Effect of Aging on Muscle-Pump Baroreflex of Individual Leg Muscles During Standing.

Activation of leg muscles is an important component in the regulation of blood pressure during standing, failure of which could result in syncope and falls. Our previous work demonstrated baroreflex mediated activation of leg muscles (muscle-pump baroreflex) as an important factor in the regulation of blood pressure during standing; however, the effect of aging on the muscle-pump baroreflex of individual leg muscles during standing remains to be understood. Here, the interaction between systolic blood pressure (SBP) and the activation of lateral gastrocnemius (LG), medial gastrocnemius (MG), tibialis anterior (TA), and soleus (SOL) muscles during standing was quantified. Beat-to-beat heart period (RR interval), SBP, electromyography impulse (EMGimp) were derived from continuously acquired electrocardiography, finger blood pressure, and calf-electromyography, respectively. The cardiac baroreflex (SBP→RR) causality (0.88 ± 0.08 vs. 0.94 ± 0.03, p = 0.01), percent time with significant coherence (%SC: 50.95 ± 23.31 vs. 76.75 ± 16.91, p = 0.001), and gain (4.39 ± 4.38 vs. 13.05 ± 8.11, p < 0.001) was lower in older (69 ± 4 years) compared to young (26 ± 2 years) persons. Muscle-pump baroreflex (SBP→EMGimp) causality of LG (0.81 ± 0.08 vs. 0.88 ± 0.05, p = 0.01) and SOL (0.79 ± 0.11 vs. 0.88 ± 0.04, p = 0.01) muscles was lower in older compared to young persons. %SC was lower for all muscles in the older group (LG, p < 0.001; MG, p = 0.01; TA, p = 0.01; and SOL, p < 0.001) compared to young. The study outcomes highlighted impairment in muscle-pump baroreflex with age in addition to cardiac baroreflex. The findings of the study can assist in the development of an effective system for monitoring orthostatic tolerance via cardiac and muscle-pump baroreflexes to mitigate syncope and falls.

Comparison of Autonomic Control of Blood Pressure During Standing and Artificial Gravity Induced via Short-Arm Human Centrifuge.

Autonomic control of blood pressure is essential toward maintenance of cerebral perfusion during standing, failure of which could lead to fainting. Long-term exposure to microgravity deteriorates autonomic control of blood pressure. Consequently, astronauts experience orthostatic intolerance on their return to gravitational environment. Ground-based studies suggest sporadic training in artificial hypergravity can mitigate spaceflight deconditioning. In this regard, short-arm human centrifuge (SAHC), capable of creating artificial hypergravity of different g-loads, provides an auspicious training tool. Here, we compare autonomic control of blood pressure during centrifugation creating 1-g and 2-g at feet with standing in natural gravity. Continuous blood pressure was acquired simultaneously from 13 healthy participants during supine baseline, standing, supine recovery, centrifugation of 1-g, and 2-g, from which heart rate (RR) and systolic blood pressure (SBP) were derived. The autonomic blood pressure regulation was assessed via spectral analysis of RR and SBP, spontaneous baroreflex sensitivity, and non-linear heart rate and blood pressure causality (RR↔SBP). While majority of these blood pressure regulatory indices were significantly different (p < 0.05) during standing and 2-g centrifugation compared to baseline, no change (p > 0.05) was observed in the same indices during 2-g centrifugation compared to standing. The findings of the study highlight the capability of artificial gravity (2-g at feet) created via SAHC toward evoking blood pressure regulatory controls analogous to standing, therefore, a potential utility toward mitigating deleterious effects of microgravity on cardiovascular performance and minimizing post-flight orthostatic intolerance in astronauts.

Non-linear Heart Rate and Blood Pressure Interaction in Response to Lower-Body Negative Pressure.

Early detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP) from 0 to -40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate (i.e., baroreflex response) is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG) signals were acquired simultaneously from young, healthy participants (27 ± 1 years, N = 27) during each LBNP stage, from which heart rate (represented by RR interval), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were derived. The heart rate and blood pressure causal interaction (RR↔SBP and RR↔MAP) was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR→SBP and RR→MAP) showed a significantly (p < 0.001) higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP→RR and MAP→RR). In response to moderate category hemorrhage (-30 mmHg LBNP), no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10) along with the RR→SBP (p = 0.76), RR→MAP (p = 0.60), and SBP→RR (p = 0.07) causality compared to the resting stage. Contrarily, a significant elevation in the MAP→RR (p = 0.004) causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP→RR) of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from the resting stage. Therefore, monitoring baroreflex causality can have a clinical utility in making triage decisions to impede hemorrhage progression.

