Temporal order memory, or remembering the order of events, is critical for everyday functioning and is difficult for patients with mild cognitive impairment (MCI). It is currently unclear whether these patients have difficulty acquiring and/or retaining such information and whether deficits in these patients are in excess of “normal” age-related declines. Therefore, the current study examined age and disease-related changes in temporal order memory as well as whether memory load played a role in such changes. Young controls (n=25), older controls (n=34), and MCI patients (n=32) completed an experimental task that required the reconstruction of sequences that were 3, 4, or 5-items in length both immediately after presentation (i.e., immediate recall) and again following a 10-minute delay (i.e., delayed recall). During the immediate recall phase, there was an effect of age largely due to reduced performance at the two longest span lengths. Older controls and MCI patients only differed during the 5 span (controls > MCI). During the delayed recall, however, there were significant effects of both age and MCI regardless of span length. In MCI patients, immediate recall was significantly correlated with measures of executive functioning while delayed recall performance was only related to other memory tests. These findings suggest that MCI patients experience initial temporal order memory deficits at the point when information begins to exceed working memory capacity and become dependent on medial temporal lobe functioning. Longer-term deficits are due to an inability to retain information, consistent with the characteristic medial temporal lobe dysfunction in MCI.

Musical improvisation offers an excellent experimental paradigm for the study of real-time human creativity. It involves moment-to-moment decision-making, monitoring of one's performance, and utilizing external feedback to spontaneously create new melodies or variations on a melody. Recent neuroimaging studies have begun to study the brain activity during musical improvisation, aiming to unlock the mystery of human creativity. What brain resources come together and how these are utilized during musical improvisation are not well understood. To help answer these questions, we recorded electroencephalography (EEG) signals from 19 experienced musicians while they played or imagined short isochronous learned melodies and improvised on those learned melodies. These four conditions (Play-Prelearned, Play-Improvised, Imagine-Prelearned, Imagine-Improvised) were randomly interspersed in a total of 300 trials per participant. From the sensor-level EEG, we found that there were power differences in the alpha (8-12 Hz) and beta (13-30 Hz) bands in separate clusters of frontal, parietal, temporal, and occipital electrodes. Using EEG source localization and dipole modeling methods for task-related signals, we identified the locations and network activities of five sources: the left superior frontal gyrus (L SFG), supplementary motor area (SMA), left inferior parietal lobule (L IPL), right dorsolateral prefrontal cortex, and right superior temporal gyrus. During improvisation, the network activity between L SFG, SMA, and L IPL was significantly less than during the prelearned conditions. Our results support the general idea that attenuated cognitive control facilitates the production of creative output.

A brief (approximately 60 min) exposure to isoflurane general anesthesia, without induced surgical stress, significantly increased serum IL-1β, a selective activation marker of systemic inflammation (IL-1β pathway).

Early insults associated with cardiac transplantation increase the immunogenicity of donor microvascular endothelial cells (ECs), which interact with recipient alloreactive memory T cells and promote responses leading to allograft rejection. Thus, modulating EC immunogenicity could potentially alter T cell responses. Recent studies have shown modulating mitochondrial fusion/fission alters immune cell phenotype. Here, we assess whether modulating mitochondrial fusion/fission reduces EC immunogenicity and alters EC‐T cell interactions. By knocking down DRP1, a mitochondrial fission protein, or by using the small molecules M1, a fusion promoter, and Mdivi1, a fission inhibitor, we demonstrate that promoting mitochondrial fusion reduced EC immunogenicity to allogeneic CD8+ T cells, shown by decreased T cell cytotoxic proteins, decreased EC VCAM‐1, MHC‐I expression, and increased PD‐L1 expression. Co‐cultured T cells also displayed decreased memory frequencies and Ki‐67 proliferative index. For in vivo significance, we used a novel murine brain‐dead donor transplant model. Balb/c hearts pretreated with M1/Mdivi1 after brain‐death induction were heterotopically transplanted into C57BL/6 recipients. We demonstrate that, in line with our in vitro studies, M1/Mdivi1 pretreatment protected cardiac allografts from injury, decreased infiltrating T cell production of cytotoxic proteins, and prolonged allograft survival. Collectively, our data show promoting mitochondrial fusion in donor ECs mitigates recipient T cell responses and leads to significantly improved cardiac transplant survival.

Despite rapid advances in the field of immunotherapy, the elimination of established tumors has not been achieved. Many promising new treatments such as adoptive cell therapy (ACT) fall short, primarily due to the loss of T cell effector function or the failure of long-term T cell persistence. With the availability of new tools and advancements in technology, our understanding of metabolic processes has increased enormously in the last decade. Redundancy in metabolic pathways and overlapping targets that could address the plasticity and heterogenous phenotypes of various T cell subsets have illuminated the need for understanding immunometabolism in the context of multiple disease states, including cancer immunology. Herein, we discuss the developing field of T cell immunometabolism and its crucial relevance to improving immunotherapeutic approaches. This in-depth review details the metabolic pathways and preferences of the antitumor immune system and the state of various metabolism-targeting therapeutic approaches.