Short-term isolation effects on the brain, cognitive performance, and sleep-The role of exercise.

Isolation is stressful and negatively affects sleep and mood and might also affect the structure and function of the brain. Physical exercise improves brain function. We investigated the influence of physical exercise during isolation on sleep, affect, and neurobehavioral function. N = 16 were isolated for 30 days with daily exercise routines (ISO100) and n = 16 isolated for 45 days with every second day exercise (ISO50). N = 27 were non-isolated controls who either exercised on a daily basis (CTRLEx) or refused exercise (CTRLNonEx) for 30 days. At the beginning and the end of each intervention, intravenous morning cortisol, melatonin, brain-derived neurotrophic factor and IGF-1, positive and negative affect scales, electroencephalography, cognitive function, and sleep patterns (actigraphy) were assessed. High levels of cortisol were observed for the isolated groups (p < .05) without negative effects on the brain, cognitive function, sleep, and mood after 4 to 6 weeks of isolation, where physical exercise was performed regularly. An increase in cortisol and impairments of sleep quality, mood, cognitive function, and neurotrophic factors (p < .05) were observed after 4 weeks of absence of physical exercise in the CTRLNonEx group. These findings raise the assumption that regular physical exercise routines are a key component during isolation to maintain brain health and function.

Cerebrovascular function and its association with systemic artery function and stiffness in older adults with and without mild cognitive impairment.

PURPOSE: Our aim was to compare cerebrovascular and systemic vascular function between older adults with and without mild cognitive impairment (MCI), and to determine which measures of vascular function best predict the presence of MCI. METHODS: In 41 adults with MCI and 33 adults without MCI (control) we compared middle cerebral artery velocity (MCAv) and cerebrovascular pulsatility index (PI) at rest, cerebrovascular reactivity to CO2, and responsiveness to changes in blood pressure (%∆MCAv/%∆MAP). Systemic vascular function was assessed by flow-mediated dilation (FMD) and stiffness by pulse wave velocity (PWV). RESULTS: Cerebrovascular PI was higher in MCI compared with control (mean ± SD: 1.17 ± 0.27 vs. 1.04 ± 0.21), and MCI exhibited a lower %∆MCAv/%∆MAP (1.26 ± 0.44 vs. 1.50 ± 0.55%). Absolute (p = 0.76) and relative cerebrovascular reactivity to CO2 (p = 0.34) was similar between MCI and control. When age was included as a covariate the significant difference in cerebral PI between groups was lost. PWV was higher (13.2 ± 2.2 vs. 11.3 ± 2.5 m s-1) and FMD% (4.41 ± 1.70 vs. 5.43 ± 2.15%) was lower in MCI compared with control. FMD% was positively associated with PI across the cohort. Logistic regression analysis indicated that FMD and PWV significantly discriminated between MCI and controls, independent of age, whereas the inclusion of cerebrovascular measures did not improve the predictive accuracy of the model. CONCLUSION: These findings raise the possibility that early changes in systemic vascular stiffness and endothelial function may contribute to altered cerebrovascular haemodynamics and impaired cognitive function, and present potential targets for prevention and treatment strategies in people with MCI.

Reduced cerebral pressure-flow responses are associated with electrophysiological markers of attention in healthy older adults.

The aim of this study was to determine the effect of age on the relationship between cerebrovascular function and the neural bases of sustained attention. Twenty-seven healthy young adults (aged 18-30 years) and 24 older adults (60-75 years) underwent assessments of cerebrovascular function and sustained attention. Blood flow velocity of the middle cerebral artery was assessed via Transcranial Doppler Ultrasound, during seated rest, in response to hypocapnic breathing (cerebrovascular reactivity) and during a repeated sit-to-stand procedure (pressure-flow response). Attentional processing was assessed using the N2 and P3 components of the event-related potential during a two-tone auditory oddball task. Poorer pressure-flow responses were significantly associated with reductions in N2 and P3 amplitude in the old group (b = -0.50, p = .029 and b = -0.46, p = .045), but not the young group. These results suggest that alterations in the brain's capacity to combat reductions in perfusion pressure are associated with age-related differences in attentional processing, supporting the hypothesis that cerebrovascular hemodynamic disturbances play a role in age-related cognitive decline.

Shifts in broadband power and alpha peak frequency observed during long-term isolation.

