Yes / Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear.

No description available.

Many epidemiological studies have named pinching, deviated wrist postures, and repetitive motion as ergonomic risk factors in the development of carpal tunnel syndrome (CTS). Evidence suggests that hypervascularization of the median nerve and increased intraneural blood flow proximal to the carpal tunnel result in response to ergonomic risk factors (finger pressing and deviated wrist postures). The purposes of this study were to 1) determine the effect of a pinch posture, with and without force exerted by the finger, thumb, or both and 2) determine the effect of repetitive wrist flexion and extension on intraneural blood flow velocity in the median nerve proximal to the carpal tunnel. Eleven healthy and eleven CTS symptomatic individuals participated in this study and completed three components: 15 pinch posture force trials, 3 repetitive wrist motion trials, and 3 static wrist posture trials. Intraneural blood flow was measured using pulse wave Doppler during each trial. Main effects of pinch posture force (F4,80 = 21.397, p < 0.001) and wrist posture (F2,40 = 14.545, p < 0.001) were observed. Trials where force was applied by the finger (2.21 cm/s), thumb (2.22 cm/s) or both (2.34 cm/s) produced higher intraneural blood flow velocities than trials with no force (1.79 cm/s) or relaxed hand (1.89 cm/s). Trials performed in flexion (2.24 cm/s) were greater than neutral (2.06 cm/s) and extension (1.97 cm/s). No interactions or main effects of time were found in response to repetitive wrist motion. These results suggest that at low force levels (6 N) it’s not how the force is applied but rather that the force is being applied that has an effect on the median nerve. Additionally these results suggest that the contribution of repetitive motion to the development of CTS may not be directly to the median nerve. / Thesis / Master of Science (MSc)

Aging results in lower exercise tolerance, manifested as decreased Critical Power (PCRIT). Aging is also associated with reduced physical activity, decreased muscle mass, and altered muscle blood flow, all of which may contribute to the age-related decrease in PCRIT. Purpose: The purpose of this study was to determine if the age-related decrease in PCRIT occurs independently of changes in physical activity and muscle mass and if it is related to impaired muscle blood flow. Methods: 10 Old (63.1 ± 2.5 years, 5 female and 5 male) and 10 Young (24.4 ± 4.0 years, 5 female and 5 male) physically active volunteers enrolled in this study. Physical activity was measured with accelerometry. Leg muscle mass was quantified with dual x-ray absorptiometry (DEXA). PCRIT and the maximum power achieved during a graded exercise test (PGXT) during single-leg knee extension exercise were determined over the course of 4 visits. On the fifth visit, vascular function of the leg was assessed with the passive leg movement (PLM) hyperemia. Subsequently, subjects performed knee extension exercise at 10 watts (W), 20 W, 90% PCRIT, and 100% PGXT while blood flow and blood pressure were measured at the femoral artery for each intensity. Results: Young and Old subjects did not differ in daily step count (Old = 13001.1  2464.0 vs Young = 13527.0  3213.8 steps, P = 0.735) or in leg lean mass (9.06  0.62 g/kg, P = 0.901). The Old subjects had a lower mass-specific PCRIT (Old = 3.20  0.94 vs Young = 4.60  0.87 W/kg, P = 0.004), vascular function (mass-specific Passive Leg Movement (PLM): Old = 79.4  38.3 vs Young = 128.8  34.9 ml/min/kg, P = 0.010) and leg blood flow at 90% PCRIT (mass-specific: Old = 378  122 vs Young = 522  124 ml/min/kg, P = 0.014) and 100% PGXT (mass-specific: Old = 391  109 vs Young = 544  136 ml/min/kg, P = 0.013). When normalized for leg muscle mass, PCRIT was strongly correlated to peak leg blood flow in response to PLM (R2 = 0.53; P < 0.001) and leg blood flow during knee extension exercise at 90% PCRIT (R2 = 0.36; P = 0.007). Conclusion: The age-related decline in PCRIT is associated with major decreases in muscle endurance and is correlated with concomitant reductions in vascular function in healthy active adults. Future research should determine if interventions known to improve vascular function can ameliorate exercise tolerance in Old adults.

