Caffeine alters resting‐state functional connectivity measured by blood oxygenation level‐dependent MRI

This study aimed to investigate the pharmacological effect of caffeine on functional connectivity measured by resting‐state blood oxygenation level‐dependent (BOLD) MRI in the motor cortex, visual cortex and default mode network (DMN). The protocols and procedures of the study were reviewed and approved by the Institutional Review Board of our institution. On a 3‐T clinical MR system, 20 healthy volunteers underwent imaging before and after oral ingestion of a 200‐mg over‐the‐counter caffeine pill (data from three individuals were excluded from further analysis because of excessive motion). The demographics of the remaining participants were as follows: female/male, 8/9; age, 21–35 years; non‐habitual caffeine consumers over the past 6 months. Functional connectivity was calculated using the general linear model, assessed in terms of connected area (voxels) and statistical significance (Student t‐values), and correlated with changes in regional cerebral blood flow as measured by arterial spin labeling MRI. Per‐subject data analysis showed that caffeine decreased functional connectivity in the motor/visual cortices, but its effects on DMN varied among subjects. Correlation analysis of the changes in functional connectivity and regional blood flow suggested that the effect of caffeine on BOLD functional connectivity was predominantly neural (motor/visual cortices) and partly vascular (DMN). Group analysis showed that, after caffeine ingestion, DMN involved more attentional networks, and more extrastriate areas were integrated into the functional connectivity of the visual cortex, which may be associated with the known pharmacological effect of caffeine in elevating alertness. Caffeine consumption should thus be considered in the experimental design and data interpretation of functional connectivity studies using resting‐state BOLD MRI. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss

Aims/hypothesis

Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss.

Methods

Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, ??-hydroxybutyrate, ketones, insulin and glucose were performed in baseline and 6?month plasma samples from 500 participants who had lost ??4?kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (?HOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n?=?22).

Results

Mean weight loss was 8.67?±?4.28?kg; mean ?HOMA-IR was ?0.80?±?1.73, range ?28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r?=?0.50, p?p?r?=?0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ?HOMA-IR (p?=?0.007).

Conclusions/interpretation

A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity.     

The western Australian court diversion service: Client profile and predictors of program completion,sentencing and re‐offending

The Western Australian Court Diversion Service (CDS) is a post‐conviction / pre‐sentence program that aims to divert substance‐using offenders from the prison system and into treatment programs. It has been in operation since 1988, though a formal evaluation has not been conducted. The present study evaluated the outcomes for offenders referred to the program in relation to program completion, sentencing and re‐offending. It utilised a quasi‐experimental within groups design using data from client files from January 1998 to June 1999. Offenders who had higher motivation, attended treatment regularly and had less than 20 prior convictions were more likely to complete the program. A custodial sentence was more likely if the offender was male, had committed a serious offence, had more than 30 prior convictions, had lower motivation and had not completed the CDS program. Predictors of re‐offending included lower motivation and a previous custodial sentence. The offender's level of motivation to change and number of prior convictions were significant predictors of all three outcomes: program completion, sentencing and re‐offending. The findings highlight the importance of considering offender characteristics when assessing eligibility for diversion programs, addressing offender motivation within diversion programs and considering issues of which offenders are most likely to benefit from which programs.