Heart-brain synchronization breakdown in Parkinson's disease

Heart rate variability (HRV) abnormalities are potential early biomarkers in Parkinson's disease (PD) but their relationship with central autonomic network (CAN) activity is not fully understood. We analyzed the synchronization between HRV and brain activity in 31 PD patients and 21 age-matched healthy controls using blood-oxygen-level-dependent (BOLD) signals from resting-state functional brain MRI and HRV metrics from finger plethysmography recorded for 7.40 min. We additionally quantified autonomic symptoms (SCOPA-AUT) and objective autonomic cardiovascular parameters (blood pressure and heart rate) during deep breathing, Valsalva, and head-up tilt, which were used to classify the clinical severity of dysautonomia. We evaluated HRV and BOLD signals synchronization (HRV-BOLD-sync) with Pearson lagged cross-correlations and Fisher's statistics for combining window-length-dependent HRV-BOLD-Sync Maps and assessed their association with clinical dysautonomia. HRV-BOLD-sync was lower significantly in PD than in controls in various brain regions within CAN or in networks involved in autonomic modulation. Moreover, heart-brain synchronization index (HBSI), which quantifies heart-brain synchronization at a single-subject level, showed an inverse exposure-response relationship with dysautonomia severity, finding the lowest HBSI in patients with severe dysautonomia, followed by moderate, mild, and, lastly, controls. Importantly, HBSI was associated in PD, but not in controls, with Valsalva pressure recovery time (sympathetic), deep breathing E/I ratio (cardiovagal), and SCOPA-AUT. Our findings support the existence of heart-brain de-synchronization in PD with an impact on clinically relevant autonomic outcomes.We want to thank all the patients and participants involved in the study. This study was partially co-funded by Michael J. Fox Foundation [RRIA 2014 (Rapid Response Innovation Awards) Program (Grant ID: 10189)], by the Carlos III Health Institute, and the European Union (ERDF/ESF, "A Way to Make Europe"/"Investing in Your Future") through the projects PI14/00679 and PI16/00005, the Juan Rodes grant "JR15/00008" (I.G.), and by the Department of Health of the Basque Government through the project "2016111009" and "2020333033". A.J.M. was supported by a predoctoral grant from the Basque Government (PRE_2019_1_0070). M.I. acknowledges financial support from"La Caixa" Foundation (ID 100010434, fellowship LCF/BQ/EU20/11810065). The Edmond and Lily Safra Center for Brain Sciences and the Basque Government (POS_2019_2_0020) to A.E. J.M.C. is funded by Ikerbasque: The Basque Foundation for Science and from the Ministerial de Economia, Industria y Competitividad (Spain) and FEDER (grant DPI2016-79874-R), and from the Department of Economic and Infrastructure Development of the Basque Country (Elkartek Program, KK-2018/00032, KK-2018/00090, and KK-2021/00009/BCB)

Time series analysis of respiration component in heart rate variability

Time series signal processing techniques (Fourier based) were applied to analyze the relationship between heart rate and respiration. This analysis takes advantage of the different timing charecteristics of the autonomic nervous system inputs to analyze their influence on the heart rate. Data from three experiments were analyzed. The first set of data was from helicopter pilots of the US Army. They injected atropine into themselves on certain days. The effect of atropine on the heart rate spectrum and the relationship between heart rate and respiration was studied. It was found that atropine abolishes the respiration peak in the heart rate spectrum indicating that the respiration peak is vagally mediated. Also the respiration spectrum could be used to locate the respiration peak in the heart rate spectrum. An experiment was then carried out to see how stable the respiration peak was in the heart rate spectrum. Five subjects were used in this study. It was found that the respiration peak is quite stable from day to day. The effect of paced breathing and stress on the heart rate spectrum was then studied. An experiment was designed for this and data was collected from eight subjects. It was found that there was a strong negative correlation between frequency of respiraton and the magnitude of the respiration peak. Further studies need to be done to learn more about this. Spectral analysis of heart rate variability and respiration is a quantitative measure of autonomic activity. It is hoped that, by understanding the various components in the heart rate spectrum, a non-invasive means of detecting heart defects could be achieved

Measurement of Autonomic Function in Renal Disease and Diabetes

Renal disease and diabetes lead to dysautonomia resulting in consequences ranging from gastroparesis to sudden death. New technologies to detect dysautonomia, such as 24-hr heart rate variability, are being evaluated and compared to traditional evoked tests. These advances have, however, lead to a lack of standardization in testing batteries, procedures, and reporting formats. This series of 3 studies psychometrically assessed measures of autonomic function (AF) and explored relationships among objective and subjective measures in healthy adults and uremic patients. Participants underwent evoked tests that included change in heart rate with deep breathing and Valsalva. In addition, measures of 24-hr HRV (time-domain: SDNN, SDANN, RMSSD; frequency-domain: total power, low and high frequency) and symptomatology were obtained. Study 1 examined the development and psychometric testing of the Autonomic Symptom Checklist (ASC), an instrument designed to assess autonomic symptomatology, with uremic patients (n=244) and healthy adults (n=34). Findings showed the ASC was able to differentiate among healthy and uremic patients with and without diabetes. Test-retest reliability was moderate to high for most categories. Study 2 established normal, borderline, and abnormal AF values and determined if these values could distinguish healthy (n=158) from uremic adults (n=363). Abnormal values were established at the 2.3 quantile of healthy adults. Uremic patients, especially those with diabetes, had much poorer values than healthy adults. The influence of age and gender on AF measures was attenuated in uremic as compared to healthy adults. Study 3 examined relationships among and the clinical utility of evoked tests, 24- hr HRV, and the ASC. Data were obtained from pre (n=130) and post (n=55) kidney and kidney-pancreas transplant recipients (n=130), and healthy adults (n=22). The frequency of abnormal values was used to identify the most sensitive measure. Measures of 24-hr HRV were more sensitive than evoked measures, with frequency measures being most sensitive. In conclusion, this series of studies established reliability and validity for the ASC, referent values for AF tests, devised a scoring system for AF tests, and found 24-hr HRV measures more sensitive than evoked measures

