To track evolution of autonomic responses during orthostasis in men and women, we used discrete pseudo-Wigner distribution based time-frequency analysis to compute dominant frequencies and spectral powers in RR intervals and Systolic Blood Pressure (SBP). Data were collected from 38 healthy volunteers (22 men, 16 women) during 10 min supine posture followed by 30 min of 700 head up tilt. The RR intervals were computed from ECG and systolic blood pressure was and spectral amplitudes of RR intervals were integrated in two regions viz., Low Frequency (LF) region defined between 0.05-0.15 Hz and High Frequency region (HF), sometimes referred to as respiratory frequency region, defined as mean breathing frequency of the individual +/- one standard deviation. Dominant frequencies of RR intervals in the LF region decreased in both men and women. There were no significant differences between men and women as far as the SBP data were concerned for the dominant frequencies, however women had higher values than men. Dominant frequencies of RR intervals in the HF region increased both in men and women from supine to tilt. No significant differences in dominant frequencies were found between men and women. Also there were no significant differences even for the SBP data, however men had higher values than women Integrated powers within the auto spectra of RR showed that in the HF region, power decreased significantly for both men (pandlt;0.005), and women (pandlt;0.001) during tilt compared to supine. However, the HF power in women was significantly higher for men during both supine (pandlt;0.001), and tilt (pandlt;0.005). In LF region integrated power spectrum showed no significant difference between men and women although women showed a slight increase from supine to tilt. These results suggest that men have a higher sympathetic control while women have greater para-sympathetic influence.

Despite recent research advances, there are still several common medical conditions whose underlying mechanisms are poorly understood. In conditions with few or diffuse physical findings, it can be difficult to diagnose and determine the state of the condition and its effects on working ability or performance, and the health care practitioners have to rely on the patient’s self-reports. Identification of objective measurements that are sensitive enough to aid in diagnosis or determination of the state of these conditions would thus be valuable. Psychophysiological measurements are generally non-invasive and have the potential to serve as such diagnostic or prognostic tools. In this thesis, psychophysiological reactions to different stressors were recorded in two selected medical conditions; namely motion sickness and chronic trapezius myalgia (musculoskeletal pain). These subjective conditions are unpleasant, unwanted and apparently serve no survival purpose. It is therefore important to elucidate any physical findings associated with them to, eventually, find new means to prevent the development of these conditions or to ameliorate symptoms. The overall aim of the thesis was to explore the development of psychophysiological responses to stressors in relation to performance and subjective reports in healthy individuals and in women with chronic trapezius myalgia. More in detail, the purpose was to identify psychophysiological responses that could provide information about the mechanisms behind, or serve as candidates for characterization of motion sickness and chronic trapezius myalgia, respectively. Responses to motion sickness, triggered by optokinetic stimulation, were studied in healthy individuals, whereas responses to repetitive low-force work and psychosocial stress were studied in women with chronic trapezius myalgia and in pain-free controls. In both medical conditions, the psychophysiological responses were accompanied by subjective reports. The effects of motion sickness on two different aspects of memory performance were tested during exposure to optokinetic stimulation. In the studies of chronic trapezius myalgia, psychophysiological responses were also related to health status, i.e., being a patient or a pain-free control and measurements of pain intensity, psychological symptoms, sleep-related problems and quality of life. The psychophysiological responses to optokinetic stimulation were inconclusive. Moderate levels of motion sickness did not affect memory performance, whereas decreased short term memory performance was seen in subjects reporting high levels of motion sickness. The autonomic responses and stress hormone secretion in response to low-force repetitive work and psychosocial stress in the chronic trapezius myalgia group were similar to those of the pain-free controls. However, muscle activity in the trapezius muscle was generally higher in the chronic trapezius myalgia group. There were indications of negative psychological states being related to a slower response and lower circadian variations of stress hormone secretion. With the present methods, it was possible to measure general stress responses but none of the measurements showed sufficient specificity to serve as predictors or indicators of motion sickness and chronic musculoskeletal pain, respectively. Summarizing, I cannot objectively measure how you feel; I still have to rely on your description of your condition.