Prolonged periods of social isolation and spatial confinement do not only represent an issue that needs to be faced by a few astronauts during space missions, but can affect all of us as recently shown during pandemic situations. The fundamental question, how the brain adapts to periods of sensory deprivation and re-adapts to normality, has only received little attention. Here, we use eyes closed and eyes open resting-state electroencephalographic (EEG) recordings to investigate how neural activity is altered during 120 days of isolation in a spatially confined, space-analogue environment. After disentangling oscillatory patterns from 1/f activity, we show that isolation leads to a reduction in broadband power and a flattening of the 1/f spectral slope. Beyond that, we observed a reduction in alpha peak frequency during isolation, but did not find strong evidence for isolation-induced changes that are of oscillatory nature. Critically, all effects reversed upon release from isolation. These findings suggest that isolation and concomitant sensory deprivation lead to an enhanced cortical deactivation which might be explained by a reduction in the mean neuronal population firing rate.

The effect of age on cerebral blood flow responses during repeated and sustained stand to sit transitions.

INTRODUCTION: Aging is associated with impaired cerebrovascular blood flow and function, attributed to reduced vasodilatory capacity of the cerebrovascular network. Older adults may also have an impaired relationship between changes in blood pressure and cerebral blood flow; however, previous reports conflict. This study aimed to compare the blood pressure and cerebral blood flow responses to both repeated and sustained stand-to-sit transitions in young and older adults, and to assess the relationship with cerebrovascular reactivity. METHODS: In 20 young (age: 24 ± 4 years) and 20 older (age: 71 ± 7 years) adults we compared middle cerebral artery flow velocity (MCAv), end-tidal partial pressure of carbon dioxide (PET CO2 ), and blood pressure (mean arterial blood pressure [MAP]) during repeated stand-to-sit (10 s standing and 10 s sitting) and sustained stand-to-sit (3 min standing followed by 2 min sitting) transitions. Cerebrovascular reactivity to changes in carbon dioxide levels was assessed using a repeated breath-hold test. RESULTS: The % change in MCAv per % change in MAP (%∆MCAv/%∆MAP) was higher in the older adults than in the young adults during repeated stand-to-sit transitions. During the sustained protocol the %∆MCAv/%∆MAP response was similar in both age groups. A high %∆MCAv/%∆MAP response during the repeated stand-to-sit protocol was associated with low cerebrovascular reactivity to CO2 (r = -.39; p < .01), which was significantly lower in the older adults. CONCLUSION: These findings suggest that the higher %∆MCAv/%∆MAP during repeated stand-sit transitions was associated with impaired cerebrovascular reactivity. Impairments in endothelial function and vascular stiffness with age may contribute to the altered transient cerebral pressure-flow responses in older adults.

Transient cerebral blood flow responses during microgravity.

PURPOSE: A number of studies has well described central cardiovascular changes caused by changing gravity levels as they occur e.g. during parabolic flight. limited data exists describing the effect of microgravity on the cerebrovascular system and brain perfusion. METHODS: In this study middle cerebral artery velocity (MCAv) of 16 participants was continuously monitored on a second-by-second basis during 15 consecutive parabolas (1G, 1,8G, 0G, 1,8G) using doppler ultrasound. Simultaneously central cardiovascular parameters (heart rate, mean arterial blood pressure, cardiac output) were assessed. RESULTS: Results revealed an immediate reaction of central cardiovascular parameters to changed gravity levels. In contrast, changes in MCAv only initially were in accordance with a normal cerebral autoregulation. Whereas all of the measured central cardiovascular parameters seemed to have reached a steady state after approximately 8 s of microgravity, MCAv, after an initial decrease with the onset of microgravity, increased again during the second half of the microgravity phase. CONCLUSION: It is concluded that this increase in MCAv during the second half of the microgravity period reflects a decrease of cerebrovascular resistance caused by a pressure driven increased venous outflow and/or a contraction of precapillary sphincters in order to avoid hyperperfusion of the brain.

Cerebrovascular Correlates of Subclinical Attentional Disturbances in Non-stroke Cardiovascular Disease.

