Figure 2 - uploaded by Andrew E Beaudin
Content may be subject to copyright.
Working memory tasks. Schematic diagrams of the verbal 0-back (A), verbal 2-back (B), spatial 0-back (C), and spatial 2-back (D) tasks. For each task, participants saw letters appearing on the screen one at a time every 3 seconds and were required to make a " yes " or " no " response to each letter. In the 0-back tasks (A and C), the first letter was the target letter. For each letter presented after the first one, participants indicated whether the identity of the letter (verbal task) or its location (spatial task) was the same as the target. In the 2-back tasks (B and D), participants indicated whether the identity (verbal task) or location (spatial task) of each letter was the same as the letter that appeared two back in the sequence. For each task, participants pressed the left and right arrow keys to indicate " yes " or " no. "
Source publication
Research Letter - no abstract available.
Citations
... Studies have shown that uncomfortable "low oxygen doses" can promote tumor metastasis [63], raise blood pressure and cholesterol levels, increase atherosclerosis, impair spatial memory, and increase inflammatory responses. In addition, hypoxia can increase the weight coefficient of the heart, liver, and lung and plasma estrogen levels, decrease estrogen receptor and progesterone receptor mRNA levels, damage ovarian and uterine tissue structure, and cause estrus disturbance [64][65][66][67][68][69][70]. However, we and others have demonstrated that IHHT, at an altitude of 5000 m, for 14 days, 4 h per day, did not induce neuronal death in the hippocampus [15,16], and that IHHT, at an altitude of 3000 m, for 28 days, 6-h per day, rescues deficits in spatial and object memory and in synaptic plasticity, in pilocarpine-treated epileptic rats [71]. ...
Major depressive disorder (MDD) is a devastating condition. Although progress has been made in the past seven decades, patients with MDD continue to receive an inadequate treatment, primarily due to the late onset of first-line antidepressant drugs and to their acute withdrawal symptoms. Resilience is the ability to rebound from adversity in a healthy manner and many people have psychological resilience. Revealing the mechanisms and identifying methods promoting resilience will hopefully lead to more effective prevention strategies and treatments for depression. In this study, we found that intermittent hypobaric hypoxia training (IHHT), a method for training pilots and mountaineers, enhanced psychological resilience in adult mice. IHHT produced a sustained antidepressant-like effect in mouse models of depression by inducing long-term (up to 3 months after this treatment) overexpression of hypoxia-inducible factor (HIF)-1α in the dorsal raphe nucleus (DRN) of adult mice. Moreover, DRN-infusion of cobalt chloride, which mimics hypoxia increasing HIF-1α expression, triggered a rapid and long-lasting antidepressant-like effect. Down-regulation of HIF-1α in the DRN serotonergic (DRN5−HT) neurons attenuated the effects of IHHT. HIF-1α translationally regulated the expression of P2X2, and conditionally knocking out P2rx2 (encodes P2X2 receptors) in DRN5−HT neurons, in turn, attenuated the sustained antidepressant-like effect of IHHT, but not its acute effect. In line with these results, a single sub-anesthetic dose of ketamine enhanced HIF-1α–P2X2 signaling, which is essential for its rapid and long-lasting antidepressant-like effect. Notably, we found that P2X2 protein levels were significantly lower in the DRN of patients with MDD than that of control subjects. Together, these findings elucidate the molecular mechanism underlying IHHT promoting psychological resilience and highlight enhancing HIF-1α–P2X2 signaling in DRN5−HT neurons as a potential avenue for screening novel therapeutic treatments for MDD.
... A number of previous studies have shown impairments in episodic memory, procedural memory, and WM in OSA patients [9][10][11], although the effect of CPAP on WM remains controversial [15,24]. Many of the animal data showed impaired spatial WM under intermittent hypoxemia [25,26], as well as another study in healthy adults [27]. Our study showed that 2 months of CPAP treatment did not have any beneficial effect on WM. ...
