Aerobic fitness associates with mnemonic discrimination as a mediator of physical activity effects: evidence for memory flexibility in young adults

A physically active lifestyle has beneficial effects on hippocampal memory function. A potential mechanism for this effect is exercise-enhanced hippocampal plasticity, particularly in the dentate gyrus (DG). Within hippocampal memory formation, the DG plays a crucial role in pattern separation, which is the ability to discriminate among similar experiences. Computational models propose a theoretical hypothesis that enhanced DG-mediated pattern separation leads to “memory flexibility”–a selective improvement in the ability to overcome moderate levels of mnemonic interference. Thus, in the current cross-sectional study of healthy young adults, we tested the working hypothesis that aerobic fitness, as a physiological indicator of endurance capacity associated with physical activity, is strongly associated with mnemonic discrimination at moderate interference levels. When divided the sample (n = 75) based on a median split of aerobic fitness, the higher fitness group had better discrimination performance for moderate interference levels compared to the lower fitness group, namely, exhibited memory flexibility. Moreover, aerobic fitness levels were positively associated with discrimination performance for moderate interference levels, as a mediator of physical activity effects. This evidence suggests that aerobic fitness levels are associated with hippocampal DG-related memory, which is consistent with literature showing positive effect of physical exercise on hippocampal memory

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Action Postponing and Restraint Varies among Sensory Modalities

Proactive inhibition is divided into two components: action postponing (AP), which refers to slowing the onset of response, and action restraint (AR), which refers to preventing the response. To date, several studies have reported alterations in proactive inhibition and its associated neural processing among sensory modalities; however, this remains inconclusive owing to several methodological issues. This study aimed to clarify the differences in AP and AR and their neural processing among visual, auditory, and somatosensory modalities using an appropriate experimental paradigm that can assess AP and AR separately. The postponing time calculated by subtracting simple reaction time from Go signal reaction time was shorter in the visual modality than in the other modalities. This was explained by faster neural processing for conflict monitoring induced by anticipating the presence of the No-go signal, supported by the shorter latency of AP-related N2. Furthermore, the percentage of false alarms, which is the reaction to No-go signals, was lower in the visual modality than in the auditory modality. This was attributed to higher neural resources for conflict monitoring induced by the presence of No-go signals, supported by the larger amplitudes of AR-related N2. Our findings revealed the differences in AP and AR and their neural processing among sensory modalities

The Effects of Acute Virtual Reality Exergaming on Mood and Executive Function: Exploratory Crossover Trial

BackgroundVirtual reality (VR) exergaming is a new intervention strategy to help humans engage in physical activity to enhance mood. VR exergaming may improve both mood and executive function by acting on the prefrontal cortex, expanding the potential benefits. However, the impact of VR exergaming on executive function has not been fully investigated, and associated intervention strategies have not yet been established. ObjectiveThis study aims to investigate the effects of 10 minutes of VR exergaming on mood and executive function. MethodsA total of 12 participants played the exergame “FitXR” under 3 conditions: (1) a VR exergame condition (ie, exercise with a head-mounted display condition [VR-EX]) in which they played using a head-mounted display, (2) playing the exergame in front of a flat display (2D-EX), and (3) a resting condition in which they sat in a chair. The color-word Stroop task (CWST), which assesses executive function; the short form of the Profile of Mood States second edition (POMS2); and the short form of the Two-Dimensional Mood Scale (TDMS), which assess mood, were administered before and after the exercise or rest conditions. ResultsThe VR-EX condition increased the POMS2 vigor activity score (rest and VR-EX: t11=3.69, P=.003) as well as the TDMS arousal (rest vs 2D-EX: t11=5.34, P<.001; rest vs VR-EX: t11=5.99, P<.001; 2D-EX vs VR-EX: t11=3.02, P=.01) and vitality scores (rest vs 2D-EX: t11=3.74, P=.007; rest vs VR-EX: t11=4.84, P=.002; 2D-EX vs VR-EX: t11=3.53, P=.006), suggesting that VR exergaming enhanced mood. Conversely, there was no effect on CWST performance in either the 2D-EX or VR-EX conditions. Interestingly, the VR-EX condition showed a significant positive correlation between changes in CWST arousal and reaction time (r=0.58, P=.046). This suggests that the effect of exergaming on improving executive function may disappear under an excessively increased arousal level in VR exergaming. ConclusionsOur findings showed that 10 minutes of VR exergaming enhanced mood but did not affect executive function. This suggests that some VR content may increase cognitive demands, leading to psychological fatigue and cognitive decline as an individual approaches the limits of available attentional capacity. Future research must examine the combination of exercise and VR that enhances both brain function and mood

