AMPED study: Protocol for a randomized controlled trial of different doses of aerobic exercise training.

Recently renamed, metabolic dysfunction-associated steatotic liver disease remains a leading cause of chronic liver disease worldwide. Regular physical activity is recommended as a treatment for all with this condition because it is highly efficacious, especially when exercise training is undertaken with a specific goal in mind. Despite decades of research demonstrating exercise's efficacy, key questions remain about the mechanism of benefit and most efficacious dose, as well as the independent impact on liver histology. To answer these questions, we present the design of a 16-week randomized controlled clinical trial of 45 adults aged 18-69 years with metabolic dysfunction-associated steatohepatitis. The primary aim of this study is to better understand the dose required and mechanisms to explain how exercise impacts multiple clinical end points in metabolic dysfunction-associated steatohepatitis. The primary outcome is MRI-measured liver fat. Secondary outcomes include other biomarkers of liver fibroinflammation, liver histology, and mechanistic pathways, as well as cardiometabolic risk and quality of life. This is the first study to compare different doses of exercise training to determine if there is a differential impact on imaging and serum biomarkers as well as liver histology.

Lexical-Semantic Search Under Different Covert Verbal Fluency Tasks: An fMRI Study.

Background: Verbal fluency is a measure of cognitive flexibility and word search strategies that is widely used to characterize impaired cognitive function. Despite the wealth of research on identifying and characterizing distinct aspects of verbal fluency, the anatomic and functional substrates of retrieval-related search and post-retrieval control processes still have not been fully elucidated. Methods: Twenty-one native English-speaking, healthy, right-handed, adult volunteers (mean age = 31 years; range = 21-45 years; 9 F) took part in a block-design functional Magnetic Resonance Imaging (fMRI) study of free recall, covert word generation tasks when guided by phonemic (P), semantic-category (C), and context-based fill-in-the-blank sentence completion (S) cues. General linear model (GLM), Independent Component Analysis (ICA), and psychophysiological interaction (PPI) were used to further characterize the neural substrate of verbal fluency as a function of retrieval cue type. Results: Common localized activations across P, C, and S tasks occurred in the bilateral superior and left inferior frontal gyrus, left anterior cingulate cortex, bilateral supplementary motor area (SMA), and left insula. Differential task activations were centered in the occipital, temporal and parietal regions as well as the thalamus and cerebellum. The context-based fluency task, i.e., the S task, elicited higher differential brain activity in a lateralized frontal-temporal network typically engaged in complex language processing. P and C tasks elicited activation in limited pathways mainly within the left frontal regions. ICA and PPI results of the S task suggested that brain regions distributed across both hemispheres, extending beyond classical language areas, are recruited for lexical-semantic access and retrieval during sentence completion. Conclusion: Study results support the hypothesis of overlapping, as well as distinct, neural networks for covert word generation when guided by different linguistic cues. The increased demand on word retrieval is met by the concurrent recruitment of classical as well as non-classical language-related brain regions forming a large cognitive neural network. The retrieval-related search and post-retrieval control processes that subserve verbal fluency, therefore, reverberates across distinct functional networks as determined by respective task demands.