Objectives:
Obstructive sleep apnea (OSA) is a sleep disorder which results in daytime sleepiness and impaired memory function. The aim of this study was to investigate the effect of continuous positive airway pressure (CPAP) on daytime sleepiness and memory function in OSA patients. We also investigated whether CPAP compliance impacted the effect of this treatment.
Materials and methods:
The nonrandomized, nonblinded clinical trial enrolled 66 patients with moderate-to-severe OSA subjects. All subjects completed a polysomnographic study, daytime sleepiness questionnaires (the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index), and four memory function tests (working memory; processing speed [PS]; logical memory [LM]; face memory [FM]).
Results:
Before CPAP treatment, no significant differences (P < 0.05) were noted in the demographic data, daytime sleepiness, or memory function between two groups (with/without CPAP). However, OSA patients treated with CPAP for 2 months showed significant improvements in daytime sleepiness, PS, mostly of LM, and FM comparing to 2 months ago. As compared to those who did not receive CPAP treatment, CPAP can improve only parts of LM (delayed LM [DLM] and LM percentage [LMP]). In addition, compared to control group, a significant improvement of daytime sleepiness and LM (LM learning, DLM, and LMP) in good compliance with CPAP treatment group and of DLM and LMP in the low compliance with CPAP treatment group was found.
Conclusion:
CPAP treatment for 2 months could improve some of LM in OSA patients, especially in patients exhibiting good CPAP compliance.
... The only difference is that the patient's mask is not connected to a CPAP device but to a setting providing cycling air. This approach has been used to mimic different apneahypopnea indices in patients: 60 cycles/h, corresponding to severe SA [150], 30 cycles/h as in intermediate SA [151][152][153][154][155][156][157][158][159], and 15 events/h as in mild SA [160][161][162]. It is worth noting that this type of mask-setting has been also applied to investigate the effects of intermittent hypercapnia (realistic cycles of 30 s of hypercapnic hypoxia followed by 2 min of air, i.e., 24 events/h)) in healthy humans [163]. ...
Sleep apnea (SA) is a very prevalent sleep breathing disorder mainly characterized by intermittent hypoxemia and sleep fragmentation, with ensuing systemic inflammation, oxidative stress, and immune deregulation. These perturbations promote the risk of end-organ morbidity, such that SA patients are at increased risk of cardiovascular, neurocognitive, metabolic and malignant disorders. Investigating the potential mechanisms underlying SA-induced end-organ dysfunction requires the use of comprehensive experimental models at the cell, animal and human levels. This review is primarily focused on the experimental models employed to date in the study of the consequences of SA and tackles 3 different approaches. First, cell culture systems whereby controlled patterns of intermittent hypoxia cycling fast enough to mimic the rates of episodic hypoxemia experienced by patients with SA. Second, animal models consisting of implementing realistic upper airway obstruction patterns, intermittent hypoxia, or sleep fragmentation such as to reproduce the noxious events characterizing SA. Finally, human SA models, which consist either in subjecting healthy volunteers to intermittent hypoxia or sleep fragmentation, or alternatively applying oxygen supplementation or temporary nasal pressure therapy withdrawal to SA patients. The advantages, limitations, and potential improvements of these models along with some of their pertinent findings are reviewed.
... The relationship between cerebral blood flow (CBF) and neural activity is known as neurovascular coupling (Girouard & Iadecola, 2006), and there is evidence to show that changes in brain function that result from perturbations in CBF can have severe physiologic and psychologic consequences. For example, COPD is associated with cognitive dysfunction (Perry & Hodges, 1999;Schou et al., 2012), whereas OSA is associated with fatigue, fluctuations in mood, and deficits in attention and memory (Champod et al., 2013;Stierer & Punjabi, 2005). Exposure to hypoxic environments also impairs cognitive function, increasing the risk of accidents for individuals who engage in work or leisure at high altitude (De Aquino Lemos et al., 2012;Kramer et al., 1993;Virues-Ortega et al., 2004). ...
