However, we discovered a subgroup of individuals for which high availability, particularly in striatum, was associated with poor performance, especially for working memory. Relative to the rest of the sample, this subgroup also had lower education, higher body-mass index, and lower resting-state connectivity between caudate nucleus and dorsolateral prefrontal cortex. We conclude that a smaller subset of individuals induces a multivariate non-linear association between dopamine D2/3R availability and cognitive performance in this group of older adults, and discuss potential reasons for these differences that await further empirical scrutiny.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
Cognitive Performance, dopamine D-2/3 Receptor Availability, Heterogeneity, Latent Profile Analysis, older Adults, Working Memory
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-153657 (URN)10.1093/cercor/bhx253 (DOI)000449432200011 ()29028935 (PubMedID)
Funder
Swedish Research Council, 446-2013-7189Forte, Swedish Research Council for Health, Working Life and Welfare, 2013-2277Knut and Alice Wallenberg FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseThe Swedish Brain FoundationVästerbotten County Council
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26Bibliographically approved
Salami, A., Rieckmann, A., Karalija, N., Avelar-Pereira, B., Andersson, M., Wåhlin, A., . . . Nyberg, L. (2018). Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction. Cerebral Cortex, 28(7), 2525-2539
Open this publication in new window or tab >>Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction
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2018 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 7, p. 2525-2539Article in journal (Refereed) Published
Abstract [en]

Individuals differ in how they perceive, remember, and think. There is evidence for the existence of distinct subgroups that differ in cognitive performance within the older population. However, it is less clear how individual differences in cognition in old age are linked to differences in brain-based measures. We used latent-profile analysis on n-back working-memory (WM) performance to identify subgroups in a large sample of older adults (n = 181; age = 64-68 years). Our analysis identified one larger normal subgroup with higher performance (n = 113; 63%), and a second smaller subgroup (n = 55; 31%) with lower performance. The low-performing subgroup showed weaker load-dependent BOLD modulation and lower connectivity within the fronto-parietal network (FPN) as well as between FPN and striatum during n-back, along with lower FPN connectivity at rest. This group also exhibited lower FPN structural integrity, lower frontal dopamine D2 binding potential, inferior performance on offline WM tests, and a trend-level genetic predisposition for lower dopamine-system efficiency. By contrast, this group exhibited relatively intact episodic memory and associated brain measures (i.e., hippocampal volume, structural, and functional connectivity within the default-mode network). Collectively, these data provide converging evidence for the existence of a group of older adults with impaired WM functioning characterized by reduced cortico-striatal coupling and aberrant cortico-cortical integrity within FPN.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
dopamine, fronto-parietal network, functional connectivity, individual differences, working memory
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-150747 (URN)10.1093/cercor/bhy062 (DOI)000437165800025 ()29901790 (PubMedID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Koehncke, Y., Papenberg, G., Jonasson, L. S., Karalija, N., Wåhlin, A., Salami, A., . . . Lövdén, M. (2018). Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition. NeuroImage, 181, 605-616
Open this publication in new window or tab >>Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition
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2018 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 181, p. 605-616Article in journal (Refereed) Published
Abstract [en]

Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity.

Place, publisher, year, edition, pages
Academic Press, 2018
Keywords
Cognition, Episodic memory, Dopamine, Physical activity, Aging
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-152374 (URN)10.1016/j.neuroimage.2018.07.036 (DOI)000445165600053 ()30041059 (PubMedID)
Funder
Swedish Research Council, 446-2013-7189Forte, Swedish Research Council for Health, Working Life and Welfare, 2013-2277Knut and Alice Wallenberg FoundationRagnar Söderbergs stiftelseTorsten Söderbergs stiftelseThe Swedish Brain FoundationVästerbotten County Council
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-10-05Bibliographically approved
Berginström, N., Nordström, P., Ekman, U., Eriksson, J., Andersson, M., Nyberg, L. & Nordström, A. (2018). Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: changes linked to altered Striato-Thalamic-Cortical Functioning. The journal of head trauma rehabilitation, 33(4), 266-274
Open this publication in new window or tab >>Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: changes linked to altered Striato-Thalamic-Cortical Functioning
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2018 (English)In: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 33, no 4, p. 266-274Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate whether functional magnetic resonance imaging (fMRI) can be used to detect fatigue after traumatic brain injury (TBI).

