| 1. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99, s. e1278-e1289
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
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| 2. |
- Månsson, Kristoffer N. T., et al.
(författare)
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Neuroplasticity in Response to Cognitive Behavior Therapy for Social Anxiety Disorder
- 2015
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Ingår i: Abstracts from the 7th Swedish Congress on internet interventions (SWEsrii). - Linköping : Linköping University Press. ; , s. 13-13
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Functional magnetic resonance imaging studies have consistently showed increased amygdala responsiveness in Social Anxiety Disorder (SAD), which decreases after anxiolytic treatment (e.g., Cognitive Behavior Therapy, CBT). However, less is known about treatment-related structural gray matter (GM) volume changes. Furthermore, the relationship between functional and structural plasticity are largely neglected in the literature. Methods: Functional and structural neuroimaging were used to assess 26 SAD patients. The patients were randomized to receive Internet-delivered CBT (ICBT), or a control condition. The Clinical Global Impression-Improvement scale (CGI-I) determined clinical response. Also, we assessed level of anticipatory speech anxiety. At pre-, and post-treatment, blood-oxygen-level dependent (BOLD) responses to self-referential criticism were recorded, and structural data was examined with voxel-based morphometry (VBM). Results: CGI-I assessment showed that eight (61%) patients were deemed as responders following ICBT, and 3 (23%) in the control group (χ2=3.90, p=0.047). Time ˙ treatment interactions showed decreased amygdala BOLD response (Z=3.28, p=0.015, Family Wise-Error corrected, FWE), and amygdala GM volume (Z=3.30, pFWE=0.024) after ICBT. At baseline, GM amygdala volume was correlated with anticipatory anxiety (Z=2.96, pFWE=0.040), and amygdala GM atrophy following ICBT was correlated with decreased anticipatory anxiety (Z>2.83, pFWE<0.055). Moreover, the amygdala BOLD response change was associated with the local GM atrophy after ICBT (Z>2.45, pFWE<0.029). Conclusions: This is the first randomized study to evaluate multiple imaging modalities and the brain´s plasticity to an anxiolytic treatment. The functional and structural plasticity was highly correlated as indicated by anxiety-related BOLD signal change and GM volume in the amygdala following ICBT.
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| 3. |
- Månsson, Kristoffer N T, et al.
(författare)
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Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder
- 2016
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brain’s adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure–function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood–oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time × treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected PFWE=0.02) and BOLD responsivity (PFWE=0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (PFWE=0.04), and CBT-induced reduction of amygdala GM volume (pre–post) correlated positively with reduced anticipatory anxiety after treatment (PFWE0.05). In addition, we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants, as compared with controls (PFWE=0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P=0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT.
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| 4. |
- Månsson, Kristoffer N.T., et al.
(författare)
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Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder
- 2017
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 318, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Effective psychiatric treatments ameliorate excessive anxiety and induce neuroplasticity immediately after the intervention, indicating that emotional components in the human brain are rapidly adapTable Still, the interplay between structural and functional neuroplasticity is poorly understood, and studies of treatment-induced long-term neuroplasticity are rare. Functional and structural magnetic resonance imaging (using 3 T MRI) was performed in 13 subjects with social anxiety disorder on 3 occasions over 1 year. All subjects underwent 9 weeks of Internet-delivered cognitive behaviour therapy in a randomized cross-over design and independent assessors used the Clinically Global Impression-Improvement (CGI-I) scale to determine treatment response. Gray matter (GM) volume, assessed with voxel-based morphometry, and functional blood-oxygen level-dependent (BOLD) responsivity to self-referential criticism were compared between treatment responders and non-responders using 2 × 2 (group × time; pretreatment to follow-up) ANOVA. At 1-year follow-up, 7 (54%) subjects were classified as CGI-I responders. Left amygdala GM volume was more reduced in responders relative to non-responders from pretreatment to 1-year follow-up (Z = 3.67, Family-Wise Error corrected p = 0.02). In contrast to previous short-term effects, altered BOLD activations to self-referential criticism did not separate responder groups at follow-up. The structure and function of the amygdala changes immediately after effective psychological treatment of social anxiety disorder, but only reduced amygdala GM volume, and not functional activity, is associated with a clinical response 1 year after CBT.