... The novel, multimodal nature of our approach meant that it was difficult to identify effect sizes from previous publications that we could use as the basis for formal power analysis. Accordingly, we based our sample size on prior work testing the effects of arterial blood gas manipulations on CBF using TCD measures (Ainslie & Poulin, 2004, n = 9;Poulin & Robbins, 1996, n = 6;Poulin et al., 1996, n = 6) as well as investigations that combine arterial blood gas manipulations with EEG measures (Kennealy et al., 1986, n = 10), MEG measures (Hall et al., 2011, n = 6), and cognitive tasks (Champod et al., 2013, Study 1: n = 8, Study 2: n = 9). Female participants were all tested during the follicular phase of their menstrual cycle. ...
Impairments of cognitive function during alterations in arterial blood gases (e.g., high-altitude hypoxia) may result from the disruption of neurovascular coupling; however, the link between changes in arterial blood gases, cognition, and cerebral blood flow (CBF) is poorly understood. To interrogate this link, we developed a multimodal empirical strategy capable of monitoring neural correlates of cognition and CBF simultaneously. Human participants performed a sustained attention task during hypoxia, hypercapnia, hypocapnia, and normoxia while electroencephalographic (EEG) activity and CBF (middle and posterior cerebral arteries; transcranial Doppler ultrasound) were simultaneously measured. The protocol alternated between rest and engaging in a visual target detection task that required participants to monitor a sequence of brief-duration colored circles and detect infrequent, longer duration circles (targets). The target detection task was overlaid on a large, circular checkerboard that provided robust visual stimulation. Spectral decomposition and event-related potential (ERP) analyses were applied to the EEG data to investigate spontaneous and task-specific fluctuations in neural activity. There were three main sets of findings: (1) spontaneous alpha oscillatory activity was modulated as a function of arterial CO2 (hypocapnia and hypercapnia), (2) task-related neurovascular coupling was disrupted by all arterial blood gas manipulations, and (3) changes in task-related alpha and theta band activity and attenuation of the P3 ERP component amplitude were observed during hypocapnia. Since alpha and theta are linked with suppression of visual processing and executive control and P3 amplitude with task difficulty, these data suggest that transient arterial blood gas changes can modulate multiple stages of cognitive information processing.
... In OSA, chronic IHH is associated with cognitive decline (Lal et al., 2012) and an elevated risk of cardiovascular disease and ischemic stroke (Redline et al., 2010;Yaggi et al., 2005). Patients with OSA and healthy humans exposed to intermittent hypoxia develop similar cerebrovascular and cardiovascular sequelae including lasting increases in central sympathetic outflow and often in blood pressure (Floras, 2018;Foster et al., 2010Foster et al., , 2009Gilmartin et al., 2010;Narkiewicz et al., 1999;Stuckless et al., 2020;Tremblay et al., 2016), reduced cerebrovascular reactivity to arterial blood gas challenges (Foster et al., , 2007(Foster et al., , 2005Querido et al., 2008;Reichmuth et al., 2009), and a decrease in cognitive function (Champod et al., 2013;Incalzi et al., 2004;Lal et al., 2012). The underlying mechanisms responsible for the reductions in cerebrovascular reactivity and cognitive function in OSA are unclear. ...
... The current results contrast the hypothesis that cerebral NVC would be reduced following IHH. Healthy individuals exposed to intermittent hypoxia paradigms involving 6-h of exposure repeated over 1-4 days have led to attenuated cerebrovascular reactivity to hypoxia, Querido et al., 2008) reduced NO bioavailability, Pialoux et al., 2009) increased oxidative stress (Pialoux et al., 2011) and impairments to cognition (Champod et al., 2013). We did not measure cerebrovascular reactivity, NO bioavailability, oxidative stress or cognition in our 40-min IHH paradigm, although the absence of reduced cerebral NVC and unaltered vascular function previously shown by our group suggest these measures are likely unaltered following our short-term exposure. ...
