Non-parametric model selection for subject-specific topological organization of resting-state functional connectivity

In recent years, graph theory has been successfully applied to study functional and anatomical connectivity networks in the human brain. Most of these networks have shown small-world topological characteristics: high efficiency in long distance communication between nodes, combined with highly interconnected local clusters of nodes. Moreover, functional studies performed at high resolutions have presented convincing evidence that resting-state functional connectivity networks exhibits (exponentially truncated) scale-free behavior. Such evidence, however, was mostly presented qualitatively, in terms of linear regressions of the degree distributions on log-log plots. Even when quantitative measures were given, these were usually limited to the r(2) correlation coefficient. However, the r(2) statistic is not an optimal estimator of explained variance, when dealing with (truncated) power-law models. Recent developments in statistics have introduced new non-parametric approaches, based on the Kolmogorov-Smirnov test, for the problem of model selection. In this work, we have built on this idea to statistically tackle the issue of model selection for the degree distribution of functional connectivity at rest. The analysis, performed at voxel level and in a subject-specific fashion, confirmed the superiority of a truncated power-law model, showing high consistency across subjects. Moreover, the most highly connected voxels were found to be consistently part of the default mode network. Our results provide statistically sound support to the evidence previously presented in literature for a truncated power-law model of resting-state functional connectivity.     

Haemodynamic parameters predicting variceal haemorrhage and survival in alcoholic cirrhosis

The relationship between the various haemodynamic abnormalities observed in cirrhosis and their prognostic value remains unclear. We report haemodynamic measurements on 96 patients with alcoholic cirrhosis (mean Childs-Pugh Score, CPS, 9.0 +/- 0.2, mean age 55.6 +/- 1.0 years) and assess their value in predicting variceal bleeding and death during a mean follow-up of 19.3 +/- 1.5 months. Baseline CPS correlated with hepatic venous pressure gradient (HVPG) (p = 0.001), azygos blood flow (p < 0.05), cardiac index (p < 0.05), and inversely with mean arterial pressure (p < 0.01) and systemic vascular resistance index (p < 0.05). Renal blood flow was not related to any haemodynamic parameter or CPS. Thirty-eight patients died during follow-up, and 16 had a variceal bleed. Death (p = 0.001) and variceal bleeding (p < 0.05) were more likely in patients with HVPG > 16 mmHg than in those with HVPG < 16 mmHg, and variceal bleeding was more likely in patients with HVPG > 12 mmHg (vs. HVPG < 12 mmHg, p < 0.05). HVPG also predicted death and variceal haemorrhage on univariate and multivariate analyses. No other haemodynamic parameter predicted death or bleeding. In alcoholic cirrhosis, severity of liver disease is related to HVPG, collateral blood flow and degree of systemic circulatory abnormalities. HVPG is a useful predictor of survival and variceal bleeding in these patients.      

A comparison of general self-efficacy and drinking refusal self-efficacy in predicting drinking behavior

A number of studies have suggested that task specific self-efficacy has more influence over behavior than general self-efficacy. However, little research has compared the impact of task-specific self-efficacy beliefs to the impact of general self-efficacy in predicting alcohol consumption. This study aimed to compare the contribution of general self-efficacy and drinking refusal self-efficacy (a form of task-specific self-efficacy) to volume and frequency of alcohol consumption. Regression analyses were performed in samples of community (n = 298) and clinical (n = 296) drinkers. Overall, drinking refusal self-efficacy was found to be a significant predictor of alcohol consumption in the community sample, while general self-efficacy was found to be a significant predictor of drinking in the clinical sample. These differences highlight the differential roles of general and task specific self-efficacy in governing drinking behavior and suggest future directions for prevention and treatment of alcohol problems.     

Down syndrome and congenital heart disease: why the regional difference as observed in the Libyan experience?

Background

Children with Down syndrome (DS) have about a 40 to 50% incidence of congenital heart disease (CHD). The objectives of this study were to evaluate the distribution and frequency of CHD patterns in Libyan children with DS.

Methods

All patients with DS who were referred to the cardiology clinic between January 1995 and December 2008 were reviewed.

