The links between physical activity and prosocial behavior: an fNIRS hyperscanning study.

The prevalence of physically inactive lifestyles in modern society raises concerns about the potential association with poor brain health, particularly in the lateral prefrontal cortex, which is crucial for human prosocial behavior. Here, we explored the relationship between physical activity and prosocial behavior, focusing on potential neural markers, including intra-brain functional connectivity and inter-brain synchrony in the lateral prefrontal cortex. Forty participants, each paired with a stranger, completed two experimental conditions in a randomized order: (i) face-to-face and (ii) face stimulus (eye-to-eye contact with a face stimulus of a fictitious person displayed on the screen). Following each condition, participants played economic games with either their partner or an assumed person displayed on the screen. Neural activity in the lateral prefrontal cortex was recorded by functional near-infrared spectroscopy hyperscanning. Sparse multiset canonical correlation analysis showed that a physically inactive lifestyle was covaried with poorer reciprocity, greater trust, shorter decision-making time, and weaker intra-brain connectivity in the dorsal lateral prefrontal cortex and poorer inter-brain synchrony in the ventral lateral prefrontal cortex. These associations were observed exclusively in the face-to-face condition. Our findings suggest that a physically inactive lifestyle may alter human prosocial behavior by impairing adaptable prosocial decision-making in response to social factors through altered intra-brain functional connectivity and inter-brain synchrony.

Effects of CD34+ cell dose on engraftment and long-term outcomes after allogeneic bone marrow transplantation.

BACKGROUND: The number of CD34+ cells in the graft is generally associated with time to engraftment and survival in transplantation using cord blood or allogeneic peripheral blood stem cells. However, the significance of abundant CD34+ in bone marrow transplantation (BMT) remained unclear. METHODS: We retrospectively reviewed 207 consecutive adult patients who underwent their first BMT at Jichi Medical University between January 2009 and June 2021. RESULTS: The median nucleated cell count (NCC) and CD34+ cell dose were 2.17 × 108/kg (range .56-8.52) and 1.75 × 106/kg (.21-5.84), respectively. Compared with 104 patients in the low CD34+ group (below the median), 103 patients in the high CD34+ group (above the median) showed faster engraftment at day +28 in terms of neutrophil (84.6% vs. 94.2%; p =  .001), reticulocyte (51.5% vs. 79.6%; p < .001), and platelet (39.4% vs. 72.8%; p < .001). There were no significant differences in overall survival, relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or infectious complications between the two groups in univariate and multivariate analyses. Low or high NCC had no significant effect on overall survival, nonrelapse mortality, cumulative incidence of relapse and graft-versus-host disease, either. While a positive correlation was observed between NCC and the CD34+ cell dose, a high CD34+ cell dose was associated with rapid hematopoietic recovery, even in patients with NCC below the median. CONCLUSION: Measurement of CD34+ cell dose in addition to NCC was useful for predicting hematopoietic recovery, but seemed to have little influence on the long-term outcome in BMT.

Relapsed and refractory multiple myeloma: A systematic review and network meta-analysis of the efficacy of novel therapies.

The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations of these novel agents. This study was a systematic review and network meta-analysis (NMA) of randomized trials in patients with relapsed and/or refractory (RR) MM. The PubMed, Cochrane, and Embase databases were searched for randomized trials from 1 January 2002 to 28 February 2022 of patients treated for MM. The primary end-point was progression-free survival (PFS), evaluated as a hazard ratio (HR) with a 95% confidence interval (95% CI) compared to dexamethasone (DEX). The p-score was used to rank treatments. Of a total of 1136 abstracts screened, 37 studies were selected, including 34 treatment options for RRMM. Daratumumab, lenalidomide and DEX was found to be the best treatment for RRMM, with the best HR compared to DEX (HR, 0.13; 95% CI, 0.08-0.20; p-score 0.9796). There was no evidence of significant heterogeneity (I2 , 41.3%; p = 0.146). The current NMA confirmed the excellent efficacy of three-drug regimens including anti-CD38 antibodies to treat RRMM and provides background data to evaluate the efficacy of chimeric antigen receptor T-cell treatments and bispecific T-cell engager therapies.