<p>MobileMe is a recently developed system for monitoring and recording physiological variables. It is wireless, and can therefore be suitable for field research, for example when measuring motion sickness symptoms.</p><p>The aim of this thesis was to conclude whether the MobileMe recording system was valid for research studies. A validation study, consisting of two parts and including 10 subjects, was performed. The first part was a laboratory study, where data from MobileMe and a reference equipment were compared. A field study was also performed, onboard a combat boat, to determine the equipment’s validity in uncontrolled environments. Furthermore, the field study included an investigation of motion sickness symptoms, and provided data for evaluation of motion sickness rating scales.</p><p>Statistical results from the laboratory study, and results from evaluation of data from the field study, showed that MobileMe was valid in both controlled and uncontrolled environments.</p>

MobileMe is a recently developed system for monitoring and recording physiological variables. It is wireless, and can therefore be suitable for field research, for example when measuring motion sickness symptoms. The aim of this thesis was to conclude whether the MobileMe recording system was valid for research studies. A validation study, consisting of two parts and including 10 subjects, was performed. The first part was a laboratory study, where data from MobileMe and a reference equipment were compared. A field study was also performed, onboard a combat boat, to determine the equipment’s validity in uncontrolled environments. Furthermore, the field study included an investigation of motion sickness symptoms, and provided data for evaluation of motion sickness rating scales. Statistical results from the laboratory study, and results from evaluation of data from the field study, showed that MobileMe was valid in both controlled and uncontrolled environments.

Motivation Hypertension is a pertinent health problem for urban black African men (hereafter referred to as African). Sympathetic hyperactivity and a dominant α-adrenergic response pattern have both been implicated as contributing factors to their poor cardiovascular health. In addition to the deleterious effect of neurogenic hypertension on target organs, sympathetic hyperactivity may promote the accelerated progression of left ventricular hypertrophy and structural vascular disease. Aim The overarching aim of this study is to scrutinize autonomic control of the cardiovascular system in a cohort of urban African and Caucasian men during a mental challenge. Associations were investigated between potential sympatho-vagal imbalance, blood pressure and target organ damage markers to determine cardiovascular risk in ethnic male groups. Methodology The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study involved the participation of 200 male teachers (99 African and 101 Caucasian) in the Kenneth Kaunda Education District of the North-West Province, South Africa. Of the participant group, HIV-infected (13 African) and clinically confirmed diabetics (1 Caucasian and 6 African men) were excluded from further analyses. Stratification was based on ethnicity and further as indicated through statistical interaction effects. Cardiovascular and autonomic responses were assessed during rest and on stressor exposure (cold pressor test and Stroop colour-word conflict test). Autonomic measures included baroreceptor sensitivity (BRS), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and nitric oxide metabolite (NOx) levels. Cardiovascular variables consisted of blood pressure, cardiac output, stroke volume, total peripheral resistance, heart rate, arterial compliance and ST-segment from the 12-lead electrocardiogram. Markers of target organ damage included the Cornell product (indication of left ventricular hypertrophy) and carotid intima-media thickness as indication of structural vascular disease. Means and proportions were compared by means of standard t-test and Chi-square test, respectively. Significant differences of mean cardiovascular and autonomic measures between ethnic male groups were also determined through analysis of covariance. Uni- and multivariate regression analyses were employed to demonstrate associations between target organ damage, cardiovascular and autonomic markers. Results and conclusion of each manuscript To assess autonomic nervous system and cardiovascular function as well as target organ damage, we clearly focussed on responses where our participants were challenged. Markers of autonomic responses assessed were baroreceptor sensitivity, 3-methoxy-4-hydroxyphenylglycol and nitric oxide metabolites.  