Publications by authors named "Sarah K Madsen"

We aimed to investigate the relationship between striatal morphology in Huntington disease (HD) and measures of motor and cognitive dysfunction. MRI scans, from the IMAGE-HD study, were obtained from 36 individuals with pre-symptomatic HD (pre-HD), 37 with early symptomatic HD (symp-HD), and 36 healthy matched controls. The neostriatum was manually segmented and a surface-based parametric mapping protocol derived two pointwise shape measures: thickness and surface dilation ratio.

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Cognitive decline in old age is tightly linked with brain atrophy, causing significant burden. It is critical to identify which biomarkers are most predictive of cognitive decline and brain atrophy in the elderly. In 566 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we used a novel unsupervised machine learning approach to evaluate an extensive list of more than 200 potential brain, blood and cerebrospinal fluid (CSF)-based predictors of cognitive decline.

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People differ in their cognitive functioning. This variability has been exhaustively examined at the behavioral, neural and genetic level to uncover the mechanisms by which some individuals are more cognitively efficient than others. Studies investigating the neural underpinnings of interindividual differences in cognition aim to establish a reliable nexus between functional/structural properties of a given brain network and higher order cognitive performance.

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Hypersynchronous (HYP) and low voltage fast (LVF) activity are two separate ictal depth EEG onsets patterns often recorded in presurgical patients with MTLE. Evidence suggests the mechanisms generating HYP and LVF onset seizures are distinct, including differential involvement of hippocampal and extra-hippocampal sites. Yet the extent of extra-hippocampal structural alterations, which could support these two common seizures, is not known.

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Individuals with body dysmorphic disorder (BDD) suffer from preoccupations with perceived defects in physical appearance, causing severe distress and disability. Although BDD affects 1-2% of the population, the neurobiology is not understood. Discrepant results in previous volumetric studies may be due to small sample sizes, and no study has investigated cortical thickness in BDD.

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Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural magnetic resonance imaging scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID).

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Introduction: Genetic variants in DAT1, the gene encoding the dopamine transporter (DAT) protein, have been implicated in many brain disorders. In a recent case-control study of Alzheimer's disease (AD), a regulatory polymorphism in DAT1 showed a significant association with the clinical stages of dementia.

Methods: We tested whether this variant was associated with increased AD risk, and with measures of cognitive decline and longitudinal ventricular expansion, in a large sample of elderly participants with genetic, neurocognitive, and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative.

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A significant portion of our risk for dementia in old age is associated with lifestyle factors (diet, exercise, and cardiovascular health) that are modifiable, at least in principle. One such risk factor, high-homocysteine levels in the blood, is known to increase risk for Alzheimer's disease and vascular disorders. Here, we set out to understand how homocysteine levels relate to 3D surface-based maps of cortical gray matter distribution (thickness, volume, and surface area) computed from brain magnetic resonance imaging in 803 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative data set.

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Dynamic changes in the brain's lateral ventricles on magnetic resonance imaging are powerful biomarkers of disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Ventricular measures can represent accumulation of diffuse brain atrophy with very high effect sizes. Despite having no direct role in cognition, ventricular expansion co-occurs with volumetric loss in gray and white matter structures.

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The C allele at the rs11136000 locus in the clusterin (CLU) gene is the third strongest known genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent genome-wide association study of LOAD found the strongest evidence of association with CLU at rs1532278, in high linkage disequilibrium with rs11136000. Brain structure and function are related to the CLU risk alleles, not just in LOAD patients but also in healthy young adults.

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The apolipoprotein E epsilon 4 allele (ApoE-ε4) is the strongest known genetic risk factor for late onset Alzheimer's disease. Expansion of the lateral ventricles occurs with normal aging, but dementia accelerates this process. Brain structure and function depend on ApoE genotype not just for Alzheimer's disease patients but also in healthy elderly individuals, and even in asymptomatic young individuals.

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A recent genome-wide association meta-analysis showed a suggestive association between alcohol intake in humans and a common single nucleotide polymorphism in the ras-specific guanine nucleotide releasing factor 2 gene. Here, we tested whether this variant - associated with lower alcohol consumption - showed associations with brain structure and longitudinal ventricular expansion over time, across two independent elderly cohorts, totaling 1,032 subjects. We first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI1).

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Importance: Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies.

Objective: To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD.

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Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are psychiatric disorders that involve distortion of the experience of one's physical appearance. In AN, individuals believe that they are overweight, perceive their body as "fat," and are preoccupied with maintaining a low body weight. In BDD, individuals are preoccupied with misperceived defects in physical appearance, most often of the face.

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Ventricular volume (VV) is a powerful global indicator of brain tissue loss on MRI in normal aging and dementia. VV is used by radiologists in clinical practice and has one of the highest obtainable effect sizes for tracking brain change in clinical trials, but it is crucial to relate VV to structural alterations underlying clinical symptoms. Here we identify patterns of thinner cortical gray matter (GM) associated with dynamic changes in lateral VV at 1-year (N=677) and 2-year (N=536) intervals, in the ADNI cohort.

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Objective: Direct neuronal loss or deafferentation of the putamen, a critical hub in corticostriatal circuits, may result in diverse and distinct cognitive and motoric dysfunction in neurodegenerative disease. Differential putaminal morphology, as a quantitative measure of corticostriatal integrity, may thus be evident in Huntington's disease (HD), Alzheimer's disease (AD) and frontotemporal dementia (FTD), diseases with differential clinical dysfunction.

Methods: HD (n = 17), FTD (n = 33) and AD (n = 13) patients were diagnosed according to international consensus criteria and, with healthy controls (n = 17), were scanned on the same MRI scanner.

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Neuroscience can be used as a tool to inspire an interest in science in school children as well as to provide teaching experience to college students.

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A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75 ± 7.

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Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents.

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Functional neuroimaging studies have implicated the involvement of the amygdala and ventrolateral prefrontal cortex (vlPFC) in the pathophysiology of bipolar disorder. Hyperactivity in the amygdala and hypoactivity in the vlPFC have been reported in manic bipolar patients scanned during the performance of an affective faces task. Whether this pattern of dysfunction persists during euthymia is unclear.

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Obesity is associated with lower brain volumes in early Alzheimer's disease, but its effects on hippocampal volumes are unclear, as weight loss is also associated with Alzheimer's disease. To address this question, we applied an automated hippocampal mapping method to brain MRI scans for 162 patients with Alzheimer's disease. We hypothesized that obesity, measured by body mass index, would be associated with lower hippocampal volumes in mildly affected patients.

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Objective: Although several lines of evidence implicate gray matter abnormalities in the prefrontal cortex and anterior cingulate cortex in patients with bipolar disorder, findings have been largely inconsistent across studies. Differences in patients' medication status or mood state or the application of traditional volumetric methods that are insensitive to subtle neuroanatomical differences may have contributed to variations in findings. The authors used MRI in conjunction with cortical pattern matching methods to assess cortical thickness abnormalities in euthymic bipolar patients who were not receiving lithium treatment.

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The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness.

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Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness.

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Ideal biomarkers of Alzheimer's disease (AD) should correlate with accepted measures of pathology in the cerebrospinal fluid (CSF); they should also correlate with, or predict, future clinical decline, and should be readily measured in hundreds to thousands of subjects. Here we explored the utility of automated 3D maps of the lateral ventricles as a possible biomarker of AD. We used our multi-atlas fluid image alignment (MAFIA) method, to compute ventricular models automatically, without user intervention, from 804 brain MRI scans with 184 AD, 391 mild cognitive impairment (MCI), and 229 healthy elderly controls (446 men, 338 women; age: 75.

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