Early reversal of the lymphocyte-to-monocyte ratio after allogeneic-hematopoietic stem cell transplantation is associated with reduced relapse and improved prognosis.

BACKGROUND: The early recovery of lymphocyte and monocyte cells is associated with a favorable prognosis after allogeneic stem cell transplantation (allo-HSCT); however, it is not clear whether the balance of lymphocyte and monocyte recovery affects the post-transplant prognosis. METHODS: We examined whether the time-point at which the number of lymphocytes exceeded the number of monocytes, which we termed lymphocyte-to-monocyte ratio reversal (LMRR), affected the prognosis after allo-HSCT. We retrospectively evaluated 235 patients who underwent their first allo-HSCT at our institution. RESULTS: The median number of days from HSCT to LMRR was 46 (range, 0-214), and the patients were divided into two groups according to the occurrence of LMRR by day 45 (LMRR45). In a multivariate analysis, early LMRR contributed favorably to overall survival (hazard ratio [HR] .519; 95% confidence interval [CI] .332-.812; p = .004) with fewer post-transplant relapses (HR .462; 95% CI, .274-.777; p = .004). Differences in the timing of LMRR did not affect non-relapse mortality (HR 1.477; 95% CI .779-2.80; p = .23) or the incidence of grade II-IV acute GVHD (LMRR45(+): 25.0% vs. LMRR45(-) 35.2%. p = .111). In subgroup analyses, LMRR45(+) was found to be a favorable factor for survival with less relapse, regardless of the disease risk, stem cell source, or the recovery of either lymphocyte or monocyte counts. CONCLUSIONS: An early LMRR may be a novel factor that is associated with reduced relapse and improved survival after allo-HSCT.

Rapid stimulation of human dentate gyrus function with acute mild exercise.

Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that stress-free mild exercise increases hippocampal neuronal activity and promotes adult neurogenesis in the dentate gyrus (DG) of the hippocampus, improving spatial memory performance. However, the rapid modification, from mild exercise, on hippocampal memory function and the exact mechanisms for these changes, in particular the impact on pattern separation acting in the DG and CA3 regions, are yet to be elucidated. To this end, we adopted an acute-exercise design in humans, coupled with high-resolution functional MRI techniques, capable of resolving hippocampal subfields. A single 10-min bout of very light-intensity exercise (30%[Formula: see text]) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3-neocortical functional connectivity.

A transferable high-intensity intermittent exercise improves executive performance in association with dorsolateral prefrontal activation in young adults.

Although growing attention has been drawn to attainable, high-intensity intermittent exercise (HIE)-based intervention, which can improve cardiovascular and metabolic health, for sedentary individuals, there is limited information on the impact and potential benefit of an easily attainable HIE intervention for cognitive health. We aimed to reveal how acute HIE affects executive function focusing on underlying neural substrates. To address this issue, we examined the effects of acute HIE on executive function using the color-word matching Stroop task (CWST), which produces a cognitive conflict in the decision-making process, and its neural substrate using functional near infrared spectroscopy (fNIRS). Twenty-five sedentary young adults (mean age: 21.0 ± 1.6 years; 9 females) participated in two counter-balanced sessions: HIE and resting control. The HIE session consisted of two minutes of warm-up exercise (50 W load at 60 rpm) and eight sets of 30 s of cycling exercise at 60% of maximal aerobic power (mean: 127 W ± 29.5 load at 100 rpm) followed by 30 s of rest on a recumbent-ergometer. Participants performed a CWST before and after the 10-minute exercise session, during both of which cortical hemodynamic changes in the prefrontal cortex were monitored using fNIRS. Acute HIE led to improved Stroop performance reflected by a shortening of the response time related to Stroop interference. It also evoked cortical activation related to Stroop interference on the left-dorsal-lateral prefrontal cortex (DLPFC), which corresponded significantly with improved executive performance. These results provide the first empirical evidence using a neuroimaging method, to our knowledge, that acute HIE improves executive function, probably mediated by increased activation of the task-related area of the prefrontal cortex including the left-DLPFC.

