| 1. |
- Grill, Filip, et al.
(författare)
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Dopamine release in human associative striatum during reversal learning
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The dopaminergic system is firmly implicated in reversal learning but human measurements of dopamine release as a correlate of reversal learning success are lacking. Dopamine release and hemodynamic brain activity in response to unexpected changes in action-outcome probabilities are here explored using simultaneous dynamic [11C]Raclopride PET-fMRI and computational modelling of behavior. When participants encounter reversed reward probabilities during a card guessing game, dopamine release is observed in associative striatum. Individual differences in absolute reward prediction error and sensitivity to errors are associated with peak dopamine receptor occupancy. The fMRI response to perseverance errors at the onset of a reversal spatially overlap with the site of dopamine release. Trial-by-trial fMRI correlates of absolute prediction errors show a response in striatum and association cortices, closely overlapping with the location of dopamine release, and separable from a valence signal in ventral striatum. The results converge to implicate striatal dopamine release in associative striatum as a central component of reversal learning, possibly signifying the need for increased cognitive control when new stimuli-responses should be learned.
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| 2. |
- Stiernman, Louise, et al.
(författare)
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Neural correlates of emotion reactivity and emotion regulation in premenstrual dysphoric disorder : evidence for menstrual cycle phase-dependent and -independent effects in key regions of the salience network
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Emotion regulation deficits have been highlighted as a transdiagnostic feature of multiple psychiatric disorders. Deficient prefrontal “top-down” regulation of key nodes of the salience network (SN) associated with emotion generation, has previously been hypothesized to be relevant also in premenstrual dysphoric disorder (PMDD).Methods: In the present study, we used functional magnetic resonance imaging (fMRI) to investigate menstrual-cycle related variations in brain activity and connectivity in response to two separate emotional tasks (emotion reactivity and regulation) in 29 women with PMDD and 27 controls. We also examined whether differential brain activation between groups is related to premenstrual symptom severity and serum levels of progesterone-derived neuroactive steroids.Results: We did not find convincing evidence for reduced activity in regions associated with the conscious control of emotion in PMDD. However, women with PMDD showed increased reactivity in key nodes of the SN and the default mode network (DMN) during the luteal phase compared to control women. Furthermore, SN hyperactivity was apparent also during the follicular phase and related to PMDD symptom severity. We found no evidence of altered network connectivity across the menstrual cycle in PMDD women.Conclusion: SN dysfunction during the luteal phase may mediate multiple network aberrations. Furthermore, higher baseline (follicular) SN activity may render PMDD women more susceptible to severe mood symptoms in response to hormonal fluctuations. What drives increased SN activity in the follicular phase is unknown, but innate and neuroplastic mechanisms are proposed.
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| 3. |
- Andersson, Sara, et al.
(författare)
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Cognitive decline in Parkinson’s disease : a subgroup of extreme decliners revealed by a data-driven analysis of longitudinal progression
- 2021
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Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive impairment is an important symptom of Parkinson’s disease (PD) and predicting future cognitive decline is crucial for clinical practice. Here, we aim to identify latent sub-groups of longitudinal trajectories of cognitive change in PD patients, and explore predictors of differences in cognitive change. Longitudinal cognitive performance data from 349 newly diagnosed PD patients and 145 healthy controls from the Parkinson Progression Marker Initiative were modeled using a multivariate latent class linear mixed model. Resultant latent classes were compared on a number of baseline demographics, and clinical variables, as well as cerebrospinal fluid (CSF) biomarkers and striatal dopamine transporter (DAT) density markers of neuropathology. Trajectories of cognitive change in PD were best described by two latent classes. A large subgroup (90%), which showed a subtle impairment in cognitive performance compared to controls but remained stable over the course of the study, and a small subgroup (10%) which rapidly declined in all cognitive performance measures. Rapid decliners did not differ significantly from the larger group in terms of disease duration, severity or motor symptoms at baseline. However, rapid decliners had lower CSF amyloidß42 levels, a higher prevalence of sleep disorder and pronounced loss of caudate DAT density at baseline. These data suggest the existence of a distinct minority sub-type of PD in which rapid cognitive change in PD can occur uncoupled from motor symptoms or disease severity, likely reflecting early pathological change that extends from motor areas of the striatum into associative compartments and cortex.
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| 4. |
- Godbersen, Godber M., et al.