The first manuscript (Chapter 2) focused on left ventricular hypertrophy as marker of target organ damage, blood pressure and baroreceptor sensitivity as marker of autonomic function. The objective was to determine whether BRS was significantly lower in African men than in the Caucasian men. Furthermore, the possible association between attenuation of BRS and increased levels of ambulatory blood pressure as well as left ventricular hypertrophy was investigated in these population groups. Results revealed that the African men had significantly lower BRS stress responses. This attenuated BRS profile was coupled with dominant α-adrenergic response patterns, which was associated with an elevation of ambulatory blood pressure. BRS attenuation (rest and stress response) was not associated with left ventricular hypertrophy. It was concluded that lower BRS, especially during stress, may pose a significant health threat for urban African men regarding the development or promotion of α-adrenergic-driven hypertension and higher cardiovascular disease risk.  The aim of the second sub-study (Chapter 3) was to investigate possible associations between structural vascular disease (carotid intima-media thickness as marker), autonomic function (MHPG as marker) and nocturnal blood pressure in the African and Caucasian men. Results showed a higher prevalence of nocturnal hypertension in the African men, with night-time blood pressure significantly higher compared to the Caucasian men. In the African and Caucasian men, carotid intima-media thickness was linearly predicted by nocturnal systolic and diastolic blood pressure respectively. In conclusion, no associations were demonstrated between MHPG and carotid intimamedia thickness or between MHPG and nocturnal blood pressure. Elevated nocturnal blood pressure evidently seems to promote structural vascular disease in this cohort of urban African and Caucasian men.  The aim of the third manuscript presented in Chapter 4, was to investigate bioavailability of NO during mental challenge (autonomic function marker) and the possible association with structural vascular disease (carotid intima-media thickness as marker). In the African men, an attenuated NOx response was demonstrated to the Stroop colour-word conflict test. After stratification into high and low NOx response groups, in the African men with a low NOx response enhanced α-adrenergic with significant STsegment depression responses was demonstrated indicating reduced myocardial oxygen supply during mental stressor exposure. Only in the African men, a ST-segment depression was significantly associated with structural vascular disease. It was concluded that the African men demonstrated a vulnerable cardiovascular profile. In this cohort of African men, the significant association between structural vascular disease and myocardial ischemia may particularly indicate a possible higher risk for future cardiovascular events. General conclusion Through the assessment of autonomic and cardiovascular responses a possible higher cardiovascular risk was demonstrated in the African men. In this cohort sympathetic hyperactivity was evident, coupled with dominant vascular response patterns and reduced myocardial oxygen supply during mental stress exposure. Based on these findings, this population group’s risk for accelerated target organ damage, as well as for future cardiovascular events, appear significantly higher than those of the Caucasian male cohort. / Thesis (PhD (Physiology))--North-West University, Potchefstroom Campus, 2013.

Motivation Hypertension is a pertinent health problem for urban black African men (hereafter referred to as African). Sympathetic hyperactivity and a dominant α-adrenergic response pattern have both been implicated as contributing factors to their poor cardiovascular health. In addition to the deleterious effect of neurogenic hypertension on target organs, sympathetic hyperactivity may promote the accelerated progression of left ventricular hypertrophy and structural vascular disease. Aim The overarching aim of this study is to scrutinize autonomic control of the cardiovascular system in a cohort of urban African and Caucasian men during a mental challenge. Associations were investigated between potential sympatho-vagal imbalance, blood pressure and target organ damage markers to determine cardiovascular risk in ethnic male groups. Methodology The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study involved the participation of 200 male teachers (99 African and 101 Caucasian) in the Kenneth Kaunda Education District of the North-West Province, South Africa. Of the participant group, HIV-infected (13 African) and clinically confirmed diabetics (1 Caucasian and 6 African men) were excluded from further analyses. Stratification was based on ethnicity and further as indicated through statistical interaction effects. Cardiovascular and autonomic responses were assessed during rest and on stressor exposure (cold pressor test and