Neural basis for reduced executive performance with hypoxic exercise.

While accumulating evidence suggests positive effects of exercise on executive function, such effects vary with environment. In particular, exercise in a hypoxic environment (hypobaric or normobaric hypoxia), leading to decreased oxygen supply, may dampen or cancel such effects. Thus, we further explore the relation between the effects of hypoxic exercise on executive function and their underlying neural mechanisms by monitoring changes of cortical activation patterns using functional near-infrared spectroscopy (fNIRS). Fifteen healthy participants performed color-word Stroop tasks (CWST) before and after a 10 min bout of moderate-intensity exercise (50%V̇O2peak) under normoxic and hypoxic conditions (fraction of inspired oxygen (FIO2) = 0.135). During the CWST, we monitored prefrontal activation using fNIRS. CWST performance under hypoxic conditions decreased compared with normoxic conditions. In addition, CWST-related activation in the left dorsolateral prefrontal cortex (DLPFC) was reduced after a bout of hypoxic exercise. There was statistically significant association between decreased CWST performance and activation in the left DLPFC. These results suggest that moderate exercise under normobaric hypoxic conditions has negative effects on executive function by reducing task-related activations in the DLPFC.

Effects of acute exercise in the sitting position on executive function evaluated by the Stroop task in healthy older adults.

[Purpose] Exercise effects on executive functioning depend on exercise mode. We tested the effects of three acute exercises in the sitting position-stepping, stretching, and finger movement-on older adults' executive functioning in comparison to a resting state (i.e., control condition). [Subjects and Methods] Participants were 26 healthy older adults (mean age, 71.8 ± 4.7 years). All participants performed the three sitting exercises for 10 minutes; resting for an equal amount of time was used as a control condition. These four conditions were presented in random order. The color-word matching Stroop task was used to evaluate executive function before and after the sitting exercises and control condition. [Results] All three sitting exercises significantly reduced Stroop interference scores, while the control condition did not. There was a significant difference between the finger movement exercise and the control condition in pre-to-post-intervention changes in Stroop interference scores. [Conclusion] The acute finger movement exercise was especially beneficial for executive function as evaluated by the color-word matching Stroop task.

Acute moderate exercise improves mnemonic discrimination in young adults.

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O2peak ) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. © 2016 Wiley Periodicals, Inc.

The association between aerobic fitness and cognitive function in older men mediated by frontal lateralization.

Previous studies have shown that higher aerobic fitness is related to higher cognitive function and higher task-related prefrontal activation in older adults. However, a holistic picture of these factors has yet to be presented. As a typical age-related change of brain activation, less lateralized activity in the prefrontal cortex during cognitive tasks has been observed in various neuroimaging studies. Thus, this study aimed to reveal the relationship between aerobic fitness, cognitive function, and frontal lateralization. Sixty male older adults each performed a submaximal incremental exercise test to determine their oxygen intake (V·O2) at ventilatory threshold (VT) in order to index their aerobic fitness. They performed a color-word Stroop task while prefrontal activation was monitored using functional near infrared spectroscopy. As an index of cognitive function, Stroop interference time was analyzed. Partial correlation analyses revealed significant correlations among higher VT, shorter Stroop interference time and greater left-lateralized dorsolateral prefrontal cortex (DLPFC) activation when adjusting for education. Moreover, mediation analyses showed that left-lateralized DLPFC activation significantly mediated the association between VT and Stroop interference time. These results suggest that higher aerobic fitness is associated with cognitive function via lateralized frontal activation in older adults.

