Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls

Vega, Jennifer N.; Hohman, Timothy J.; Pryweller, Jennifer R.; Dykens, Elisabeth M.; Thornton‐Wells, Tricia A.

doi:10.1089/brain.2014.0266

Cited by 61 publications

(78 citation statements)

References 84 publications

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“…This pattern of DMN hyper‐connectivity is similar to findings reported from previous fMRI investigations of brain connectivity involving people with Down's syndrome (Anderson et al, ; Vega et al, ). These studies found increased inter‐network connectivity in people with Down's syndrome compared to controls, including greater positive connectivity between the default mode network and numerous other large‐scale functional brain networks.…”

Section: Discussionsupporting

confidence: 89%

Differential effects of Down's syndrome and Alzheimer's neuropathology on default mode connectivity

Wilson

Vatansever

Annus

et al. 2019

Human Brain Mapping

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Down's syndrome is a chromosomal disorder that invariably results in both intellectual disability and Alzheimer's disease neuropathology. However, only a limited number of studies to date have investigated intrinsic brain network organisation in people with Down's syndrome, none of which addressed the links between functional connectivity and Alzheimer's disease. In this cross‐sectional study, we employed 11C‐Pittsburgh Compound‐B (PiB) positron emission tomography in order to group participants with Down's syndrome based on the presence of fibrillar beta‐amyloid neuropathology. We also acquired resting state functional magnetic resonance imaging data to interrogate the connectivity of the default mode network; a large‐scale system with demonstrated links to Alzheimer's disease. The results revealed widespread positive connectivity of the default mode network in people with Down's syndrome (n = 34, ages 30–55, median age = 43.5) and a stark lack of anti‐correlation. However, in contrast to typically developing controls (n = 20, ages 30–55, median age = 43.5), the Down's syndrome group also showed significantly weaker connections in localised frontal and posterior brain regions. Notably, while a comparison of the PiB‐negative Down's syndrome group (n = 19, ages 30–48, median age = 41.0) to controls suggested that alterations in default mode connectivity to frontal brain regions are related to atypical development, a comparison of the PiB‐positive (n = 15, ages 39–55, median age = 48.0) and PiB‐negative Down's syndrome groups indicated that aberrant connectivity in posterior cortices is associated with the presence of Alzheimer's disease neuropathology. Such distinct profiles of altered connectivity not only further our understanding of the brain physiology that underlies these two inherently linked conditions but may also potentially provide a biomarker for future studies of neurodegeneration in people with Down's syndrome.

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Section: Discussionsupporting

confidence: 89%

Differential effects of Down's syndrome and Alzheimer's neuropathology on default mode connectivity

Wilson

Vatansever

Annus

et al. 2019

Human Brain Mapping

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“…Only a few in vivo imaging studies have been published in humans [76–84] or mouse models [85–89] of DS. In humans, positron emission tomography (PET) measurements of β-amyloid burden [77, 79, 81], regional PET measurements of the cerebral metabolic rate for glucose [76] and structural and functional connectivity differences by anatomical and functional magnetic resonance imaging (MRI) studies [78, 80, 82, 84] demonstrate the safety, efficacy, and acceptability of these imaging techniques to study DS-AD progression. Using diffusion tensor imaging (DTI), Powell et al [83] recently reported that changes in white matter integrity, particularly in the frontal tracts, were associated with poorer cognition in adults with DS.…”

Section: Neuroimaging Of Mouse Models Of Down Syndromementioning

confidence: 99%

Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome

Hamlett¹,

Boger²,

Ledreux³

et al. 2015

CAR

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Down syndrome (DS) is the most common non-lethal genetic condition that affects approximately 1 in 700 births in the United States of America. DS is characterized by complete or segmental chromosome 21 trisomy, which leads to variable intellectual disabilities, progressive memory loss, and accelerated neurodegeneration with age. During the last three decades, people with DS have experienced a doubling of life expectancy due to progress in treatment of medical comorbidities, which has allowed this population to reach the age when they develop early onset Alzheimer’s disease (AD). Individuals with DS develop cognitive and pathological hallmarks of AD in their fourth or fifth decade, and are currently lacking successful prevention or treatment options for dementia. The profound memory deficits associated with DS-related AD (DS-AD) have been associated with degeneration of several neuronal populations, but mechanisms of neurodegeneration are largely unexplored. The most successful animal model for DS is the Ts65Dn mouse, but several new models have also been developed. In the current review, we discuss recent findings and potential treatment options for the management of memory loss and AD neuropathology in DS mouse models. We also review age-related neuropathology, and recent findings from neuroimaging studies. The validation of appropriate DS mouse models that mimic neurodegeneration and memory loss in humans with DS can be valuable in the study of novel preventative and treatment interventions, and may be helpful in pinpointing gene-gene interactions as well as specific gene segments involved in neurodegeneration.

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“…frontoparietal‐DMN network pair) and decreased within‐network connectivity (e.g. DMN, ventral attention and somatomotor networks), when compared with typically developing individuals, suggesting a global lack of differentiation between the DMN and other resting state networks in WS (Vega et al ., ). These results may be related with specificities of the brain tissue organization in WS.…”

Section: Introductionmentioning

confidence: 97%

Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach

Sampaio

Moreira

Osório

et al. 2016

Developmental Science

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Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype.

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Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls

Cited by 61 publications

References 84 publications

Differential effects of Down's syndrome and Alzheimer's neuropathology on default mode connectivity

Differential effects of Down's syndrome and Alzheimer's neuropathology on default mode connectivity

Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome

Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach

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