A Calibrated Cuff Plethysmography device was built, tested for verification, and used to experiment on human subjects to measure the cardiovascular response of consuming a beet supplement, specifically looking at arterial compliance and pressure-area curves. Each subject was tested four times. A baseline was measured under normal conditions and after five-minute hyperemia conditions. 10 subjects were given 6 ounces of water mixed with either purple Kool-Aid (control), a SuperBeets supplement, or a SuperBeets Sport supplement and after 45 minutes, measurements were taken undergoing normal and hyperemia conditions once more. The verification testing demonstrated the calibration of the device was effectively able to measure volume changes using a stationary metal pipe and IV bag, showing an average percent error of 3.11%. Data collected during the patient experiment resulted in the expected arterial compliance curves as well as pressure-area curves, when measurements were taken properly, and the subject didn’t move. These tests were able to validate the use of the device for measuring arterial compliance and seeing distinctions between normal and hyperemic conditions. However, many issues were presented and are thoroughly addressed in this paper for future research using the same device.

This thesis investigates the effect of acute isometric handgrip exercise on cognitive function in young healthy adults / Acute whole-body exercise transiently improves cognitive function which may be mediated by increased cerebral blood flow (CBF) and arousal. Interestingly, small muscle mass exercise, like isometric handgrip exercise (IHG) may stimulate the same physiological responses as whole body-exercise and improve cognitive function. However, these effects are poorly understood, and whether sex-based differences exist in the cognitive response to IHG is unknown. Therefore, the purpose of this study was to investigate whether acute IHG improves cognitive function in young healthy adults and examine potential sex differences in the cognitive response to IHG. We hypothesized that acute IHG would improve cognitive function compared to a control condition, and that females would have greater improvements in cognitive function due to a lower exercise pressor response. To test this, 30 participants (n=15 females, mean age=23.8±3.3 years;BMI=25.3±4.1 kg/m2) completed either IHG or a control condition in a randomized-crossover design separated by at least 2 days. IHG consisted of four sets of 2-min unilateral squeezing a handgrip dynamometer at 30% maximal voluntary contraction separated by 3-min of rest. The control condition watched a nature documentary for 20-min. Hemodynamics (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate) were assessed throughout. Executive function, working memory, and processing speed were assessed via the 4-Choice, Corsi Block, and N-Back tests. Arousal was assessed using the Felt Arousal Scale (FAS). Middle cerebral artery blood velocity (MCAv) was assessed using transcranial Doppler ultrasound. Compared to the control condition, IHG significantly increased MAP (∆ 26 ± 17 mmHg; P<0.001), HR(∆ 18 ±13 bpm; P<0.001), MCAv (∆ 5.27 ± 19.4 cm/s; P<0.001), cerebrovascular resistance (∆ 0.71 ±0.69 mmHg/cm/s; P=0.003), and arousal (∆ 2 ± 2 FAS score; P<0.001). Cerebrovascular resistance was calculated as MAP/MCAv. Overall, despite increases in MCAv and arousal, there was no effect of IHG on cognitive performance, and no sex differences were observed in the cognitive response to IHG. These findings stand in opposition to emerging work and suggests that increased CBF and arousal via acute IHG are an insufficient stimulus to enhance cognitive function in young adults. Furthermore, there seems to be no moderating effect of biological sex on the cognitive response to acute IHG. / Thesis / Master of Science (MSc) / It is well known that whole-body exercise, such as running, swimming, or lifting weights, improves cognitive function. Cognitive function encompasses our ability to pay attention, remember new information, and make important decisions. We sought to investigate whether isometric handgrip exercise (IHG) could improve cognitive function in young adults, because it may be a new and accessible way to improve cognitive abilities. We also wanted to know if IHG had a different effect on cognitive function in females compared to males. To test cognitivefunction, participants played computer games that measured how their cognitive abilities were affected by IHG. In particular, we examined how IHG impacted a participant’s memory, decision making, and speed to completion. Our results show that IHG increased blood flow to the brain and made participants feel more alert compared to a control condition, however, IHG did not improve performance on the computer games. Males and females also did not differ in terms of their performance on the cognitive tests. Overall, a single session of IHG did not improve cognitive function in young adults. Although IHG did not improve cognitive function in young adults, it should be investigated in other individuals, such as older adults and people with hypertension, who may stand to gain more from IHG.