Positive effect of acute mild exercise on executive function via arousal-related prefrontal activations: an fNIRS study.

Despite the practical implication of mild exercise, little is known about its influence on executive function and its neural substrates. To address these issues, the present study examined the effect of an acute bout of mild exercise on executive function and attempted to identify potential neural substrates using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-five young individuals performed a color-word matching Stroop task (CWST) and a two-dimensional scale to measure changes of psychological mood states both before and after a 10-minute exercise session on a cycle ergometer at light intensity (30% v(·)o2peak) and, for the control session, without exercise. Cortical hemodynamic changes in the prefrontal area were monitored with fNIRS during the CWST in both sessions. The acute bout of mild exercise led to improved Stroop performance, which was positively correlated with increased arousal levels. It also evoked cortical activations regarding Stroop interference on the left dorsolateral prefrontal cortex and frontopolar area. These activations significantly corresponded with both improved cognitive performance and increased arousal levels. Concurrently, this study provides empirical evidence that an acute bout of mild exercise improves executive function mediated by the exercise-induced arousal system, which intensifies cortical activation in task-related prefrontal sub-regions.

The effects of wearing face masks on the perception and mood of male healthy male adults during treadmill running: A pilot study.

In the past few years, the face mask has been recommended for the prevention of exposing others to COVID-19. Wearing a face mask may have the potential to increase dyspnea and discomfort during exercise; however, controversy exists on whether wearing face masks during exercise affects exercise performance, perception, and mood in runners. We investigated the physiological and perceptual responses of healthy male adults who had experienced long-distance running while exercising at different intensities. Nine healthy young adults who were long-distance runners wearing surgical face mask conducted an incremental treadmill protocol. The protocol was three 6-min stages (20%, 40%, and 60% of maximal heart rate, respectively). The rating of perceived exertion (RPE) and the feeling scale (FS) were measured. RPE was higher in mask condition than in unmask condition (No mask vs. Face mask, light; 8.22 vs. 8.78, p = 0.615, middle; 10.00 vs. 10.78, p = 0.345, high; 12.33 vs. 13.67, p = 0.044.), while FS was not different between conditions. The present study shows that wearing a mask may increase rating of perceived exertion and discomfort when the exercise intensity exceeds a certain threshold in healthy male adults who have experienced long-distance running.

Mild exercise improves executive function with increasing neural efficiency in the prefrontal cortex of older adults.

This study examined whether a 3-month mild-exercise intervention could improve executive function in healthy middle-aged and older adults in a randomized control trial. Ultimately, a total of 81 middle-aged and older adults were randomly assigned to either an exercise group or a control group. The exercise group received 3 months of mild cycle exercise intervention (3 sessions/week, 30-50 min/session). The control group was asked to behave as usual for the intervention period. Before and after the intervention, participants did color-word matching Stroop tasks (CWST), and Stroop interference (SI)-related reaction time (RT) was assessed as an indicator of executive function. During the CWST, prefrontal activation was monitored using functional near-infrared spectroscopy (fNIRS). SI-related oxy-Hb changes and SI-related neural efficiency (NE) scores were assessed to examine the underlying neural mechanism of the exercise intervention. Although the mild-exercise intervention significantly decreased SI-related RT, there were no significant effects of exercise intervention on SI-related oxy-Hb changes or SI-related NE scores in prefrontal subregions. Lastly, changes in the effects of mild exercise on NE with advancing age were examined. The 81 participants were divided into two subgroups (younger-aged subgroup [YA], older-aged subgroup [OA], based on median age [68 years.]). Interestingly, SI-related RT significantly decreased, and SI-related NE scores in all ROIs of the prefrontal cortex significantly increased only in the OA subgroup. These results reveal that a long-term intervention of very light-intensity exercise has a positive effect on executive function especially in older adults, possibly by increasing neural efficiency in the prefrontal cortex.

