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Salami, Alireza
Publications (10 of 63) Show all publications
Pedersen, R., Johansson, J., Nordin, K., Rieckmann, A., Wåhlin, A., Nyberg, L., . . . Salami, A. (2024). Dopamine D1-receptor organization contributes to functional brain architecture. Journal of Neuroscience, 44(11), Article ID e0621232024.
Open this publication in new window or tab >>Dopamine D1-receptor organization contributes to functional brain architecture
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2024 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 44, no 11, article id e0621232024Article in journal (Refereed) Published
Abstract [en]

Recent work has recognized a gradient-like organization in cortical function, spanning from primary sensory to transmodal cortices. It has been suggested that this axis is aligned with regional differences in neurotransmitter expression. Given the abundance of dopamine D1-receptors (D1DR), and its importance for modulation and neural gain, we tested the hypothesis that D1DR organization is aligned with functional architecture, and that inter-regional relationships in D1DR co-expression modulate functional cross talk. Using the world's largest dopamine D1DR-PET and MRI database (N = 180%, 50% female), we demonstrate that D1DR organization follows a unimodal–transmodal hierarchy, expressing a high spatial correspondence to the principal gradient of functional connectivity. We also demonstrate that individual differences in D1DR density between unimodal and transmodal regions are associated with functional differentiation of the apices in the cortical hierarchy. Finally, we show that spatial co-expression of D1DR primarily modulates couplings within, but not between, functional networks. Together, our results show that D1DR co-expression provides a biomolecular layer to the functional organization of the brain.

Place, publisher, year, edition, pages
Society for Neuroscience, 2024
Keywords
architecture, dopamine, functional connectivity, gradients, organization
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-222641 (URN)10.1523/JNEUROSCI.0621-23.2024 (DOI)38302439 (PubMedID)2-s2.0-85187783583 (Scopus ID)
Available from: 2024-04-19 Created: 2024-04-19 Last updated: 2024-04-19Bibliographically approved
Karalija, N., Papenberg, G., Johansson, J., Wåhlin, A., Salami, A., Andersson, M., . . . Nyberg, L. (2024). Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline. Neurobiology of Aging, 136, 125-132
Open this publication in new window or tab >>Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
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2024 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 136, p. 125-132Article in journal (Refereed) Published
Abstract [en]

Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64–68 years; 5-year follow-up: n = 129) who underwent positron emission tomography with 11C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.

Keywords
11C-raclopride, Aging, Dopamine D2-like receptor, Longitudinal, Magnetic resonance imaging, Positron emission tomography, Working memory
National Category
Geriatrics
Identifiers
urn:nbn:se:umu:diva-221540 (URN)10.1016/j.neurobiolaging.2024.02.001 (DOI)38359585 (PubMedID)2-s2.0-85185304249 (Scopus ID)
Funder
Swedish Research Council, 421-2012-648Swedish Research Council, 2017-02217Swedish Research Council, 2022-01804Umeå UniversityKnut and Alice Wallenberg Foundation, 2015.0277Jonas and Christina af Jochnick FoundationAlzheimerfonden, AF-967710Riksbankens Jubileumsfond, P20-0779Region Västerbotten
Available from: 2024-03-15 Created: 2024-03-15 Last updated: 2024-03-15Bibliographically approved
Johansson, J., Nordin, K., Pedersen, R., Karalija, N., Papenberg, G., Andersson, M., . . . Salami, A. (2023). Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan. Cell Reports, 42(9), Article ID 113107.
Open this publication in new window or tab >>Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan
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2023 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 42, no 9, article id 113107Article in journal (Refereed) Published
Abstract [en]

Age-related alterations in D1-like dopamine receptor (D1DR) have distinct implications for human cognition and behavior during development and aging, but the timing of these periods remains undefined. Enabled by a large sample of in vivo assessments (n = 180, age 20 to 80 years of age, 50% female), we discover that age-related D1DR differences pivot at approximately 40 years of age in several brain regions. Focusing on the most age-sensitive dopamine-rich region, we observe opposing pre- and post-forties interrelations among caudate D1DR, cortico-striatal functional connectivity, and memory. Finally, particularly caudate D1DR differences in midlife and beyond, but not in early adulthood, associate with manifestation of white matter lesions. The present results support a model by which excessive dopamine modulation in early adulthood and insufficient modulation in aging are deleterious to brain function and cognition, thus challenging a prevailing view of monotonic D1DR function across the adult lifespan.