Stroop colour-word conflict test). Autonomic measures included baroreceptor sensitivity (BRS), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and nitric oxide metabolite (NOx) levels. Cardiovascular variables consisted of blood pressure, cardiac output, stroke volume, total peripheral resistance, heart rate, arterial compliance and ST-segment from the 12-lead electrocardiogram. Markers of target organ damage included the Cornell product (indication of left ventricular hypertrophy) and carotid intima-media thickness as indication of structural vascular disease. Means and proportions were compared by means of standard t-test and Chi-square test, respectively. Significant differences of mean cardiovascular and autonomic measures between ethnic male groups were also determined through analysis of covariance. Uni- and multivariate regression analyses were employed to demonstrate associations between target organ damage, cardiovascular and autonomic markers. Results and conclusion of each manuscript To assess autonomic nervous system and cardiovascular function as well as target organ damage, we clearly focussed on responses where our participants were challenged. Markers of autonomic responses assessed were baroreceptor sensitivity, 3-methoxy-4-hydroxyphenylglycol and nitric oxide metabolites.  The first manuscript (Chapter 2) focused on left ventricular hypertrophy as marker of target organ damage, blood pressure and baroreceptor sensitivity as marker of autonomic function. The objective was to determine whether BRS was significantly lower in African men than in the Caucasian men. Furthermore, the possible association between attenuation of BRS and increased levels of ambulatory blood pressure as well as left ventricular hypertrophy was investigated in these population groups. Results revealed that the African men had significantly lower BRS stress responses. This attenuated BRS profile was coupled with dominant α-adrenergic response patterns, which was associated with an elevation of ambulatory blood pressure. BRS attenuation (rest and stress response) was not associated with left ventricular hypertrophy. It was concluded that lower BRS, especially during stress, may pose a significant health threat for urban African men regarding the development or promotion of α-adrenergic-driven hypertension and higher cardiovascular disease risk.  The aim of the second sub-study (Chapter 3) was to investigate possible associations between structural vascular disease (carotid intima-media thickness as marker), autonomic function (MHPG as marker) and nocturnal blood pressure in the African and Caucasian men. Results showed a higher prevalence of nocturnal hypertension in the African men, with night-time blood pressure significantly higher compared to the Caucasian men. In the African and Caucasian men, carotid intima-media thickness was linearly predicted by nocturnal systolic and diastolic blood pressure respectively. In conclusion, no associations were demonstrated between MHPG and carotid intimamedia thickness or between MHPG and nocturnal blood pressure. Elevated nocturnal blood pressure evidently seems to promote structural vascular disease in this cohort of urban African and Caucasian men.  The aim of the third manuscript presented in Chapter 4, was to investigate bioavailability of NO during mental challenge (autonomic function marker) and the possible association with structural vascular disease (carotid intima-media thickness as marker). In the African men, an attenuated NOx response was demonstrated to the Stroop colour-word conflict test. After stratification into high and low NOx response groups, in the African men with a low NOx response enhanced α-adrenergic with significant STsegment depression responses was demonstrated indicating reduced myocardial oxygen supply during mental stressor exposure. Only in the African men, a ST-segment depression was significantly associated with structural vascular disease. It was concluded that the African men demonstrated a vulnerable cardiovascular profile. In this cohort of African men, the significant association between structural vascular disease and myocardial ischemia may particularly indicate a possible higher risk for future cardiovascular events. General conclusion Through the assessment of autonomic and cardiovascular responses a possible higher cardiovascular risk was demonstrated in the African men. In this cohort sympathetic hyperactivity was evident, coupled with dominant vascular response patterns and reduced myocardial oxygen supply during mental stress exposure. Based on these findings, this population group’s risk for accelerated target organ damage, as well as for future cardiovascular events, appear significantly higher than those of the Caucasian male cohort. / Thesis (PhD (Physiology))--North-West University, Potchefstroom Campus, 2013.