Significant role of the cardiopostural interaction in blood pressure regulation during standing.

Cardiovascular and postural control systems have been studied independently despite the increasing evidence showing the importance of cardiopostural interaction in blood pressure regulation. In this study, we aimed to assess the role of the cardiopostural interaction in relation to cardiac baroreflex in blood pressure regulation under orthostatic stress before and after mild exercise. Physiological variables representing cardiovascular control (heart rate and systolic blood pressure), lower limb muscle activation (electromyography), and postural sway (center of pressure derived from force and moment data during sway) were measured from 17 healthy participants (25 ± 2 yr, 9 men and 8 women) during a sit-to-stand test before and after submaximal exercise. The cardiopostural control (characterized by baroreflex-mediated muscle-pump effect in response to blood pressure changes, i.e., muscle-pump baroreflex) was assessed using wavelet transform coherence and causality analyses in relation to the baroreflex control of heart rate. Significant cardiopostural blood pressure control was evident counting for almost half of the interaction time with blood pressure changes that observed in the cardiac baroreflex (36.6-72.5% preexercise and 34.7-53.9% postexercise). Thus, cardiopostural input to blood pressure regulation should be considered when investigating orthostatic intolerance. A reduction of both cardiac and muscle-pump baroreflexes in blood pressure regulation was observed postexercise and was likely due to the absence of excessive venous pooling and a less stressed system after mild exercise. With further studies using more effective protocols evoking venous pooling and muscle-pump activity, the cardiopostural interaction could improve our understanding of the autonomic control system and ultimately lead to a more accurate diagnosis of cardiopostural dysfunctions.NEW & NOTEWORTHY We examined the interaction between cardiovascular and postural control systems during standing before and after mild exercise. Significant cardiopostural input to blood pressure regulation was shown, suggesting the importance of cardiopostural integration when investigating orthostatic hypotension. In addition, we observed a reduction of baroreflex-mediated blood pressure regulation after exercise.

Vertical ground reaction force marker for Parkinson's disease.

Parkinson's disease (PD) patients regularly exhibit abnormal gait patterns. Automated differentiation of abnormal gait from normal gait can serve as a potential tool for early diagnosis as well as monitoring the effect of PD treatment. The aim of current study is to differentiate PD patients from healthy controls, on the basis of features derived from plantar vertical ground reaction force (VGRF) data during walking at normal pace. The current work presents a comprehensive study highlighting the efficacy of different machine learning classifiers towards devising an accurate prediction system. Selection of meaningful feature based on sequential forward feature selection, the swing time, stride time variability, and center of pressure features facilitated successful classification of control and PD gaits. Support Vector Machine (SVM), K-nearest neighbor (KNN), random forest, and decision trees classifiers were used to build the prediction model. We found that SVM with cubic kernel outperformed other classifiers with an accuracy of 93.6%, the sensitivity of 93.1%, and specificity of 94.1%. In comparison to other studies, utilizing same dataset, our designed prediction system improved the classification performance by approximately 10%. The results of the current study underscore the ability of the VGRF data obtained non-invasively from wearable devices, in combination with a SVM classifier trained on meticulously selected features, as a tool for diagnosis of PD and monitoring effectiveness of therapy post pathology.

Skeletal Muscle Pump Drives Control of Cardiovascular and Postural Systems.

The causal interaction between cardio-postural-musculoskeletal systems is critical in maintaining postural stability under orthostatic challenge. The absence or reduction of such interactions could lead to fainting and falls often experienced by elderly individuals. The causal relationship between systolic blood pressure (SBP), calf electromyography (EMG), and resultant center of pressure (COPr) can quantify the behavior of cardio-postural control loop. Convergent cross mapping (CCM) is a non-linear approach to establish causality, thus, expected to decipher nonlinear causal cardio-postural-musculoskeletal interactions. Data were acquired simultaneously from young participants (25 ± 2 years, n = 18) during a 10-minute sit-to-stand test. In the young population, skeletal muscle pump was found to drive blood pressure control (EMG → SBP) as well as control the postural sway (EMG → COPr) through the significantly higher causal drive in the direction towards SBP and COPr. Furthermore, the effect of aging on muscle pump activation associated with blood pressure regulation was explored. Simultaneous EMG and SBP were acquired from elderly group (69 ± 4 years, n = 14). A significant (p = 0.002) decline in EMG → SBP causality was observed in the elderly group, compared to the young group. The results highlight the potential of causality to detect alteration in blood pressure regulation with age, thus, a potential clinical utility towards detection of fall proneness.

Analysis of causal cardio-postural interaction under orthostatic stress using convergent cross mapping.