Hair cortisol concentration is associated with executive function in female college football players

Chronic stress in athletes can diminish brain functions and mental health which can potentially affect health and sports performance. However, its influences on mental health and executive function remain unknown. This study examined the effects of chronic stress change on mental health and executive function in college female football players by analyzing hair cortisol concentration (HCC) as a chronic stress indicator. Measurements were taken in August and December, just before the Japan college national tournament. The results indicated a positive correlation trend between HCC and self-reported training load, suggesting a potential HCC decrease in athletes with reduced training load before the December competition. A significant negative correlation existed between changes in HCC and spatial Stroop task reaction time, indicating that as HCC decreased, executive function also decreased. These findings suggest that an excessively reduced training load may decrease executive function during fatigue recovery before competitions. This study implies that HCC could serve as a physiological training plan evaluation index

The Effects of Acute Virtual Reality Exergaming on Mood and Executive Function: Exploratory Crossover Trial

application/pdfBackground: Virtual reality (VR) exergaming is a new intervention strategy to help humans engage in physical activity to enhance mood. VR exergaming may improve both mood and executive function by acting on the prefrontal cortex, expanding the potential benefits. However, the impact of VR exergaming on executive function has not been fully investigated, and associated intervention strategies have not yet been established. Objective: This study aims to investigate the effects of 10 minutes of VR exergaming on mood and executive function. Methods: A total of 12 participants played the exergame “FitXR” under 3 conditions: (1) a VR exergame condition (ie, exercise with a head-mounted display condition [VR-EX]) in which they played using a head-mounted display, (2) playing the exergame in front of a flat display (2D-EX), and (3) a resting condition in which they sat in a chair. The color-word Stroop task (CWST), which assesses executive function; the short form of the Profile of Mood States second edition (POMS2); and the short form of the Two-Dimensional Mood Scale (TDMS), which assess mood, were administered before and after the exercise or rest conditions. Results: The VR-EX condition increased the POMS2 vigor activity score (rest and VR-EX: t11=3.69, P=.003) as well as the TDMS arousal (rest vs 2D-EX: t11=5.34, P<.001; rest vs VR-EX: t11=5.99, P<.001; 2D-EX vs VR-EX: t11=3.02, P=.01) and vitality scores (rest vs 2D-EX: t11=3.74, P=.007; rest vs VR-EX: t11=4.84, P=.002; 2D-EX vs VR-EX: t11=3.53, P=.006), suggesting that VR exergaming enhanced mood. Conversely, there was no effect on CWST performance in either the 2D-EX or VR-EX conditions. Interestingly, the VR-EX condition showed a significant positive correlation between changes in CWST arousal and reaction time (r=0.58, P=.046). This suggests that the effect of exergaming on improving executive function may disappear under an excessively increased arousal level in VR exergaming. Conclusions: Our findings showed that 10 minutes of VR exergaming enhanced mood but did not affect executive function. This suggests that some VR content may increase cognitive demands, leading to psychological fatigue and cognitive decline as an individual approaches the limits of available attentional capacity. Future research must examine the combination of exercise and VR that enhances both brain function and mood

