Earle Arthur Johnson

BACKGROUND AND PURPOSE: In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease. MATERIALS AND METHODS: Local field shift, calculated from 7T MR phase images, was quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift. RESULTS: Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function. CONCLUSIONS: Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease.

I argue that Plato's thought evolves from the epistemology of the Meno, Phaedo, and Republic to the Combined Doctrine of the Theaetetus. The Combined Doctrine maintains that both Forms and certain objects rooted in perception are objects of knowledge. Specifically, the doctrine holds that a person acquires knowledge of Forms through recollection and through apprehension of the relations among Forms and that only with knowledge of Forms and the relations among Forms is a person able to know cognized objects through perception. ;According to the epistemology of the middle period, one obtains knowledge through questioning one's assumptions many times and in many ways . These assumptions are produced through the method of recollection , the method of hypothesis, and dialectic and they are true beliefs which have been tested for consistency . Dialectic results in reasoning up to knowledge of the Good and then back down, converting true beliefs into knowledge along the way . Further, the apprehension of the Good, and consequently of being, brings about a permanent change in a person's state of mind enabling her to know dialectical assumptions she previously believed. ;I conclude that only through a particular state of mind is one able to know Forms and that one acquires this state of mind by recollecting assumptions which direct one to reason up to an apprehension of the Good. I infer from this conclusion that one must have knowledge of Forms in order to know what appear to be physical objects, if such objects can be known. I also argue that Plato uses the Secret Doctrine as a theory of perception which explains the nature of cognized objects and that the Combined Doctrine, in its employment of the Theaeteus' theory of perception, is a theory of critical realism. Finally, I use the Combined Doctrine to resolve the paradoxes of the refutations of the Theaetetus. It turns out that the difference between true belief and knowledge for Plato amounts to a difference in states of mind. The Theaeteus' search for knowledge supports the complex epistemological and ontological underpinnings of the Combined Doctrine of Knowledge