Neuroimaging-based functional connectivity (FC) analyses have revealed significant developmental trends in specific intrinsic connectivity networks linked to cognitive and behavioral maturation. However, knowledge of how brain functional maturation is associated with FC dynamics at rest is limited. Here, we examined age-related differences in the temporal variability of FC dynamics with data publicly released by the Nathan Kline Institute (NKI; n = 183, ages 7–30) and showed that dynamic inter-region interactions can be used to accurately predict individual brain maturity across development. Furthermore, we identified a significant age-dependent trend underlying dynamic inter-network FC, including increasing variability of the connections between the visual network, default mode network (DMN) and cerebellum as well as within the cerebellum and DMN and decreasing variability within the cerebellum and between the cerebellum and DMN as well as the cingulo-opercular network. Overall, the results suggested significant developmental changes in dynamic inter-network interaction, which may shed new light on the functional organization of typical developmental brains.

Background-Sustained cardiac pressure overload-induced hypertrophy and pathological remodeling frequently leads to heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) has been identified to be an important regulator of cell proliferation, differentiation, and apoptosis. However, the physiological role of CKIP-1 in the heart is unknown. Methods and Results-The results of echocardiography and histology demonstrate that CKIP-1-deficient mice exhibit spontaneous cardiac hypertrophy with aging and hypersensitivity to pressure overload-induced pathological cardiac hypertrophy, as well. Transgenic mice with cardiac-specific overexpression of CKIP-1 showed resistance to cardiac hypertrophy in response to pressure overload. The results of GST pull-down and coimmunoprecipitation assays showed the interaction between CKIP-1 and histone deacetylase 4 (HDAC4), through which they synergistically inhibited transcriptional activity of myocyte-specific enhancer factor 2C. By directly interacting with the catalytic subunit of phosphatase 2A, CKIP-1 overexpression enhanced the binding of catalytic subunit of phosphatase-2A to HDAC4 and promoted HDAC4 dephosphorylation. Conclusions-CKIP-1 was found to be an inhibitor of cardiac hypertrophy by upregulating the dephosphorylation of HDAC4 through the recruitment of protein phosphatase 2A. These results demonstrated a unique function of CKIP-1, by which it suppresses cardiac hypertrophy through its capacity to regulate HDAC4 dephosphorylation and fetal cardiac genes expression. (Circulation. 2012;126:3028-3040.)Key Words: hypertrophy Ⅲ molecular biology Ⅲ cardiomyopathy Ⅲ heart failure D espite recent treatment advances, heart failure continues to impose a substantial healthcare burden. One of the major risk factors for developing heart failure is preexisting cardiac hypertrophy resulting from pathological stimuli, such as long-standing hypertension or myocardial infarction. 1,2 Among the intracellular signaling pathways involved in the regulation of cardiac hypertrophy, class II histone deacetylases (HDACs) act as signal-responsive repressors by inhibiting the activity of myocyte-specific enhancer factor 2C (MEF2C) in the nucleus. [3][4][5] Dynamic nucleocytoplasmic shuttling has been proposed as one of the most fundamental mechanisms regulating the function of class II HDACs. 4,6,7 Phosphorylation of class II HDACs at specific serine residues after hypertrophic stimulation induces its interaction with 14-3-3, through which the class II HDACs are exported to the cytosol, where they can no longer suppress target transcription factors. 4,8 -10 In the heart, nuclear export of class II HDACs directly elicits activation of myocyte enhancer factor-2 (MEF2), which is a master positive regulator of cardiac hypertrophy. Serine/threonine protein phosphatase 2A (PP2A) could interact with and dephosphorylate HDAC4, thus reinforcing its nuclear accumulation. 11,12 However, little is known about the regulation of HDAC4 dephosphorylation in response to extracellular stimuli leading to car...

Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI) to study whether the functional architecture of the brain is altered after 45 days of −6° head-down tilt (HDT) bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of −6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC), to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC) analysis. We found decreased DC in two regions, the left anterior insula (aINS) and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies), in the male volunteers after 45 days of −6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS–MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function, and central neural activity.

For future interplanetary manned spaceflight, mental issues, as well as physiological problems, must inevitably be considered and solved. Mars500 is a high-fidelity ground simulation experiment that involved 520 days of confined isolation for six multinational crewmembers. This experiment provided a good opportunity to perform psycho-physiological and psycho-social researches on such missions. To investigate emotional responses and psychological adaptation over long-term confinement, the International Affective Pictures System (IAPS) was selected as the visual emotional stimuli in this study. Additional data collected and analyzed included the Profile of Mood States (POMS) questionnaire and the levels of four types of plasma hormones: cortisol, 5-hydroxy tryptamine, dopamine, and norepinephrine. The results demonstrated an obvious bias on valence rating for unpleasant stimuli with time (p<0.05), and the correlation between psychological and biochemical data was identified (p<0.05). Overall, we concluded that the confined crew tended to assign positive ratings to negative pictures with time, which might be driven by a defensive system. There was a stage-changing pattern of psychological adaptation of the Mars500 crew, which is similar to the third-quarter phenomenon.

The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth’s environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.

Prolonged bed rest may cause changes in the autonomic nervous system that are related to cognition and emotion. This study adopted an emotional flanker task to evaluate the effect of 45 days -6° head-down bed rest (HDBR) on executive functioning in 16 healthy young men at each of six time points: the second-to-last day before the bed rest period, the eleventh, twentieth, thirty-second and fortieth day during the bed rest period, and the eighth day after the bed rest period. In addition, self-report inventories (Beck Anxiety Inventory, BAI; Beck Depression Inventory, BDI; Positive Affect and Negative Affect Scale, PANAS) were conducted to record emotional changes, and the participants’ galvanic skin response (GSR), heart rate (HR) and heart rate variability (HRV) were assessed as measures of physiological activity. The results showed that the participants’ reaction time on the flanker task increased significantly relative to their responses on the second-to-last day before the period of bed rest, their galvanic skin response weakened and their degrees of positive affect declined during the bed rest period. Our results provide some evidence for a detrimental effect of prolonged bed rest on executive functioning and positive affect. Whether this stems from a lack of aerobic physical activity and/or the effect of HDBR itself remains to be determined.

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Space is characterized by risk and uncertainty. As humans play an important role in long-duration space missions, the ability to make risky decisions effectively is important for astronauts who spend extended time periods in space. The present study used the Balloon Analog Risk Task to conduct both behavioral and fMRI experiments to evaluate the effects of simulated microgravity on individuals' risk-taking behavior and the neural basis of the effect. The results showed that participants' risk-taking behavior was not affected by bed rest. However, we found that the ventromedial prefrontal cortex (VMPFC) showed less deactivation after bed rest and that the VMPFC activation in the active choice condition showed no significant difference between the win outcome and the loss outcome after bed rest, although its activation was significantly greater in the win outcome than in the loss outcome before bed rest. These results suggested that the participants showed a decreased level of value calculation after the bed rest. Our findings can contribute to a better understanding of the effect of microgravity on individual higher-level cognitive functioning.