O núcleo leito da estria terminal (NLET) é uma estrutura límbica envolvida na expressão de respostas relacionadas à ansiedade. O NLET é um dos principais alvos de inervação noradrenérgica no sistema nervoso central e evidências sugerem uma ativação desta neurotransmissão em situações aversivas, em particular aquelas associadas ao medo condicionado. Assim, o presente estudo investigou o envolvimento do sistema noradrenérgico do NLET na modulação de respostas comportamentais e autonômicas induzidas pelo medo condicionado contextual (MCC) em ratos. Animais condicionados apresentaram resposta comportamental (congelamento) e alterações autonômicas, como aumento da pressão arterial média e da frequência cardíaca e queda da temperatura cutânea após serem re-expostos ao contexto previamente pareado com choques nas patas. Esses efeitos foram atenuados pela injeção de L-propranolol e fentolamina, antagonistas não seletivos dos adrenoceptores e , respectivamente, no NLET. Adicionalmente, também foi observado que a administração de WB4101, antagonista seletivo de adrenoceptores 1, e de CGP20712, antagonista seletivo de adrenoceptores 1, no NLET, reduziu a resposta emocional condicionada (REC) contextual, sugerindo que a neurotransmissão noradrenérgica no NLET, através da ativação dos receptores 1 e 1 adrenérgicos estaria envolvida na expressão das respostas induzidas pelo MCC. Além disso, dados da literatura indicam que a ativação dos receptores adrenérgicos 1 no NLET aumenta a liberação de glutamato de forma dependente da ativação de receptores CRF1. Portanto, o presente estudo também investigou uma possível interação entre a neurotransmissão noradrenérgica e os sistemas CRFérgico, glutamatérgico e nitrérgico no NLET sobre a modulação da REC contextual. A administração de reboxetina, um inibidor da recaptação de noradrenalina, aumentou o tempo de congelamento e as respostas autonômicas após reexposição ao contexto aversivo. Esses efeitos foram bloqueados pela administração prévia de antagonista dos adrenoceptores 1 e 1, WB4101 e CGP20712 respectivamente, do antagonista CRF1, CP376395, do antagonista de receptores NMDA, AP7 e do inibidor da óxido nítrico sintase neuronal, NPLA. Similar à reboxetina, a urocortina, um agonista de receptores CRF, aumentou a REC após a re-exposição ao contexto aversivo. Esses efeitos foram bloqueados pelo CP376395 e também pelo AP7 e NPLA, mas não pelo WB4101 e CGP20712. O presente estudo demonstra que o sistema noradrenérgico no NLET está envolvido na REC observada no modelo do MCC de forma dependente da ativação de receptores CRF1 e dos sistemas glutamatérgico e nitrérgico. / The bed nucleus of the stria terminalis (BNST) is a limbic structure that has been associated to the expression of anxiety responses. BNST is one of the main targets of noradrenergic innervation in the central nervous system and evidence suggests an activation of this neurotransmission in aversive situations, particularly fear conditioning. Thus, the present study investigated the involvement of BNST noradrenergic system in modulating of behavioral and autonomic responses induced by contextual fear conditioning (CFC) in rats. The conditioned animals showed significant behavioral response (freezing) and autonomic changes such as increased in mean arterial pressure, heart rate and decreased in the tail temperature after re-exposure to context. These effects were attenuated by intra-BNST injection of L-propranolol and phentolamine, non-selective antagonists of and -adrenoceptors, respectively. Additionally, it was also observed that the administration of WB4101, a selective 1 adrenoceptor antagonist, and CGP20712, selective 1 adrenoceptor antagonist, in the BNST reduced conditioned emotional response (CER), suggesting that the BNST noradrenergic neurotransmission through the activation of adrenergic receptors, especially 1 and 1-adrenergic receptors, is involved in the expression of CER. Moreover, evidence shows that activation of 1 adrenoreceptor increases the release of glutamate by CRF1 receptor activation. Therefore, this study also investigated the involvement of CRF, glutamatergic and nitrergic systems in the noradrenergic neurotransmission modulation of CER induced by CFC. Administration of reboxetine, a norepinephrine reuptake inhibitor, significantly increased freezing behavior and induced autonomic responses after re-exposure to aversive context. These effects were blocked by previous administration of the antagonist of 1 and 1-adrenoceptor, WB4101 and CGP20712 respectively, CRF1 antagonist, CP376395, an NMDA receptor antagonist, AP7, and inhibitor of neuronal nitric oxide synthase, NPLA. Similar to reboxetine, urocortin significantly induced CER. These effects induced by urocortin were blocked by CP376395, NPLA and AP7, but not by CGP20712 and WB4101. The present study demonstrates that BNST noradrenergic system is involved in CER observed in CFC model, possibly interacting with CRF, nitrergic and glutamatergic systems.

