| 51. |
- Salami, Alireza, et al.
(författare)
-
Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer’s Disease and Longitudinal Change in Hippocampus Function
- 2022
-
Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 85:3, s. 1309-1320
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 52. |
- 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.
|
|
| 53. |
- Salami, Alireza
(författare)
-
Decoding the complex brain : multivariate and multimodal analyses of neuroimaging data
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Functional brain images are extraordinarily rich data sets that reveal distributed brain networks engaged in a wide variety of cognitive operations. It is a substantial challenge both to create models of cognition that mimic behavior and underlying cognitive processes and to choose a suitable analytic method to identify underlying brain networks.Most of the contemporary techniques used in analyses of functional neuroimaging data are based on univariate approaches in which single image elements (i.e. voxels) are considered to be computationally independent measures. Beyond univariate methods (e.g. statistical parametric mapping), multivariate approaches, which identify a network across all regions of the brain rather than a tessellation of regions, are potentially well suited for analyses of brain imaging data. A multivariate method (e.g. partial least squares) is a computational strategy that determines time-varying distributed patterns of the brain (as a function of a cognitive task). Compared to its univariate counterparts, a multivariate approach provides greater levels of sensitivity and reflects cooperative interactions among brain regions. Thus, by considering information across more than one measuring point, additional information on brain function can be revealed.Similarly, by considering information across more than one measuring technique, the nature of underlying cognitive processes become well-understood. Cognitive processes have been investigated in conjunction with multiple neuroimaging modalities (e.g. fMRI, sMRI, EEG, DTI), whereas the typical method has been to analyze each modality separately. Accordingly, little work has been carried out to examine the relation between different modalities. Indeed, due to the interconnected nature of brain processing, it is plausible that changes in one modality locally or distally modulate changes in another modality.This thesis focuses on multivariate and multimodal methods of image analysis applied to various cognitive questions. These methods are used in order to extract features that are inaccessible using univariate / unimodal analytic approaches. To this end, I implemented multivariate partial least squares analysis in study I and II in order to identify neural commonalities and differences between the available and accessible information in memory (study I), and also between episodic encoding and episodic retrieval (study II). Study I provided evidence of a qualitative differences between availability and accessibility signals in memory by linking memory access to modality-independent brain regions, and availability in memory to elevated activity in modality-specific brain regions. Study II provided evidence in support of general and specific memory operations during encoding and retrieval by linking general processes to the joint demands on attentional, executive, and strategic processing, and a process-specific network to core episodic memory function. In study II, III, and IV, I explored whether the age-related changes/differences in one modality were driven by age-related changes/differences in another modality. To this end, study II investigated whether age-related functional differences in hippocampus during an episodic memory task could be accounted for by age-related structural differences. I found that age-related local structural deterioration could partially but not entirely account for age-related diminished hippocampal activation. In study III, I sought to explore whether age-related changes in the prefrontal and occipital cortex during a semantic memory task were driven by local and/or distal gray matter loss. I found that age-related diminished prefrontal activation was driven, at least in part, by local gray matter atrophy, whereas the age-related decline in occipital cortex was accounted for by distal gray matter atrophy. Finally, in study IV, I investigated whether white matter (WM) microstructural differences mediated age-related decline in different cognitive domains. The findings implicated WM as one source of age-related decline on tasks measuring processing speed, but they did not support the view that age-related differences in episodic memory, visuospatial ability, or fluency were strongly driven by age-related differences in white-matter pathways.Taken together, the architecture of different aspects of episodic memory (e.g. encoding vs. retrieval; availability vs. accessibility) was characterized using a multivariate partial least squares. This finding highlights usefulness of multivariate techniques in guiding cognitive theories of episodic memory. Additionally, competing theories of cognitive aging were investigated by multimodal integration of age-related changes in brain structure, function, and behavior. The structure-function relationships were specific to brain regions and cognitive domains. Finally, we urged that contemporary theories on cognitive aging need to be extended to longitudinal measures to be further validated.
|
|
| 54. |
- Salami, Alireza, et al.
