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Salami, Alireza
Publications (10 of 67) Show all publications
Papenberg, G., Karalija, N., Salami, A., Johansson, J., Wåhlin, A., Andersson, M., . . . Bäckman, L. (2025). Aging-related losses in dopamine D2/3 receptor availability are linked to working-memory decline across five years. Cerebral Cortex, 35(2), Article ID bhae481.
Open this publication in new window or tab >>Aging-related losses in dopamine D2/3 receptor availability are linked to working-memory decline across five years
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2025 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 35, no 2, article id bhae481Article in journal (Refereed) Published
Abstract [en]

Although age differences in the dopamine system have been suggested to contribute to age-related cognitive decline based on cross-sectional data, recent large-scale cross-sectional studies reported only weak evidence for a correlation among aging, dopamine receptor availability, and cognition. Regardless, longitudinal data remain essential to make robust statements about dopamine losses as a basis for cognitive aging. We present correlations between changes in D2/3 dopamine receptor availability and changes in working memory measured over 5 yr in healthy, older adults (n = 128, ages 64 to 68 yr at baseline). Greater decline in D2/3 dopamine receptor availability in working memory-relevant regions (caudate, middle frontal cortex, hippocampus) was related to greater decline in working memory performance in individuals who exhibited working memory reductions across time (n = 43; caudate: rs = 0.494; middle frontal cortex: rs = 0.506; hippocampus; rs = 0.423), but not in individuals who maintained performance (n = 41; caudate: rs = 0.052; middle frontal cortex: rs = 0.198; hippocampus; rs = 0.076). The dopamine–working memory link in decliners was not observed in the orbitofrontal cortex, which does not belong to the core working memory network. Our longitudinal analyses support the notion that aging-related changes in the dopamine system contribute to working memory decline in aging.

Place, publisher, year, edition, pages
Oxford University Press, 2025
Keywords
aging, cognitive decline, dopamine 2/3-receptor availability, longitudinal, working memory
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:umu:diva-236191 (URN)10.1093/cercor/bhae481 (DOI)001389805300001 ()39756432 (PubMedID)2-s2.0-85217150219 (Scopus ID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationRagnar Söderbergs stiftelseThe Swedish Brain Foundation
Available from: 2025-03-17 Created: 2025-03-17 Last updated: 2025-03-17Bibliographically approved
Korkki, S. M., Johansson, J., Nordin, K., Pedersen, R., Bäckman, L., Rieckmann, A. & Salami, A. (2025). Dedifferentiation of caudate functional organization is linked to reduced D1 dopamine receptor availability and poorer memory function in aging. Imaging Neuroscience, 3, Article ID imag_a_00462.
Open this publication in new window or tab >>Dedifferentiation of caudate functional organization is linked to reduced D1 dopamine receptor availability and poorer memory function in aging
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2025 (English)In: Imaging Neuroscience, E-ISSN 2837-6056, Vol. 3, article id imag_a_00462Article in journal (Refereed) Published
Abstract [en]

Age-related alterations in cortico-striatal function have been highlighted as an important determinant of declines in flexible, higher-order, cognition in older age. However, the mechanisms underlying such alterations remain poorly understood. Computational accounts propose age-related dopaminergic decreases to impoverish neural gain control, possibly contributing to reduced specificity of cortico-striatal circuits, that are modulated by dopamine, in older age. Using multi-modal neuroimaging data (fMRI, PET) from a large lifespan cohort (n = 180), we assessed the relationship between dopamine D1-like receptors (D1DRs) and cortico-striatal function during rest and an n-back working memory task. The results revealed gradual age-related decreases in the specificity of functional coupling between the centrolateral caudate and cortical association networks during both rest and working memory, which, in turn, was associated with poorer short- and long-term memory performance with older age. Critically, reduced D1DR availability in the caudate and the prefrontal cortex predicted less differentiated caudate-cortical coupling across the lifespan, in part accounting for the age-related declines observed on this metric. These findings provide novel empirical evidence for a key role of dopamine in maintaining functional specialization of cortico-striatal circuits as individuals age, bridging with computational models of deficient catecholaminergic neuromodulation underpinning age-related dedifferentiation of brain function.

Place, publisher, year, edition, pages
MIT Press, 2025
Keywords
aging, dopamine, functional connectivity, memory, neural dedifferentiation, striatum
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-239215 (URN)10.1162/imag_a_00462 (DOI)2-s2.0-105000144499 (Scopus ID)
Funder
Swedish Research Council, 2016-01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, RJ, P20-0515
Available from: 2025-05-27 Created: 2025-05-27 Last updated: 2025-05-27Bibliographically approved
Mooraj, Z., Salami, A., Campbell, K. L., Dahl, M. J., Kosciessa, J. Q., Nassar, M. R., . . . Garrett, D. D. (2025). Toward a functional future for the cognitive neuroscience of human aging. Neuron, 113(1), 154-183
Open this publication in new window or tab >>Toward a functional future for the cognitive neuroscience of human aging
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2025 (English)In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 113, no 1, p. 154-183Article, review/survey (Refereed) Published
Abstract [en]