Knowledge of a cause-and-effect relationship between different physiological systems is helpful in predicting their performance under perturbations, such as orthostatic challenge. The causal coupling between representative signals of the cardiovascular and postural systems under orthostatic challenge remains unknown. Understanding the causal relationship between these two systems is critical, as their interplay is vital to maintain stable upright posture of the human body during quiet standing. In this research, convergent cross mapping (CCM) method was applied to study the causal relationship between the cardiovascular and postural systems previously shown to have coherent activity during quiet standing. Causality was studied between Systolic blood pressure (SBP)-EMG (calf muscles), EMG-COPr (resultant center of pressure), and COPr-SBP signal pairs. These signals were simultaneously recorded in a 5-minute sit-to-stand test from five young healthy participants. Strength of causality was obtained between the signal pairs in a 30-second time segments. The results from this study indicate that there exists a bidirectional causal relationship between the cardio-postural signal pairs, indicating a system level interaction to counter perturbation due to orthostatic challenge. Skeletal muscle pump was found to be driving control of SBP and COPr as the value of EMG→SBP (0.54±0.09) and EMG→COPr (0.52±0.07) were higher than the reverse causality of SBP→EMG (0.19±0.16) and COPr→EMG (0.29±0.16).

Morphological alterations in the caudate, putamen, pallidum, and thalamus in Parkinson's disease.

Like many neurodegenerative diseases, the clinical symptoms of Parkinsons disease (PD) do not manifest until significant progression of the disease has already taken place, motivating the need for sensitive biomarkers of the disease. While structural imaging is a potentially attractive method due to its widespread availability and non-invasive nature, global morphometric measures (e.g., volume) have proven insensitive to subtle disease change. Here we use individual surface displacements from deformations of an average surface model to capture disease related changes in shape of the subcortical structures in PD. Data were obtained from both the University of British Columbia (UBC) [n = 54 healthy controls (HC) and n = 55 Parkinsons disease (PD) patients] and the publicly available Parkinsons Progression Markers Initiative (PPMI) [n = 137 (HC) and n = 189 (PD)] database. A high dimensional non-rigid registration algorithm was used to register target segmentation labels (caudate, putamen, pallidum, and thalamus) to a set of segmentation labels defined on the average-template. The vertex-wise surface displacements were significantly different between PD and HC in thalamic and caudate structures. However, overall displacements did not correlate with disease severity, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). The results from this study suggest disease-relevant shape abnormalities can be robustly detected in subcortical structures in PD. Future studies will be required to determine if shape changes in subcortical structures are seen in the prodromal phases of the disease.

Physiological interdependence of the cardiovascular and postural control systems under orthostatic stress.

The cardiovascular system has been observed to respond to changes in human posture and the environment. On the same lines, frequent fallers have been observed to suffer from cardiovascular deficits. The present article aims to demonstrate the existence of interactions between the cardiovascular and postural control systems. The behavior of the two systems under orthostatic challenge was studied through novel adaptations of signal processing techniques. To this effect, the interactions between the two systems were assessed with two metrics, coherence and phase lock value, based on the wavelet transform. Measurements from the cardiovascular system (blood pressure), lower limb muscles (surface electromyography), and postural sway (center of pressure) were acquired from young healthy adults (n = 28, men = 12, age = 20-28 yr) during quiet stance. The continuous wavelet transform was applied to decompose the representative signals on a time-scale basis in a frequency region of 0.01 to 0.1 Hz. Their linear coupling was quantified through a coherence metric, and the synchrony was characterized via the phase information. The outcomes of this study present evidence that the cardiovascular and postural control systems work together to maintain homeostasis under orthostatic challenge. The inferences open a new direction of study for effects under abnormalities and extreme environmental conditions.

Alteration in cardiovascular and postural control relationship in non-fainting elderly individuals.

It is known that standing induces orthostatic stress on the cardiovascular system. Our previous works have presented that the postural control during standing and cardiovascular changes are related to each other in the health young individuals. However, it remains to be checked if such a relationship is present in the elderly individuals as well. The present study conducted experiments similar to our previous studies and collected data for the muscle activation in lower leg muscles along with blood pressure during a passive stand test. Application of wavelet transform coherence method provided time frequency distribution of the coherence between the two signals. High coherence (>threshold) was observed between the two signals suggesting a strong relationship. Additionally, a frequency dependent behavior was observed between the two signals. The results from this study present strong evidence that there is a change in the relationship between the two signals with aging.

Posture muscle relationship with cardiovascular changes under orthostatic challenge.