(författare)
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Task-evoked metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks
- 2023
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- External tasks evoke characteristic fMRI BOLD signal deactivations in the default mode network (DMN). However, for the corresponding metabolic glucose demands both decreases and increases have been reported. To resolve this discrepancy, functional PET/MRI data from 50 healthy subjects performing Tetris were combined with previously published data sets of working memory, visual and motor stimulation. We show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive networks. Specifically, the dorsal attention and frontoparietal network shape the glucose metabolism of the posteromedial DMN in opposing directions. While tasks that mainly require an external focus of attention lead to a consistent downregulation of both metabolism and the BOLD signal in the posteromedial DMN, cognitive control during working memory requires a metabolically expensive BOLD suppression. This indicates that two types of BOLD deactivations with different oxygen-to-glucose index may occur in this region. We further speculate that consistent downregulation of the two signals is mediated by decreased glutamate signaling, while divergence may be subject to active GABAergic inhibition. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation.
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| 5. |
- Hou, Meijun, et al.
(författare)
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Human dopaminergic system in the exercise-cognition link
- 2024
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Ingår i: Trends in Molecular Medicine. - : Elsevier. - 1471-4914 .- 1471-499X. ; 30:8, s. 708-712
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Tidskriftsartikel (refereegranskat)abstract
- While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research.
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| 6. |
- Jakobson Mo, Susanna, et al.
(författare)
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VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT
- 2022
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Ingår i: Nuclear medicine communications. - : Wolters Kluwer. - 0143-3636 .- 1473-5628. ; 43:3, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the potential impact of polymorphism in the 3'-untranslated region (3'UTR) of the SLC6A3 gene (DAT1) on normal variation in dopamine transporter (DAT) imaging with [18F]FE-PE2I PET and [123I]FP-Cit SPECT.METHODS: Thirty-six individuals (mean age 70.4±5.4 years) with normal [18F]FE-PE2I PET and [123I]FP-Cit SPECT were genotyped for variable number of tandem repeats (VNTR) in the 3′UTR of the DAT1 gene. The DAT-availability in the caudate and putamen as measured with [18F]FE-PE2I PET and [123I]FP-Cit SPECT, as well as in the substantia nigra with [18F]FE-PE2I PET were compared between the participants carrying one or two 9-repeat alleles (i.e. 9R+10R or 9R+9R; 47%) and the participants without a 9R allele (i.e. 10R+10R or 10R+11R; 53%). Nonparametric tests, linear regression analysis and mixed model analysis were used to assess any statistical difference in measured DAT availability between the two allele groups.RESULTS: The measured DAT-availability in PET- and SPECT-imaging tended to be slightly higher in the 9R-group; however, the difference did not reach statistical significance in either the caudate or the putamen or the substantia nigra. Instead, age did have a significant effect on the DAT level (P < 0.05) notwithstanding the genotype.CONCLUSION: No significant effect of DAT1-genotype was detectable in imaging with [18F]FE-PE2I PET or [123I]FP-Cit, instead, age accounted for the normal variation in DAT-PET and DAT-SPECT.
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| 7. |
- Jonasson Stiernman, Lars, 1983-, et al.
(författare)
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Dissociations between glucose metabolism and blood oxygenation in the human default mode network revealed by simultaneous PET-fMRI
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:27
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Tidskriftsartikel (refereegranskat)abstract
- The finding of reduced functional MRI (fMRI) activity in the default mode network (DMN) during externally focused cognitive control has been highly influential to our understanding of human brain function. However, these negative fMRI responses, measured as relative decreases in the blood-oxygenation-level-dependent (BOLD) response between rest and task, have also prompted major questions of interpretation. Using hybrid functional positron emission tomography (PET)-MRI, this study shows that task-positive and -negative BOLD responses do not reflect antagonistic patterns of synaptic metabolism. Task-positive BOLD responses in attention and control networks were accompanied by concomitant increases in glucose metabolism during cognitive control, but metabolism in widespread DMN remained high during rest and task despite negative BOLD responses. Dissociations between glucose metabolism and the BOLD response specific to the DMN reveal functional heterogeneity in this network and demonstrate that negative BOLD responses during cognitive control should not be interpreted to reflect relative increases in metabolic activity during rest. Rather, neurovascular coupling underlying BOLD response patterns during rest and task in DMN appears fundamentally different from BOLD responses in other association networks during cognitive control.
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| 8. |
- Simonsson, Emma, et al.