... Further, whether treatment of OSA with continuous positive airway pressure to relieve IHH results in improvements on cerebral NVC with concomitant changes in cognition is unknown. Future work should aim to characterize cerebral NVC following repeated IHH over multiple days known to impair cognition in healthy individuals (Champod et al., 2013). ...
The decline in cognition observed in obstructive sleep apnea is linked to intermittent hypercapnic hypoxia (IHH), which is known to impair cerebrovascular reactivity. Whether acute IHH impairs the matching of cerebral blood flow to metabolism (i.e., neurovascular coupling, NVC) is unknown. We hypothesized that acute IHH would reduce cerebral NVC. Healthy participants (N = 17, 8 females, 9 males; age: 22 ± 3 years) had cerebral NVC measured at baseline and following 40-min of IHH at 1-min cycles with 40-s of hypercapnic hypoxia (target PETO2 = 50 mmHg, PETCO2 = +4 mmHg above baseline) and 20-s of normoxia. Cerebral NVC was quantified as the absolute and relative posterior cerebral artery blood velocity (PCAV; transcranial Doppler) and conductance (PCACVC; PCAV/mean arterial pressure [MAP]) response to a visual stimulus paradigm. Following IHH, resting PCAV was unchanged, MAP increased (+4 ± 6 mmHg, P < 0.01) and PCACVC was reduced (-0.05 ± 0.04 cm/s/mmHg, P < 0.01). The peak PCAV response to visual stimuli was unchanged following IHH, but the absolute and relative peak PCACVC response was increased (+0.011 ± 0.019 cm/s/mmHg, P < 0.05 and +4.8 ± 6.1%, P < 0.01, respectively) suggesting an increased cerebral vasodilatory response. No change occurred in the plateau cerebral NVC response following IHH. Changes in resting MAP induced by IHH did not correlate with changes in relative peak PCACVC (r2 = 0.095, P = 0.23). Cerebral NVC did not differ between sexes across all time points and was unchanged following a time-matched air-breathing control. In summary, acute IHH increases peak but not plateau cerebral NVC potentially through IHH mediated neuroplasticity.
... Several studies involving animal models and able-bodied humans show intermittent hypoxia protocols that involve less than 9% oxygen concentration and episodes that exceed 48/day result in serious pathologies across multiple physiological systems simultaneously. These parameters correspond to an increase in blood pressure, atherosclerosis, sympathetic activity, and inflammation, as well as an increase in learning and working memory impairment [33][34][35][36][37][38][39]. In some cases, severe exposures may preferentially induce a competing cellular cascade via adenosine 2A receptor activation that inhibits the serotonin-dependent pathway [40]. ...
Purpose of Review
The reacquisition and preservation of walking ability are highly valued goals in spinal cord injury (SCI) rehabilitation. Recurrent episodes of breathing low oxygen (i.e., acute intermittent hypoxia, AIH) are a potential therapy to promote walking recovery after incomplete SCI via endogenous mechanisms of neuroplasticity. Here, we report on the progress of AIH, alone or paired with other treatments, on walking recovery in persons with incomplete SCI. We evaluate the evidence of AIH as a therapy ready for clinical and home use and the real and perceived challenges that may interfere with this possibility.
Recent Findings
Repetitive AIH is a safe and an efficacious treatment to enhance strength, walking speed, and endurance, as well as dynamic balance in persons with chronic, incomplete SCI.
Summary
The potential for AIH as a treatment for SCI remains high, but further research is necessary to understand treatment targets and effectiveness in a large cohort of persons with SCI.
... In animal OSA models, IH exposures and long-term sleep fragmentation could lead to endothelial dysfunction [10], thereby supporting a potential causal relationship between OSA and endothelial dysfunction. In two previous studies, they clearly indicated that the impairment of endothelial function was restored with improvement of IH exposures [11,12]. However, the potential mechanisms involved in the occurrence of OSA-induced endothelial dysfunction are still poorly understood. ...