Evidence suggests that cerebrovascular hemodynamic disturbances underlie cognitive deterioration secondary to cardiovascular disease (CVD), including manifestations other than stroke, but the mechanisms remain unclear. To date, the majority of studies have used neuropsychological measures validated for the detection of clinically significant cognitive decline but lack the sensitivity to accurately detect subclinical or subtle cognitive changes. The N2 and P3 components of the event-related potential are sensitive markers of attention and cognitive processing, and are valuable in the assessment of age-related cognitive changes and neurodegenerative disease. The aims of this study were to test (a) the sensitivity of N2 and P3 components in differentiating older adults with CVD from healthy controls, and (b) whether cerebrovascular hemodynamics are associated with alterations in attention in persons with non-stroke CVD. Older adults with CVD (n = 20) and healthy older adults (n = 20) without cognitive impairment or history of stroke and matched for age, were recruited. Cerebral blood flow velocity of the middle cerebral artery (MCAv) and Gosling's Pulsatility Index (PI) were assessed using Transcranial Doppler ultrasound (TCD). ERPs were elicited using a two-tone auditory oddball task. N2 amplitude was significantly reduced in the CVD group at midline frontal, central and parietal sites (p < .05, d > 0.6). No significant group differences were observed in N2 latency, P3 amplitude, or P3 latency. Further, MCAv and PI were strongly associated with N2 amplitude in the CVD group, such that greater MCAv was associated with reductions in N2 amplitude (b = -0.58, p = .018), whilst PI was associated with increases in N2 amplitude (b = 0.66, p = .006). No relationships between MCAv or PI with N2 or P3 ERP components were observed in the healthy control group. The data reported here suggest that a reduction in N2 amplitude may be an important objective indicator of subclinical cognitive and attentional alterations in non-stroke CVD, and support the notion that cerebrovascular hemodynamic disturbances play a role in the pathogenesis of cognitive deterioration secondary to non-stroke CVD.

Healthy aging affects cerebrovascular reactivity and pressure-flow responses, but not neurovascular coupling: A cross-sectional study.

BACKGROUND AND PURPOSE: Aging leads to alterations in cerebrovascular function, and these are thought to contribute to cognitive decline/dementia. Disturbances to cerebral blood flow regulation have been reported, but the findings are inconsistent and to date no study has comprehensively tested the collective and independent contribution of these parameters in the same age range. Such lines of enquiry are vital since aging is a heterogeneous and complex process, with cerebrovascular parameters being differentially affected depending on the individual. A multicomponent comprehensive measure of cerebrovascular function, which accounts for such diversity, is needed to differentiate between healthy young and old adults. METHODS: We tested the effect of aging on cerebrovascular function by comparing healthy young adults aged 18-30 and older adults aged 60-75, without cognitive impairments. Cerebrovascular blood flow velocity was assessed using transcranial Doppler ultrasound. Parameters included resting middle cerebral artery velocity (MCAv), neurovascular coupling, cerebrovascular reactivity to CO2 (hypercapnia and hypocapnia), and the pressure-flow response during a sit-to-stand procedure. RESULTS: MANOVA revealed that collectively, the parameters discriminated the groups (p < .001). MCAv and pressure-flow responses were lower in the older group (p < .001). While there were no differences in hypercapnic responses (p = .908) and neurovascular coupling (p = .517), hypocapnic responses were elevated in the old (p = .002). CONCLUSIONS: Collectively, cerebrovascular parameters can distinguish between healthy young and older adults, with aging leading to reductions in MCAv, and altering cerebrovascular reactivity and pressure-flow responses under hypotensive conditions.

Neurocognitive performance is enhanced during short periods of microgravity-Part 2.

Previous studies showed a decrease in reaction time during the weightlessness phase of a parabolic flight. This effect was found to be stronger with increasing task complexity and was independent of previous experience of weightlessness as well as anti-nausea medication. Analysis of event related potentials showed a decreased amplitude of the N100-P200 complex in weightlessness but was not able to distinguish a possible effect of task complexity. The present study aimed to extend this previous work, by comparing behavioral (reaction time) and neurological (event related potentials analysis) performance to a simple (oddball) and a complex (mental arithmetic + oddball) task during weightlessness. 28 participants participated in two experiments. 11 participants performed a simple oddball experiment in the 1G and 0G phases of a parabolic flight. 17 participants were presented a complex arithmetic task in combination with an oddball task during the 1G and 0G phases of a parabolic flight. Reaction time as well as event related potentials (ERP) were assessed. Results revealed a reduced reaction time (p < .05) for the complex task during 0G. No gravity effects on reaction time were found for the simple task. In both experiments a reduction of typical ERP amplitudes was noticeable in weightlessness. It is assumed that the weightlessness induced fluid shift to the brain is positively affecting neuro-behavioral performance.

Neurophysiological, neuropsychological, and cognitive effects of 30 days of isolation.

