Model specification and the reliability of fMRI results: Implications for longitudinal neuroimaging studies in psychiatry

Functional Magnetic Resonance Imagine (fMRI) is an important assessment tool in longitudinal studies of mental illness and its treatment. Understanding the psychometric properties of fMRI-based metrics, and the factors that influence them, will be critical for properly interpreting the results of these efforts. The current study examined whether the choice among alternative model specifications affects estimates of test-retest reliability in key emotion processing regions across a 6-month interval. Subjects (N = 46) performed an emotional-faces paradigm during fMRI in which neutral faces dynamically morphed into one of four emotional faces. Median voxelwise intraclass correlation coefficients (mvICCs) were calculated to examine stability over time in regions showing task-related activity as well as in bilateral amygdala. Four modeling choices were evaluated: a default model that used the canonical hemodynamic response function (HRF), a flexible HRF model that included additional basis functions, a modified CompCor (mCompCor) model that added corrections for physiological noise in the global signal, and a final model that combined the flexible HRF and mCompCor models. Model residuals were examined to determine the degree to which each pipeline met modeling assumptions. Results indicated that the choice of modeling approaches impacts both the degree to which model assumptions are met and estimates of test-retest reliability. ICC estimates in the visual cortex increased from poor (mvICC = 0.31) in the default pipeline to fair (mvICC = 0.45) in the full alternative pipeline - an increase of 45%. In nearly all tests, the models with the fewest assumption violations generated the highest ICC estimates. Implications for longitudinal treatment studies that utilize fMRI are discussed. © 2014 Fournier et al

Music notation: a new method for visualizing social interaction in animals and humans

BACKGROUND: Researchers have developed a variety of techniques for the visual presentation of quantitative data. These techniques can help to reveal trends and regularities that would be difficult to see if the data were left in raw form. Such techniques can be of great help in exploratory data analysis, making apparent the organization of data sets, developing new hypotheses, and in selecting effects to be tested by statistical analysis. Researchers studying social interaction in groups of animals and humans, however, have few tools to present their raw data visually, and it can be especially difficult to perceive patterns in these data. In this paper I introduce a new graphical method for the visual display of interaction records in human and animal groups, and I illustrate this method using data taken on chickens forming dominance hierarchies. RESULTS: This new method presents data in a way that can help researchers immediately to see patterns and connections in long, detailed records of interaction. I show a variety of ways in which this new technique can be used: (1) to explore trends in the formation of both group social structures and individual relationships; (2) to compare interaction records across groups of real animals and between real animals and computer-simulated animal interactions; (3) to search for and discover new types of small-scale interaction sequences; and (4) to examine how interaction patterns in larger groups might emerge from those in component subgroups. In addition, I discuss how this method can be modified and extended for visualizing a variety of different kinds of social interaction in both humans and animals. CONCLUSION: This method can help researchers develop new insights into the structure and organization of social interaction. Such insights can make it easier for researchers to explain behavioural processes, to select aspects of data for statistical analysis, to design further studies, and to formulate appropriate mathematical models and computer simulations

Variability of insulin sensitivity during the first 4 days of critical illness

1-pageSafe, effective tight glycaemic control (TGC) can improve outcomes in critical care patients, but is difficult to achieve consistently. Insulin sensitivity defines the metabolic balance between insulin concentration and insulin mediated glucose disposal. Hence, variability of insulin sensitivity can cause variable glycaemia. This study investigates the daily evolution of model-based insulin sensitivity level and variability for critical care patients receiving TGC during the first four days of their ICU stay

Validation of a virtual patient and virtual trials method for accurate prediction of tight glycemic control protocol performance

Peer reviewe

Does tight glycemic control positively impact on patient mortality?

peer reviewe

Enhanced insulin sensitivity variability in the first 3 days of ICU stay: implications for tight glycemic control

Effective tight glycemic control (TGC) can improve outcomes, particularly in cardiovascular surgery, but is difficult to achieve. Variability in insulin sensitivity/resistance resulting from the level and evolution of stress response, particularly early in a patient’s stay, can lead to hyperglycemia and variability, which are associated with mortality. This study quantifies the daily evolution of the variability of insulin sensitivity for cardiovascular surgical and all other ICU patients

Towards a better understanding of the development of the strength in Asymmetrical Friction Connections (AFC)

In the current design practice, the strength of Asymmetric Friction Connections (AFCs) is calculated considering the friction force developed at both sliding interfaces using the bolt tension reduced by the moment – shear - axial interaction (MPV) effect. However, available models do not consider the friction induced by the bolt assembly force, termed assembly effect, or the bolt inclination effect, which is the increase in the AFC strength due to the horizontal component of the bolt tension produced when the bolt inclines. This paper proposes a model for quantifying the strength of AFCs considering the assembly, MPV, and inclination effects for the cases: i). Before the slotted plate breakaway, ii). Bolts inclining up to the angle defined by the bole hole oversize and termed bolt elastic inclination, iii) Bolts inclination angles larger than the angle defined by the bole hole oversize and produced by bolt flexural yielding and termed bolt yielding inclination. The proposed model is validated from the testing of an AFC scaled prototype, and from the quasi – static testing of 18 AFCs in real scale and assembled with Bisalloy 500 shims, and 2 M16 Grade 8.8 bolts with bolt grip lengths between 52.5mm and 172.5mm. It is shown that before breakaway the hysteresis loop is linear, and the peak strength depends only on the assembly effect. For the bolt elastic inclination, the hysteresis loop shape is bilinear, and the peak strength depends on the combined action of the assembly, MPV, and inclination effects. For the bolt yielding inclination, the hysteresis loop is square and pinched and the average strength across the plateau of the hysteresis loop depends on the MPV and inclination effects. For the three cases considered, the proposed model predicts the AFC strength with accuracies of 76% – 120%. The proposed model shows the horizontal component of the bolt tension from the bolt inclination effect was 6% - 28% of the AFC strength for the bolt elastic inclination, and 38% - 53% of the AFC strength for the bolt yielding inclination

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns

Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics

Alcohol dehydrogenases (ADH) participate in the biosynthetic pathway of aroma volatiles in fruit by interconverting aldehydes to alcohols and providing substrates for the formation of esters. Two highly divergent ADH genes (15% identity at the amino acid level) of Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis) have been isolated. Cm-ADH1 belongs to the medium-chain zinc-binding type of ADHs and is highly similar to all ADH genes expressed in fruit isolated so far. Cm-ADH2 belongs to the short-chain type of ADHs. The two encoded proteins are enzymatically active upon expression in yeast. Cm-ADH1 has strong preference for NAPDH as a co-factor, whereas Cm-ADH2 preferentially uses NADH. Both Cm-ADH proteins are much more active as reductases with Kms 10–20 times lower for the conversion of aldehydes to alcohols than for the dehydrogenation of alcohols to aldehydes. They both show strong preference for aliphatic aldehydes but Cm-ADH1 is capable of reducing branched aldehydes such as 3-methylbutyraldehyde, whereas Cm-ADH2 cannot. Both Cm-ADH genes are expressed specifically in fruit and up-regulated during ripening. Gene expression as well as total ADH activity are strongly inhibited in antisense ACC oxidase melons and in melon fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. These data suggest that each of the Cm-ADH protein plays a specific role in the regulation of aroma biosynthesis in melon fruit