Keywords
aging, cognition, CP: Neuroscience, dopamine D1, functional connectivity, neuromodulation, protracted development
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-214414 (URN)10.1016/j.celrep.2023.113107 (DOI)2-s2.0-85169884676 (Scopus ID)
Funder
Swedish Research Council, 2016-01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond
Available from: 2023-09-18 Created: 2023-09-18 Last updated: 2024-01-17Bibliographically approved
Pedersen, R., Johansson, J. & Salami, A. (2023). Dopamine D1-signaling modulates maintenance of functional network segregation in aging. Aging Brain, 3, Article ID 100079.
Open this publication in new window or tab >>Dopamine D1-signaling modulates maintenance of functional network segregation in aging
2023 (English)In: Aging Brain, ISSN 2589-9589, Vol. 3, article id 100079Article in journal (Refereed) Published
Abstract [en]

Past research has shown that as individuals age, there are decreases in within-network connectivity and increases in between-network connectivity, a pattern known as functional dedifferentiation. While the mechanisms behind reduced network segregation are not fully understood, evidence suggests that age-related differences in the dopamine (DA) system may play a key role. The DA D1-receptor (D1DR) is the most abundant and age-sensitive receptor subtype in the dopaminergic system, known to modulate synaptic activity and enhance the specificity of the neuronal signals. In this study from the DyNAMiC project (N = 180, 20-79y), we set out to investigate the interplay among age, functional connectivity, and dopamine D1DR availability. Using a novel application of multivariate Partial Least squares (PLS), we found that older age, and lower D1DR availability, were simultaneously associated with a pattern of decreased within-network and increased between-network connectivity. Individuals who expressed greater distinctiveness of large-scale networks exhibited more efficient working memory. In line with the maintenance hypotheses, we found that older individuals with greater D1DR in caudate exhibited less dedifferentiation of the connectome, and greater working memory, compared to their age-matched counterparts with less D1DR. These findings suggest that dopaminergic neurotransmission plays an important role in functional dedifferentiation in aging with consequences for working memory function at older age. 

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Aging, D1DR, Dedifferentiation, Dopamine, Functional connectivity, Working memory
National Category
Neurosciences
Research subject
molecular medicine (medical sciences)
Identifiers
urn:nbn:se:umu:diva-212688 (URN)10.1016/j.nbas.2023.100079 (DOI)
Funder
Swedish Research Council, 2016–01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20-0515
Available from: 2023-08-08 Created: 2023-08-08 Last updated: 2023-08-08Bibliographically approved
Li, X., Salami, A. & Persson, J. (2023). Hub architecture of the human structural connectome: Links to aging and processing speed. NeuroImage, 278, Article ID 120270.
Open this publication in new window or tab >>Hub architecture of the human structural connectome: Links to aging and processing speed
2023 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 278, article id 120270Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Aging, Connectome, Diffusion-weighted imaging, Fiber bundle capacity, Processing speed
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-212415 (URN)10.1016/j.neuroimage.2023.120270 (DOI)37423273 (PubMedID)2-s2.0-85165230998 (Scopus ID)
Funder
Swedish Research Council, 421-2013-1039Swedish Research Council, F02014-0224
Available from: 2023-07-28 Created: 2023-07-28 Last updated: 2023-07-28Bibliographically approved
Gustavsson, J., Johansson, J., Falahati, F., Andersson, M., Papenberg, G., Avelar-Pereira, B., . . . Salami, A. (2023). The iron-dopamine D1 coupling modulates neural signatures of working memory across adult lifespan. NeuroImage, 279, Article ID 120323.
Open this publication in new window or tab >>The iron-dopamine D1 coupling modulates neural signatures of working memory across adult lifespan
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2023 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 279, article id 120323Article in journal (Refereed) Published
Abstract [en]

Brain iron overload and decreased integrity of the dopaminergic system have been independently reported as brain substrates of cognitive decline in aging. Dopamine (DA), and iron are co-localized in high concentrations in the striatum and prefrontal cortex (PFC), but follow opposing age-related trajectories across the lifespan. DA contributes to cellular iron homeostasis and the activation of D1-like DA receptors (D1DR) alleviates oxidative stress-induced inflammatory responses, suggesting a mutual interaction between these two fundamental components. Still, a direct in-vivo study testing the iron-D1DR relationship and their interactions on brain function and cognition across the lifespan is rare. Using PET and MRI data from the DyNAMiC study (n=180, age=20-79, %50 female), we showed that elevated iron content was related to lower D1DRs in DLPFC, but not in striatum, suggesting that dopamine-rich regions are less susceptible to elevated iron. Critically, older individuals with elevated iron and lower D1DR exhibited less frontoparietal activations during the most demanding task, which in turn was related to poorer working-memory performance. Together, our findings suggest that the combination of elevated iron load and reduced D1DR contribute to disturbed PFC-related circuits in older age, and thus may be targeted as two modifiable factors for future intervention.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Age, BOLD, Dopamine, Iron, Working memory
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-214277 (URN)10.1016/j.neuroimage.2023.120323 (DOI)37582419 (PubMedID)2-s2.0-85168445561 (Scopus ID)
Funder
Swedish Research Council, 2016-01936Swedish Research Council, 2014-00940Swedish Research Council, 2018-01327Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20- 0515The Karolinska Institutet's Research Foundation, 2019-00916Swedish National Infrastructure for Computing (SNIC)
Available from: 2023-09-11 Created: 2023-09-11 Last updated: 2023-09-11Bibliographically approved
Vaisvilaite, L., Andersson, M., Salami, A. & Specht, K. (2023). Time of day dependent longitudinal changes in resting-state fMRI. Frontiers in Neurology, 14, Article ID 1166200.
Open this publication in new window or tab >>Time of day dependent longitudinal changes in resting-state fMRI
2023 (English)In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 14, article id 1166200Article in journal (Refereed) Published
Abstract [en]