Investigation of the relevance of heart rate variability changes after heart transplantation

Heart transplantation has become an established treatment for end-stage heart disease. However, the shortage of donor organs is a major problem and long-term results are limited by allograft rejection. Heart rate variability (HRV) has emerged as a popular noninvasive research tool in cardiology. Analysis of HRV is regarded as a valid technique to assess the sympathovagal balance of the heart. The primary goal of this study was to investigate the relevance of heart rate variability changes after heart transplantation. It was found that spectral analysis of HRV is useful in detecting rejection episodes. Heart transplantation leaves the donor heart denervated. Spectral analysis of HRV was found appropriate to detect functional autonomous reinnervation. Extensive literature review was done to validate the findings. The paper is divided into two parts. The first part of the paper deals mainly with the techniques and current status of heart transplantation. The second part, deals with the relevance of heart rate variability and reinnervation after heart transplantation. The results of the study suggest that heart rate variability analysis is a valuable tool in assessing the cardiovascular status after heart transplantation

A study of cardiovascular autonomic functions and serum leptin levels in young obese individuals.

Over 312 million people are obese worldwide. Obesity has become a major nutritional health problem in India. It is associated with adverse cardiac events. Obesity is considered as a leading preventable cause of death. Autonomic function tests are early non invasive tool to assess the cardiac distress. Adipose tissue acts as highly active metabolic and secretary endocrine organ. Leptin is one of the main adipocytokines secreted by the adipocytes Autonomic Function tests in young obese individuals indicate that there is a definite sympathovagal imbalance in the form of sympathetic over activity and parasympathetic withdrawal. Elevated serum leptin levels play a direct vital role in stimulating the sympathetic nervous system. Chronic activation of the sympathetic nervous system makes them more prone for adverse cardiovascular events. The battery of autonomic function tests is an effective tool in identifying the autonomic dysfunction at an earlier stage. Understanding the role of the sympathetic nervous system and the serum leptin levels in obesity might help in the treatment of obesity and prevent further complications in this disease. Early diagnosis, behavioral and life style modification, health education and medication, may alleviate such problems

Impact of Cancer and Chemotherapy on Autonomic Nervous System Function and Cardiovascular Reactivity in Young Adults with Cancer: A Feasibility Study

Despite therapeutic advances, cancer patients demonstrate an increased risk of developing disease- and treatment-related cardiovascular (CV) and metabolic morbidity, as compared to their peers. In light of emerging evidence, cancer- and treatment-related damage to the autonomic nervous system (ANS) may play a role in the development of the aforementioned morbidity risks. This assertion needs to be verified. The purpose of this study was to assess the feasibility of conducting concurrent ANS and CV evaluations in adolescent and young adult (AYA) cancer patients undergoing treatment for various cancers by defining the i) methodological pitfalls and best-practice criteria for ANS testing in cancer, and ii) provide initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS). Thirteen patients were assessed, pre-treatment (T1) and following 4 cycles of chemotherapy (T2), using CASS and a modified Astrand-Rhyming cycle ergometer protocol, and their results compared to 13 sex and age-match controls. Overall, the average success rate in achieving the targeted feasibility criteria (FC) was 98.5%. Additionally, according to the CASS, there was evidence of ANS impairment at T1 in 5 of 13 patients, which persisted in 4 of 12 patients at T2, compared to 0 of 13 controls at T1 and 1 of 12 controls at T2. Using a 2 x 2 repeated measures ANOVA, treatment led to a significant improvement in patient heart rate (HR) recovery [F=6.188, p=0.027]. Results from this feasibility study suggest the investigation of ANS function in AYA cancer patients undergoing chemotherapy is possible, provided the proper precautions are taken. Furthermore, to the best of our knowledge, this is the first study to report evidence of ANS impairment using CASS and sudomotor dysfunction in this population

Post-exercise heart rate recovery and mortality in chronic obstructive pulmonary disease

SummaryAbnormal heart rate recovery (HRR) after exercise, a marker of cardiac autonomic dysfunction, is associated with poor prognosis in various populations. As chronic obstructive pulmonary disease (COPD) is associated with cardiac autonomic dysfunction, we tested the hypothesis that patients with COPD have a lower HRR than healthy people, and evaluated whether a delay in HRR is associated with an increased risk of mortality in COPD. The records of 147 COPD patients were reviewed (65.1±9.1 years, mean±sd, 42 women/105 men, forced expiratory volume in 1s (FEV1): 42±15% predicted) and compared to 25 healthy subjects (61.6±4.5 years, 5 women/20 men, FEV1: 100±14% predicted) during recovery after an exercise test. Heart rate was measured at peak exercise and at 1-min recovery, the difference between the two being defined as HRR (11±9 beats in COPD patients vs. 20±9 beats in healthy subjects, P<0.0001). During a mean follow-up of 43.1±22.0 months, 32 patients died. Abnormal HRR (⩽14 beats) was a strong predictor of mortality in COPD patients (adjusted hazard ratio: 5.12, 95% CI [1.54–17.00]). In conclusion, COPD patients have a lower HRR than healthy subjects, and have a worse prognosis when presenting abnormal HRR