Effects of effortful swallowing on cardiac autonomic control in individuals with neurogenic dysphagia: A prospective observational analytical study

Considering that neurogenic oropharyngeal dysphagia is a prevalent condition with or without cardiac disease we should contemplate issues surrounding cardiovascular difficulties during rehabilitation. This study aims to evaluate the effects of effortful swallowing maneuver (ESM) on heart rate variability (HRV) in subjects with neurogenic oropharyngeal dysphagia. We studied 22 individuals [8 Stroke and 14 Parkinson Disease (PD) subjects aged between 41 and 75 years old] with neurogenic oropharyngeal dysphagia regardless of gender. HRV was assessed under two circumstances: spontaneous swallowing versus ESM. Surface electromyography of the suprahyoid muscles was undertaken to measure the swallowing muscle excitation, which then confirmed higher muscle activity during ESM. We attained no changes in HRV between the two swallowing events [HR: spontaneous swallowing 78.68 ± 13.91 bpm vs. ESM 102.57 ± 107.81 bpm, p = 0.201; RMSSD (root-mean square of differences between adjacent normal RR intervals in a time interval): spontaneous swallowing 16.99 ± 15.65 ms vs. ESM 44.74 ± 138.85 ms, p = 0.312; HF (high frequency): spontaneous swallowing 119.35 ± 273 ms2 vs. ESM 99.83 ± 194.58 ms2, p = 0.301; SD1 (standard deviation of the instantaneous variability of the beat-to-beat heart rate): spontaneous swallowing 12.02 ± 1.07 ms vs. ESM 31.66 ± 98.25 ms, p = 0.301]. The effortful swallowing maneuver did not cause clinically significant changes in autonomic control of HR in this group of subjects with oropharyngeal dysphagia

Autonomic control in preterm infants - what we can learn from mathematical descriptions of vital signs

Background: Preterm birth is a major burden, affecting approximately 15 million infants each year. Recent advances in reproductive medicine increases that number even more. The population of preterm infants in particular suffers from autonomic dysregulation that manifests as temperature instability and poor control of heart rate and breathing. Thermal care, monitoring of vital signs in a neonatal intensive care unit, pharmacotherapy, and respiratory support over weeks to months is necessary. Improvements in neonatal care in the past years lead to a decrease in mortality, especially in very preterm infants. However, former preterm infants still are a high-risk population for acute and chronic sequelae as a result of the interruption of the physiological development. A better understanding of the pathophysiology of the autonomic dysregulation in that population would be very useful. Unfortunately, accurate diagnostic tools that objectively assess and quantify the immature autonomic control in neonates are lacking. Methods: In this PhD thesis we examined different effects of the immature autonomic control in very preterm infants under clinically relevant conditions. We conducted a prospective single center observational study, where we assessed fluctuations in body temperature, sleep behavior, and heart rate variability in very preterm infants. We described the different regulatory systems using distinct mathematical expressions, such as detrended fluctuation analysis and sample entropy. We assessed associations between these outcome parameters and relevant factors of the infant’s history, such as demographic parameters and co-morbidities. Besides that, we analyzed lung function measurements of preterm infants and healthy term controls at a comparable postconceptional age, to describe respiratory control. Results: This study is systematically assessing different physiological signals of autonomic dysregulation in preterm infants during their first days of life. We found associations between parameters describing the complexity of time series analysis and maturity or relevant co-morbidities of the infants. In the analysis of heart rate variability we even found that parameters derived from time series analysis, assessed during the infants first days of life, improve our ability to predict future evolution of the infants’ autonomic stability. Lastly, several weeks after the expected due date, tidal breathing pattern of preterm infants showed a different reaction in response to a sigh when compared to term born controls at equivalent postmenstrual age indicating that autonomic dysregulation in preterm infants is still present well beyond the expected due date. Conclusion: A better understanding about the resolution of autonomic dysregulation in this population is not only important for the infant and its family but has the potential to support resource allocation and identification of patients with elevated risk for future deterioration. We thus think that the insights about the immature autonomic control in preterm infants, gained through this PhD work, are of substantial scientific and clinical relevance

Emotional responses to pleasant and unpleasant oral flavour stimuli

The hedonic valence of taste perception plays a crucial role in the control of responses related to feeding behaviour. Taste and olfaction perception can induce autonomic responses, such as heart rate variability (HRV), which are involved in the evoked emotional reactions. Analysis of HRV can help distinguish sympathetic from parasympathetic regulation of the sinoatrial node. In this work, we analysed the HRV associated with oral flavour stimuli with opposite hedonic dimension and assessed their sympathovagal balance. ECGs were recorded continuously on 11 men and 12 women before and after stimulations. Experiments were performed in two sessions for comparison. ANOVA highlighted the decreases and increases of sinusal rhythm associated with pleasant and unpleasant flavour stimulations, respectively. Time and frequency domain analysis of HRV indicates that bradycardia induced by the pleasant stimulus can be attributed to an increase in the vagal tone, whilst tachycardia evoked by the unpleasant stimulus denotes a reduction of the vagal tone in women and an increase of the sympathetic tone in men. In conclusion, our data suggest that the HRV analysis may represent a valuable tool for autonomic nervous system response characterization associated to the hedonic dimension of the complex flavour sensations induced by food and/or beverages. © Springer Science+Business Media, LLC 2011

