Reproducibility of regional structural and functional MRI networks in cerebral small vessel disease compared to age matched and stroke-free controls.

Abnormalities in structural and functional MRI connectivity measures have been reported in cerebral small vessel disease (SVD). Previous research has shown that whole-brain structural connectivity was highly reproducible in SVD patients, while whole-brain functional connectivity showed low reproducibility. It remains unclear whether the lower reproducibility of functional networks reported in SVD is due to selective disruption of reproducibility in specific networks or is generalised in patients with SVD. In this case-control study 15 SVD and 10 age-matched control participants were imaged twice with diffusion tensor imaging and resting state fMRI. Structural and functional connectivity matrices were constructed from this data and the default mode, fronto-parietal, limbic, salience, somatomotor and visual networks were extracted and the average connectivity between connections calculated and used to determine their reproducibility. Regional structural networks were more reproducible than functional networks, all structural networks showed ICC values ≥0.64 (except the salience network in SVD). The functional networks showed greater reproducibility in the controls compared to SVD with ICC values >0.7 for control participants and <=0.5 for the SVD group. The default mode network showed the greatest reproducibility for both control and SVD groups. Reproducibility of functional networks was affected by disease status with lower reproducibility in SVD compared with controls.

Education is power: preserving cognition in the UK biobank.

Introduction: Dementia is a debilitating syndrome characterized by the gradual loss of memory and cognitive function. Although there are currently limited, largely symptomatic treatments for the diseases that can lead to dementia, its onset may be prevented by identifying and modifying relevant life style risk factors. Commonly described modifiable risk factors include diet, physical inactivity, and educational attainment. Importantly, however, to maximize the utility of our understanding of these risk factors, tangible and meaningful changes to policy must also be addressed. Objectives: Here, we aim to identify the mechanism(s) by which educational attainment influences cognition. Methods: We investigated data from 502,357 individuals (Mage = 56.53, SDage = 8.09, 54.40% female) from the UK Biobank cohort via Structural Equation Modelling to illustrate links between predictor variables (i.e., Townsend Deprivation Index, coastal distance, greenspace, years of education), covariates (i.e., participant age) and cognitive function as outcome variables (i.e., pairs-matching, trail-making task B, fluid intelligence). Results: Our model demonstrated that higher education was associated with better cognitive performance (ps < 0.001), and this relationship was mediated by indices of deprivation, and coastal distance. Conclusion: Accordingly, our model evinces the mediating effect of socioeconomic and environmental factors on the relationship between years of education and cognitive function. These results further demonstrate the utility and necessity of adapting public policy to encourage equitable access to education and other supports in deprived areas.

Effects of seven-day diazepam administration on resting-state functional connectivity in healthy volunteers: a randomized, double-blind study.

RATIONALE: Benzodiazepines, such as diazepam, are anxiolytic-sedative drugs, used for the treatment of several different disorders. The pharmacological mechanism of action of benzodiazepines is well understood; however, it remains unclear which neural networks and systems are involved in translating these neurochemical actions into their therapeutic effects. OBJECTIVES: The objective of this study was to investigate the effects of 7-day diazepam administration compared to placebo on resting-state functional connectivity in healthy adults independent of any task. METHODS: Thirty-four healthy participants were randomly assigned to receive either diazepam (N = 17) or placebo (15 mg daily for 7 days) and underwent resting-state functional magnetic resonance acquisition. Model-free data analysis was performed using independent component analysis and dual regression. RESULTS: Consistent with previous research, 11 resting-state networks were identified. Increased connectivity in response to diazepam administration was found in the medial visual network and middle/inferior temporal network. Diazepam did not cause any decreases in functional connectivity. CONCLUSIONS: Diazepam administration increases functional connectivity in areas of emotional processing independent of any task. Diazepam also enhanced functional connectivity in the medial visual system, which is a brain region rich in GABAA receptors, and shows high binding of GABAergic drugs. These increases in functional connectivity are characteristic of CNS depressants.

Effects of short-term varenicline administration on cortisol in healthy, non-smoking adults: a randomized, double-blind, study.

RATIONALE: Varenicline is the most effective drug for smoking cessation, but its use decreased because of reports of depressogenic side effects. However, because smoking and smoking cessation on their own are associated with depression, it remains unclear whether reported depressogenic effects are attributable to varenicline, or to smoking, and/or smoking cessation themselves. OBJECTIVES: Previously, we observed no depressogenic effects of varenicline on a psychological level. In the present study, we aimed at investigating potential depressogenic effects of the partial nicotinergic acetylcholine receptor agonist varenicline on a biological level. A possible pathway would be an effect of varenicline on the hypothalamic-pituitary-adrenal (HPA) axis, considering the relation between the HPA axis and (1) the cholinergic system and (2) depression. METHODS: In a randomized, double-blind design, we administered varenicline or placebo for 7 days (0.5 mg/day first 3 days, then 1 mg/day) to healthy never-smoking subjects, thereby eliminating bias by (previous) smoking status. We used repeated measures (before and after treatment) of the salivary free cortisol awakening response to measure HPA axis activity and flexibility. RESULTS: Salivary cortisol data of 34 subjects were included in the analysis. Results showed no effect of varenicline on height (F1,32 = 0.405; P = 0.529) or shape (F2,31 = 0.110; P = 0.164) of the cortisol awakening response. CONCLUSIONS: Results do not suggest depressogenic effects of varenicline on the HPA axis. Although this does not preclude other biological depressogenic effects of varenicline, it seems that concerns about effects of varenicline on the HPA axis should not limit its potential to treat nicotine and related addictions.