MRI-based diagnostic biomarkers for early onset pediatric multiple sclerosis.

Currently, it is unclear whether pediatric multiple sclerosis (PMS) is a pathoetiologically homogeneous disease phenotype due to clinical and epidemiological differences between early and late onset PMS (EOPMS and LOPMS). Consequently, the question was raised whether diagnostic guidelines need to be complemented by specific EOPMS markers. To search for such markers, we analyzed cerebral MRI images acquired with standard protocols using computer-based classification techniques. Specifically, we applied classification algorithms to gray (GM) and white matter (WM) tissue probability parameters of small brain regions derived from T2-weighted MRI images of EOPMS patients (onset <12 years), LOPMS patients (onset ≥12 years), and healthy controls (HC). This was done for PMS subgroups matched for disease duration and participant age independently. As expected, maximal diagnostic information for distinguishing PMS patients and HC was found in a periventricular WM area containing lesions (87.1% accuracy, p < 2.2 × 10(-5)). MRI-based biomarkers specific for EOPMS were identified in prefrontal cortex. Specifically, a coordinate in middle frontal gyrus contained maximal diagnostic information (77.3%, p = 1.8 × 10(-4)). Taken together, we were able to identify biomarkers reflecting pathognomonic processes specific for MS patients with very early onset. Especially GM involvement in the separation between PMS subgroups suggests that conventional MRI contains a richer set of diagnostically informative features than previously assumed.

Impulse control in the dorsolateral prefrontal cortex counteracts post-diet weight regain in obesity.

A variety of studies suggest that efficient treatments to induce short-term dietary success in obesity exist. However, sustained maintenance of reduced weight is rare as a large proportion of patients start to regain weight when treatment is discontinued. Thus, from a clinical perspective, it would be desirable to identify factors that counteract post-diet weight regain across longer time-scales. To address this question, we extended our previous work on neural impulse control mechanisms of short-term dietary success in obesity and now investigated the mechanisms counteracting long-term weight regain after a diet. Specifically, we measured neural impulse control during a delay discounting task with fMRI at two time points, i.e. the beginning ('T0') and the end ('T12') of a one-year follow-up interval after a 12-week diet. Then, we tested whether activity in the dorsolateral prefrontal cortex (DLPFC) at T0 and whether activity changes across the follow-up period (T0-T12) are linked to success in weight maintenance. The analyses conducted show that control-related DLPFC activity at T0 was coupled to the degree of success in weight maintenance. Consistently, also behavioral measures of control were linked to the degree of success in maintenance. A direct comparison of neural and behavioral control parameters for prognostic weight change modeling revealed that neural signals were more informative. Taken together, neural impulse control in the DLPFC measured with fMRI directly after a diet predicts real-world diet success in obese patients across extended time periods.

Tract-based spatial statistics of the olfactory brain in patients with multiple sclerosis.

PURPOSE: To investigate diffusion tensor abnormalities, e.g. fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD), in olfactory structures of multiple sclerosis (MS) patients using diffusion tensor imaging (DTI). METHODS: Institutional review board-approved prospective study on 30 MS patients and 12 healthy controls investigated with MRI including DTI. Central olfactory structures were labelled on each patient's and healthy contro''s DTI volume. The diffusion tensor was determined in the central olfactory structures in MS patients. Tract-based spatial statistics (TBSS) was used to quantify the streamlines outgoing from the olfactory structures and to quantify changes in FA, MD, and RD within olfactory structures. These brain changes were correlated with olfactory function measured as TDI (Threshold, Discrimination, Identification) scores in patients and compared to our own reference group of 30 healthy volunteers. RESULTS: Central olfactory structures in the MNI (Montreal Neurological Institute) data volume comprise 4808 voxels (4808 mm(3)). TFCE (Threshold-free cluster enhancement) and cluster analysis of patients identified a total of 127 voxels in one cluster with a significantly decreased FA (p<0.05) and none for MD and RD within olfactory structures compared to healthy controls. The correlation with the age-normalised Identification subscore of the TDI score increased the significant number of voxels with decreased FA to 208 voxels, with increased MD to 370 and with increased RD 364 voxels at the same region. CONCLUSION: The decrease in FA and increase of MD and RD correlate with the degree of identification impairment of olfactory function in MS patients and clusters of abnormalities were identified on a MNI data volume.