Results

Of the 1 193 patients reviewed, 537 (45%) had an associated CHD. Overall there were 349 (65%) patients who had a single cardiac lesion, and 188 (35%) had multiple cardiac lesions. The most common isolated cardiac lesion was atrial septal defect (ASD), found in 125 (23%) patients, followed by atrioventricular septal defect (AVSD) in 103 (19%), and ventricular septal defect (VSD) in 76 (14%).

Conclusion

Atrial septal defect was the most common cardiac lesion. The distribution of CHDs in Libyan children with DS was similar to what has been reported internationally, but the frequency was not compared with international rates.     

Beyond acute social stress: increased functional connectivity between amygdala and cortical midline structures

Whereas we know a fair amount on the role of the amygdala in the acute stress response, virtually nothing is known about its role during the recovery period after the stress has waned. Functional connectivity analysis of the amygdala during this period might be useful in revealing brain circuits promoting adaptive recovery from a stressful event, as well as consolidation of emotionally relevant information in preparing for future challenges. Healthy participants were randomly assigned to either a psychosocial stress task (n=18; stress group) or a comparable non-stressful control procedure (n=20; controls). To study the prolonged effects of stress on amygdala functional connectivity, resting-state fMRI scans were acquired an hour after the stress task. Amygdala functional connectivity with other brain regions was assessed using seed-based correlations. The stress group exhibited a strong physiological and behavioral reaction to psychosocial stress exposure. Compared with controls the stress group showed increased amygdala functional connectivity with three cortical midline structures: the posterior cingulate cortex and precuneus (p<.05, corrected), and the medial prefrontal cortex (p<.05, small volume corrected). An hour after psychosocial stress, changes in amygdala functional connectivity were detected with cortical midline structures involved in the processing and regulation of emotions, as well as autobiographical memory. It is hypothesized that these effects could relate to top-down control of the amygdala and consolidation of self-relevant information after a stressful event. These results on functional connectivity in the recovery phase after stress might provide an important new vantage point in studying both sensitivity and resilience to stress.     

A Comparison of General Self-Efficacy and Drinking Refusal Self-Efficacy in Predicting Drinking Behavior

A number of studies have suggested that task specific self-efficacy has more influence over behavior than general self-efficacy. However, little research has compared the impact of task-specific self-efficacy beliefs to the impact of general self-efficacy in predicting alcohol consumption. This study aimed to compare the contribution of general self-efficacy and drinking refusal self-efficacy (a form of task-specific self-efficacy) to volume and frequency of alcohol consumption. Regression analyses were performed in samples of community (n = 298) and clinical (n = 296) drinkers. Overall, drinking refusal self-efficacy was found to be a significant predictor of alcohol consumption in the community sample, while general self-efficacy was found to be a significant predictor of drinking in the clinical sample. These differences highlight the differential roles of general and task specific self-efficacy in governing drinking behavior and suggest future directions for prevention and treatment of alcohol problems.     

Demonstration of antibodies to human T-cell lymphotropic virus-I tax in patients with the cutaneous T-cell lymphoma, mycosis fungoides, who are seronegative for antibodies to the structural proteins of the virus

Although most patients with the cutaneous T-cell lymphoma, mycosis fungoides (MF), are seronegative for human T-cell lymphotropic virus-I or -II (HTLV-I/II) when tested by assays that measure only antibodies to the viral structural proteins, the majority of such patients harbor HTLV-I-related pol and tax proviral sequences that encode proteins not included in routinely used serologic tests. Tax mRNA has also been detected in their peripheral blood mononuclear cells (PBMC). Therefore, it seemed possible that these patients have antibodies to the tax protein. To investigate this, enzyme-linked immunosorbent assays (ELI- SAs) and Western blot assays were set up, using as antigens the full- length HTLV-I tax cloned from the prototypic HTLV-I-infected cell line, C91PL, and from PBMC of a MF patient, as well as a synthetic peptide made to the carboxy-terminal 20 amino acids of tax-I. Of 60 MF patients whose PBMC were shown to be positive for tax proviral DNA and mRNA, 50 (83%) were shown to have tax antibodies. The antigen derived from the MF patient was most useful in detecting such antibodies. These results demonstrate the need for including other HTLV-related antigens in addition to gag and env in serologic tests used to identify HTLV- infected individuals. The findings underscore the fact that individuals considered seronegative on the basis of currently used tests can be infected with HTLV.     