Objective:
The functions and molecular regulatory mechanisms of miR-193a-3p in cardiac injury induced by obstructive sleep apnea (OSA) are poorly understood. This study aimed to explore the role of miR-193a-3p in intermittent hypoxia(IH)-induced human umbilical vein endothelial cells (HUVECs) injury.
Results:
In this study, we found that IH significantly decreased viability but enhanced cell apoptosis. Concurrently, the miR-193a-3p expression level was increased in HUVECs after IH. Subsequent experiments showed that IH-induced injury was ameliorated through miR-193a-3p silence. Fas apoptotic inhibitory molecule 2 (FAIM2) was predicted by bioinformatics analysis and further identified as a direct target gene of miR-193a-3p. Interestingly, the effect of miR-193a-3p inhibition under IH could be reversed by down-regulating FAIM2 expression.
Conclusion:
In conclusion, our study first revealed that miR-193a-3p inhibition could protect HUVECs against intermittent hypoxia-induced damage by negatively regulating FAIM2. These findings could advance our understanding of the underlying mechanisms for OSA-related cardiac injury.
Methods:
We exposed HUVECs to IH condition; the expression levels of miR-193a-3p were detected by RT-qPCR. Cell viability, and the expressions of apoptosis-associated proteins were examined via CCK-8, and western blotting, respectively. Target genes of miR-193a-3p were confirmed by dual-luciferase reporter assay.
... However, previous investigations related to this topic are far from being conclusive. While cognitive deteriorations do include impaired executive functions [12,13] and working memory [14][15][16], hypoxia related impairments are also detected in cognitive domains which are less related to frontal functions [13,17,18]. Furthermore, several confounding factors must be taken into account when interpreting the relationship between hypoxia and cognitive functioning (for a review, see [7,8]). ...
The current study investigated how experimentally induced acute normobaric hypoxia affects attentional control functions during easy, monotonous visual sustained attention and response inhibition (modified Continuous Performance Task) and executive control tasks (number-size Stroop task). Along with behavioral efficiency, task-relevant and task-irrelevant information processing were investigated by measuring event related brain potentials (ERP) evoked by target stimuli (Target P3), task-relevant stimuli with no response needed (NoGo P3), and task-irrelevant novel stimuli (Novelty P3) during acute hypoxia exposure. Normobaric hypoxia was induced by adjusting the O 2 content of the breathing mixture to obtain 80% peripheral oxygen saturation, equivalent of 5500 m above sea level. Here we report decreased Novelty P3 during acute normobaric hypoxia exposure, while Target P3 and NoGo P3, as well as behavioral efficiency remained intact. Our paper is the first to provide evidence for impaired novelty processing along with intact task-relevant information processing and response inhibition during normobaric hypoxic exposure.
... These alterations result in cardiovascular derangements including hypertension and increased atherogenesis, along with metabolic perturbations that include insulin resistance and dyslipidemia even in non-obese animals fed with regular diet [16][17][18][19][20][21]. These findings have been replicated in a very small number of experimental studies involving humans, usually involving relatively short 2-14-day exposures to intermittent hypoxia in young healthy volunteers, and have also resulted in measurable alterations in memory, systemic blood pressure, glucose disposition, and calculated sensitivity of peripheral tissues to insulin [22][23][24][25]. ...
Purpose of the review:
To summarize the potential interactions between obstructive sleep apnea (OSA), atrial fibrillation (AF), and connexins.