The effect of respiratory event type and duration on heart rate variability in suspected obstructive sleep apnea patients

Abstract. Obstructive sleep apnea (OSA) patients have often reduced long-term heart rate variability (HRV) which is a known risk factor for several cardiovascular diseases such as hypertension and stroke. Albeit OSA being actively studied, it has remained uncharacterized how the duration and type of respiratory events affect the heart rate (HR), i.e. RR intervals, and ultra-short-term HRV during and immediately after the individual respiratory events. This study aimed to investigate whether the changes in ultra-short-term HRV and HR are modulated by the duration and type of the individual respiratory events and whether these changes are sex-specific. It was hypothesized that longer respiratory events cause higher ultra-short-term HRV and greater differences between RR intervals during and after the respiratory event. Moreover, it was hypothesized that the higher HRV and greater differences in HR are associated with apneas and men stronger than hypopneas and women. Electrocardiograms (ECG) of 862 suspected OSA patients were collected during clinical polysomnography (PSG) at the Princess Alexandra Hospital (Brisbane, Australia) and they were analyzed retrospectively. Ultra-short-term HRV was studied with time-domain parameters determined from the ECG segments measured during (in-event) and 15 seconds after (post-event) the respiratory event. The respiratory events of all subjects were divided into groups based on the sex, the type of the respiratory events (apneas and hypopneas), and the duration of the respiratory events (10–20 s, 20–30 s, over 30 s). A clear bradycardia-tachycardia rhythm associated with respiratory events was observed. The ultra-short-term HRV and the difference between in- and post-event RR intervals increased with increasing respiratory event duration. However, the difference between in- and post-event HRV parameter values decreased with increasing duration of the respiratory events. Furthermore, higher ultra-short-term HRV and a greater decrease in RR interval were observed in apneas and men. Based on the results, the duration and type of the respiratory events modulate the HR and ultra-short-term HRV during and after the respiratory events, and these phenomena appear to be sex-specific. Therefore, considering the characteristics of respiratory events and ultra-short-term HRV could be useful in OSA diagnostics when estimating the OSA-related cardiac consequences. A scientific article based on the results of this thesis, Hietakoste et al. Longer apneas and hypopneas are associated with greater ultra-short-term HRV in OSA, has been submitted to a peer-reviewed scientific journal.Tiivistelmä. Uniapneapotilailla havaitaan usein matalaa pitkän aikavälin sykevälivaihtelua, jonka tiedetään myös olevan riskitekijä useille sydän- ja verisuonisairauksille. Ei kuitenkaan tiedetä, miten uniapneaan liittyvät erimittaiset hengityskatkot tai niiden tyyppi vaikuttavat yksittäisten hengityskatkojen aikaiseen ja jälkeiseen ultralyhyeen sykevälivaihteluun ja sydämen lyöntien väliseen kestoon, ts. RR-intervalleihin. Tässä tutkimuksessa tavoitteena oli tutkia ultralyhyen sykevälivaihtelun ja RR-intervallien sukupuolisidonnaisia muutoksia eri mittaisten apneoiden ja hypopneoiden aikana ja jälkeen. Hypoteesina oli, että pidemmät hengityskatkot aiheuttavat suurempia muutoksia hengityskatkojen aikaisen ja jälkeisen keskimääräisen RR-intervallien kestojen välille ja siten korkeampaa ultralyhyttä sykevälivaihtelua. Oletettiin myös, että apneat aiheuttavat suurempia muutoksia kuin hypopneat ja havaitut muutokset ovat suurempia miehillä kuin naisilla. Potilasaineisto koostui 862 uniapneasta epäillyn potilaan sydänsähkökäyristä (EKG), jotka oli mitattu Prinsessa Alexandran sairaalassa (Brisbane, Australia) osana kliinistä unipolygrafiaa. Ultralyhyen sykevälivaihtelun määrittämiseen käytettiin keskimääräistä RR-intervallien kestoa ja aikatason sykevälivaihteluparametreja, jotka määritettiin hengityskatkojen aikaisista ja jälkeisistä (15 s hengityskatkon jälkeen) EKG-segmenteistä. Tutkittavat hengityskatkot jaettiin ryhmiin niiden tyypin (apneat ja hypopneat) ja keston (10–20 s, 20–30 s ja yli 30 s) perusteella. Lisäksi miesten ja naisten hengityskatkoja tutkittiin erikseen. Tutkimuksessa havaittiin, että hengityskatkojen aikaisten ja jälkeisten RR-intervallien ero sekä ultralyhyt sykevälivaihtelu kasvoivat hengityskatkojen keston kasvaessa riippumatta sukupuolesta tai hengityskatkojen tyypistä. Havaittiin myös, että ero hengityskatkojen aikaisten ja jälkeisten sykevälivaihteluparametrien arvojen välillä pieneni hengityskatkojen pidentyessä riippumatta sukupuolesta tai hengityskatkojen tyypistä. Apneat kuitenkin aiheuttivat suuremman muutoksen kuin hypopneat, ja muutokset olivat suurempia miehillä. Tulosten perusteella hengityskatkojen tyyppi ja kesto vaikuttavat ultralyhyeen sykevälivaihteluun ja RR-intervalleihin. Ultralyhyen sykevälivaihtelun ja hengityskatkojen ominaisuuksien huomioonottaminen uniapnean diagnostiikassa voisi olla hyödyllistä arvioitaessa taudin vakavuutta ja sydänterveyteen liittyviä riskejä. Tämän tutkimuksen tuloksista on kirjoitettu tieteellinen artikkeli Hietakoste ym. Longer apneas and hypopneas are associated with greater ultra-short-term HRV in OSA, joka on lähetetty vertaisarvioitavaksi alan kansainväliseen tieteelliseen julkaisusarjaan