Longitudinal studies have become more common in the past years due to their superiority over cross-sectional samples. In light of the ongoing replication crisis, the factors that may introduce variability in resting-state networks have been widely debated. This publication aimed to address the potential sources of variability, namely, time of day, sex, and age, in longitudinal studies within individual resting-state fMRI data. DCM was used to analyze the fMRI time series, extracting EC connectivity measures and parameters that define the BOLD signal. In addition, a two-way ANOVA was used to assess the change in EC and parameters that define the BOLD signal between data collection waves. The results indicate that time of day and gender have significant model evidence for the parameters that define the BOLD signal but not EC. From the ANOVA analysis, findings indicate that there was a significant change in the two nodes of the DMN and their connections with the fronto-parietal network. Overall, these findings suggest that in addition to age and gender, which are commonly accounted for in the fMRI data collection, studies should note the time of day, possibly treating it as a covariate in longitudinal samples.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
circadian rythm, dynamic causal modeling (DCM), fMRI, resting-state, time of day (ToD)
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-212413 (URN)10.3389/fneur.2023.1166200 (DOI)37475742 (PubMedID)2-s2.0-85165167111 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council, K2010-61X-21446-01The Research Council of Norway, 276044
Available from: 2023-07-28 Created: 2023-07-28 Last updated: 2023-08-28Bibliographically approved
Stiernman, L., Grill, F., McNulty, C., Bahrd, P., Panes Lundmark, V., Axelsson, J., . . . Rieckmann, A. (2023). Widespread fMRI BOLD signal overactivations during cognitive control in older adults are not matched by corresponding increases in fPET glucose metabolism. Journal of Neuroscience, 43(14), 2527-2536
Open this publication in new window or tab >>Widespread fMRI BOLD signal overactivations during cognitive control in older adults are not matched by corresponding increases in fPET glucose metabolism
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2023 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 43, no 14, p. 2527-2536Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Society for Neuroscience, 2023
Keywords
aging, fMRI, glucose metabolism, overactivation, PET, working memory
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-206761 (URN)10.1523/JNEUROSCI.1331-22.2023 (DOI)000976532300008 ()36868855 (PubMedID)2-s2.0-85152165890 (Scopus ID)
Funder
EU, European Research Council, ERC-STG-716065EU, Horizon 2020Swedish Research Council, 2016-01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20-0515
Available from: 2023-05-02 Created: 2023-05-02 Last updated: 2023-09-05Bibliographically approved
Salami, A., Adolfsson, R., Andersson, M., Blennow, K., Lundquist, A., Nordin Adolfsson, A., . . . Nyberg, L. (2022). Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function. Journal of Alzheimer's Disease, 85(3), 1309-1320
Open this publication in new window or tab >>Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function
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2022 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 85, no 3, p. 1309-1320Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The Apolipoprotein E (APOE) ɛ4 allele has been linked to increased tau phosphorylation and tangle formation. APOE ɛ4 carriers with elevated tau might be at the higher risk for Alzheimer's disease (AD) progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe. Similarly, APOE ɛ4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether the influence of elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE ɛ4 carriers.

OBJECTIVE: We related ɛ4 carriage to levels of plasma phosphorylated tau (p-tau181) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity.

METHODS: Plasma p-tau181 was analyzed in 142 clinically defined AD cases and 126 matched controls. The longitudinal analysis involved 87 non-demented individuals (from population-based study) with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding.

RESULTS: Increased p-tau181 was observed for both ɛ4 carriers and non-carriers close to AD onset, but exclusively for ɛ4 carriers in the early preclinical groups (7- and 13-years pre-AD). In ɛ4 carriers, longitudinal p-tau181 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity.

CONCLUSION: Our findings support an association of APOE ɛ4 and p-tau181 with preclinical AD and hippocampus functioning.

Place, publisher, year, edition, pages
IOS Press, 2022
Keywords
Alzheimer’s disease, APOE, fMRI, hippocampus, longitudinal, magnetic resonance imaging, p-tau181, phosphorylated tau, population-based
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-192513 (URN)10.3233/JAD-210673 (DOI)000752449800030 ()34924376 (PubMedID)2-s2.0-85124174700 (Scopus ID)
Available from: 2022-02-22 Created: 2022-02-22 Last updated: 2024-04-08Bibliographically approved
Nordin, K., Gorbach, T., Pedersen, R., Panes Lundmark, V., Johansson, J., Andersson, M., . . . Salami, A. (2022). DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes: A new window into cognitive aging. Journal of Neuroscience Research, 100(6), 1296-1320
Open this publication in new window or tab >>DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes: A new window into cognitive aging
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2022 (English)In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 100, no 6, p. 1296-1320Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
aging, cognition, connectome, dopamine, lifespan, PET
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-193314 (URN)10.1002/jnr.25039 (DOI)000769326800001 ()35293013 (PubMedID)2-s2.0-85126323267 (Scopus ID)
Funder
Swedish Research Council, 2016– 01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20-0515
Available from: 2022-03-29 Created: 2022-03-29 Last updated: 2023-04-25Bibliographically approved
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