Cognitive fatigue due to exercise under normobaric hypoxia is related to hypoxemia during exercise

application/pdfWe previously found that a 10-min bout of moderate-intensity exercise (50% maximal oxygen uptake) under normobaric and hypoxic conditions (fraction of inspired oxygen [ FIO2] = 0.135) reduced executive performance and neural activity in the left dorsolateral prefrontal cortex (DLPFC). To examine whether this cognitive fatigue is due to a decrease in SpO2 during exercise, we compared executive performance and related prefrontal activation between two experimental conditions, in which the participants inhaled normobaric hypoxic gas ( FIO2= 0.135) (hypoxic exercise [HE]) or hypoxic gas adjusted so that SpO2 during exercise remained at the resting level (milder hypoxic exercise [ME]). ME condition showed that reaction time in executive performance decreased (t[13] = 2.228, P < 0.05, d = 0.34, paired t-test) and left DLPFC activity increased (t[13] = -2.376, P < 0.05, d = 0.63, paired t-test) after exercise compared with HE condition. These results showed that the HE-induced reductions in the left DLPFC activity and executive performance were both suppressed in the ME condition, supporting the hypothesis that exercise-induced cognitive fatigue under hypoxic environment is due to hypoxemia during exercise. This may lead to the development of a method of coping with cognitive fatigue due to exercise that causes hypoxemia

Positive Mood while Exercising Influences Beneficial Effects of Exercise with Music on Prefrontal Executive Function: A Functional NIRS Study

Much attention has been focused on physical exercise benefits to mental health such as mood and cognitive function. Our recent studies have consistently shown that a single bout of exercise elicits increased task-related brain activation mainly in the dorsolateral part of the prefrontal cortex (DLPFC), which results in improved executive performance. As the DLPFC is associated with the modulation of mood as well as executive function, it is tempting to hypothesize that exercising while in a positive mood would facilitate the beneficial effects of exercise on executive function via DLPFC activation. Thus, we conceived an experiment that used music to elicit a positive mood during exercise. Thirty-three young adults performed ten minutes of moderate-intensity (50% V.Opeak) pedaling exercise with two experimental conditions: listening to music and listening to beeps at a steady tempo. Mood and executive function were respectively assessed using the Two-Dimensional Mood Scale and a color-word-matching Stroop task before and after the exercise sessions. Prefrontal activation during the Stroop task was monitored using functional near-infrared spectroscopy. Exercise with music elicited greater enhancement of a positive mood (vitality) than did exercise with beeps. Contrary to our hypothesis, there were no significant differences between conditions in improvement in Stroop task performance and task-related cortical activation in the left-DLPFC. The correlation analyses, however, revealed significant correlations among increased vitality, shortened Stroop interference time and increased activation in the left-DLPFC. These results support the hypothesis that positive mood while exercising influences the benefit of exercise on prefrontal activation and executive performance

Transcranial high-frequency random noise stimulation does not modulate Nogo N2 and Go/Nogo reaction times in somatosensory and auditory modalities

application/pdfTranscranial random noise stimulation (tRNS) of the primary sensory or motor cortex can improve sensorimotor functions by enhancing circuit excitability and processing fidelity. However, tRNS is reported to have little effect on higher brain functions, such as response inhibition when applied to associated supramodal regions. These discrepancies suggest differential effects of tRNS on the excitability of the primary and supramodal cortex, although this has not been directly demonstrated. This study examined the effects of tRNS on supramodal brain regions on somatosensory and auditory Go/Nogo task performance, a measure of inhibitory executive function, while simultaneously recording event-related potentials (ERPs). Sixteen participants received sham or tRNS stimulation of the dorsolateral prefrontal cortex in a single-blind crossover design study. Neither sham nor tRNS altered somatosensory and auditory Nogo N2 amplitudes, Go/Nogo reaction times, or commission error rates. The results suggest that current tRNS protocols are less effective at modulating neural activity in higher-order cortical regions than in the primary sensory and motor cortex. Further studies are required to identify tRNS protocols that effectively modulate the supramodal cortex for cognitive enhancement