Lower leg muscles are known to be activated during standing. On the other hand, standing is known to induce orthostatic stress. Our recent work presented that the posture control and cardiovascular systems are related to each other. However, the relationship of the individual muscle activation with blood pressure changes is not fully understood. The present preliminary study conducted experiments to collect data for muscle activation (EMG) and blood pressure (BP) changes during quiet standing. High coherence (>threshold) values observed between the EMG and BP signals suggest a strong relationship between the two. Additionally, the results of the study suggest a compensatory relationship of different lower leg muscles with blood pressure changes during quiet standing.

Manually segmented template library for 8-year-old pediatric brain MRI data with 16 subcortical structures.

Manual segmentation of anatomy in brain MRI data taken to be the closest to the "gold standard" in quality is often used in automated registration-based segmentation paradigms for transfer of template labels onto the unlabeled MRI images. This study presents a library of template data with 16 subcortical structures in the central brain area which were manually labeled for MRI data from 22 children (8 male, [Formula: see text]). The lateral ventricle, thalamus, caudate, putamen, hippocampus, cerebellum, third vevntricle, fourth ventricle, brainstem, and corpuscallosum were segmented by two expert raters. Cross-validation experiments with randomized template subset selection were conducted to test for their ability to accurately segment MRI data under an automated segmentation pipeline. A high value of the dice similarity coefficient ([Formula: see text], [Formula: see text], [Formula: see text]) and small Hausdorff distance ([Formula: see text], [Formula: see text], [Formula: see text]) of the automated segmentation against the manual labels was obtained on this template library data. Additionally, comparison with segmentation obtained from adult templates showed significant improvement in accuracy with the use of an age-matched library in this cohort. A manually delineated pediatric template library such as the one described here could provide a useful benchmark for testing segmentation algorithms.

Statistical validation of wavelet transform coherence method to assess the transfer of calf muscle activation to blood pressure during quiet standing.

BACKGROUND: Continuous and discrete wavelet transforms have been established as valid tools to analyze non-stationary and transient signals over Fourier domain methods. Additionally, Fourier transform based coherence methods provide aggregate results but do not provide insights into the changes in coherent behavior over time, hence limiting their utility. METHODS: Statistical validation of the wavelet transform coherence (WTC) was conducted with simulated data sets. Time frequency maps of signal coherence between calf muscle electromyography (EMG) and blood pressure (BP) were obtained by WTC to provide further insight into their interdependent time-varying behavior via the skeletal muscle pump during quiet stance. Data were collected from healthy young males (n = 5, 19-28 years) during a quiet stance on a balance platform. Waveforms for EMG and BP were acquired and processed for further analysis. RESULTS: Low values of bias and standard deviation (< 0.1) were observed and the use of both simulated and real data demonstrated that the WTC method was able to identify time points of significant coherence (> Threshold) and objectively detect existence of interdependent activity between the calf muscle EMG and blood pressure. CONCLUSIONS: The WTC method effectively identified the presence of linear coupling between the EMG and BP signals during quiet standing. Future studies with more human data are needed to establish the exact characteristics of the identified relationship.

Neonatal pain-related stress predicts cortical thickness at age 7 years in children born very preterm.

BACKGROUND: Altered brain development is evident in children born very preterm (24-32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age. METHODS: 42 right-handed children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling. RESULTS: After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes. CONCLUSIONS: In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors.

Wavelet transform coherence based investigation of existence of relationship between the cardiovascular and postural control systems during orthostatic challenge.

Previous studies have established the effects of orthostatic challenge on the cardiovascular and postural control systems, but the interdependent behavior of the systems under such condition is unclear. In the present study we examined the simultaneous changes in posture muscle electromyography (EMG) and systolic blood pressure (SBP) during quiet standing in healthy young individuals. Photoplethysmography based SBP, surface EMG, electrocardiogram (Lead II ECG) and posturography data were acquired during the experiment. Wavelet transform coherence (WTC) analysis was applied to identify the zones of interdependent behavior of the systems. The WTC thresholds were identified for the specific data under investigation. The coherence was analyzed in three frequency bands namely, LF (0.05 - 0.1 Hz), VLF (0.01-0.05 Hz) and ULF (0.005 - 0.01 Hz). WTC estimates for the EMG - SBP comparison showed greater than threshold values in all three frequency bands (LF: 0.31 ± 0.02; VLF: 0.41 ± 0.01; ULF: 0.45 ± 0.01). In conclusion this study showed the existence of relationship between the posture muscle EMG and blood pressure during natural orthostatic stress, by validation based on wavelet transform coherence. Further validation is required to objectively characterize this relationship between the two systems during orthostatic stress.