In vivo imaging of pituitary tumours using a radiolabelled dopamine D2 receptor radioligand

OBJECTIVE Knowledge of the dopamine D2 receptor status of pituitary tumours may play a predictive role in differential diagnosis and therapeutic decisions. This study was performed to evaluate the value of pituitary dopamine D2 receptor scintigraphy with (S)-2-hydroxy-3-¹²³I-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide (¹²³I-IBZM) in the diagnostic evaluation of patients with pituitary tumours. DESIGN AND PATIENTS Scintigraphy using ¹²³I-IBZM was performed in 5 patients with PRL-secreting macroadenomas, 2 patients with PRL-secreting microadenomas, 17 patients with clinically non- functioning pituitary adenomas (NFPAs), 12 patients with GH-secreting adenomas and 1 patient with a TSH-secreting macroadenoma. RESULTS Single-photon emission tomography (SPECT) showed significant uptake of ¹²³I-IBZM in the pituitary region in 3/5 macroprolactinoma patients. These results closely correlated with the response of plasma PRL levels to the dopamine D2 receptor agonist quinagolide. In two scan-positive prolactinoma patients, repeated SPECTs during therapy with quinagolide showed a reduction in the pituitary uptake of ¹²³I-IBZM. Pituitary SPECT was negative in the 2 microprolactinoma patients, who responded to quinagolide administration. In 4/17 patients with NFPA, significant uptake of the radioligand in the pituitary region was observed. In 2/3 scan-positive NFPA patients, who were treated with quinagolide, shrinkage of the pituitary tumours was observed. Treatment with quinagolide resulted in stabilization of tumour growth in the other scan- positive patients. Four out of 17 patients with NFPA and a negative SPECT were treated with quinagolide. Tumour growth was observed in 1 patient, and tumour size did not change in the other 3 patients. The pituitary region of none of the 12 acromegaly patients showed significant uptake of ¹²³I-IBZM. Sensitivity of the GH-secreting adenomas to quinagolide was demonstrated in 8/12 patients in vivo by an acute test, and in 6/9 of the tumours in vitro. Pituitary SPECT was negative in the patient with the TSH-secreting macroadenoma and this tumour also showed no sensitivity to quinagolide in vivo or in vitro. CONCLUSIONS We conclude that ¹²³I-IBZM is a ligand for in vivo imaging of dopamine agonist- sensitive macroprolactinomas, but not for microprolactinomas or GH-secreting adenomas. The technique potentially provides a means of predicting the dopamine agonist-responses of non-functioning pituitary adenomas in vivo.     

Dopamine modulates reward system activity during subconscious processing of sexual stimuli

Dopaminergic medication influences conscious processing of rewarding stimuli, and is associated with impulsive-compulsive behaviors, such as hypersexuality. Previous studies have shown that subconscious subliminal presentation of sexual stimuli activates brain areas known to be part of the 'reward system'. In this study, it was hypothesized that dopamine modulates activation in key areas of the reward system, such as the nucleus accumbens, during subconscious processing of sexual stimuli. Young healthy males (n=53) were randomly assigned to two experimental groups or a control group, and were administered a dopamine antagonist (haloperidol), a dopamine agonist (levodopa), or placebo. Brain activation was assessed during a backward-masking task with subliminally presented sexual stimuli. Results showed that levodopa significantly enhanced the activation in the nucleus accumbens and dorsal anterior cingulate when subliminal sexual stimuli were shown, whereas haloperidol decreased activations in those areas. Dopamine thus enhances activations in regions thought to regulate 'wanting' in response to potentially rewarding sexual stimuli that are not consciously perceived. This running start of the reward system might explain the pull of rewards in individuals with compulsive reward-seeking behaviors such as hypersexuality and patients who receive dopaminergic medication.