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Late onset Pompe disease (LOPD) is a slowly progressive metabolic myopathy with variable clinical severity. The advent of enzyme replacement therapy (ERT) has modified the natural course of the disease, though the treatment effect on adult patients is modest compared to infants with the classic form. This study aims to describe the long-term clinical outcome of the Greek LOPD cohort, as assessed by 6 min walk test, muscle strength using MRC grading scale and spirometry. ERT efficacy was estimated using statistical methodology that is novel in the context of Pompe disease, which at the same time is well-suited to longitudinal studies with small samples and missing data (local non-linear regression analysis). Improvement over baseline was significant at 1 year for motor performance and muscle strength (p < 0.05), and at 2 years for FVC-U and FVC-S (p < 0.05). A subgroup analysis showed that the onset of the disease before adulthood (18 years), a male gender, and a latency of more than 2 years between the onset of symptoms and ERT administration are unfavorable prognostic factors. Conclusively, this study presents longitudinal data from the Greek LOPD cohort supporting previous observations, that therapeutic delay is related to worse prognosis and treatment effects may decline after several years of ERT.

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An exciting avenue of neuroscientific research involves quantifying the time-varying properties of functional connectivity networks. As a result, many methods have been proposed to estimate the dynamic properties of such networks. However, one of the challenges associated with such methods involves the interpretation and visualization of high-dimensional, dynamic networks. In this work, we employ graph embedding algorithms to provide low-dimensional vector representations of networks, thus facilitating traditional objectives such as visualization, interpretation and classification. We focus on linear graph embedding methods based on principal component analysis and regularized linear discriminant analysis. The proposed graph embedding methods are validated through a series of simulations and applied to fMRI data from the Human Connectome Project.

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Two novel and exciting avenues of neuroscientific research involve the study of task-driven dynamic reconfigurations of functional connectivity networks and the study of functional connectivity in real-time. While the former is a well-established field within neuroscience and has received considerable attention in recent years, the latter remains in its infancy. To date, the vast majority of real-time fMRI studies have focused on a single brain region at a time. This is due in part to the many challenges faced when estimating dynamic functional connectivity networks in real-time. In this work, we propose a novel methodology with which to accurately track changes in time-varying functional connectivity networks in real-time. The proposed method is shown to perform competitively when compared to state-of-the-art offline algorithms using both synthetic as well as real-time fMRI data. The proposed method is applied to motor task data from the Human Connectome Project as well as to data obtained from a visuospatial attention task. We demonstrate that the algorithm is able to accurately estimate task-related changes in network structure in real-time. Hum Brain Mapp 38:202-220, 2017. © 2016 Wiley Periodicals, Inc.

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Functional neuroimaging typically explores how a particular task activates a set of brain regions. Importantly though, the same neural system can be activated by inherently different tasks. To date, there is no approach available that systematically explores whether and how distinct tasks probe the same neural system. Here, we propose and validate an alternative framework, the Automatic Neuroscientist, which turns the standard fMRI approach on its head. We use real-time fMRI in combination with modern machine-learning techniques to automatically design the optimal experiment to evoke a desired target brain state. In this work, we present two proof-of-principle studies involving perceptual stimuli. In both studies optimization algorithms of varying complexity were employed; the first involved a stochastic approximation method while the second incorporated a more sophisticated Bayesian optimization technique. In the first study, we achieved convergence for the hypothesized optimum in 11 out of 14 runs in less than 10 min. Results of the second study showed how our closed-loop framework accurately and with high efficiency estimated the underlying relationship between stimuli and neural responses for each subject in one to two runs: with each run lasting 6.3 min. Moreover, we demonstrate that using only the first run produced a reliable solution at a group-level. Supporting simulation analyses provided evidence on the robustness of the Bayesian optimization approach for scenarios with low contrast-to-noise ratio. This framework is generalizable to numerous applications, ranging from optimizing stimuli in neuroimaging pilot studies to tailoring clinical rehabilitation therapy to patients and can be used with multiple imaging modalities in humans and animals.

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At the forefront of neuroimaging is the understanding of the functional architecture of the human brain. In most applications functional networks are assumed to be stationary, resulting in a single network estimated for the entire time course. However recent results suggest that the connectivity between brain regions is highly non-stationary even at rest. As a result, there is a need for new brain imaging methodologies that comprehensively account for the dynamic nature of functional networks. In this work we propose the Smooth Incremental Graphical Lasso Estimation (SINGLE) algorithm which estimates dynamic brain networks from fMRI data. We apply the proposed algorithm to functional MRI data from 24 healthy patients performing a Choice Reaction Task to demonstrate the dynamic changes in network structure that accompany a simple but attentionally demanding cognitive task. Using graph theoretic measures we show that the properties of the Right Inferior Frontal Gyrus and the Right Inferior Parietal lobe dynamically change with the task. These regions are frequently reported as playing an important role in cognitive control. Our results suggest that both these regions play a key role in the attention and executive function during cognitively demanding tasks and may be fundamental in regulating the balance between other brain regions.

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