Setting: Neurorehabilitation clinic.

Participants: Patients with TBI (n = 57) and self-experienced fatigue more than 1 year postinjury, and age- and gender-matched healthy controls (n = 27).

Main Measures: Self-assessment scales of fatigue, a neuropsychological test battery, and fMRI scanning during performance of a fatiguing 27-minute attention task.

Results: During testing within the fMRI scanner, patients showed a higher increase in self-reported fatigue than controls from before to after completing the task (P < .001).The patients also showed lower activity in several regions, including bilateral caudate, thalamus, and anterior insula (all P < .05). Furthermore, the patients failed to display decreased activation over time in regions of interest: the bilateral caudate and anterior thalamus (all P < .01). Left caudate activity correctly identified 91% of patients and 81% of controls, resulting in a positive predictive value of 91%.

Conclusion: The results suggest that chronic fatigue after TBI is associated with altered striato-thalamic-cortical functioning. It would be of interest to study whether fMRI can be used to support the diagnosis of chronic fatigue in future studies.

Place, publisher, year, edition, pages
Wolters Kluwer, 2018
Keywords
fatigue, functional magnetic resonance imaging, neuropsychology, traumatic brain injury
National Category
Neurology
Research subject
Rehabilitation Medicine
Identifiers
urn:nbn:se:umu:diva-140021 (URN)10.1097/HTR.0000000000000340 (DOI)000442745900013 ()
Funder
Västerbotten County CouncilTorsten Söderbergs stiftelse
Available from: 2017-09-29 Created: 2017-09-29 Last updated: 2019-01-15Bibliographically approved
Berginström, N., Nordström, P., Ekman, U., Eriksson, J., Andersson, M., Nyberg, L. & Nordström, A. (2017). Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning. In: Brain Injury: Accepted Abstracts from the International Brain Injury Association’s 12th World Congress on Brain Injury. Paper presented at International Brain Injury Association’s 12th World Congress on Brain Injury (pp. 755-755). , 31
Open this publication in new window or tab >>Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning
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2017 (English)In: Brain Injury: Accepted Abstracts from the International Brain Injury Association’s 12th World Congress on Brain Injury, 2017, Vol. 31, p. 755-755Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

Mental fatigue is a common symptom in the chronic phase of traumatic brain injury. Despite its high prevalence, no treatmentis available for this disabling symptom, and the mechanisms underlying fatigue are poorly understood. Some studies have suggested that fatigue in traumatic brain injury and other neurological disorders might reflect dysfunction within striato-thalamic-cortical loops. In the present study, we investigated whether functional magnetic resonance imaging(fMRI) can be used to detect chronic fatigue after traumatic brain injury (TBI), with emphasis on the striato-thalamic cortical-loops. We included patients who had suffered traumatic brain injury (n = 57, age range 20–64 years) and experienced mental fatigue > 1 year post injury (mean = 8.79 years, SD = 7.35), and age- and sex-matched healthycontrols (n = 27, age range 25–65 years). All participants completed self-assessment scales of fatigue and other symptoms, underwent an extensive neuropsychological test battery and performed a fatiguing 27-minute attention task (the modified Symbol Digit Modalities Test) during fMRI. Accuracy did not differ between groups, but reaction times were slower in the traumatic brain injury group (p < 0.001). Patients showed a greater increase in fatigue than controls from before to after task completion (p < 0.001). Patients showed less fMRI blood oxygen level–dependent activity in several a priori hypothesized regions (family-wise error corrected,p < 0.05), including the bilateral caudate, thalamus and anterior insula. Using the left caudate as a region of interest and testing for sensitivity and specificity, we identified 91% of patients and 81% of controls. As expected, controls showed decreased activation over time in regions of interest—the bilateral caudate and anterior thalamus (p < 0.002, uncorrected)—whereas patients showed no corresponding activity decrease. These results suggest that chronic fatigue after TBI is linked to altered striato-thalamic-cortical functioning. The high precision of fMRI for the detection of fatigue is of great clinical interest, given the lack of objective measures for the diagnosis of fatigue.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-138649 (URN)10.1080/02699052.2017.1312145 (DOI)000406734000076 ()
Conference
International Brain Injury Association’s 12th World Congress on Brain Injury
Available from: 2017-08-25 Created: 2017-08-25 Last updated: 2018-06-09
Bäckman, L., Waris, O., Johansson, J., Andersson, M., Rinne, J. O., Alakurtti, K., . . . Nyberg, L. (2017). Increased dopamine release after working-memory updating training: Neurochemical correlates of transfer. Scientific Reports, 7, Article ID 7160.
Open this publication in new window or tab >>Increased dopamine release after working-memory updating training: Neurochemical correlates of transfer
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 7160Article in journal (Refereed) Published
Abstract [en]

