Cerebrovascular reactivity among native-raised high altitude residents: an fMRI study

Background: The impact of long term residence on high altitude (HA) on human brain has raised concern among researchers in recent years. This study investigated the cerebrovascular reactivity among native-born high altitude (HA) residents as compared to native sea level (SL) residents. The two groups were matched on the ancestral line, ages, gender ratios, and education levels. A visual cue guided maximum inspiration task with brief breath holding was performed by all the subjects while Blood-Oxygenation-Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) data were acquired from them

Effects of normobaric hypoxia on the activation of motor and visual cortex areas in functional magnetic resonance imaging (fMRI)

Aims: Hypoxia due to high altitude or otherwise altered fraction of inspired O2 affects cerebral mechanisms. Human brain function can be assessed indirectly via examination of local changes in haemodynamics in fMRI. The aim of this study was to examine if adaptation to normobaric hypoxia determines divergent activation in the brain regions supplied by the main cerebral arterial vessels. Methods: Visual and motor paradigms were used to shed light on the activation of different brain regions in fMRI under normobaric hypoxic conditions in 16 healthy male subjects. Hypoxia was produced by reducing the percentage of O2 in an inhaled gas mixture resulting in normobaric hypoxia with an FiO2 of 13 %. Participants had to complete a total of 3 MRI sessions to study different oxygen conditions: normoxia (FiO2 = 0.21, normal pressure), short-time (7 ± 1 min, FiO2 = 0.13, normal pressure), longtime hypoxia (8 h and 29 ± 24 min, FiO2 = 0.13, normal pressure). Each session lasted approximately 30 min, consisting of two fMRI runs (1 visual task, 1 motor task) which were pseudo-randomized between participants, followed by the structural sequence. Cerebral symptoms of AMS were assessed by means of the LLS and it was examined if symptomatic AMS has consequences on brain activation patterns measured as ∆S values. Results: Mean ∆S during normoxia was 2.43 ± 0.80 % due to motor stimulation, and 3.49 ± 1.41 % due to visual stimulation. During motor stimulation, the mean signal change due to short-time hypoxia was 0.55 ± 0.30 % and 0.82 ± 0,62 % due to longtime hypoxia. During visual stimulation, the mean signal change due to short-time hypoxia was 1.79 ± 0.69 %. Long-time hypoxia led to a mean signal change of 2.02 ± 1.18 %. Repeated ANOVA measures with factors task (motor, visual) and the hypoxic conditions (short-time hypoxia, long-time hypoxia) showed a main effect of task (F (1,15) = 52.10, p < 0.001), but no main effect of the hypoxic condition (F (1, 15) = 1.79, p = ns). Conclusions: Hypoxia led to diminished cerebral activation during motor and visual stimulation in spite of a preserved cerebral function. The oxygenation changes associated with brain activation seem more influential on the motor area, rather than the visual cortex. Therefore, the capability of the human brain to acclimatise to chronic hypoxic conditions may vary in the motor and the visual system.Ziele: Hypoxie aufgrund großer Höhe oder eines anderweitig veränderten Anteils von eingeatmetem O2-Gehalts beeinflusst zerebrale Mechanismen. Die menschliche Gehirnfunktion kann indirekt über den Nachweis lokaler hämodynamischer Veränderungen im fMRT bestimmt werden. Das Ziel dieser Studie war es, zu untersuchen, ob die Anpassung an normobare Hypoxie eine unterschiedliche Aktivierung in von den drei Hauptgefäßen versorgten Gehirnregionen erzeugt. Methoden: Bei 16 gesunden, männlichen Probanden wurden visuelle und motorische Testparadigmen angewendet, um die Aktivierung verschiedener Hirnregionen im fMRT unter normobaren, hypoxischen Bedingungen aufzuklären. Hypoxie wurde mit Hilfe eines sauerstoffreduzierten Gasgemischs (O2-Anteil 13%) erzeugt. Die Probanden mussten insgesamt 3 MRT-Sitzungen absolvieren, um verschiedene Sauerstoffzustände zu untersuchen: Normoxie (FiO2 = 0,21), Kurzzeithypoxie (7 ± 1 min Hypoxie, FiO2 = 0,13), Langzeithypoxie (8 h und 29 ± 24 min Hypoxie, FiO2 = 0,13). Jede Sitzung dauerte ca. 30 min und bestand aus je zwei fMRI-Durchgängen (1 visuelle Aufgabe, 1 motorische Aufgabe). Die zerebralen Symptome einer Höhenkrankheit wurden mittels des LLS bewertet und der Einfluss einer Höhenkrankheit auf die Gehirnaktivierungsmuster im fMRT untersucht. Resultate: Die mittlere BOLD-Signalveränderung während Normoxie betrug bei motorischer Stimulation 2,43 ± 0,80% und bei visueller Stimulation 3,49 ± 1,41%. Bei motorischer Stimulation betrug sie nach Kurzzeithypoxie 0,55 ± 0,30% und 0,82 ± 0,62% nach Langzeithypoxie. Bei visueller Stimulation betrug die mittlere Signaländerung aufgrund von Kurzzeithypoxie 1,79 ± 0,69 und aufgrund Langzeithypoxie 2,02 ± 1,18%. ANOVA-Messungen mit den Faktoren Aufgabe (motorisch, visuell) und hypoxische Bedingungen (Kurzzeithypoxie, Langzeithypoxie) zeigten einen Effekt der Aufgabe (F (1, 15) = 52.10, p <0.001), aber keinen Effekt der hypoxischen Bedingung (F (1, 15) = 1,79, p = ns) auf die BOLD Signalwertänderungen. Schlussfolgerungen: Hypoxie führte zu einer verminderten Hirnaktivität im fMRT bei motorischer und visueller Stimulation trotz erhaltener Hirnfunktion. Die mit der Gehirnaktivierung verbundenen Veränderungen der Oxygenierung scheinen eher Einfluss auf den motorischen Bereich als den visuellen Kortex zu haben. Die Adaptationsfähigkeit an chronische hypoxische Zustände scheint sich demzufolge zwischen dem motorischen und dem visuellen System zu unterscheiden