(författare)
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Dopamine d2/3-receptor availability and its association with autonomous motivation to exercise in older adults : an exploratory [11c]-raclopride study
- 2022
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media S.A.. - 1662-5161. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autonomous motivation to exercise occurs when the activity is voluntary and with a perceived inherent satisfaction from the activity itself. It has been suggested that autonomous motivation is related to striatal dopamine D2/3-receptor (D2/3R) availability within the brain. In this study, we hypothesized that D2/3R availability in three striatal regions (nucleus accumbens, caudate nucleus, and putamen) would be positively associated with self-reported autonomous motivation to exercise. We also examined this relationship with additional exploratory analyses across a set of a priori extrastriatal regions of interest (ROI).Methods: Our sample comprised 49 older adults (28 females) between 64 and 78 years of age. The D2/3R availability was quantified from positron emission tomography using the non-displaceable binding potential of [11C]-raclopride ligand. The exercise-related autonomous motivation was assessed with the Swedish version of the Behavioral Regulations in Exercise Questionnaire-2.Results: No significant associations were observed between self-reported autonomous motivation to exercise and D2/3R availability within the striatum (nucleus accumbens, caudate nucleus, and putamen) using semi-partial correlations controlling for ROI volume on D2/3R availability. For exploratory analyses, positive associations were observed for the superior (r = 0.289, p = 0.023) and middle frontal gyrus (r = 0.330, p = 0.011), but not for the inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, or anterior insular cortex.Conclusion: This study could not confirm the suggested link between striatal D2/3R availability and subjective autonomous motivation to exercise among older adults. The exploratory findings, however, propose that frontal brain regions may be involved in the intrinsic regulation of exercise-related behaviors, though this has to be confirmed by future studies using a more suitable ligand and objective measures of physical activity levels.
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| 9. |
- Stiernman Jonasson, Lars, 1983-, et al.
(författare)
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Impact of aerobic exercise on brain structure in models of aging : Hippocampus and beyond
- 2021
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Ingår i: Factors Affecting Neurological Aging. - : Elsevier. - 9780128179901 ; , s. 403-413
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Bokkapitel (refereegranskat)abstract
- Evidence from multiple scientific disciplines indicates that aerobic exercise could be effective in enhancing brain health and function in aging, and reducing the risk for cognitive impairment and dementia. Animal models have provided convincing evidence that exercise increases the expression of growth factors involved in neuroplasticity. By triggering signaling cascades in the brain, these growth factors promote proliferation, neurogenesis, neural differentiation, and cell survival in the hippocampus, and angiogenesis and/or synaptic plasticity and neural growth throughout the brain more generally. These growth factor-induced effects partly explain why exercise improves memory. Furthermore, they engender neuroprotective effects by influencing regeneration, remyelination, cell survival, and waste removal. Whereas human intervention evidence supports hippocampal plasticity, cross-sectional studies highlight effects in the cortex too, indicating that exercise-induced gross morphological changes may be regionally specific. Aerobic exercise is a promising nonpharmacological therapy to maintain brain health, although knowledge about the effects of specific exercise parameters (i.e., intensity) on different populations is still lacking.
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| 10. |
- Stiernman, Lars, 1983-, et al.
(författare)
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Widespread fMRI BOLD signal overactivations during cognitive control in older adults are not matched by corresponding increases in fPET glucose metabolism
- 2023
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 43:14, s. 2527-2536
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Tidskriftsartikel (refereegranskat)abstract
- A common observation in fMRI studies using the BOLD signal is that older adults, compared with young adults, show overactivations, particularly during less demanding tasks. The neuronal underpinnings of such overactivations are not known, but a dominant view is that they are compensatory in nature and involve recruitment of additional neural resources. We scanned 23 young (20-37 years) and 34 older (65-86 years) healthy human adults of both sexes with hybrid positron emission tomography/MRI. The radioligand [18F]fluoro-deoxyglucose was used to assess dynamic changes in glucose metabolism as a marker of task-dependent synaptic activity, along with simultaneous fMRI BOLD imaging. Participants performed two verbal working memory (WM) tasks: one involving maintenance (easy) and one requiring manipulation (difficult) of information in WM. Converging activations to the WM tasks versus rest were observed for both imaging modalities and age groups in attentional, control, and sensorimotor networks. Upregulation of activity to WM-demand, comparing the more difficult to the easier task, also converged between both modalities and age groups. For regions in which older adults showed task-dependent BOLD overactivations compared with the young adults, no corresponding increases in glucose metabolism were found. To conclude, findings from the current study show that task-induced changes in the BOLD signal and synaptic activity as measured by glucose metabolism generally converge, but overactivations observed with fMRI in older adults are not coupled with increased synaptic activity, which suggests that these overactivations are not neuronal in origin.
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