The increasing demand of space flights requires a profound knowledge of the chronologic reactions of the human body to extreme conditions. Prior studies already have shown the adverse effects of long-term isolation on psycho-physiological well-being. The chronology of the effects and whether short-term isolation periods already lead to similar effects has not been investigated. Therefore, the aim of the current study was to investigate the effects of short-term isolation (30 days) on mood, cognition, cortisol, neurotrophic factors, and brain activity. 16 participants were isolated in the Human Exploration Research Analog at NASA for 30 days. 17 non-isolated control participants were tested simultaneously. On mission days - 5, 7, 14, 28, and + 5, multiple tests including the Positive and Negative Affect Schedule-X and cognitive tests were conducted, and a 5-min resting electroencephalography was recorded. A fasted morning blood drawing was also done. Increased stress was observed via augmented cortisol levels during the isolation period. Activity within the parietal cortex was reduced over time, probably representing a neural adaptation to less external stimuli. Cognitive performance was not affected, but rather enhanced in both groups. No further significant changes in neurotrophic factors BDNF/IGF-1 and mood could be detected. These results suggest that 30 days of isolation do not have a significant impact on brain activity, neurotrophic factors, cognition, or mood, even though stress levels were significantly increased during isolation. Further studies need to address the question as to what extent increased levels of stress do not affect mental functions during isolation periods.

Cerebral Blood Flow during Interval and Continuous Exercise in Young and Old Men.

PURPOSE: Aging is associated with impaired cerebral blood flow (CBF) and increased risk of cerebrovascular disease. Acute increases in CBF during exercise may initiate improvements in cerebrovascular health, but the CBF response is diminished during continuous exercise in older adults. The effect of interval exercise for promoting increases in CBF in young and old adults is unknown. METHODS: We compared middle cerebral artery blood velocity (MCAv), end-tidal CO2 (PETCO2) and blood pressure (mean arterial pressure [MAP]) during intensity- and work-matched bouts of continuous (10-min 60%Wmax, followed by 10-min rest) and interval cycling (10 × 1-min 60%Wmax, separated by 1-min rest) in 11 young (25 ± 3 yr) and 10 old (69 ± 3 yr) men. RESULTS: Middle cerebral artery velocity was higher during continuous compared with interval exercise in the young (P < 0.001), but not in the old. This trend was also seen for changes in PETCO2. Although absolute MAP was higher in the old, the relative rise (%[INCREMENT]) in MAP was similar between age groups and was greater during continuous exercise than interval. When we assessed the total accumulated change in MCAv (area under curve: exercise + recovery), it was higher with interval compared with continuous exercise in both groups (P = 0.018). CONCLUSION: These findings suggest that interval exercise may be an effective alternative for promoting acute increases in CBF velocity, particularly in those older adults who may have difficulty sustaining continuous exercise.

The influence of microgravity on cerebral blood flow and electrocortical activity.

Changes in gravity conditions have previously been reported to influence brain hemodynamics as well as neuronal activity. This paper attempts to identify a possible link between changes in brain blood flow and neuronal activity during microgravity. Middle cerebral artery flow velocity (MCAv) was measured using Doppler ultrasound. Brain cortical activity (i.e., cortical current density) was measured using electroencephalography. Finger blood pressure was recorded and exported to generate beat-by-beat systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and cerebrovascular conductance index (CVCi). Seventeen participants were evaluated under normal gravity conditions and microgravity conditions, during 15 bouts of 22-s intervals of weightlessness during a parabolic flight. Although MAP decreased and CO increased, MCAv remained unchanged in the microgravity condition. CVCi as the quotient of MCAv and MAP increased in microgravity. Cortical current density showed a global decrease. Our data support earlier data reporting a decrease in the amplitude of event-related potentials recorded during microgravity. However, the general decrease in neural excitability in microgravity seems not to be dependent on hemodynamic changes.

The effect of 6 h of running on brain activity, mood, and cognitive performance.

Long-duration exercise has been linked with the psychological model of flow. It is expected that the flow experience is characterized by specific changes in cortical activity, especially a transient hypofrontality, which has recently been connected with an increase in cognitive performance post-exercise. Nevertheless, data on neuro-affective and neuro-cognitive effects during prolonged exercise are rare. The cognitive performance, mental state, flow experience, and brain cortical activity of 11 ultramarathon runners (6 female, 5 male) were assessed before, several times during, and after a 6-h run. A decrease in cortical activity (beta activity) was measured in the frontal cortex, whereas no changes were measured for global beta, frontal or global alpha activity. Perceived physical relaxation and flow state increased significantly after 1 h of running but decreased during the following 5 h. Perceived physical state and motivational state remained stable during the first hour of running but then decreased significantly. Cognitive performance as well as the underlying neurophysiological events (recorded as event-related potentials) remained stable across the 6-h run. Despite the fact that women reported significant higher levels of flow, no further gender effects were noticeable. Supporting the theory of a transient hypofrontality, a clear decrease in frontal cortex activity was noticeable. Interestingly, this had no effect on cognitive performance. The fact that self-reported flow experience only increased during the first hour of running before decreasing, leads us to assume that changes in cortical activity, and the experience of flow may not be linked as previously supposed.