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Methodological approaches for the study of resting-state functional magnetic resonance imaging in Down syndrome
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[eng] Down syndrome is the most common chromosomal condition associated with intellectual disability. Although many researchers have focused on their physiological and cognitive characteristics, the underlying brain dysfunction of this syndrome is still unknown.
The present thesis has five original studies that address two principal aims. Firstly, the two first studies try to overcome some methodological issues that arise from working with the Down syndrome population: missing data and small sample sizes. The recruitment of the Down syndrome population is strenuous, and missing data is very common, especially when working with neuroimaging tools. In this sense, neuroimaging studies are usually characterized by small sample sizes, which leads to low and inconsistent effects. Both first studies have also an applied aim: operationalize the cognitive reserve concept in Down syndrome population and summarize the principal results of functional magnetic resonance imaging (fMRI) studies in intellectual disability population. The second aim of the present thesis is to study the state-of-art in the field of fMRI in Down syndrome and to use different strategies of resting-state analysis in a sample of young people with Down syndrome compared with age and gender-matched controls. All the studies were successfully published and are under the “Studies” section.
For study 1, 35 persons with Down syndrome (25.7% women, Mage=24.4; SDage=5.42) participated. On the one hand, to solve the missing data problem, we performed multiple imputations. Confirmatory factor analysis with bayesian estimations was performed on the final database with non-informative priors, to operationalize the construct of cognitive reserve for people with Down syndrome. On the other hand, to solve the sample size problem, two additional corrections were made: first, we followed the Jiang and Yuan (2017) schema, and second, we made a Jackknife correlation correction, recommended for these cases. When there is no possibility to resample, the proposed methodologies and techniques could be useful. From an applied point of view, we resolved these challenges for operationalizing the cognitive reserve concept in Down syndrome population. This study demonstrates the feasibility of assessing the cognitive reserve in Down syndrome considering factors such as quality of life, physical activity levels, cognitive outcome, and personal conditions of the person with intellectual disability. This finding may provide a starting point in studying the individual differences in both clinical and neuropathological appearance of dementias.
Study 2 is a meta-analysis, which includes the 10 studies matching our inclusion criteria. The included papers were both qualitative and quantitative analysed. For the final quantitative results, we used Seed-based d-Mapping software. Results showed that small sample sizes are very typical when using populations with intellectual disability. This issue is even graver with
neuroimaging studies, as they involve more expensive costs and more complications in the registration. Meta-analyses tools can help summarize the qualitative and quantitive findings found throughout different studies. Regarding the results of the study, a clear pattern of dysconnectivity was found in participants with intellectual disability in the right temporal gyrus compared with controls. However, more task-fMRI studies on this field must be published by adding larger samples to address the pathophysiological questions more directly.
Study 3 is a systematic review that includes a total of 9 studies. It was a qualitative analysis performed by three independent reviewers, with a high percentage of agreement. The third study reviews the main works published concerning fMRI data and people with Down syndrome. Despite the scarcity of studies published in the field, fMRI could be a valued tool to evaluate the cognitive state of a person with Down syndrome, taking into account some difficulties found in this population, such as excessive head movement. There is evidence of functional and structural differences in this population, demonstrating the lower cerebral volume in some areas and differences in functional connectivity. However, in light of the literature, differences found are not congruent within studies and do not enable the establishment of a stable and regular pattern typical of Down syndrome people.
Regarding the sample for studies 4 and 5, it comprised 18 persons with Down syndrome (27.8% women, Mage=28.7; SDage=4.2) and 18 controls matched by age and gender (27.8% women, Mage=28.6; SDage=4.3). For study four, fALFF and ReHo techniques, resting-state measures of spontaneous brain activity were used to disentangle brain differences among Down syndrome participants and controls. Finally, in the fifth study, degree centrality, seed-based functional connectivity, and brain network analyses were used to find brain abnormalities in the Down syndrome sample compared with controls. With the last two studies, Data Processing Assistant for Resting-State fMRI software was used to perform image preprocessing and the following analyses. Both resting-state techniques allow us to affirm that Down syndrome population presents abnormal spontaneous brain activity and functional connectivity, and these abnormalities found could be related to their cognitive profile, finding alterations in the frontal and temporal lobes. These regions are engaged in language, executive functions and memory, functions highly altered in Down syndrome. The areas that displayed differences between both populations are also engaged in early amyloid deposition in young and cognitive stable adults with Down syndrome. Finally, those areas are also related to structural abnormalities already found in this population.
The results and conclusions of the present thesis highlight the use of resting-state fMRI analysis to disentangle the underlying brain mechanism of the Down syndrome population, and the possibility to use this as a biomarker of cognitive function, as well as for dementia appearance detetction.
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CAÑETE MASSÉ, Cristina. Methodological approaches for the study of resting-state functional magnetic resonance imaging in Down syndrome. [consulta: 15 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/203143]