One-year changes in brain microstructure differentiate preclinical Huntington's disease stages.

OBJECTIVE: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. METHODS: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period. RESULTS: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the corpus callosum. This overall effect was driven by significant differences between the group far-from-onset (FAR) of symptoms and the groups midway- (MID) and near-the-onset (NEAR) of symptoms. In particular, an initial decrease of mean diffusivity in the FAR group was followed by a subsequent increase in groups closer to onset of symptoms. The seemingly counter-intuitive decrease of mean diffusivity in the group furthest from onset of symptoms might be an early indicator of neuroinflammatory process preceding the neurodegenerative phase. In contrast, the only clinical measure that was able to capture a difference in 1y changes between the preclinical stages was the UHDRS confidence in motor score. CONCLUSIONS: With sensitivity to longitudinal changes in brain microstructure within and between preclinical stages, and potential differential response to distinct pathophysiological mechanisms, diffusion imaging is a promising state marker for monitoring treatment response and identifying the optimal therapeutic window of opportunity in preclinical Huntington's disease

Stability of resting fMRI interregional correlations analyzed in subject-native space: a one-year longitudinal study in healthy adults and premanifest Huntington's disease.

The pattern of interregional functional MRI correlations at rest is being actively considered as a potential noninvasive biomarker in multiple diseases. Before such methods can be used in clinical studies it is important to establish their usefulness in three ways. First, the long-term stability of resting correlation patterns should be characterized, but there have been very few such studies. Second, analysis of resting correlations should account for the unique neuroanatomy of each subject by taking measurements in native space and avoiding transformation of functional data to a standard volume space (e.g., Talairach-Tournox or Montreal Neurological Institute atlases). Transformation to a standard volume space has been shown to variably influence the measurement of functional correlations, and this is a particular concern in diseases which may cause structural changes in the brain. Third, comparisons within the patient population of interest and comparisons between patients and age-matched controls, should demonstrate sensitivity to any disease-related disruption of resting functional correlations. Here we examine the test-retest stability of resting fMRI correlations over a period of one year in a group of healthy adults and in a group of cognitively intact individuals who are gene-positive for Huntington's disease. A recently-developed method is used to measure functional correlations in the native space of individual subjects. The utility of resting functional correlations as a biomarker in premanifest Huntington's disease is also investigated. Results in control and premanifest Huntington's populations were both highly consistent at the group level over one year. We thus show that when resting fMRI analysis is performed in native space (to reduce confounds in registration between subjects and groups) it has good long-term stability at the group level. Individual-subject level results were less consistent between visit 1 and visit 2, suggesting further work is required before resting fMRI correlations can be useful diagnostically for individual patients. No significant effect of premanifest Huntington's disease on prespecified interregional fMRI correlations was observed relative to the control group using either baseline or longitudinal measures. Within the premanifest Huntington's group, though, there was evidence that decreased striatal functional correlations might be associated with disease severity, as gauged by estimated years to symptom onset or by striatal volume

Sex differences in own and other body perception.

Own body perception, and differentiating and comparing one's body to another person's body, are common cognitive functions that have relevance for self-identity and social interactions. In several psychiatric conditions, including anorexia nervosa, body dysmorphic disorder, gender dysphoria, and autism spectrum disorder, self and own body perception, as well as aspects of social communication are disturbed. Despite most of these conditions having skewed prevalence sex ratios, little is known about whether the neural basis of own body perception differs between the sexes. We addressed this question by investigating brain activation using functional magnetic resonance imaging during a Body Perception task in 15 male and 15 female healthy participants. Participants viewed their own body, bodies of same-sex, or opposite-sex other people, and rated the degree that they appeared like themselves. We found that men and women did not differ in the pattern of brain activation during own body perception compared to a scrambled control image. However, when viewing images of other bodies of same-sex or opposite-sex, men showed significantly stronger activations in attention-related and reward-related brain regions, whereas women engaged stronger activations in striatal, medial-prefrontal, and insular cortices, when viewing the own body compared to other images of the opposite sex. It is possible that other body images, particularly of the opposite sex, may be of greater salience for men, whereas images of own bodies may be more salient for women. These observations provide tentative neurobiological correlates to why women may be more vulnerable than men to conditions involving own body perception

Mesolimbic Neurobehavioral Mechanisms of Reward Motivation in Anorexia Nervosa: A Multimodal Imaging Study

Diminished motivation to pursue and obtain primary and secondary rewards has been demonstrated in anorexia nervosa (AN). However, the neurobehavioral mechanisms underlying the behavioral activation component of aberrant reward motivation remains incompletely understood. This work aims to explore this underexplored facet of reward motivation in AN. We recruited female adolescents with AN, restricting type (n = 32) and a healthy control group (n = 28). All participants underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. Diffusion MRI data was also collected to examine the reward motivation circuit's structural connectivity. Behavioral results demonstrated slower speed of reward-seeking behavior in those with AN compared with controls. Accompanying this was lower functional connectivity and reduced white matter structural integrity of the connection between the ventral tegmental area/substantia nigra pars compacta and the nucleus accumbens within the mesolimbic circuit. Further, there was evidence of neurobehavioral decoupling in AN between reward-seeking behavior and mesolimbic regional activation and functional connectivity. Aberrant activity of the bed nucleus of the stria terminalis (BNST) and its connectivity with the mesolimbic system was also evident in AN during the reward motivation period. Our findings suggest functional and structural dysconnectivity within a mesolimbic reward circuit, neurofunctional decoupling from reward-seeking behavior, and abnormal BNST function and circuit interaction with the mesolimbic system. These results show behavioral indicators of aberrant reward motivation in AN, particularly in its activational component. This is mediated neuronally by mesolimbic reward circuit functional and structural dysconnectivity as well as neurobehavioral decoupling. Based on these findings, we suggest a novel circuit-based mechanism of impaired reward processing in AN, with the potential for translation to developing more targeted and effective treatments in this difficult-to-treat psychiatric condition

Patterns of Care for Non–Small-Cell Lung Cancer at an Academic Institution Affiliated With a National Cancer Institute–Designated Cancer Center

These data point toward the need for improved evidence-based use of resources in the third-line setting of stage IV NSCLC