Calcium channel blockade with nimodipine reverses MRI evidence of cerebral oedema following acute hypoxia

Acute cerebral hypoxia causes rapid calcium shifts leading to neuronal damage and death. Calcium channel antagonists improve outcomes in some clinical conditions, but mechanisms remain unclear. In 18 healthy participants we: (i) quantified with multiparametric MRI the effect of hypoxia on the thalamus, a region particularly sensitive to hypoxia, and on the whole brain in general; (ii) investigated how calcium channel antagonism with the drug nimodipine affects the brain response to hypoxia. Hypoxia resulted in a significant decrease in apparent diffusion coefficient (ADC), a measure particularly sensitive to cell swelling, in a widespread network of regions across the brain, and the thalamus in particular. In hypoxia, nimodipine significantly increased ADC in the same brain regions, normalizing ADC towards normoxia baseline. There was positive correlation between blood nimodipine levels and ADC change. In the thalamus, there was a significant decrease in the amplitude of low frequency fluctuations (ALFF) in resting state functional MRI and an apparent increase of grey matter volume in hypoxia, with the ALFF partially normalized towards normoxia baseline with nimodipine. This study provides further evidence that the brain response to acute hypoxia is mediated by calcium, and importantly that manipulation of intracellular calcium flux following hypoxia may reduce cerebral cytotoxic oedem

Effects of normobaric hypoxia on the activation of motor and visual cortex areas in functional magnetic resonance imaging (fMRI)