The role of the vagus nerve during fetal development and its relationship with the environment

The autonomic nervous system (ANS) regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development. Several studies have shown how vagus nerve is involved in many vital processes during fetal, perinatal and postnatal life: from the regulation of inflammation through the anti-inflammatory cholinergic pathway, which may affect the functioning of each organ, to the production of hormones involved in bioenergetic metabolism. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Therefore, this hypothesis paper aims to review the development of ANS during fetal and perinatal life, focusing particularly on the vagus nerve, to identify possible "critical windows" that could impact its maturation. These "critical windows" could help clinicians know when to monitor fetuses to effectively assess the developmental status of both ANS and specifically the vagus nerve. In addition, this paper will focus on which factors (i.e. fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposure) may have an impact on the development of the vagus during the above-mentioned "critical window" and how. This analysis could help clinicians and stakeholders define precise guidelines for improving the management of fetuses and newborns, particularly to reduce the potential adverse environmental impacts on ANS development that may lead to persistent long-term consequences. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses.Comment: Word count: 16,009 Tables: 1 Figures:

Eating and Swallowing, Oral Health, and Saliva Production

Eating and maintaining optimal nutrition are essential to health and quality of life. In both health and disease, eating is influenced by multiple factors including swallowing, oral health, and saliva production. Perturbations to any, or all, of these inter-related factors may result in consequences that negatively affect the health and wellness of an individual. Eating and swallowing impairment are common symptoms of neurodegenerative diseases such as dementia, and these symptoms are associated with a host of negative sequelae such as malnutrition, dehydration, aspiration pneumonia, and reduced quality of life. The studies reported in this dissertation explored elements of eating and swallowing, saliva production, and saliva modulation in healthy individuals and in persons with Alzheimer’s disease (AD). This dissertation is composed of three studies. First, a scoping review methodology was used to examine literature that addressed autonomic nervous system and/or swallowing dysfunction in individuals with AD. Then, systematic review and meta-analysis methodologies were used to examine a potential effect of aging on saliva production. Finally, a within-subjects methodology was used to examine the modulation of salivary flow by tooth brushing in healthy older adults. In the first study, swallowing dysfunction and autonomic nervous system dysfunction, including salivary flow dysfunction, were found to occur in persons with AD. In the second study, salivary flow was found to be reduced in adults aged 60 years and older who were free of major systemic disease. In the third and final study, the use of manual and electric tooth brushing was found to increase whole salivary flow rates in adults aged 60 years of age and older who were free of major systemic disease. The results of this dissertation have very important implications for the future research and management of eating and swallowing, oral health, and saliva production in a variety of populations, including aging individuals and persons with AD

Phenotypic And Electrophysiologic Characterization of a Mouse Model of Fragile X Syndrome

