1.
Giddaluru, Sudheer, et al.
(författare)
Genetics of structural connectivity and information processing in the brain
2016
Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 221:9, s. 4643-4661
Tidskriftsartikel (refereegranskat) abstract
Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.
2.
Nyberg, Lars, et al.
(författare)
Longitudinal evidence for diminished frontal-cortex function in aging
2010
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
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.
3.
Salami, Alireza, et al.
(författare)
Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition
2012
Ingår i: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier. - 0925-4439 .- 1879-260X. ; 1822:3, s. 408-415
Tidskriftsartikel (refereegranskat) abstract
Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n = 287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest. WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
4.
Li, Xin, et al.
(författare)
Hub architecture of the human structural connectome : Links to aging and processing speed
2023
Ingår i: NeuroImage. - : Academic Press. - 1053-8119 .- 1095-9572. ; 278
Tidskriftsartikel (refereegranskat) abstract
The human structural brain network, or connectome, has a rich-club organization with a small number of brain regions showing high network connectivity, called hubs. Hubs are centrally located in the network, energy costly, and critical for human cognition. Aging has been associated with changes in brain structure, function, and cognitive decline, such as processing speed. At a molecular level, the aging process is a progressive accumulation of oxidative damage, which leads to subsequent energy depletion in the neuron and causes cell death. However, it is still unclear how age affects hub connections in the human connectome. The current study aims to address this research gap by constructing structural connectome using fiber bundle capacity (FBC). FBC is derived from Constrained Spherical Deconvolution (CSD) modeling of white-matter fiber bundles, which represents the capacity of a fiber bundle to transfer information. Compared to the raw number of streamlines, FBC is less bias for quantifying connection strength within biological pathways. We found that hubs exhibit longer-distance connections and higher metabolic rates compared to peripheral brain regions, suggesting that hubs are biologically costly. Although the landscape of structural hubs was relatively age-invariant, there were wide-spread age effects on FBC in the connectome. Critically, these age effects were larger in connections within hub compared to peripheral brain connections. These findings were supported by both a cross-sectional sample with wide age-range (N = 137) and a longitudinal sample across 5 years (N = 83). Moreover, our results demonstrated that associations between FBC and processing speed were more concentrated in hub connections than chance level, and FBC in hub connections mediated the age-effects on processing speed. Overall, our findings indicate that structural connections of hubs, which demonstrate greater energy demands, are particular vulnerable to aging. The vulnerability may contribute to age-related impairments in processing speed among older adults.
5.
Salami, Alireza, et al.
(författare)
Longitudinal Evidence for Dissociation of Anterior and Posterior MTL Resting-State Connectivity in Aging : Links to Perfusion and Memory
2016
Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 26:10, s. 3953-3963
Tidskriftsartikel (refereegranskat) abstract
Neuroimaging studies of spontaneous signal fluctuations as measured by resting-state functional magnetic resonance imaging have revealed age-related alterations in the functional architecture of brain networks. One such network is located in the medial temporal lobe (MTL), showing structural and functional variations along the anterior-posterior axis. Past cross-sectional studies of MTL functional connectivity (FC) have yielded discrepant findings, likely reflecting the fact that specific MTL subregions are differentially affected in aging. Here, using longitudinal resting-state data from 198 participants, we investigated 5-year changes in FC of the anterior and posterior MTL. We found an opposite pattern, such that the degree of FC within the anterior MTL declined after age 60, whereas elevated FC within the posterior MTL was observed along with attenuated posterior MTL-cortical connectivity. A significant negative change-change relation was observed between episodic-memory decline and elevated FC in the posterior MTL. Additional analyses revealed age-related cerebral blood flow (CBF) increases in posterior MTL at the follow-up session, along with a positive relation of elevated FC and CBF, suggesting that elevated FC is a metabolically demanding alteration. Collectively, our findings indicate that elevated FC in posterior MTL along with increased local perfusion is a sign of brain aging that underlie episodic-memory decline.
6.
Salami, Alireza, et al.
