Reorganisation of Brain Hubs across Altered States of Consciousness.

Patterns of functional interactions across distributed brain regions are suggested to provide a scaffold for the conscious processing of information, with marked topological alterations observed in loss of consciousness. However, establishing a firm link between macro-scale brain network organisation and conscious cognition requires direct investigations into neuropsychologically-relevant architectural modifications across systematic reductions in consciousness. Here we assessed both global and regional disturbances to brain graphs in a group of healthy participants across baseline resting state fMRI as well as two distinct levels of propofol-induced sedation. We found a persistent modular architecture, yet significant reorganisation of brain hubs that formed parts of a wider rich-club collective. Furthermore, the reduction in the strength of rich-club connectivity was significantly associated with the participants' performance in a semantic judgment task, indicating the importance of this higher-order topological feature for conscious cognition. These results highlight a remarkable interplay between global and regional properties of brain functional interactions in supporting conscious cognition that is relevant to our understanding of clinical disorders of consciousness.

Left dorsolateral prefrontal cortex supports context-dependent prioritisation of off-task thought.

When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when 'on-task' under demanding conditions and 'off-task' in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC.

Angular default mode network connectivity across working memory load.

Initially identified during no-task, baseline conditions, it has now been suggested that the default mode network (DMN) engages during a variety of working memory paradigms through its flexible interactions with other large-scale brain networks. Nevertheless, its contribution to whole-brain connectivity dynamics across increasing working memory load has not been explicitly assessed. The aim of our study was to determine which DMN hubs relate to working memory task performance during an fMRI-based n-back paradigm with parametric increases in difficulty. Using a voxel-wise metric, termed the intrinsic connectivity contrast (ICC), we found that the bilateral angular gyri (core DMN hubs) displayed the greatest change in global connectivity across three levels of n-back task load. Subsequent seed-based functional connectivity analysis revealed that the angular DMN regions robustly interact with other large-scale brain networks, suggesting a potential involvement in the global integration of information. Further support for this hypothesis comes from the significant correlations we found between angular gyri connectivity and reaction times to correct responses. The implication from our study is that the DMN is actively involved during the n-back task and thus plays an important role related to working memory, with its core angular regions contributing to the changes in global brain connectivity in response to increasing environmental demands. Hum Brain Mapp 38:41-52, 2017. © 2016 Wiley Periodicals, Inc.

Do obesity and age effect the clinicopathological features and survival outcomes in premenopausal women with endometrial cancer?

PURPOSE: The purpose of this study was to review the effect of age and body mass index (BMI) on the prognosis, demographic characteristics, and pathological features of patients diagnosed with endometrial cancer, specifically before menopause. MATERIALS AND METHODS: Patients that were diagnosed with endometrial cancer before menopause, were screened retrospectively. Between 1999 and 2011, 163 patients were identified while 40 were excluded. Patients were classified into three groups according to age (under 40 years, between 40-45 years, more than 45 years) and BMI (normal weight group, overweight group, and obese weight group). Demographical characteristics, histopathological features (Stage, grade and histology of the tumor, the presence of myometrial and/or lymphovascular invasion, history of diabetes mellitus, history of hypertension, hormonal contraception method, smoking, parity, infertility, family history, and recurrences) and survival rates were compared among the groups. RESULTS: In total, 123 patients with a mean of 65.0 months follow up were enrolled into the study. The majority of the patients had endometrioid type in all age-related subgroups. Advanced stage endometrium cancer (Stage 2 and greater) was seen more commonly in the group of patient over 45 years of age against the other age-related subgroups (27.9% vs. 8% vs. 3.3%). Ratio of myometrial invasion more than 50% and occurrence of well-differentiated tumor were seen with a similar ratio among the age-related subgroups. Ratio of nulliparity and infertility were found statistically significant in the group of patients under 45 years of age against the group of patients over 45 years of age (p = 0.001, p = 0.03). The five-year estimated disease-free survival rates of women under 40 years of, women with an age between 40-45 years, and women over the age of 45 years were calculated as 73%, 95%, and 87%, respectively (p = 0.152). Concerning the histopathological features, there were no statistical differences between weight related subgroups. Comorbid conditions (hypertension and diabetes mellitus) were found as statistically high in the obese patients' group (43.5%-25.8%). In contrast to comorbid conditions, nulliparity and infertility histories were observed more often within the normal weight group (55.6%-38.5%). Mean disease-free survival time was calculated as 155.81 months in the normal weight group; 114.691 months in the overweight group, and 144.677 months in the obese group. Five-year disease-free survival rate was calculated as 91%, 81%, and 87%, respectively (p = 0.452). CONCLUSION: Women with premenopausal cancers generally exhibit early and favorable histopathological symptoms. Although advanced stage endometrium cancer incidence was detected to be higher in the premenopausal endometrium cancer patients aged above 45 years compared to other age subgroups. A significant difference in terms of survival rates between these groups was not reached. In the same manner, the authors did not find a significant difference in survival rates among different weight subgroups of premenopausal endometrium cancer patients. As a secondary result, the authors discovered that diabetes mellitus and hypertension play a key role in patients with a BMI above 30 kg/m2 and nulliparity and infertility play a key role in patients with a BMI below 25 kg/m2 in the development of premenopausal endometrial cancer.

Default mode network connectivity during task execution.

Initially described as task-induced deactivations during goal-directed paradigms of high attentional load, the unresolved functionality of default mode regions has long been assumed to interfere with task performance. However, recent evidence suggests a potential default mode network involvement in fulfilling cognitive demands. We tested this hypothesis in a finger opposition paradigm with task and fixation periods which we compared with an independent resting state scan using functional magnetic resonance imaging and a comprehensive analysis pipeline including activation, functional connectivity, behavioural and graph theoretical assessments. The results indicate task specific changes in the default mode network topography. Behaviourally, we show that increased connectivity of the posterior cingulate cortex with the left superior frontal gyrus predicts faster reaction times. Moreover, interactive and dynamic reconfiguration of the default mode network regions' functional connections illustrates their involvement with the task at hand with higher-level global parallel processing power, yet preserved small-world architecture in comparison with rest. These findings demonstrate that the default mode network does not disengage during this paradigm, but instead may be involved in task relevant processing.