Sepsis is a deadly and debilitating condition resulting from a hyperinflammatory response to infection. Most organ systems are severely impacted, including the neurological complications for survivors of sepsis. Sepsis associated encephalopathy (SAE) is characterized by dysregulated molecular pathways of the immune response impinging upon normal central nervous system (CNS) function and ultimately resulting in lasting cognitive and behavioral impairments. Sepsis predominantly occurs in a few neonates but mostly elderly individuals where they are at high risk of sepsis-induced delirium and other neurological implications that may have overlap with neurodegenerative diseases. This study seeks to identify gene candidates that exhibit altered transcriptional expression in tissues between pigs injected with saline control vs lipopolysaccharide (LPS) to model the early inflammatory aspects of the septic response. Specifically, brain frontal cortex was examined to see which genes and pathways are altered at these early stages and could be targeted for further investigation to alter the cognitive/behavioral decline seen in sepsis survivors. This experiment uses a bulk RNA-seq approach on Yorkshire pigs to identify the variance in gene expression profile. Data analysis showed several gene candidates that were downregulated in the brain in response to LPS that point to early endothelial cell disruption, including OCLN (occludin), SLC19A3 (thiamine transporter), and SLC52A3 (riboflavin transporter). Genes that were upregulated in LPS brain samples implicate endothelial cell dysfunction as well as immune/inflammatory alterations, possibly due to alterations in microglia, the primary immune cell of the brain. Several studies are now underway to understand the cellular origin of these transcriptional changes, as well as analyzing the molecular signatures altered in response to sepsis in whole blood and kidney using bulk RNAseq. In conclusion, specific gene candidates were identified as early changes in the septic brain that could be targets to prevent long-term cognitive and behavioral changes in future studies, establishing a baseline panel to interrogate in animal models with the goal of advancing treatments for human patients who experience sepsis.

In the study of the human brain’s ability to multitask, there are two perspectives: concurrent multitasking (performing multiple tasks simultaneously) and sequential multitasking (switching between tasks). The goal of this study is to investigate the human brain’s ability to “multitask” with multiple demanding stimuli of approximately equal concentration, from an electrophysiological perspective different than that of stimuli which don’t require full attention or exhibit impulsive multitasking responses. This study investigates the P3 component which has been experimentally proven to be associated with mental workload through information processing and cognitive function in visual and auditory tasks, where in the multitasking domain the greater attention elicited, the larger P3 waves are produced. This experiment compares the amplitude of the P3 component of individual stimulus presentation to that of multitasking trials, taking note of the brain workload. This study questions if the average wave amplitude in a multitasking ERP experiment will be the same as the grand average when performing the two tasks individually with respect to the P3 component. The hypothesis is that the P3 amplitude will be smaller in the multitasking trial than in the individual stimulus presentation, indicating that the brain is not actually concentrating on both tasks at once (sequential multitasking instead of concurrent) and that the brain is not focusing on each stimulus to the same degree when it was presented individually. Twenty undergraduate students at Barrett, the Honors College at Arizona State University (10 males and 10 females, with a mean age of 18.75 years, SD= 1.517) right handed, with normal or corrected visual acuity, English as first language, and no evidence of neurological compromise participated in the study. The experiment results revealed that one- hundred percent of participants undergo sequential multitasking in the presence of two demanding stimuli in the electrophysiological data, behavioral data, and subjective data. In this particular study, these findings indicate that the presence of additional demanding stimuli causes the workload of the brain to decrease as attention deviates in a bottleneck process to the multiple requisitions for focus, indicated by a reduced P3 voltage amplitude with the multitasking stimuli when compared to the independent. This study illustrates the feasible replication of P3 cognitive workload results for demanding stimuli, not only impulsive-response experiments, to suggest the brain’s tendency to undergo sequential multitasking when faced with multiple demanding stimuli. In brief, this study demonstrates that when higher cognitive processing is required to interpret and respond to the stimuli, the human brain results to sequential multitasking (task- switching, not concurrent multitasking) in the face of more challenging problems with each stimulus requiring a higher level of focus, workload, and attention.