Functional and Structural Network Recovery after Mild Traumatic Brain Injury: A 1-Year Longitudinal Study.

Brain connectivity after mild traumatic brain injury (mTBI) has not been investigated longitudinally with respect to both functional and structural networks together within the same patients, crucial to capture the multifaceted neuropathology of the injury and to comprehensively monitor the course of recovery and compensatory reorganizations at macro-level. We performed a prospective study with 49 mTBI patients at an average of 5 days and 1 year post-injury and 49 healthy controls. Neuropsychological assessments as well as resting-state functional and diffusion-weighted magnetic resonance imaging were obtained. Functional and structural connectome analyses were performed using network-based statistics. They included a cross-sectional group comparison and a longitudinal analysis with the factors group and time. The latter tracked the subnetworks altered at the early phase and, in addition, included a whole-brain group × time interaction analysis. Finally, we explored associations between the evolution of connectivity and changes in cognitive performance. The early phase of mTBI was characterized by a functional hypoconnectivity in a subnetwork with a large overlap of regions involved within the classical default mode network. In addition, structural hyperconnectivity in a subnetwork including central hub areas such as the cingulate cortex was found. The impaired functional and structural subnetworks were strongly correlated and revealed a large anatomical overlap. One year after trauma and compared to healthy controls we observed a partial normalization of both subnetworks along with a considerable compensation of functional and structural connectivity subsequent to the acute phase. Connectivity changes over time were correlated with improvements in working memory, divided attention, and verbal recall. Neuroplasticity-induced recovery or compensatory processes following mTBI differ between brain regions with respect to their time course and are not fully completed 1 year after trauma.

Expertise-related functional brain network efficiency in healthy older adults.

BACKGROUND: In view of age-related brain changes, identifying factors that are associated with healthy aging are of great interest. In the present study, we compared the functional brain network characteristics of three groups of healthy older participants aged 61-75 years who had a different cognitive and motor training history (multi-domain group: participants who had participated in a multi-domain training; visuomotor group: participants who had participated in a visuomotor training; control group: participants with no specific training history). The study's basic idea was to examine whether these different training histories are associated with differences in behavioral performance as well as with task-related functional brain network characteristics. Based on a high-density electroencephalographic measurement one year after training, we calculated graph-theoretical measures representing the efficiency of functional brain networks. RESULTS: Behaviorally, the multi-domain group performed significantly better than the visuomotor and the control groups on a multi-domain task including an inhibition domain, a visuomotor domain, and a spatial navigation domain. In terms of the functional brain network features, the multi-domain group showed significantly higher functional connectivity in a network encompassing visual, motor, executive, and memory-associated brain areas in the theta frequency band compared to the visuomotor group. These brain areas corresponded to the multi-domain task demands. Furthermore, mean connectivity of this network correlated positively with performance across both the multi-domain and the visuomotor group. In addition, the multi-domain group showed significantly enhanced processing efficiency reflected by a higher mean weighted node degree (strength) of the network as compared to the visuomotor group. CONCLUSIONS: Taken together, our study shows expertise-dependent differences in task-related functional brain networks. These network differences were evident even a year after the acquisition of the different expertise levels. Hence, the current findings can foster understanding of how expertise is positively associated with brain functioning during aging.

Strength of Structural and Functional Frontostriatal Connectivity Predicts Self-Control in the Healthy Elderly.

Self-regulation refers to the successful use of executive functions and initiation of top-down processes to control one's thoughts, behavior, and emotions, and it is crucial to perform self-control. Self-control is needed to overcome impulses and can be assessed by delay of gratification (DoG) and delay discounting (DD) paradigms. In children/adolescents, good DoG/DD ability depends on the maturity of frontostriatal connectivity, and its decline in strength with advancing age might adversely affect self-control because prefrontal brain regions are more prone to normal age-related atrophy than other regions. Here, we aimed at highlighting the relationship between frontostriatal connectivity strength and DoG performance in advanced age. We recruited 40 healthy elderly individuals (mean age 74.0 ± 7.7 years) and assessed the DoG ability using the German version of the DoG test for adults in addition to the delay discounting (DD) paradigm. Based on diffusion-weighted and resting-state functional magnetic resonance imaging data, respectively, the structural and functional whole-brain connectome were reconstructed based on 90 different brain regions of interest in addition to a 12-node frontostriatal DoG-specific network and the resulting connectivity matrices were subjected to network-based statistics. The 90-nodes whole-brain connectome analyses revealed subnetworks significantly associated with DoG and DD with a preponderance of frontostriatal nodes involved suggesting a high specificity of the findings. Structural and functional connectivity strengths between the putamen, caudate nucleus, and nucleus accumbens on the one hand and orbitofrontal, dorsal, and ventral lateral prefrontal cortices on the other hand showed strong positive correlations with DoG and negative correlations with DD corrected for age, sex, intracranial volume, and head motion parameters. These associations cannot be explained by differences in impulsivity and executive functioning. This pattern of correlations between structural or functional frontostriatal connectivity strength and self-control suggests that, in addition to the importance of the frontostriatal nodes itself, the structural and functional properties of different connections within the frontostriatal network are crucial for self-controlled behaviors in the healthy elderly. Because high DoG/low DD is a significant predictor of willpower and wellbeing in the elderly population, interventions aiming at strengthening frontostriatal connectivity to strengthen self-controlled behavior are needed in the future.

Epigenetic mechanisms regulate stage differentiation in the minimized protozoan Giardia lamblia.

Histone modification is an important mechanism regulating both gene expression and the establishment and maintenance of cellular phenotypes during development. Regulation of histone acetylation via histone acetylases and deacetylases (HDACs) appears to be particularly crucial in determining gene expression patterns. In this study we explored the effect of HDAC inhibition on the life cycle of the human pathogen Giardia lamblia, a highly reduced parasitic protozoan characterized by minimized cellular processes. We found that the HDAC inhibitor FR235222 increased the level of histone acetylation and induced transcriptional regulation of approximately 2% of genes in proliferating and encysting parasites. In addition, our analyses showed that the levels of histone acetylation decreased during differentiation into cysts, the infective stage of the parasite. Importantly, FR235222 treatment during encystation reversed this histone hypo-acetylation and potently blocked the formation of cysts. These results provide the first direct evidence for epigenetic regulation of gene expression in this simple eukaryote. This suggests that regulation of histone acetylation is involved in the control of Giardia stage differentiation, and identifies epigenetic mechanisms as a promising target to prevent Giardia transmission.

A high-quality catalog of the Drosophila melanogaster proteome.

Understanding how proteins and their complex interaction networks convert the genomic information into a dynamic living organism is a fundamental challenge in biological sciences. As an important step towards understanding the systems biology of a complex eukaryote, we cataloged 63% of the predicted Drosophila melanogaster proteome by detecting 9,124 proteins from 498,000 redundant and 72,281 distinct peptide identifications. This unprecedented high proteome coverage for a complex eukaryote was achieved by combining sample diversity, multidimensional biochemical fractionation and analysis-driven experimentation feedback loops, whereby data collection is guided by statistical analysis of prior data. We show that high-quality proteomics data provide crucial information to amend genome annotation and to confirm many predicted gene models. We also present experimentally identified proteotypic peptides matching approximately 50% of D. melanogaster gene models. This library of proteotypic peptides should enable fast, targeted and quantitative proteomic studies to elucidate the systems biology of this model organism.