(författare)
-
Dopamine D-2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion
- 2019
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 39:3, s. 537-547
-
Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA(measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA-BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 low-performing) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n-back task along with DA D-2/3 PET assessment using [C-11] raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D-2/3 receptors to BOLD response in the thalamo-striatalcortical circuit, which supports WM functioning. Critically, the DA-BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA-BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA-BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.
|
|
| 55. |
- Salami, Alireza, et al.
(författare)
-
Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging
- 2014
-
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. ; 111:49, s. 17654-17659
-
Tidskriftsartikel (refereegranskat)abstract
- The brain is not idle during rest. Functional MRI (fMRI) studies have identified several resting-state networks, including the default mode network (DMN), which contains a set of cortical regions that interact with a hippocampus (HC) subsystem. Age-related alterations in the functional architecture of the DMN and HC may influence memory functions and possibly constitute a sensitive biomarker of forthcoming memory deficits. However, the exact form of DMN-HC alterations in aging and concomitant memory deficits is largely unknown. Here, using both task and resting data from 339 participants (25-80 y old), we have demonstrated age-related decrements in resting-state functional connectivity across most parts of the DMN, except for the HC network for which age-related elevation of connectivity between left and right HC was found along with attenuated HC-cortical connectivity. Elevated HC connectivity at rest, which was partly accounted for by age-related decline in white matter integrity of the fornix, was associated with lower cross-sectional episodic memory performance and declining longitudinal memory performance over 20 y. Additionally, elevated HC connectivity at rest was associated with reduced HC neural recruitment and HC-cortical connectivity during active memory encoding, which suggests that strong HC connectivity restricts the degree to which the HC interacts with other brain regions during active memory processing revealed by task fMRI. Collectively, our findings suggest a model in which age-related disruption in cortico-hippocampal functional connectivity leads to a more functionally isolated HC at rest, which translates into aberrant hippocampal decoupling and deficits during mnemonic processing.
|
|
| 56. |
- Salami, Alireza, et al.
(författare)
-
Elevated Neuroinflammation Contributes to the Deleterious Impact of Iron Overload on Brain Function in Aging
- 2021
-
Ingår i: NeuroImage. - : Academic Press. - 1053-8119 .- 1095-9572. ; 230
-
Tidskriftsartikel (refereegranskat)abstract
- Intracellular iron is essential for many neurobiological mechanisms. However, at high concentrations, iron may induce oxidative stress and inflammation. Brain iron overload has been shown in various neurodegenerative disorders and in normal aging. Elevated brain iron in old age may trigger brain dysfunction and concomitant cognitive decline. However, the exact mechanism underlying the deleterious impact of iron on brain function in aging is unknown. Here, we investigated the role of iron on brain function across the adult lifespan from 187 healthy participants (20-79 years old, 99 women) who underwent fMRI scanning while performing a working-memory n-back task. Iron content was quantified using R2* relaxometry, whereas neuroinflammation was estimated using myo-inositol measured by magnetic resonance spectroscopy. Striatal iron increased non-linearly with age, with linear increases at both ends of adulthood. Whereas higher frontostriatal activity was related to better memory performance independent of age, the link between brain activity and iron differed across age groups. Higher striatal iron was linked to greater frontostriatal activity in younger, but reduced activity in older adults. Further mediation analysis revealed that, after age 40, iron provided unique and shared contributions with neuroinflammation to brain activations, such that neuroinflammation partly mediated brain-iron associations. These findings promote a novel mechanistic understanding of how iron may exert deleterious effects on brain function and cognition with advancing age.
|
|
| 57. |
- Salami, Alireza, et al.