Aims: Hypoxia due to high altitude or otherwise altered fraction of inspired O2 affects cerebral mechanisms. Human brain function can be assessed indirectly via examination of local changes in haemodynamics in fMRI. The aim of this study was to examine if adaptation to normobaric hypoxia determines divergent activation in the brain regions supplied by the main cerebral arterial vessels. Methods: Visual and motor paradigms were used to shed light on the activation of different brain regions in fMRI under normobaric hypoxic conditions in 16 healthy male subjects. Hypoxia was produced by reducing the percentage of O2 in an inhaled gas mixture resulting in normobaric hypoxia with an FiO2 of 13 %. Participants had to complete a total of 3 MRI sessions to study different oxygen conditions: normoxia (FiO2 = 0.21, normal pressure), short-time (7 ± 1 min, FiO2 = 0.13, normal pressure), longtime hypoxia (8 h and 29 ± 24 min, FiO2 = 0.13, normal pressure). Each session lasted approximately 30 min, consisting of two fMRI runs (1 visual task, 1 motor task) which were pseudo-randomized between participants, followed by the structural sequence. Cerebral symptoms of AMS were assessed by means of the LLS and it was examined if symptomatic AMS has consequences on brain activation patterns measured as ∆S values. Results: Mean ∆S during normoxia was 2.43 ± 0.80 % due to motor stimulation, and 3.49 ± 1.41 % due to visual stimulation. During motor stimulation, the mean signal change due to short-time hypoxia was 0.55 ± 0.30 % and 0.82 ± 0,62 % due to longtime hypoxia. During visual stimulation, the mean signal change due to short-time hypoxia was 1.79 ± 0.69 %. Long-time hypoxia led to a mean signal change of 2.02 ± 1.18 %. Repeated ANOVA measures with factors task (motor, visual) and the hypoxic conditions (short-time hypoxia, long-time hypoxia) showed a main effect of task (F (1,15) = 52.10, p < 0.001), but no main effect of the hypoxic condition (F (1, 15) = 1.79, p = ns). Conclusions: Hypoxia led to diminished cerebral activation during motor and visual stimulation in spite of a preserved cerebral function. The oxygenation changes associated with brain activation seem more influential on the motor area, rather than the visual cortex. Therefore, the capability of the human brain to acclimatise to chronic hypoxic conditions may vary in the motor and the visual system.Ziele: Hypoxie aufgrund großer Höhe oder eines anderweitig veränderten Anteils von eingeatmetem O2-Gehalts beeinflusst zerebrale Mechanismen. Die menschliche Gehirnfunktion kann indirekt über den Nachweis lokaler hämodynamischer Veränderungen im fMRT bestimmt werden. Das Ziel dieser Studie war es, zu untersuchen, ob die Anpassung an normobare Hypoxie eine unterschiedliche Aktivierung in von den drei Hauptgefäßen versorgten Gehirnregionen erzeugt. Methoden: Bei 16 gesunden, männlichen Probanden wurden visuelle und motorische Testparadigmen angewendet, um die Aktivierung verschiedener Hirnregionen im fMRT unter normobaren, hypoxischen Bedingungen aufzuklären. Hypoxie wurde mit Hilfe eines sauerstoffreduzierten Gasgemischs (O2-Anteil 13%) erzeugt. Die Probanden mussten insgesamt 3 MRT-Sitzungen absolvieren, um verschiedene Sauerstoffzustände zu untersuchen: Normoxie (FiO2 = 0,21), Kurzzeithypoxie (7 ± 1 min Hypoxie, FiO2 = 0,13), Langzeithypoxie (8 h und 29 ± 24 min Hypoxie, FiO2 = 0,13). Jede Sitzung dauerte ca. 30 min und bestand aus je zwei fMRI-Durchgängen (1 visuelle Aufgabe, 1 motorische Aufgabe). Die zerebralen Symptome einer Höhenkrankheit wurden mittels des LLS bewertet und der Einfluss einer Höhenkrankheit auf die Gehirnaktivierungsmuster im fMRT untersucht. Resultate: Die mittlere BOLD-Signalveränderung während Normoxie betrug bei motorischer Stimulation 2,43 ± 0,80% und bei visueller Stimulation 3,49 ± 1,41%. Bei motorischer Stimulation betrug sie nach Kurzzeithypoxie 0,55 ± 0,30% und 0,82 ± 0,62% nach Langzeithypoxie. Bei visueller Stimulation betrug die mittlere Signaländerung aufgrund von Kurzzeithypoxie 1,79 ± 0,69 und aufgrund Langzeithypoxie 2,02 ± 1,18%. ANOVA-Messungen mit den Faktoren Aufgabe (motorisch, visuell) und hypoxische Bedingungen (Kurzzeithypoxie, Langzeithypoxie) zeigten einen Effekt der Aufgabe (F (1, 15) = 52.10, p <0.001), aber keinen Effekt der hypoxischen Bedingung (F (1, 15) = 1,79, p = ns) auf die BOLD Signalwertänderungen. Schlussfolgerungen: Hypoxie führte zu einer verminderten Hirnaktivität im fMRT bei motorischer und visueller Stimulation trotz erhaltener Hirnfunktion. Die mit der Gehirnaktivierung verbundenen Veränderungen der Oxygenierung scheinen eher Einfluss auf den motorischen Bereich als den visuellen Kortex zu haben. Die Adaptationsfähigkeit an chronische hypoxische Zustände scheint sich demzufolge zwischen dem motorischen und dem visuellen System zu unterscheiden

Trigger factors and mechanisms in migraine

Migraine is a severe headache syndrome, affecting approximately 33% of females and 13% of males. Patients suffer from recurring headache episodes in combination with nausea, vomiting, phono and photophobia. It is a paroxysmal disorder for which several several trigger factors have been identified by patients. This thesis has focused on the relation between i) psychosocial stress, ii) nitroglycerin and iii) hypoxia and the occurrence of a migraine attack, as well as the mechanism of action. The first conclusion is that, in contrast to previous studies, we could not detect a correlation between psychosocial stress and migraine. The second conclusion is that normobaric hypoxia might be a trigger factor for migraine possibly through the development of mild cerebral edema. The third conclusion is that migraine can be triggered by nitroglycerin through a vascular effect without any indication of vasodilation in cerebral or meningeal arteries during the delayed provoked attack.Leiden University, Astra Zeneca B.V., Stichting Het Remmert Adriaan Laan Fonds, Janssen-Cilag B.V., Menarini Farma Nederland, Glaxo Smith Kline, Teva Pharma NL, Sanofi Aventis, Nederlandse Hoofdpijn Vereniging, JE Jurriaanse StichtingUBL - phd migration 201