O núcleo leito da estria terminal (NLET) é uma estrutura límbica envolvida na expressão de respostas relacionadas à ansiedade. O NLET é um dos principais alvos de inervação noradrenérgica no sistema nervoso central e evidências sugerem uma ativação desta neurotransmissão em situações aversivas, em particular aquelas associadas ao medo condicionado. Assim, o presente estudo investigou o envolvimento do sistema noradrenérgico do NLET na modulação de respostas comportamentais e autonômicas induzidas pelo medo condicionado contextual (MCC) em ratos. Animais condicionados apresentaram resposta comportamental (congelamento) e alterações autonômicas, como aumento da pressão arterial média e da frequência cardíaca e queda da temperatura cutânea após serem re-expostos ao contexto previamente pareado com choques nas patas. Esses efeitos foram atenuados pela injeção de L-propranolol e fentolamina, antagonistas não seletivos dos adrenoceptores e , respectivamente, no NLET. Adicionalmente, também foi observado que a administração de WB4101, antagonista seletivo de adrenoceptores 1, e de CGP20712, antagonista seletivo de adrenoceptores 1, no NLET, reduziu a resposta emocional condicionada (REC) contextual, sugerindo que a neurotransmissão noradrenérgica no NLET, através da ativação dos receptores 1 e 1 adrenérgicos estaria envolvida na expressão das respostas induzidas pelo MCC. Além disso, dados da literatura indicam que a ativação dos receptores adrenérgicos 1 no NLET aumenta a liberação de glutamato de forma dependente da ativação de receptores CRF1. Portanto, o presente estudo também investigou uma possível interação entre a neurotransmissão noradrenérgica e os sistemas CRFérgico, glutamatérgico e nitrérgico no NLET sobre a modulação da REC contextual. A administração de reboxetina, um inibidor da recaptação de noradrenalina, aumentou o tempo de congelamento e as respostas autonômicas após reexposição ao contexto aversivo. Esses efeitos foram bloqueados pela administração prévia de antagonista dos adrenoceptores 1 e 1, WB4101 e CGP20712 respectivamente, do antagonista CRF1, CP376395, do antagonista de receptores NMDA, AP7 e do inibidor da óxido nítrico sintase neuronal, NPLA. Similar à reboxetina, a urocortina, um agonista de receptores CRF, aumentou a REC após a re-exposição ao contexto aversivo. Esses efeitos foram bloqueados pelo CP376395 e também pelo AP7 e NPLA, mas não pelo WB4101 e CGP20712. O presente estudo demonstra que o sistema noradrenérgico no NLET está envolvido na REC observada no modelo do MCC de forma dependente da ativação de receptores CRF1 e dos sistemas glutamatérgico e nitrérgico. / The bed nucleus of the stria terminalis (BNST) is a limbic structure that has been associated to the expression of anxiety responses. BNST is one of the main targets of noradrenergic innervation in the central nervous system and evidence suggests an activation of this neurotransmission in aversive situations, particularly fear conditioning. Thus, the present study investigated the involvement of BNST noradrenergic system in modulating of behavioral and autonomic responses induced by contextual fear conditioning (CFC) in rats. The conditioned animals showed significant behavioral response (freezing) and autonomic changes such as increased in mean arterial pressure, heart rate and decreased in the tail temperature after re-exposure to context. These effects were attenuated by intra-BNST injection of L-propranolol and phentolamine, non-selective antagonists of and -adrenoceptors, respectively. Additionally, it was also observed that the administration of WB4101, a selective 1 adrenoceptor antagonist, and CGP20712, selective 1 adrenoceptor antagonist, in the BNST reduced conditioned emotional response (CER), suggesting that the BNST noradrenergic neurotransmission through the activation of adrenergic receptors, especially 1 and 1-adrenergic receptors, is involved in the expression of CER. Moreover, evidence shows that activation of 1 adrenoreceptor increases the release of glutamate by CRF1 receptor activation. Therefore, this study also investigated the involvement of CRF, glutamatergic and nitrergic systems in the noradrenergic neurotransmission modulation of CER induced by CFC. Administration of reboxetine, a norepinephrine reuptake inhibitor, significantly increased freezing behavior and induced autonomic responses after re-exposure to aversive context. These effects were blocked by previous administration of the antagonist of 1 and 1-adrenoceptor, WB4101 and CGP20712 respectively, CRF1 antagonist, CP376395, an NMDA receptor antagonist, AP7, and inhibitor of neuronal nitric oxide synthase, NPLA. Similar to reboxetine, urocortin significantly induced CER. These effects induced by urocortin were blocked by CP376395, NPLA and AP7, but not by CGP20712 and WB4101. The present study demonstrates that BNST noradrenergic system is involved in CER observed in CFC model, possibly interacting with CRF, nitrergic and glutamatergic systems.