Fragile X syndrome (FXS) is the most common form of inherited mental retardation. It is caused by a mutation in the fragile X mental retardation (FMR1) gene on the X chromosome. Many children with FXS exhibit autistic behaviors and deficits in motor coordination including speech articulation deficits. The development of the FMR1 knockout (Fmr1 KO) mouse, in which the Fmr1 gene is inactivated, has provided an animal model that can be used to investigate underlying neuro-physiological mechanisms associated with FXS as well as to evaluate potential therapeutic treatments. In this study, quantitative behavioral assays were used, such as long term fluid licking observations, measurements of ultrasonic vocalizations (USV), and 3D tracking of whisker movements to test Fmr1 KO mice for behavioral deficits compared to their Wild type (WT) littermates. Electrophysiological techniques were employed to evaluate the functional properties of the neocortex. Pyramidal neurons in the neocortex of human FXS patients and Fmr1 KO mice are characterized by abnormally long, thin and numerous dendritic spines. Multiple electrode recordings were used to study how loss of Fmr1 expression affects several aspects of the neocortical network activities in Fmr1 KO mice. Single and multi unit spike activities and local field potentials (LFPs) were recorded in the whisker barrel cortex of awake mice. Baseline spike activity was significantly lower in cortical neurons of Fmr1 KO mice. Synchronous activity at the LFP was strongly reduced in Fmr1 KO mice. Relative power in the delta range frequency band of LFP activity was significantly reduced in the neocortex of Fmr1 KO mice. Furthermore, relative power in the beta frequency band was significantly higher in Fmr1 KO compared to WT mice. Our behavioral assays identified several phenotypical differences between Fmr1 KO and WT mice. Orofacial behavioral deficits in fluid licking and USV may be comparable to speech deficits in fragile X patients. Severely impaired dynamics of neocortical network activity may be causally linked to the cognitive and sensorimotor impairments associated with fragile X syndrome

Psychosomatic response to acute emotional stress in healthy students

The multidimensionality of the stress response has shown the complexity of this phenomenon and therefore the impossibility of finding a unique biomarker among the physiological variables related to stress. An experimental study was designed and performed to guarantee the correct synchronous and concurrent measure of psychometric tests, biochemical variables and physiological features related to acute emotional stress. The population studied corresponds to a group of 120 university students between 20 and 30 years of age, with healthy habits and without a diagnosis of chronic or psychiatric illnesses. Following the protocol of the experimental pilot, each participant reached a relaxing state and a stress state in two sessions of measurement for equivalent periods. Both states are correctly achieved evidenced by the psychometric test results and the biochemical variables. A Stress Reference Scale is proposed based on these two sets of variables. Then, aiming for a non-invasive and continuous approach, the Acute Stress Model correlated to the previous scale is also proposed, supported only by physiological signals. Preliminary results support the feasibility of measuring/quantifying the stress level. Although the results are limited to the population and stimulus type, the procedure and methodological analysis used for the assessment of acute stress in young people can be extrapolated to other populations and types of stress

Anatomical and physiological investigation of pathways mediating the effects of electrical stimulation of the external auricle of the ear on autonomic nervous system activity in rats

The Auricular Branch of the Vagus Nerve (ABVN) is a sensory nerve that innervates select areas of the external auricular dermatome. Electrical stimulation of the auricular region innervated by the ABVN influences the autonomic nervous system, observed by changes in control of the heart in humans and animals. However, the pathways and mechanisms for these effects are unknown. This thesis investigated in rats the pathways mediating the effects of electrical stimulation of the external auricle, comparing an ABVN innervated site of the external ear (the tragus) to an area not reported to receive ABVN innervation, the earlobe. Injection of the neuronal tracer cholera toxin B chain (CTB) into the right tragus (n=4) and right earlobe (n=4) revealed a large degree of similarity in sensory afferent termination sites. Afferent terminals were predominantly labelled ipsilateral to the injection site, with the densest labelling within laminae III-IV of the dorsal horn of the upper cervical spinal cord. In the medulla oblongata, CTB labelled afferents were observed in the paratrigeminal nucleus, cuneate nucleus, and to a minor extent in the nucleus tractus solitarius. Efforts were made to identify the targets of labelled afferents using immunofluorescence for choline acetyltransferase, calbindin, parvalbumin, glutamate decarboxylase 67 and neurokinin receptor 1 expressing cells, but inputs to each cell type were rare. Physiological recordings of the responses to ear stimulation were made in an anaesthetic free Working Heart Brainstem Preparation (WHBP) of the rat. Autonomic profiles of WHBP rats were first examined. Recordings made from rats at night time, revealed more robust sympathetic activity in comparison to day time rats, thus subsequent experiments were conducted in rats at night time. Electrical stimulation (100 Hz, 2.5 mA) was delivered for 5 minutes into the auricular stimulation sites in the WHBP. Direct recording from the sympathetic chain revealed a central sympathoinhibition from both tragus and earlobe stimulation. Sectioning of upper cervical afferent nerve roots silenced the sympathoinhibitory effects of tragus stimulation. Considering the predominance of afferent labelling in the cervical spinal cord dorsal horn and that cervical afferent nerve section reduced the sympathoinhibition evoked by tragus stimulation, this suggests that the autonomic effects of auricular stimulation are conveyed through somatosensory afferents rather than the ABVN