| 1. |
- Kaboodvand, Neda, et al.
(författare)
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Macroscopic resting state model predicts theta burst stimulation response : A randomized trial
- 2023
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Ingår i: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 19:3
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Tidskriftsartikel (refereegranskat)abstract
- Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative therapy for treatment-resistant depression, although its limited remission rate indicates room for improvement. As depression is a phenomenological construction, the biological heterogeneity within this syndrome needs to be considered to improve the existing therapies. Whole-brain modeling provides an integrative multi-modal framework for capturing disease heterogeneity in a holistic manner.Computational modelling combined with a probabilistic nonparametric fitting was applied to the resting-state fMRI data from 42 patients (21 women), to parametrize baseline brain dynamics in depression. All patients were randomly assigned to two treatment groups, namely active (i.e., rTMS, n = 22) or sham (n = 20). The active treatment group received rTMS treatment with an accelerated intermittent theta burst protocol over the dorsomedial prefrontal cortex. The sham treatment group underwent the identical procedure but with the magnetically shielded side of the coil.We stratified the depression sample into distinct covert subtypes based on their baseline attractor dynamics captured by different model parameters. Notably, the two detected depression subtypes exhibited different phenotypic behaviors at baseline. Our stratification could predict the diverse response to the active treatment that could not be explained by the sham treatment. Critically, we further found that one group exhibited more distinct improvement in certain affective and negative symptoms. The subgroup of patients with higher responsiveness to treatment exhibited blunted frequency dynamics for intrinsic activity at baseline, as indexed by lower global metastability and synchrony.Our findings suggested that whole-brain modeling of intrinsic dynamics may constitute a determinant for stratifying patients into treatment groups and bringing us closer towards precision medicine.
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| 2. |
- Kaboodvand, Neda
(författare)
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Modelling and quantifying brain connectivity and dynamics with applications in aging and ADHD
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human brain is a complex organ and made up of integrative networks encompassing a large number of regions. These regions communicate with each other to share information involved in complex cognitive processes. Functional connectivity (FC) represents the level of synchronization between different brain regions/networks. Studying functional interactions of the brain creates a platform for understanding functional architecture of the brain as an integrative network and has implications for understanding human cognition. Furthermore, there is evidence that FC patterns are sensitive to different diseases. In addition, age is a significant determinant of intra-/inter-individual variability in the FC patterns. Therefore, key aims for the studies included in this thesis were to apply and develop novel resting-state FC methodologies, with applications in healthy aging and ADHD. Indeed, measures of the brain’s FC may serve as a useful tool to diagnose and predict the course of disease, and useful in developing individualized therapies. Age- or disease-related alterations in the FC could reflect a multitude of factors, including changes in structural connectivity. However, we still have limited knowledge of the emergence of brain dynamics from the underlying anatomy. The interplay between the brain’s structure and dynamics underlies all brain functions. Therefore, in the last study we focused on the systematic modeling of the brain network dynamics. Large-scale computational models are uniquely suited to address difficult questions related to the role of brain’s structural network in shaping functional interactions. In addition, computational modeling of the brain enables us to test different hypotheses without any experimental complication while it provides us with a platform for improving our understanding of different brain mechanisms. A new macroscopic computational model of the brain oscillations for resting-state fMRI was introduced in this thesis, which outperforms previous model in the same class. Then, the effects of malfunctions in different brain regions were simulated and subsequently predicted perturbation patterns were recruited for local vulnerability mapping as well as quantification of hazard rates induced after perturbing any brain region.
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| 3. |
- Kaboodvand, Neda, et al.
(författare)
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The retrosplenial cortex : a memory gateway between the cortical default mode network and the medial temporal lobe
- 2018
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 39:5, s. 2020-2034
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Tidskriftsartikel (refereegranskat)abstract
- The default mode network (DMN) involves interacting cortical areas, including the posterior cingulate cortex (PCC) and the retrosplenial cortex (RSC), and subcortical areas, including the medial temporal lobe (MTL). The degree of functional connectivity (FC) within the DMN, particularly between MTL and medial-parietal subsystems, relates to episodic memory (EM) processes. However, past resting-state studies investigating the link between posterior DMN-MTL FC and EM performance yielded inconsistent results, possibly reflecting heterogeneity in the degree of connectivity between MTL and specific cortical DMN regions. Animal work suggests that RSC has structural connections to both cortical DMN regions and MTL, and may thus serve as an intermediate layer that facilitates information transfer between cortical and subcortical DMNs. We studied 180 healthy old adults (aged 64-68 years), who underwent comprehensive assessment of EM, along with resting-state fMRI. We found greater FC between MTL and RSC than between MTL and the other cortical DMN regions (e.g., PCC), with the only significant association with EM observed for MTL-RSC FC. Mediational analysis showed that MTL-cortical DMN connectivity increased with RSC as a mediator. Further analysis using a graph-theoretical approach on DMN nodes revealed the highest betweenness centrality for RSC, confirming that a high proportion of short paths among DMN regions pass through RSC. Importantly, the degree of RSC mediation was associated with EM performance, suggesting that individuals with greater mediation have an EM advantage. These findings suggest that RSC forms a critical gateway between MTL and cortical DMN to support EM in older adults.
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| 4. |
- Salami, Alireza, et al.
(författare)
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Longitudinal Evidence for Dissociation of Anterior and Posterior MTL Resting-State Connectivity in Aging : Links to Perfusion and Memory
- 2016
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 26:10, s. 3953-3963
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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.
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