Improvement of mnemonic discrimination with acute light exercise is mediated by pupil-linked arousal in healthy older adults.

Physical exercise has positive impacts on hippocampal memory decline with aging. One of the postulated neurobiological mechanisms of the decline is reduced catecholaminergic projections from the locus coeruleus to the hippocampus. Recent human studies revealed that very light exercise rapidly enhances memory and pupil diameter, which suggests that light exercise may improve memory via neural circuits involved in the ascending arousal system, including the locus coeruleus, even in older adults. Thus, we aimed to clarify the effects of a single bout of light-intensity exercise (60% ventilatory threshold) on mnemonic discrimination performance, an index of hippocampal memory function, in healthy older adults using a randomized crossover design. Pupil diameter was measured during exercise as a physiological marker of the ascending arousal system. Discrimination of highly similar stimuli to the targets improved after exercise when compared to the resting control performance. Importantly, causal mediation analysis showed that pupil dilation during exercise mediated the memory improvement. These results suggest that brief light exercise rapidly enhances memory, possibly by upregulating the ascending arousal system.

Cost-Effectiveness of Anti-BCMA Chimeric Antigen Receptor T Cell Therapy in Relapsed/Refractory Multiple Myeloma.

Despite its promising outcomes, anti-BCMA chimeric antigen receptor T cell therapy (CAR-T) is the most expensive myeloma treatment developed to date, and its cost-effectiveness is an important issue. This study aimed to assess the cost-effectiveness of anti-BCMA CAR-T compared to standard antimyeloma therapy in patients with relapsed/refractory multiple myeloma. The model included myeloma patients in Japan and the United States who have received ≥3 prior lines of antimyeloma therapy, including immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. A Markov model was constructed to compare the CAR-T strategy, in which patients receive either idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) followed by 3 lines of multiagent chemotherapy after relapse, and the no CAR-T strategy, in which patients receive only chemotherapy. Data from the LocoMMotion, KarMMa, and CARTITUDE-1 trials were extracted. Several assumptions were made regarding long-term progression-free survival (PFS) with CAR-T. Extensive scenario analyses were made regarding regimens for no CAR-T strategies. The outcome was an incremental cost-effectiveness ratio (ICER) with willingness-to-pay thresholds of ¥7,500,000 in Japan and $150,000 in the United States. When a 5-year PFS of 40% with cilta-cel was assumed, the ICER of the CAR-T strategy versus the no CAR-T strategy was ¥7,603,823 per QALY in Japan and $112,191 per QALY in the United States over a 10-year time horizon. When a 5-year PFS of 15% with ide-cel was assumed, the ICER was ¥20,388,711 per QALY in Japan and $261,678 per QALY in the United States over a 10-year time horizon. The results were highly dependent on the PFS assumption with CAR-T and were robust to changes in most other parameters and scenarios. Although anti-BCMA CAR-T can be cost-effective even under current pricing, a high long-term PFS is necessary.

T-ALL presenting with i-TLP-like indolent clinical course with repeated spontaneous regressions.

Rapidly progressing ALL, a potentially fatal disease, demands timely diagnosis and treatment. On the other hand, spontaneous remission/regression (SR) is reported in various cancers including aggressive tumors like ALL. Infection or trauma-mediated immune system activation is assumed to cause SR, with the duration in cases of ALL typically being short. Indolent T-lymphoblastic proliferation (i-TLP) exhibits the uniform proliferation of TdT-positive T-cells, despite being a non-neoplastic disease, underscoring the significance of distinguishing it from T-cell acute lymphoblastic leukemia (T-ALL). i-TLP is expected to gain wider recognition and further advancements in understanding its pathology. Here, we present the case of a 59-year-old woman with T-ALL characterized by cycles of progression and SR followed by a rapid blast proliferation. This is the first reported case of T-ALL with repeated SR for more than one year, making this case an extremely rare clinical presentation. This challenging case will enhance comprehension of T-cell tumor pathogenesis.