Recent findings:
OSA is highly prevalent in patients with cardiovascular disease, and is associated with increased risk for end-organ substantial morbidities linked to autonomic nervous system imbalance, increased oxidative stress and inflammation, ultimately leading to reduced life expectancy. Epidemiological studies indicate that OSA is associated with increased incidence and progression of coronary heart disease, heart failure, stroke, as well as arrhythmias, particularly AF. Conversely, AF is very common among subjects referred for suspected OSA, and the prevalence of AF increases with OSA severity. The interrelationships between AF and OSA along with the well-known epidemiological links between these two conditions and obesity may reflect shared pathophysiological pathways, which may depend on the intercellular diffusion of signaling molecules into either the extracellular space or require cell-to-cell contact. Connexin signaling is accomplished via direct exchanges of cytosolic molecules between adjacent cells at gap membrane junctions for cell-to-cell coupling. The role of connexins in AF is now quite well established, but the impact of OSA on cardiac connexins has only recently begun to be investigated. Understanding the biology and regulatory mechanisms of connexins in OSA at the transcriptional, translational, and post-translational levels will undoubtedly require major efforts to decipher the breadth and complexity of connexin functions in OSA-induced AF.
Summary:
The risk of end-organ morbidities has initiated the search for circulating mechanistic biomarker signatures and the implementation of biomarker-based algorithms for precision-based diagnosis and risk assessment. Here we summarize recent findings in OSA as they relate to AF risk, and also review potential mechanisms linking OSA, AF and connexins.
... However, Dykiert et al. suggest more pronounced changes in mean reaction times only above 4,000 m. Different types of hypoxic exposures such as field (Subudhi et al., 2014;Davranche et al., 2016), simulated hypobaric hypoxia (Hornbein et al., 1989;Asmaro et al., 2013;Malle et al., 2013), normobaric hypoxia (Turner et al., 2015) and intermittent hypoxia (Champod et al., 2013) have been investigated. Davranche et al. showed impaired information processing (speed and accuracy) at high altitude while Hornbein et al. reported impaired visual longterm memory during chamber simulation. ...
Objective: Neurocognitive functions are affected by high altitude, however the altitude effects of acclimatization and repeated exposures are unclear. We investigated the effects of acute, subacute and repeated exposure to 5,050 m on cognition among altitude-naïve participants compared to control subjects tested at low altitude.
Methods: Twenty-one altitude-naïve individuals (25.3 ± 3.8 years, 13 females) were exposed to 5,050 m for 1 week (Cycle 1) and re-exposed after a week of rest at sea-level (Cycle 2). Baseline (BL, 520 m), acute (Day 1, HA1) and acclimatization (Day 6, HA6, 5,050 m) measurements were taken in both cycles. Seventeen control subjects (24.9 ± 2.6 years, 12 females) were tested over a similar period in Calgary, Canada (1,103 m). The Reaction Time (RTI), Attention Switching Task (AST), Rapid Visual Processing (RVP) and One Touch Stockings of Cambridge (OTS) tasks were administered and outcomes were expressed in milliseconds/frequencies. Lake Louise Score (LLS) and blood oxygen saturation (SpO2) were recorded.
Results: In both cycles, no significant changes were found with acute exposure on the AST total score, mean latency and SD. Significant changes were found upon acclimatization solely in the altitude group, with improved AST Mean Latency [HA1 (588 ± 92) vs. HA6 (526 ± 91), p < 0.001] and Latency SD [HA1 (189 ± 86) vs. HA6 (135 ± 65), p < 0.001] compared to acute exposure, in Cycle 1. No significant differences were present in the control group. When entering Acute SpO2 (HA1-BL), Acclimatization SpO2 (HA6-BL) and LLS score as covariates for both cycles, the effects of acclimatization on AST outcomes disappeared indicating that the changes were partially explained by SpO2 and LLS. The changes in AST Mean Latency [ΔBL (−61.2 ± 70.2) vs. ΔHA6 (−28.0 ± 58), p = 0.005] and the changes in Latency SD [ΔBL (−28.4 ± 41.2) vs. ΔHA6 (−0.2235 ± 34.8), p = 0.007] across the two cycles were smaller with acclimatization. However, the percent changes did not differ between cycles. These results indicate independent effects of altitude across repeated exposures.
Conclusions: Selective and sustained attention are impaired at altitude and improves with acclimatization.The observed changes are associated, in part, with AMS score and SpO2. The gains in cognition with acclimatization during a first exposure are not carried over to repeated exposures.
