Growing evidence suggests that healthy aging affects the configuration of large-scale functional brain networks. This includes reducing network modularity and local efficiency. However, the stability of these effects over time and their potential role in learning remain poorly understood. The goal of the present study was to further clarify previously reported age effects on “resting-state” networks, to test their reliability over time, and to assess their relation to subsequent learning during training. Resting-state fMRI data from 23 young (YA) and 20 older adults (OA) were acquired in 2 sessions 2 weeks apart. Graph-theoretic analyses identified both consistencies in network structure and differences in module composition between YA and OA, suggesting topological changes and less stability of functional network configuration with aging. Brain-wide, OA showed lower modularity and local efficiency compared to YA, consistent with the idea of age-related functional dedifferentiation, and these effects were replicable over time. At the level of individual networks, OA consistently showed greater participation and lower local efficiency and within-network connectivity in the cingulo-opercular network, as well as lower intra-network connectivity in the default-mode network and greater participation of the somato-sensorimotor network, suggesting age-related differential effects at the level of specialized brain modules. Finally, brain-wide network properties showed associations, albeit limited, with learning rates, as assessed with 10 days of computerized working memory training administered after the resting-state sessions, suggesting that baseline network configuration may influence subsequent learning outcomes. Identification of neural mechanisms associated with learning-induced plasticity is important for further clarifying whether and how such changes predict the magnitude and maintenance of training gains, as well as the extent and limits of cognitive transfer in both younger and older adults.

Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials.

Background: Spaceflight has been associated with changes in gait and balance; it is unclear whether it affects cognition. Head down tilt bed rest (HDBR) is a microgravity analog that mimics cephalad fluid shifts and body unloading. In consideration of astronaut’s health and mission success, we investigated the effects of HDBR on cognition and sensorimotor function. Furthermore, we investigated if exercise mitigates any cognitive and sensorimotor sequelae of spaceflight.Method: We conducted a 70-day six-degree HDBR study in 10 male subjects who were randomly assigned to a HDBR supine exercise or a HDBR control group. Cognitive measures (i.e., processing speed, manual dexterity, psychomotor speed, visual dependency, and 2D and 3D mental rotation) and sensorimotor performance (functional mobility (FMT) and balance performance) were collected at 12 and 8 days pre-HDBR, at 7, 50, and 70 days in HDBR, and at 8 and 12 days post-HDBR. Exercise comprised resistance training, and continuous and high-intensity interval aerobic exercise. We also repeatedly assessed an outside-of-bed rest control group to examine metric stability.Results: Small practice effects were observed in the control group for some tasks; these were taken into account when analyzing effects of HDBR. No significant effects of HDBR on cognition were observed, although visual dependency during HDBR remained stable in HDBR controls whereas it decreased in HDBR exercise subjects. Furthermore, HDBR was associated with loss of FMT and standing balance performance, which were almost fully recovered 12 days post-HDBR. Aerobic and resistance exercise partially mitigated the effects of HDBR on FMT and accelerated the recovery time course post-HDBR.Discussion: HDBR did not significantly affect cognitive performance but did adversely affect FMT and standing balance performance. Exercise had some protective effects on the deterioration and recovery of FMT.

No abstract