Cerebral hemodynamics monitoring is vital in the neuroscience intensive care unit to assess brain health. Diffuse optical methods using near-infrared light, e.g., near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS), allow for non-invasive prolonged monitoring of cerebral hemoglobin oxygenation and blood flow. For patients suffering from cerebral fluid or tissue volume buildup, intracranial pressure (ICP) is monitored invasively as its elevation compromises cerebral perfusion. The critical closing pressure (CrCP) is a transcranial doppler (TCD) derived non-invasive parameter that correlates with ICP; however, its use is limited due to discomfort during extended TCD measurement. I expanded on Sutin’s preliminary study using DCS to estimate CrCP and found high correlations between DCS obtained CrCP against TCD (R2: 0.77-0.83) in stroke patients. The use of DCS to monitor CrCP is advantageous because its sensors are comfortable to wear and easy to use continuously without the need of a specialized operator. However, the low DCS signal-to-noise ratio (SNR) limits the depth sensitivity and temporal resolution of CrCP measures. Following these encouraging results, I built a low-cost wireless cerebral oximeter based on multi-distance continuous wave NIRS called FlexNIRS, which exhibits high SNR (NEP < 70 fw/Hz0.5) and high sampling rate (266 Hz). This device not only quantifies cerebral oxygenation but resolves the pulsatile blood volume signal at large source-detector separations (33 mm). Using the relationship between blood flow and volume, I augmented pulsatile DCS blood flow measurements with FlexNIRS pulsatile signals. I experimentally demonstrated the high fidelity (R2: 0.98) and > 50-fold SNR improvement of the method, resulting in a one order of magnitude increase in the temporal resolution of CrCP estimates. / 2024-06-12T00:00:00Z

This dissertation develops uncertainty quantification methodologies for modeling, response analysis and optimization of diverse dynamical systems. Two distinct application platforms are considered pertaining to engineering dynamics and precision medicine. First, the recently developed Wiener path integral (WPI) technique for determining, accurately and in a computationally efficient manner, the stochastic response of diverse dynamical systems is employed for solving a high-dimensional, nonlinear system of stochastic differential equations governing the dynamics of a representative model of electrostatically coupled micromechanical oscillators. Compared to alternative modeling and solution treatments in the literature, the current development exhibits the following novelties: a) typically adopted linear, or higher-order polynomial, approximations of the nonlinear electrostatic forces are circumvented; and b) stochastic modeling is employed, for the first time, by considering a random excitation component representing the effect of diverse noise sources on the system dynamics. Further, the WPI technique is enhanced and extended based on a Bayesian compressive sampling (CS) treatment. Specifically, sparse expansions for the system response joint PDF are utilized. Next, exploiting the localization capabilities of the WPI technique for direct evaluation of specific PDF points leads to an underdetermined linear system of equations for the expansion coefficients. Furthermore, relying on a Bayesian CS solution formulation yields a posterior distribution for the expansion coefficient vector. In this regard, a significant advantage of the herein-developed methodology relates to the fact that the uncertainty of the response PDF estimates obtained by the WPI technique is quantified. Also, an adaptive scheme is proposed based on the quantified uncertainty of the estimates for the optimal selection of PDF sample points. This yields considerably fewer boundary value problems to be solved as part of the WPI technique, and thus, the associated computational cost is significantly reduced. Second, modeling and analysis of the physiological mechanism of dynamic cerebral autoregulation (DCA) is pursued based on the concept of diffusion maps. Specifically, a state-space description of DCA dynamics is considered based on arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), and their time derivatives. Next, an eigenvalue analysis of the Markov matrix of a random walk on a graph over the dataset domain yields a low-dimensional representation of the intrinsic dynamics. Further dimension reduction is made possible by accounting only for the two most significant eigenvalues. The value of their ratio indicates whether the underlying system is governed by active or hypoactive dynamics, indicating healthy or impaired DCA function, respectively. The reliability of the technique is assessed by considering healthy individuals and patients with unilateral carotid artery stenosis or occlusion. It is shown that the proposed ratio of eigenvalues can be used as a reliable and robust biomarker for assessing how active the intrinsic dynamics of the autoregulation is and for indicating healthy versus impaired DCA function. Further, an alternative joint time-frequency analysis methodology based on generalized harmonic wavelets is utilized for assessing DCA performance in patients with preeclampsia within one week postpartum, which is associated with an increased risk for postpartum maternal cerebrovascular complications. The results are compared with normotensive postpartum individuals and healthy non-pregnant female volunteers and suggest a faster, but less effective response of the cerebral autoregulatory mechanism in the first week postpartum, regardless of preeclampsia diagnosis.