Association of the pre-transplant CD4/CD8 ratio with the prognosis following allogeneic hematopoietic stem cell transplantation.

The tumor microenvironment's cells can promote or inhibit tumor formation, and there are no reports on the CD4/CD8 ratio's association with outcomes post allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the pre-transplant peripheral blood CD4/CD8 ratio in 168 patients who underwent their first allo-HSCT for hematological malignancies at our institution. When patients were divided into two groups according to the median CD4/CD8 ratio 1.35 (range, 0.09-19.89), the high CD4/CD8 ratio group had a higher incidence of relapse, equivalent non-relapse mortality and worse overall survival (OS) than the low CD4/CD8 ratio group. In a multivariate analysis, the CD4/CD8 ratio was significantly associated with an increased risk of relapse, although there was a marginally significant difference in OS. The pre-transplant peripheral blood CD4/CD8 ratio could be a novel biomarker for predicting the prognosis of allo-HSCT.

Feasibility, Safety, Enjoyment, and System Usability of Web-Based Aerobic Dance Exercise Program in Older Adults: Single-Arm Pilot Study.

BACKGROUND: During the COVID-19 epidemic, opportunities for social interaction and physical activity among older people are decreasing, which may have a negative impact on their health. As a solution, a web-based group exercise program provided through a videoconferencing platform would be useful. As a web-based exercise program that older adults can easily, safely, and enjoyably perform at home, we developed a short-duration, light-intensity aerobic dance exercise program. Before studying the effectiveness of this exercise program, its characteristics, such as feasibility, safety, enjoyment, and system usability, should be examined among older adults. OBJECTIVE: This pilot study aimed to examine the feasibility, safety, and enjoyment of a web-based aerobic dance exercise program and the usability of a web-based exercise delivery system using a videoconferencing platform for older adults. METHODS: This study was designed as a prospective single-arm pilot study. A total of 16 older adults participated in an 8-week web-based aerobic dance program held every morning (8:30 AM to 8:50 AM) on weekdays at home. Retention and adherence rates were measured for the program's feasibility. Safety was assessed by the heart rate reserve, an index of exercise intensity calculated from heart rate, and the number of adverse events during exercise sessions. Enjoyment of this exercise program was assessed by an 11-point Likert scale ranging from 0 (not enjoyable at all) to 10 (extremely enjoyable) obtained through telephone interviews after the first-, third-, sixth-, and eighth-week intervention. For usability, the ease of the videoconferencing platform system was assessed through telephone interviews after the intervention. RESULTS: A female participant with hypertension dropped out in the second week because of the continuously reported high blood pressure (≥180 mmHg) before attending the exercise session in the first week. Therefore, the retention rate was 93.8% (15/16). Among the remaining participants, the median (IQR) overall adherence rate was 97.4% (94.7-100). Regarding safety, the mean (SD) heart rate reserve during the aerobic dance exercise was 29.8% (6.8%), showing that the exercise was relatively safe with very light to light intensity. There were no adverse events during the exercise session. The enjoyment score (0-10 points) significantly increased from the first (6.7 [1.7]) to sixth (8.2 [1.3]) and eighth week (8.5 [1.3]). Regarding usability, 11 participants reported difficulties at the beginning, such as basic touch panel operations and the use of unfamiliar applications; however, all got accustomed to it and subsequently reported no difficulty. CONCLUSIONS: This study showed high feasibility, enjoyment, and safety of the web-based aerobic dance exercise program in older adults, and the web-based exercise delivery system may have areas for improvement, albeit without serious problems. Our web-based aerobic dance exercise program may contribute to an increase in physical and social activities among older adults.

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

We previously found that a 10-min bout of moderate-intensity exercise (50% maximal oxygen uptake) under normobaric and hypoxic conditions (fraction of inspired oxygen [[Formula: see text]] = 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 ([Formula: see text]= 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.