Migraine with aura in women is not associated with structural thalamic abnormalities.

Migraine with aura is a highly prevalent disorder involving transient neurological disturbances associated with migraine headache. While the pathophysiology is incompletely understood, findings from clinical and basic science studies indicate a potential key role of the thalamus in the mechanisms underlying migraine with and without aura. Two recent, clinic-based MRI studies investigated the volumes of individual thalamic nuclei in migraine patients with and without aura using two different data analysis methods. Both studies found differences of thalamic nuclei volumes between patients and healthy controls, but the results of the studies were not consistent. Here, we investigated whether migraine with aura is associated with changes in thalamic volume by analysing MRI data obtained from a large, cross-sectional population-based study which specifically included women with migraine with aura (N = 156), unrelated migraine-free matched controls (N = 126), and migraine aura-free co-twins (N = 29) identified from the Danish Twin Registry. We used two advanced, validated analysis methods to assess the volume of the thalamus and its nuclei; the MAGeT Brain Algorithm and a recently developed FreeSurfer-based method based on a probabilistic atlas of the thalamic nuclei combining ex vivo MRI and histology. These approaches were very similar to the methods used in each of the two previous studies. Between-group comparisons were corrected for potential effects of age, educational level, BMI, smoking, alcohol, and hypertension using a linear mixed model. Further, we used linear mixed models and visual inspection of data to assess relations between migraine aura frequency and thalamic nuclei volumes in patients. In addition, we performed paired t-tests to compare volumes of twin pairs (N = 29) discordant for migraine with aura. None of our analyses showed any between-group differences in volume of the thalamus or of individual thalamic nuclei. Our results indicate that the pathophysiology of migraine with aura does not involve alteration of thalamic volume.

The influence of prolonged strength training upon muscle and fat in healthy and chronically diseased older adults.

BACKGROUND: Physical muscle function and brain hippocampus size declines with age, accelerating after the age of 60. Strength training over a few months improves physical function, but less is known about how long-term strength training affects physical function and hippocampus volume. Therefore, we aimed to investigate the effect of 1-year strength training of two different intensities upon muscle mass, function, and hippocampus volume in retirement-age individuals. METHODS: In this multidisciplinary randomized controlled trial (clinicaltrials.gov: NCT02123641), participants were allocated to either a) supervised, heavy resistance training (HRT, n = 149, 3/wk), b) moderate intensity resistance training (MIT, n = 154, 3/wk) or c) non-exercise activities (CON, n = 148). 451 participants were randomized (62-70 yrs., women 61%, ≈80% with a chronic medical disease) and 419 were included in the intention-to-treat analysis (n = 143, 144 and 132; HRT, MIT and CON). Changes in muscle power (primary outcome), strength and size, physical function, body composition, hippocampus volume and physical/mental well-being were analyzed. FINDINGS: Of the participants (HRT + MIT), 83% completed training at least 2/week. Leg extensor power was unchanged in all groups, but strength training had a positive effect on isometric knee extensor strength in both groups, whereas an increased muscle mass, cross-sectional area of vastus lateralis muscle, a decreased whole-body fat percentage, visceral fat content and an improved mental health (SF-36) occurred in HRT only. Further, chair-stand performance improved in all groups, whereas hippocampus volume decreased in all groups over time with no influence of strength training. INTERPRETATION: Together, the results indicate that leg extensor power did not respond to long-term supervised strength training, but this type of training in a mixed group of healthy and chronically diseased elderly individuals can be implemented with good compliance and induces consistent changes in physiological parameters of muscle strength, muscle mass and abdominal fat.

Migraine with visual aura associated with thicker visual cortex.

Until recent years it was believed that migraine with aura was a disorder causing intermittent neurological symptoms, with no impact on brain structure. However, recent MRI studies have reported increased cortical thickness of visual and somatosensory areas in patients with migraine with aura, suggesting that such structural alterations were either due to increased neuronal density in the areas involved, or a result of multiple episodes of cortical spreading depression as part of aura attacks. Subsequent studies have yielded conflicting results, possibly due to methodological reasons, e.g. small number of subjects. In this cross-sectional study, we recruited females aged 30-60 years from the nationwide Danish Twin Registry. Brain MRI of females with migraine with aura (patients), their co-twins, and unrelated migraine-free twins (controls) were performed at a single centre and assessed for cortical thickness in predefined cortical areas (V1, V2, V3A, MT, somatosensory cortex), blinded to headache diagnoses. The difference in cortical thickness between patients and controls adjusted for age, and other potential confounders was assessed. Comparisons of twin pairs discordant for migraine with aura were also performed. Comparisons were based on 166 patients, 30 co-twins, and 137 controls. Compared with controls, patients had a thicker cortex in areas V2 [adjusted mean difference 0.032 mm (95% confidence interval 0.003 to 0.061), V3A [adjusted mean difference 0.037 mm (95% confidence interval 0.008 to 0.067)], while differences in the remaining areas examined were not statistically significant [adjusted mean difference (95% confidence interval): V1 0.022 (-0.007 to 0.052); MT: 0.018 (-0.011 to 0.047); somatosensory cortex: 0.020 (-0.009 to 0.049)]. We found no association between the regions of interest and active migraine, or number of lifetime aura attacks. Migraine with aura discordant twin pairs (n = 30) only differed in mean thickness of V2 (0.039 mm, 95% CI 0.005 to 0.074). In conclusion, females with migraine with aura have a thicker cortex corresponding to visual areas and our results indicate this may be an inherent trait rather than a result of repeated aura attacks.