Recent evidence suggests that heat, a major byproduct of exercise, may be the mediator for many vascular adaptations that come from exercise. Thus, heat therapy that increases muscle temperature in a comparable way to exercise may be an advantageous alternative for enhancing cardiovascular health in individuals where treatment with exercise is either not possible or undesired. PURPOSE: Compare the effects of exercise and heat training on resistance artery function at rest and during exercise. METHODS: Thirty-five (18 female) healthy, untrained subjects completed a 6-week training program utilizing either high intensity knee extension (KE) exercise (40 min), localized heat therapy (pulsed shortwave diathermy; 120 min), or a sham heat therapy protocol (120 min). We randomly selected 8 subjects from each group to have a temperature probe inserted into their vastus lateralis muscle during one of their training sessions to evaluate the effect of the interventions on muscle temperature. We assessed resistance artery function at rest with the passive leg movement technique (PLM) prior to and after completion of the training protocols. We assessed peak exercise blood flow (KE peak flow) and peak power output (KE peak power) during the KE graded exercise test and prior to and after completion of the training protocols. RESULTS: Peak muscle treatment temperature was significantly different between all groups with those assigned to the diathermy heat training exhibiting a higher peak temperature (~40.80°C) than those in the exercise (~37.75°C, P < 0.001) and sham training groups (~36.10°C, P < 0.001). KE peak flow during PLM increased to the same extent (P = 0.625) in both the exercise (~10.5% increase, P = 0.009) and heating groups (~8.5% increase, P = 0.044); but tended to decrease in the sham group (P = 0.087). KE peak flow increased in the exercise group (~19%, P = 0.005), but did not change in the heat group (P = 0.523) and decreased in the sham group (~7%, P = 0.020). Peak vascular conductance during KE significantly increased by ~25% in the exercise (P = 0.030) and heat (P = 0.012) groups. KE peak power increased in the exercise group by ~27% (P = 0.001) but did not significantly change in the heat (P = 0.175) and sham groups (P = 0.111). The change in vascular function, assessed via PLM, showed a correlation with both ∆KE peak flow (R = 0.55, P = 0.01) and ∆KE peak power (R = 0.56, P = .010). Likewise, ∆KE peak flow showed a strong association with ∆KE peak power (R = 0.64, P < 0.001). CONCLUSION: Localized diathermy heat treatment increased resistance artery function at rest and during exercise to a similar extent as single-leg KE exercise training but did not yield significant improvements in performance. Thus, heat training mimics some but not all of the benefits associated with exercise and may be used to replace exercise treatment to some extent.

Low-load blood flow restriction (LLBFR) training has been shown to elicit greater increases in muscle hypertrophy and strength compared to traditional low-load training, yet few studies have compared the effectiveness of different LLBFR protocols. To our knowledge, no previous study has compared the acute neuromuscular changes induced by two common LLBFR protocols: 30-15-15-15 repetitions (BFR-75) and four sets of repetitions performed to volitional failure (BFR-F). Therefore, the purpose of this study was to use surface electromyography (sEMG) to compare changes in muscle excitation and fatigue during BFR-75 and BFR-F protocols. Ten women (mean ± SD age = 22 ± 3.5 years) volunteered to participate in this investigation. Participants performed isokinetic, unilateral, concentric-eccentric, leg extension muscle actions at 30% maximal voluntary isometric contraction torque with BFR applied at 60% arterial occlusion pressure using a 12-centimeter-wide cuff. The sEMG amplitude and frequency values were measured from the rectus femoris muscle during the beginning and end of each set of exercise and analyzed using separate 2 [condition (BFR-75 and BFR-F)] x 8 [time (B1, E1, B2, E2, B3, E3, B4, E4)] repeated measures ANOVAs. For sEMG amplitude, there was no significant 2-way interaction (p = 0.486; ηₚ² = 0.118) or significant main effect for condition (p = 0.617; ηₚ² = 0.038), but there was a significant main effect for time (p < 0.001; ηₚ² = 0.520). SEMG amplitude increased across time during both protocols (B1 < E1, E2, B3, E3, B4, E4, p ≤ 0.001–0.049). For sEMG frequency, there was no significant 2-way interaction (p = 0.847; ηₚ² = 0.064) or significant main effect for condition (p = 0.825; ηₚ² = 0.007), but there was a significant main effect for time (p = 0.006; ηₚ² = 0.478). SEMG frequency decreased across time during both protocols (B1 > E1, B2, E2, B3, E3, B4, E4, p = 0.002–0.035). Thus, the implementation of the BFR-75 and BFR-F protocols elicited comparable neuromuscular responses that were consistent with fatiguing exercise, but investigators and clinicians may consider other factors such as participant/patient comfort, time, and rating of perceived exertion when determining which protocol to use.