The role of neural impulse control mechanisms for dietary success in obesity.

Deficits in impulse control are discussed as key mechanisms for major worldwide health problems such as drug addiction and obesity. For example, obese subjects have difficulty controlling their impulses to overeat when faced with food items. Here, we investigated the role of neural impulse control mechanisms for dietary success in middle-aged obese subjects. Specifically, we used a food-specific delayed gratification paradigm and functional magnetic resonance imaging to measure eating-related impulse-control in middle-aged obese subjects just before they underwent a twelve-week low calorie diet. As expected, we found that subjects with higher behavioral impulse control subsequently lost more weight. Furthermore, brain activity before the diet in VMPFC and DLPFC correlates with subsequent weight loss. Additionally, a connectivity analysis revealed that stronger functional connectivity between these regions is associated with better dietary success and impulse control. Thus, the degree to which subjects can control their eating impulses might depend on the interplay between control regions (DLPFC) and regions signaling the reward of food (VMPFC). This could potentially constitute a general mechanism that also extends to other disorders such as drug addiction or alcohol abuse.

Olfactory function in patients with multiple sclerosis: a diffusion tensor imaging study.

BACKGROUND: Previous research has shown that multiple sclerosis (MS) patients can develop olfactory disturbances. OBJECTIVE: The purpose of our study was to investigate how olfactory function in MS patients correlates with cerebral magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI). METHODS: Olfactory performance was tested in 30 MS patients and 30 controls to determine odour threshold (T), odour discrimination (D), and odour identification (I) summarised in the TDI score. The lesion load (number and total volume of lesions) was measured on proton-density (PD)- and T2-weighted images of the olfactory brain and the total brain. Fractional anisotropy (FA) of the lesions and the surrounding normal-appearing brain tissue (NABT) was quantified using DTI. RESULTS: The median FA of white matter lesions was 0.29 and was on average 11.1% lower than in the surrounding NABT. The normalised TDI score and the normalised I subscore were significantly poorer in the MS group compared to controls (p<0.0001), while the T and D subscores were similar in both groups. The median FA of lesions in the olfactory brain correlated inversely with the decreased I subscore (p=0.001). There was also a strong correlation between the TDI score and the Expanded Disability Status Scale (EDSS) (p=0.001). CONCLUSION: A strong inverse relationship between decreased odour identification ability of MS patients and FA values in the olfactory brain indicates that the reduction in I is more strongly affected by lesions in areas with high FA values, i.e., with an increased amount of affected white matter tracts.

Septal grafts and evoked acetylcholine release in the rat hippocampus after 192 IgG-saporin lesions.

Adult rats received intraseptal injections of 192 IgG-saporin and intrahippocampal grafts of septal cells. Between 6 and 10 months later, we assessed baseline and electrically-evoked release of tritium in hippocampal slices preloaded with [(3)H]choline, and the uptake of [(3)H]choline, [(3)H]noradrenaline and [(3)H]serotonin by hippocampal synaptosomes. The lesions reduced the accumulation of [(3)H]choline by approximately 40%, the evoked release of [(3)H]acetylcholine by approximately 90%, and the uptake of [(3)H]choline by synaptosomes by 90% in the dorsal hippocampus, but increased the relative baseline release of [(3)H]choline by +43%, and the synaptosomal uptake of [(3)H]noradrenaline (66%) and [(3)H]serotonin (58%) in the ventral hippocampus. The increased noradrenaline uptake may account for sympathetic ingrowth. Although the grafts of fetal septal neurons produced modest cholinergic effects, these effects were positive and significant.