Physical activity as intervention for age-related loss of muscle mass and function: protocol for a randomised controlled trial (the LISA study).

INTRODUCTION: Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative. The primary aim of this randomised controlled trial is to compare the efficacy of two different 1 year strength training regimens on immediate and long-lasting improvements in muscle power in retirement-age individuals. Secondary aims are to evaluate the effect on muscle strength, muscle mass, physical and cognitive function, mental well-being, health-related quality of life and brain morphology. METHODS AND ANALYSIS: The study includes 450 home-dwelling men and women (62-70 years). Participants are randomly allocated to (1) 1 year of supervised, centre-based heavy resistance training, (2) home-based moderate intensity resistance training or (3) habitual physical activity (control). Changes in primary (leg extensor power) and secondary outcomes are analysed according to the intention to treat principle and per protocol at 1, 2, 4, 7 and 10 years. ETHICS AND DISSEMINATION: The study is expected to generate new insights into training-induced promotion of functional ability and independency after retirement and will help to formulate national recommendations regarding physical activity schemes for the growing population of older individuals in western societies. Results will be published in scientific peer-reviewed journals, in PhD theses and at public meetings. The study is approved by the Regional Ethical Committee (Capital Region, Copenhagen, Denmark, number H-3-2014-017). TRIAL REGISTRATION NUMBER: NCT02123641.

Simultaneous Assessment of White Matter Changes in Microstructure and Connectedness in the Blind Brain.

Magnetic resonance imaging (MRI) of the human brain has provided converging evidence that visual deprivation induces regional changes in white matter (WM) microstructure. It remains unclear how these changes modify network connections between brain regions. Here we used diffusion-weighted MRI to relate differences in microstructure and structural connectedness of WM in individuals with congenital or late-onset blindness relative to normally sighted controls. Diffusion tensor imaging (DTI) provided voxel-specific microstructural features of the tissue, while anatomical connectivity mapping (ACM) assessed the connectedness of each voxel with the rest of the brain. ACM yielded reduced anatomical connectivity in the corpus callosum in individuals with congenital but not late-onset blindness. ACM did not identify any brain region where blindness resulted in increased anatomical connectivity. DTI revealed widespread microstructural differences as indexed by a reduced regional fractional anisotropy (FA). Blind individuals showed lower FA in the primary visual and the ventral visual processing stream relative to sighted controls regardless of the blindness onset. The results show that visual deprivation shapes WM microstructure and anatomical connectivity, but these changes appear to be spatially dissociated as changes emerge in different WM tracts. They also indicate that regional differences in anatomical connectivity depend on the onset of blindness.

Training shortest-path tractography: Automatic learning of spatial priors.

Tractography is the standard tool for automatic delineation of white matter tracts from diffusion weighted images. However, the output of tractography often requires post-processing to remove false positives and ensure a robust delineation of the studied tract, and this demands expert prior knowledge. Here we demonstrate how such prior knowledge, or indeed any prior spatial information, can be automatically incorporated into a shortest-path tractography approach to produce more robust results. We describe how such a prior can be automatically generated (learned) from a population, and we demonstrate that our framework also retains support for conventional interactive constraints such as waypoint regions. We apply our approach to the open access, high quality Human Connectome Project data, as well as a dataset acquired on a typical clinical scanner. Our results show that the use of a learned prior substantially increases the overlap of tractography output with a reference atlas on both populations, and this is confirmed by visual inspection. Furthermore, we demonstrate how a prior learned on the high quality dataset significantly increases the overlap with the reference for the more typical yet lower quality data acquired on a clinical scanner. We hope that such automatic incorporation of prior knowledge and the obviation of expert interactive tract delineation on every subject, will improve the feasibility of large clinical tractography studies.