UNASSIGNED: Although homeostasis of the cardiovascular system is regulated by the cerebral cortex via the autonomic nervous system, the role of abnormal brain functional connectivity (FC) networks in patients with cardiac dysfunction remains unclear. Here, we report thalamus-based FC alterations and their relationship with clinical characteristics in patients with coronary heart disease (CHD).
UNASSIGNED: We employed resting-state functional magnetic resonance imaging (rs-fMRI) to acquire imaging data in twenty-six patients with CHD alongside sixteen healthy controls (HCs). Next, we performed a thalamus-based FC analysis to profile abnormal FC patterns in the whole brain. Subsequently, the mean time series of the brain regions that survived in the FC analysis were used to determine correlations with clinical parameters in patients with CHD.
UNASSIGNED: We found no statistically significant differences in demographic and clinical data between patients with CHD and HCs. Patients with CHD showed decreased FC patterns between bilateral thalami and left hemisphere, encompassing supplementary motor area, superior frontal gyrus, superior parietal gyrus, inferior parietal gyrus, middle cingulate cortex, lingual gyrus and calcarine sulcus.
UNASSIGNED: These findings not only have implications in clarifying the relationship between cerebral functional imbalance and cardiovascular system, but also provide valuable insights to guide future evaluation and management of cardiac autonomic regulation via the brain-heart axis.

This virtual workshop was convened by the National Heart, Lung, and Blood Institute, in partnership with the Office of Strategic Coordination of the Office of the National Institutes of Health Director, and held September 2 to 3, 2020. The intent was to assemble a multidisciplinary group of experts in basic, translational, and clinical research in neuroscience and cardiopulmonary disorders to identify knowledge gaps, guide future research efforts, and foster multidisciplinary collaborations pertaining to autonomic neural mechanisms of cardiopulmonary regulation. The group critically evaluated the current state of knowledge of the roles that the autonomic nervous system plays in regulation of cardiopulmonary function in health and in pathophysiology of arrhythmias, heart failure, sleep and circadian dysfunction, and breathing disorders. Opportunities to leverage the Common Fund\'s SPARC (Stimulating Peripheral Activity to Relieve Conditions) program were characterized as related to nonpharmacologic neuromodulation and device-based therapies. Common themes discussed include knowledge gaps, research priorities, and approaches to develop novel predictive markers of autonomic dysfunction. Approaches to precisely target neural pathophysiological mechanisms to herald new therapies for arrhythmias, heart failure, sleep and circadian rhythm physiology, and breathing disorders were also detailed.

OBJECTIVE: To evaluate the effect of prematurity on choroidal structure in children born preterm with no history of retinopathy of prematurity (ROP) by comparing them with age-matched healthy children born at full term.
METHODS: Enhanced depth imaging optical coherence tomography (EDI-OCT) scans of children aged 5 to 9 years with a history of prematurity but no history of ROP, and age-matched full-term healthy children were evaluated, retrospectively. Choroidal thicknesses (CTs) were measured at subfoveal (SFCT), 1000 µm temporal and nasal from the fovea (T1, N1), and 2000 µm temporal and nasal (T2, N2) from the fovea. The EDI-OCT images were binarized to stromal (SA) and luminal areas (LA) using the ImageJ software. The choroidal vascularity index (CVI) was calculated by dividing LA by the total choroidal area (TCA).
RESULTS: Twenty-nine eyes of 15 preterm children and 41 eyes of 26 full-term children were included. Demographic characteristics including axial length (AL), eye side, age, and the sex of the children in the groups were similar (p>0.05). There was no statistically significant difference in the mean CVI, SFCT, N1, and T1 values between the groups (p>0.05); however, the mean T2 and N2 values were significantly higher in the full-term group than in the preterm group (p<0.05). There was a significant positive correlation between the birth week and the T1 (p<0.05) CONCLUSION: : Prematurity can affect CT even with no history of ROP. The decreases in CTs were significant at 2000 µm nasal and temporal from the fovea. The impairment of temporal choroidal region was more evident than nasal choroidal region. The mean CVI values were similar between the groups.

There is an increasing recognition of the importance of interactions between the heart and the autonomic nervous system in the pathophysiology of arrhythmias. These interactions play a role in both the initiation and maintenance of arrhythmias and are important in both atrial and ventricular arrhythmia. Given the importance of the autonomic nervous system in the pathophysiology of arrhythmias, there has been notable effort in the field to improve existing therapies and pioneer additional interventions directed at cardiac-autonomic targets. The interventions are targeted to multiple and different anatomic targets across the neurocardiac axis. The purpose of this review is to provide an overview of the rationale for neuromodulation in the treatment of arrhythmias and to review the specific treatments under evaluation and development for the treatment of both atrial fibrillation and ventricular arrhythmias.