Previous work demonstrates that working-memory (WM) updating training results in improved performance on a letter-memory criterion task, transfers to an untrained n-back task, and increases striatal dopamine (DA) activity during the criterion task. Here, we sought to replicate and extend these findings by also examining neurochemical correlates of transfer. Four positron emission tomography (PET) scans using the radioligand raclopride were performed. Two of these assessed DAD2 binding (letter memory; n-back) before 5 weeks of updating training, and the same two scans were performed post training. Key findings were (a) pronounced training-related behavioral gains in the lettermemory criterion task, (b) altered striatal DAD2 binding potential after training during letter-memory performance, suggesting training-induced increases in DA release, and (c) increased striatal DA activity also during the n-back transfer task after the intervention, but no concomitant behavioral transfer. The fact that the training-related DA alterations during the transfer task were not accompanied by behavioral transfer suggests that increased DA release may be a necessary, but not sufficient, condition for behavioral transfer to occur.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-138584 (URN)10.1038/s41598-017-07577-y (DOI)000406816300033 ()28769095 (PubMedID)
Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2018-06-09Bibliographically approved
Malmberg Gavelin, H., Stigsdotter Neely, A., Andersson, M., Eskilsson, T., Slunga Järvholm, L. & Boraxbekk, C.-J. (2017). Neural activation in stress-related exhaustion: cross-sectional observations and interventional effects. Psychiatry Research: Neuroimaging, 269, 17-25
Open this publication in new window or tab >>Neural activation in stress-related exhaustion: cross-sectional observations and interventional effects
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2017 (English)In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 269, p. 17-25Article in journal (Refereed) Published
Abstract [en]

The primary purpose of this study was to investigate the association between burnout and neural activation during working memory processing in patients with stress-related exhaustion. Additionally, we investigated the neural effects of cognitive training as part of stress rehabilitation. Fifty-five patients with clinical diagnosis of exhaustion disorder were administered the n-back task during fMRI scanning at baseline. Ten patients completed a 12-week cognitive training intervention, as an addition to stress rehabilitation. Eleven patients served as a treatment-as-usual control group. At baseline, burnout level was positively associated with neural activation in the rostral prefrontal cortex, the posterior parietal cortex and the striatum, primarily in the 2-back condition. Following stress rehabilitation, the striatal activity decreased as a function of improved levels of burnout. No significant association between burnout level and working memory performance was found, however, our findings indicate that frontostriatal neural responses related to working memory were modulated by burnout severity. We suggest that patients with high levels of burnout need to recruit additional cognitive resources to uphold task performance. Following cognitive training, increased neural activation was observed during 3-back in working memory-related regions, including the striatum, however, low sample size limits any firm conclusions.

Place, publisher, year, edition, pages
Clare: Elsevier, 2017
Keywords
Working memory fMRI, Burnout, Stress rehabilitation, Exhaustion disorder, Cognitive training
National Category
Neurosciences Applied Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:umu:diva-139932 (URN)10.1016/j.pscychresns.2017.08.008 (DOI)000412461700003 ()28917154 (PubMedID)
Available from: 2017-10-10 Created: 2017-10-10 Last updated: 2019-01-07Bibliographically approved
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