The cognitive neuroscience of human aging seeks to identify neural mechanisms behind the commonalities and individual differences in age-related behavioral changes. This goal has been pursued predominantly through structural or “task-free” resting-state functional neuroimaging. The former has elucidated the material foundations of behavioral decline, and the latter has provided key insight into how functional brain networks change with age. Crucially, however, neither is able to capture brain activity representing specific cognitive processes as they occur. In contrast, task-based functional imaging allows a direct probe into how aging affects real-time brain-behavior associations in any cognitive domain, from perception to higher-order cognition. Here, we outline why task-based functional neuroimaging must move center stage to better understand the neural bases of cognitive aging. In turn, we sketch a multi-modal, behavior-first research framework that is built upon cognitive experimentation and emphasizes the importance of theory and longitudinal design.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
aging, behavior, brain, cognition, EEG, fMRI, multimodal, neurochemistry, neuroimaging, PET
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-233856 (URN)10.1016/j.neuron.2024.12.008 (DOI)001415682500001 ()2-s2.0-85213895004 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationGerman Research Foundation (DFG)
Available from: 2025-01-09 Created: 2025-01-09 Last updated: 2025-04-24Bibliographically approved
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)001271840300007 ()38302439 (PubMedID)2-s2.0-85187783583 (Scopus ID)
Available from: 2024-04-19 Created: 2024-04-19 Last updated: 2025-04-24Bibliographically approved
Stålnacke, M., Eriksson, J., Salami, A., Andersson, M., Nyberg, L. & Sjöberg, R. L. (2024). Functional connectivity of the sensorimotor network before and after surgery in the supplementary motor area. Neuropsychologia, 204, Article ID 109004.
Open this publication in new window or tab >>Functional connectivity of the sensorimotor network before and after surgery in the supplementary motor area
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2024 (English)In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 204, article id 109004Article in journal (Refereed) Published
Abstract [en]

After resective glioma surgery in the Supplementary Motor Area (SMA), patients often experience a transient disturbance of the ability to initiate speech and voluntary motor actions, known as the SMA syndrome (SMAS). It has been proposed that enhanced interhemispheric functional connectivity (FC) within the sensorimotor system may serve as a potential mechanism for recovery, enabling the non-resected SMA to assume the function of the resected region. The purpose of the present study was to investigate the extent to which changes in FC can be observed in patients after resolution of the SMAS.

Eight patients underwent resection of left SMA due to suspected gliomas, resulting in various levels of the SMA syndrome. Resting-state functional MR images were acquired prior to the surgery and after resolution of the syndrome.

At the group level we found an increased connectivity between the unaffected (right) SMA and the primary motor cortex on the same side following surgery. However, no significant increase in interhemispheric connectivity was observed.

These findings challenge the prevailing notion that increased interhemispheric FC serves as the only mechanism underlying recovery from SMA syndrome and suggest the presence of one or more alternative mechanisms.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Glioma, Supplementary motor area, SMA, Interhemispheric connectivity, Functional imaging
National Category
Neurosciences
Research subject
Neurosurgery
Identifiers
urn:nbn:se:umu:diva-206849 (URN)10.1016/j.neuropsychologia.2024.109004 (DOI)001325130500001 ()39299453 (PubMedID)2-s2.0-85204550323 (Scopus ID)
Funder
Region VästerbottenSjöberg FoundationCancerforskningsfonden i Norrland
Available from: 2023-04-18 Created: 2023-04-18 Last updated: 2024-10-14Bibliographically 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)001185299100001 ()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: 2025-04-24Bibliographically 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)001072462000001 ()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: 2025-04-24Bibliographically approved
Johansson, J., Karalija, N. & Salami, A. (2023). Cerebrovascular integrity affects gradients of aging-related dopamine D1 differences in the striatum. Aging Brain, 4, Article ID 100094.
Open this publication in new window or tab >>Cerebrovascular integrity affects gradients of aging-related dopamine D1 differences in the striatum
2023 (English)In: Aging Brain, E-ISSN 2589-9589, Vol. 4, article id 100094Article in journal (Refereed) Published
Abstract [en]

Extant research suggest aging-related losses of different dopaminergic markers, including presynaptic dopamine transporters as well as post-synaptic DA receptors. Given the central role of DA in neurocognitive functions, maintenance of a healthy DA system may be a key to mitigate age-related cognitive decline. Mechanisms behind DA losses in aging are however largely uncharted. Past research documented an association between dopaminergic integrity and cerebrovascular health (via white matter lesion volumes). However, it remains unclear whether proximity to lesions affected the spatial patterns of age-related D1DR differences within the striatum, and whether such differences are related to mnemonic function. Here, a large cohort of middle-aged to older healthy participants (age = 40-80 years, n = 119, 50 % women) was assessed for D1-receptor (D1DR) availability with positron emission tomography using [11C] SCH23390, and for white matter lesions using FLAIR-MRI. We found evidence for variations in degree of age-related differences along the ventro-dorsal axis, with more pronounced differences in the dorsal caudate. Further analyses revealed an association between distance to lesions and extent of D1DR losses in the caudate. Furthermore, D1DR differences in dorsal caudate (proximal to lesions) was more strongly associated with memory performance. In conclusion, the present findings suggest that maintenance of cerebrovascular health may be a key factor in promoting successful dopaminergic and memory aging.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Dopamine, Aging, Cerebrovascular integrity, Cognition, White matter lesions
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-228658 (URN)10.1016/j.nbas.2023.100094 (DOI)001133877600001 ()37645244 (PubMedID)2-s2.0-85206596677 (Scopus ID)
Funder
Swedish Research CouncilRiksbankens JubileumsfondKnut and Alice Wallenberg Foundation
Available from: 2024-08-21 Created: 2024-08-21 Last updated: 2024-10-25Bibliographically 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, E-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)001133835900001 ()37408790 (PubMedID)2-s2.0-85166740552 (Scopus ID)
Funder
Swedish Research Council, 2016–01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20-0515
Available from: 2023-08-08 Created: 2023-08-08 Last updated: 2024-10-25Bibliographically 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)001041595400001 ()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: 2025-04-24Bibliographically approved
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