Menthol mouth swilling and endurance running performance in the heat

Heat challenges multiple physiological systems, and its effects are heavily felt by endurance athletes due to the duration and intensity that must be sustained in competition and training sessions. Runners may demonstrate impaired thermoregulatory responses or opportunities due to lower rates of convective cooling and fewer opportunities to provide cooling interventions during exercise than other endurance athletes e.g. cyclists. Cooling strategies may be employed before or during exercise to minimise the effects of heat exposure, and their effects have been studied for at least three Olympic cycles. Hence, the optimisation of timing and method of delivery of cooling provision, with the addition of any novel strategies, would be of benefit to the contemporary sport and exercise science practitioner. Initially this thesis sought to better understand the effects of cooling strategies upon time trial performance in endurance sports with a systematic review and meta-analysis. The efficacy of strategies was assessed with respect to intervention timing (pre or per-cooling or both) and method of delivery (oral or topical or both). Cooling strategies were found to provide small but ecologically relevant improvements in time trial performance, especially when administered during the exercise bout to the oral cavity; the addition of menthol was seen to possibly enhance ergogenic effects. Hence, a second systematic review regarding external or internal application of menthol was conducted and found that menthol demonstrated improvements in performance when applied internally, most likely due to altered thermal and ventilatory responses. A range in menthol concentrations and dilution methods was noted in the literature, establishing a clear need for a randomised trial to ascertain menthol concentration preference. Following appropriate dilution, 0.1% menthol was determined to be preferred; colour preference was also established to maximise the perceptual cooling effect of menthol solution. This solution was then used (without colour to ensure blindness) in subsequent investigations. At rest this solution was shown to improve perceptions of thermal comfort, thermal sensation and thirst, when compared to carbohydrate and water swilling. Two exercise trials were conducted: the first examined the effects of menthol mouth swilling upon physiological and perceptual markers over four minute intervals at a range of pertinent running speeds (14-20km.h-1), and following 1km time trial performance. Effects on time trial performance were unclear, as were the effects in physiological parameters. Thermal comfort however was improved, with menthol mouth swilling counterintuitively increasing thermal sensation and thirst in the heat (35oC), but i ameliorating these factors in the cold (15oC). Secondly, at a fixed rating of perceived exertion, corresponding to 2mmol.L-1 blood lactate, runners demonstrated a lower oxygen consumption following menthol mouth swilling for the latter two thirds of a 30-minute training session than compared to no swill or ice swilling. No changes in ventilation were shown, and the perceptual responses at a group level were unclear – suggesting that whilst menthol may improve the oxygen cost of running at a fixed rating of perceived exertion, this does not correspond to improvements in thermoregulatory perception in this sample. Qualitative responses regarding the swill from the athletes involved in the exercise studies were collated and menthol was considered an enjoyable and useful strategy by the athletes. Further research is required to assess if these hedonic and utilitarian perspectives are rated as highly in more ecologically valid environments; the athletes indicated this would be the case. The findings presented in this thesis demonstrate that a light blue or light green 0.1% menthol mouth rinse is preferred and can alleviate thermal sensation and thirst, and improve thermal comfort at rest in the heat. During exercise in a small sample of trained distance runners, menthol mouth swilling may alleviate perceptual symptoms of heat exposure without necessarily improving performance, dependent upon the running speeds chosen. Furthermore, menthol mouth swilling is considered a pleasant and potentially ergogenic strategy by athletes who have used it, suggesting that even in the absence of performance or physiological enhancements that exceed the typical coefficient of variation in performance, menthol mouth swilling is a viable nutritional support strategy for trained distance runners, when exercising in the heat

Modern Telemetry

Telemetry is based on knowledge of various disciplines like Electronics, Measurement, Control and Communication along with their combination. This fact leads to a need of studying and understanding of these principles before the usage of Telemetry on selected problem solving. Spending time is however many times returned in form of obtained data or knowledge which telemetry system can provide. Usage of telemetry can be found in many areas from military through biomedical to real medical applications. Modern way to create a wireless sensors remotely connected to central system with artificial intelligence provide many new, sometimes unusual ways to get a knowledge about remote objects behaviour. This book is intended to present some new up to date accesses to telemetry problems solving by use of new sensors conceptions, new wireless transfer or communication techniques, data collection or processing techniques as well as several real use case scenarios describing model examples. Most of book chapters deals with many real cases of telemetry issues which can be used as a cookbooks for your own telemetry related problems