(författare)
Characterizing the neural correlates of modality-specific and modality-independent accessibility and availability signals in memory using partial-least squares
2010
Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 52:2, s. 686-698
Tidskriftsartikel (refereegranskat) abstract
Previous studies have shown that information that currently cannot be retrieved but will be retrieved on a subsequent, more supported task (i.e. is available but not accessible) has a distinct neural signature compared with non-available information. For verbal paired-associates, an availability signal has been revealed in left middle temporal cortex, an area potentially involved in the storage of such information, raising the possibility that availability signals are expressed in modality-specific storage sites. In the present study subjects encoded pictures and sounds representing concrete objects. One day later, during fMRI scanning, a verbal cued-recall task was administrated followed by a post-scan recognition task. Items remembered on both tasks were classified as accessible; items not remembered on the first but on the second task were classified as available; and items not remembered on any of the tasks were classified as not available. Multivariate partial-least-squares analyses revealed a modality-independent accessibility network with dominant contributions of left inferior parietal cortex, left inferior frontal cortex, and left hippocampus. Additionally, a modality-specific availability network was identified which included increased activity in visual regions for available pictorial information and in auditory regions for available sound information. These findings show that availability in memory, at least in part, is characterized by systematic changes in brain activity in sensory regions whereas memory access reflects differential activity in a modality-independent, conceptual network, thus indicating qualitative differences between availability and accessibility in memory.
7.
Karalija, Nina, 1984-, et al.
(författare)
Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
2022
Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99, s. e1278-e1289
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.
8.
Köhncke, Ylva, et al.
(författare)
Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition
2018
Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 181, s. 605-616
Tidskriftsartikel (refereegranskat) abstract
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.
9.
Nordin, Kristin, et al.
(författare)
DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes : A new window into cognitive aging
2022
Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 100:6, s. 1296-1320
Tidskriftsartikel (refereegranskat) abstract
Concomitant exploration of structural, functional, and neurochemical brain mechanisms underlying age-related cognitive decline is crucial in promoting healthy aging. Here, we present the DopamiNe, Age, connectoMe, and Cognition (DyNAMiC) project, a multimodal, prospective 5-year longitudinal study spanning the adult human lifespan. DyNAMiC examines age-related changes in the brain’s structural and functional connectome in relation to changes in dopamine D1 receptor availability (D1DR), and their associations to cognitive decline. Critically, due to the complete lack of longitudinal D1DR data, the true trajectory of one of the most age-sensitive dopamine systems remains unknown. The first DyNAMiC wave included 180 healthy participants (20–80 years). Brain imaging included magnetic resonance imaging assessing brain structure (white matter, gray matter, iron), perfusion, and function (during rest and task), and positron emission tomography (PET) with the [11C]SCH23390 radioligand. A subsample (n = 20, >65 years) was additionally scanned with [11C]raclopride PET measuring D2DR. Age-related variation was evident for multiple modalities, such as D1DR; D2DR, and performance across the domains of episodic memory, working memory, and perceptual speed. Initial analyses demonstrated an inverted u-shaped association between D1DR and resting-state functional connectivity across cortical network nodes, such that regions with intermediate D1DR levels showed the highest levels of nodal strength. Evident within each age group, this is the first observation of such an association across the adult lifespan, suggesting that emergent functional architecture depends on underlying D1DR systems. Taken together, DyNAMiC is the largest D1DR study worldwide, and will enable a comprehensive examination of brain mechanisms underlying age-related cognitive decline.
10.
Nyberg, Lars, 1966-, et al.
(författare)
Longitudinal stability in working memory and frontal activity in relation to general brain maintenance
2022
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
Tidskriftsartikel (refereegranskat) abstract
Cognitive functions are well-preserved for some older individuals, but the underlying brain mechanisms remain disputed. Here, 5-year longitudinal 3-back in-scanner and offline data classified individuals in a healthy older sample (baseline age = 64–68 years) into having stable or declining working-memory (WM). Consistent with a vital role of the prefrontal cortex (PFC), WM stability or decline was related to maintained or reduced longitudinal PFC functional responses. Subsequent analyses of imaging markers of general brain maintenance revealed higher levels in the stable WM group on measures of neurotransmission and vascular health. Also, categorical and continuous analyses showed that rate of WM decline was related to global (ventricles) and local (hippocampus) measures of neuronal integrity. Thus, our findings support a role of the PFC as well as general brain maintenance in explaining heterogeneity in longitudinal WM trajectories in aging.
