BACKGROUND AND PURPOSE:DTI is an MR imaging measure of brain tissue integrity and provides an attractive metric for use in neuroprotection clinical trials. The purpose of our study was to use DTI to evaluate the longitudinal changes in brain tissue integrity in a group of patients with MS.

Purpose To assess for associations between hippocampal atrophy and measures of cognitive function, hippocampal magnetization transfer ratio (MTR), and diffusion measures of the fornix, the largest efferent white matter tract from the hippocampus, in patients with multiple sclerosis (MS) and controls. Materials and Methods A total of 53 patients with MS and 20 age- and sex-matched healthy controls participated in cognitive testing and scanning including high spatial-resolution diffusion imaging and a T1-MPRAGE scan. Hippocampal volume and fornicial thickness measures were calculated and compared to mean values of fornicial transverse diffusivity, mean diffusivity, longitudinal diffusivity, fractional anisotropy, mean hippocampal MTR, and scores on measures of episodic memory, processing speed, and working memory tasks. Results In patients with MS, hippocampal volume was significantly related to fornicial diffusion measures (P < 7 × 10−4) and to measures of verbal (P = 0.030) and visual spatial (P = 0.004) episodic memory and a measure of information processing speed (P < 0.037). Discussion These results highlight the role of the hippocampus in cognitive dysfunction in patients with MS and suggest that measures of hippocampal atrophy could be used to capture aspects of disease progression.

Background Imaging can provide noninvasive neural markers of disease progression in multiple sclerosis that are related to behavioral and cognitive symptoms. Past work suggests that diffusion tensor imaging (DTI) provides a measure of white matter pathology, including demyelination and axonal counts. Objectives In the current study, the authors investigate the relationship of DTI measures in the cingulum bundle to common deficits in MS, including episodic memory, working memory, and information processing speed. Methods Fifty-seven patients with MS and 17 age- and education-matched controls underwent high-spatial resolution diffusion scans and cognitive testing. Probabilistic tracking was used to generate tracks from the posterior cingulate cortex to the entorhinal cortex. Results Radial and axial diffusivity values were significantly different between patients and controls (p<0.031), and in patients bilateral diffusion measures were significantly related to measures of episodic memory and speed of processing (p<0.033). Conclusions The tractography-based measures of posterior cingulum integrity reported here support further development of DTI as a viable measure of axonal integrity and cognitive function in patients with MS.

Subtle changes in motor function have been observed in individuals with prodromal Huntington disease (prHD), but the underlying neural mechanisms are not well understood nor is the cumulative effect of the disease (disease burden) on functional connectivity. The present study examined the resting-state functional magnetic resonance imaging (rs-fMRI) connectivity of the primary motor cortex (M1) in 16 gene-negative (NEG) controls and 48 gene-positive prHD participants with various levels of disease burden. The results showed that the strength of the left M1 connectivity with the ipsilateral M1 and somatosensory areas decreased as disease burden increased and correlated with motor symptoms. Weakened M1 connectivity within the motor areas was also associated with abnormalities in long-range connections that evolved with disease burden. In this study, M1 connectivity was decreased with visual centers (bilateral cuneus), but increased with a hub of the default mode network (DMN; posterior cingulate cortex). Changes in connectivity measures were associated with worse performance on measures of cognitive-motor functioning. Short- and long-range functional connectivity disturbances were also associated with volume loss in the basal ganglia, suggesting that weakened M1 connectivity is partly a manifestation of striatal atrophy. Altogether, the results indicate that the prodromal phase of HD is associated with abnormal interhemispheric interactions among motor areas and disturbances in the connectivity of M1 with visual centers and the DMN. These changes may, respectively, contribute to increased motor symptoms, visuomotor integration problems, and deficits in the executive control of movement as individuals approach a manifest diagnosis.

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