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| 5. |
- Nyberg, Lars, et al.
(författare)
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Longitudinal evidence for diminished frontal-cortex function in aging
- 2010
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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. ; 107:52, s. 22682-22686
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.
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| 6. |
- Nyberg, Lars, et al.
(författare)
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The APOE epsilon 4 allele in relation to brain white-matter microstructure in adulthood and aging
- 2014
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 55:3, s. 263-267
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Tidskriftsartikel (refereegranskat)abstract
- The Apolipoprotein E (ApoE) epsilon 4 allele is a major genetic risk factor for sporadic Alzheimer's disease and has been associated with structural and functional brain alterations across the adult life span. Recent studies have presented evidence that epsilon 4 affects microstructural properties of brain white matter (WM) in non-demented carriers of the epsilon 4 allele, but conflicting evidence has been presented as well. The main purpose of the present study was therefore to examine ApoE effects on WM in a large sample of middle-aged and older adults (N=273). Diffusion tensor imaging (DTI) data was acquired, and tract-based as well as voxel-wise analyses were conducted. The tract-based analyses revealed no significant ApoE effects, and no significant interactions between genotype and age were observed. Taken together, the findings of the present study suggest that ApoE effects on white-matter microstructure are less abundant than has been suggested in some previous studies.
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| 7. |
- Papenberg, Goran, et al.
(författare)
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Genetics and Functional Imaging : Effects of APOE, BDNF, COMT, and KIBRA in Aging
- 2015
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Ingår i: Neuropsychology Review. - : Springer. - 1040-7308 .- 1573-6660. ; 25:1, s. 47-62
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Forskningsöversikt (refereegranskat)abstract
- Increasing evidence from cross-sectional and longitudinal molecular-genetic studies suggests that effects of common genetic variations on cognitive functioning increase with aging. We review the influence of candidate genes on brain functioning in old age, focusing on four genetic variations that have been extensively investigated: APOE, BDNF, COMT, and KIBRA. Similar to the behavioral evidence, there are reports from age-comparative studies documenting stronger genetic effects on measures of brain functioning in older adults compared to younger adults. This pattern suggests disproportionate impairments of neural processing among older individuals carrying disadvantageous genotypes. We discuss various factors, including gene-gene interactions, study population characteristics, lifestyle factors, and diseases, that need to be considered in future studies and may help understand inconsistent findings in the extant literature.
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| 8. |
- Papenberg, Goran, et al.
(författare)
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The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms
- 2019
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Ingår i: Journal of cognitive neuroscience. - : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 31:9, s. 1422-1429
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 10. |
- Ziaei, Maryam, et al.
(författare)
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Age-related alterations in functional connectivity patterns during working memory encoding of emotional items
- 2017
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Ingår i: Neuropsychologia. - : Elsevier. - 0028-3932 .- 1873-3514. ; 94, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Previous findings indicate age-related differences in frontal-amygdala connectivity during emotional processing. However, direct evidence for age differences in brain functional activation and connectivity during emotional processing and concomitant behavioral implications is lacking. In the present study, we examined the impact of aging on the neural signature of selective attention to emotional information during working memory (WM) encoding. Participants completed an emotional WM task in which they were asked to attend to emotional targets and ignore irrelevant distractors. Despite an overall reduction in accuracy for older relative to younger adults, no behavioral age effect was observed as a function of emotional valence. The functional connectivity patterns of left ventrolateral prefrontal cortex showed that younger adults recruited one network for encoding of both positive and negative emotional targets and this network contributed to higher memory accuracy in this cohort. Older adults, on the other hand, engaged two distinct networks for encoding of positive and negative targets. The functional connectivity analysis using left amygdala further demonstrated that older adults recruited one single network during encoding of positive as well as negative targets whereas younger adults recruited this network only for encoding of negative items. The engagement of amygdala functional network also contributed to higher memory performance and faster response times in older adults. Our findings provide novel insights into the differential roles of functional brain networks connected to the medial PFC and amygdala during encoding of emotionally-valenced items with advancing age.
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