The mechanisms underlying the protective effects of remote ischemic preconditioning (RIPC) are not presently clear. Recent studies in experimental models suggest the involvement of the autonomic nervous system (ANS) in cardioprotection. The aim of this study was to investigate the changes in ANS in healthy young volunteers divided into RIPC (n = 22) or SHAM (n = 18) groups. RIPC was induced by 1 cycle of 4 min inflation/5 min deflation followed by 2 cycles of 5 min inflation/5 min deflation of a cuff placed on the upper left limb. The study included analysis of heart rate (HR), blood pressure (BP), heart rate variability (HRV), measurements of microcirculation and porphyrin fluorescence in the limb before and after the RIPC. RIPC caused reactive hyperemia in the limb and reduced blood porphyrin level. A mental load (serial sevens test) and mild motor stress (hyperventilation) were performed on all subjects before and after RIPC or corresponding rest in the SHAM group. Reduction of HR occurred during the experiments in both RIPC and SHAM groups reflecting RIPC-independent adaptation of the subjects to the experimental procedure. However, in contrast to the SHAM group, RIPC altered several of the spectral indices of HRV during the serial sevens test and hyperventilation. This was expressed predominantly as an increase in power of the very low-frequency band of the spectrum, increased values of detrended fluctuation analysis and weakening of correlation between the HRV parameters and HR. In conclusion, RIPC induces changes in the activity of ANS that are linked to stress resistance.

UNASSIGNED: To examine the role of the hippocampus in stress regulation in older adults with amnestic mild cognitive impairment (aMCI).
UNASSIGNED: This study combined resting-state functional MRI, structural MRI, self-reported chronic stress exposure, and an electrocardiography-based acute stress protocol to compare aMCI group (n = 17) to their cognitively healthy counterparts (HC, n = 22).
UNASSIGNED: For the entire sample, there was a positive correlation between chronic stress exposure and acute stress regulation. The aMCI group showed significantly smaller volumes in the right hippocampus than HC. The two groups did not differ in chronic stress exposure or acute stress regulation. In the HC group, the left hippocampal connectivity with inferior parietal lobe was significantly correlated with both the chronic stress and acute stress. In the aMCI group, the left hippocampal connectivity with both the right insula and the left precentral gyrus was significantly correlated to chronic stress exposure and acute stress regulation. Additionally, the left hippocampal connectivity with right insula significantly mediated the relationship between chronic stress exposure and acute stress regulation in aMCI group.
UNASSIGNED: Extra hippocampal networks may be recruited as compensation to attend the maintenance of relatively normal stress regulation in aMCI by alleviating the detrimental effects of chronic stress exposure on acute stress regulation.

UNASSIGNED: Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations.
UNASSIGNED: We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients.
UNASSIGNED: Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes.
UNASSIGNED: ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment.

Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases.

There is a rapidly accumulating body of evidence regarding the influential role of early life stress (ELS) upon medical and psychiatric conditions. While self-report instruments, with their intrinsic limitations of recall, remain the primary means of detecting ELS in humans, biological measures are generally limited to a single biological system. This paper describes the design, rationale and feasibility of a study to simultaneously measure neuroendocrine, immune and autonomic nervous system (ANS) responses to psychological and physiological stressors in relation to ELS. Five healthy university students were recruited by advertisement. Exclusion criteria included chronic medical conditions, psychotic disorders, needle phobia, inability to tolerate pain, and those using anti-inflammatory medications. They were clinically interviewed and physiological recordings made over a two-hour period pre, during and post two acute stressors: the cold pressor test and recalling a distressing memory. The Childhood Trauma Questionnaire and the Parental Bonding Index were utilised to measure ELS. Other psychological measures of mood and personality were also administered. Measurements of heart rate, blood pressure, respiratory rate, skin conductance, skin blood flow and temporal plasma samples were successfully obtained before, during and after acute stress. Participants reported the extensive psychological and multisystem physiological data collection and stress provocations were tolerable. Most (4/5) participants indicated a willingness to return to repeat the protocol, indicating acceptability. Our protocol is viable and safe in young physically healthy adults and allows us to assess simultaneously neuroendocrine, immune and autonomic nervous system responses to stressors in persons assessed for ELS.

BACKGROUND: Imbalances of the autonomic nervous (ANS), the cardiovascular system, and ionics might contribute to the manifestation of The Brugada Syndrome (BrS). Thus, this study has aimed to investigate the cardio-respiratory fitness and the responses of the ANS both at rest and during a sub-maximal exercise stress test, in BrS patients and in gender-matched and age-matched healthy sedentary controls.
METHODS: Eleven BrS patients and 23 healthy controls were recruited in Khon Kaen, Thailand. They performed an exercise test on a cycle ergometer, and during the exercise, expired gas samples and electrocardiograms were collected. Blood glucose and electrolyte concentrations were analyzed before and after exercise. Then the heart rate variability (HRV) and the heart rate recovery (HRR) were analyzed from the electrocardiograms.
RESULTS: The BrS patients showed a higher parasympathetic activation during exercise recovery than baseline. They had a smaller level of sympathetic activation during the period of exercise recovery than the controls did. They also showed a significantly lower peak HR, HRR, and peak oxygen consumption than the controls (p<0.05). All subjects had a significantly lower percentage of peak oxygen consumption and respiratory exchange ratio during low-intensity (p<0.01) and moderate-intensity (p<0.05) exercise than during high-intensity exercise. The BrS patients had mild hyperkalemia which is reduced according to the exercise.
CONCLUSIONS: Thai BrS patients had a more rapid rate of restoration of the parasympathetic and smaller level of sympathetic activation after exercise. They had mild hyperkalemia which is reduced according to the exercise. Furthermore, they exhibited impaired cardio-respiratory fitness.