(författare)
-
Functional coherence of striatal resting-state networks is modulated by striatal iron content
- 2018
-
Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 183, s. 495-503
-
Tidskriftsartikel (refereegranskat)abstract
- Resting-state spontaneous fluctuations have revealed individual differences in the functional architecture of brain networks. Previous research indicates that the striatal network shows alterations in neurological conditions but also in normal aging. However, the neurobiological mechanisms underlying individual differences in striatal resting-state networks (RSNs) have been less explored. One candidate that may account for individual differences in striatal spontaneous activity is the level of local iron accumulation. Excessive iron in the striatum has been linked to a loss of structural integrity and reduced brain activity during task performance in aging. Using independent component analysis in a sample of 42 younger and older adults, we examined whether higher striatal iron content, quantified using relaxometry, underlies individual differences in spontaneous fluctuations of RSNs in general, and of the striatum in particular. Higher striatal iron content was linked to lower spontaneous coherence within both caudate and putamen RSNs regardless of age. No such links were observed for other RSNs. Moreover, the number of connections between the putamen and other RSNs was negatively associated with iron content, suggesting that iron modulated the degree of cross-talk between the striatum and cerebral cortex. Importantly, these associations were primarily driven by the older group. Finally, a positive association was found between coherence in the putamen and motor performance, suggesting that this spontaneous activity is behaviorally meaningful. A follow-up mediation analysis also indicated that functional connectivity may mediate the link between striatal iron and motor performance. Our preliminary findings suggest that striatal iron potentially accounts for individual differences in spontaneous striatal fluctuations, and might be used as a locus of intervention.
|
|
| 58. |
- 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.
|
|
| 59. |
- Salami, Alireza, et al.
(författare)
-
Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction
- 2018
-
Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 28:7, s. 2525-2539
-
Tidskriftsartikel (refereegranskat)abstract
- Individuals differ in how they perceive, remember, and think. There is evidence for the existence of distinct subgroups that differ in cognitive performance within the older population. However, it is less clear how individual differences in cognition in old age are linked to differences in brain-based measures. We used latent-profile analysis on n-back working-memory (WM) performance to identify subgroups in a large sample of older adults (n = 181; age = 64-68 years). Our analysis identified one larger normal subgroup with higher performance (n = 113; 63%), and a second smaller subgroup (n = 55; 31%) with lower performance. The low-performing subgroup showed weaker load-dependent BOLD modulation and lower connectivity within the fronto-parietal network (FPN) as well as between FPN and striatum during n-back, along with lower FPN connectivity at rest. This group also exhibited lower FPN structural integrity, lower frontal dopamine D2 binding potential, inferior performance on offline WM tests, and a trend-level genetic predisposition for lower dopamine-system efficiency. By contrast, this group exhibited relatively intact episodic memory and associated brain measures (i.e., hippocampal volume, structural, and functional connectivity within the default-mode network). Collectively, these data provide converging evidence for the existence of a group of older adults with impaired WM functioning characterized by reduced cortico-striatal coupling and aberrant cortico-cortical integrity within FPN.
|
|
| 60. |
- Salami, Alireza, et al.
(författare)
-
Opposing effects of aging on large-scale brain systems for memory encoding and cognitive control
- 2012
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:31, s. 10749-10757
-
Tidskriftsartikel (refereegranskat)abstract
- Episodic memory declines with advancing age. Neuroimaging studies have associated such decline to age-related changes in general cognitive-control networks as well as to changes in process-specific encoding or retrieval networks. To assess the specific influence of aging on encoding and retrieval processes and associated brain systems, it is vital to dissociate encoding and retrieval from each other and from shared cognitive-control processes. We used multivariate partial-least-squares to analyze functional magnetic resonance imaging data from a large population-based sample (n = 292, 25-80 years). The participants performed a face-name paired-associates task and an active baseline task. The analysis revealed two significant network patterns. The first reflected a process-general encoding-retrieval network that included frontoparietal cortices and posterior hippocampus. The second pattern dissociated encoding and retrieval networks. The anterior hippocampus was differentially engaged during encoding. Brain scores, representing whole-brain integrated measures of how strongly an individual recruited a brain network, were correlated with cognitive performance and chronological age. The scores from the general cognitive-control network correlated negatively with episodic memory performance and positively with age. The encoding brain scores, which strongly reflected hippocampal functioning, correlated positively with episodic memory performance and negatively with age. Univariate analyses confirmed that bilateral hippocampus showed the most pronounced activity reduction in older age, and brain structure analyses found that the activity reduction partly related to hippocampus atrophy. Collectively, these findings suggest that age-related structural brain changes underlie age-related reductions in the efficient recruitment of a process-specific encoding network, which cascades into upregulated recruitment of a general cognitive-control network.
|
|
