PurposeThe heart receives cervical and thoracic sympathetic contributions. Although the stellate ganglion is considered the main contributor to cardiac sympathetic innervation, the superior... Show morePurposeThe heart receives cervical and thoracic sympathetic contributions. Although the stellate ganglion is considered the main contributor to cardiac sympathetic innervation, the superior cervical ganglia (SCG) is used in many experimental studies. The clinical relevance of the SCG to cardiac innervation is controversial. We investigated current morphological and functional evidence as well as controversies on the contribution of the SCG to cardiac innervation.MethodsA systematic literature review was conducted in PubMed, Embase, Web of Science, and COCHRANE Library. Included studies received a full/text review and quality appraisal.ResultsSeventy-six eligible studies performed between 1976 and 2023 were identified. In all species studied, morphological evidence of direct or indirect SCG contribution to cardiac innervation was found, but its contribution was limited. Morphologically, SCG sidedness may be relevant. There is indirect functional evidence that the SCG contributes to cardiac innervation as shown by its involvement in sympathetic overdrive reactions in cardiac disease states. A direct functional contribution was not found. Functional data on SCG sidedness was largely unavailable. Information about sex differences and pre- and postnatal differences was lacking.ConclusionCurrent literature mainly supports an indirect involvement of the SCG in cardiac innervation, via other structures and plexuses or via sympathetic overdrive in response to cardiac diseases. Morphological evidence of a direct involvement was found, but its contribution seems limited. The relevance of SCG sidedness, sex, and developmental stage in health and disease remains unclear and warrants further exploration.Graphical abstractAn overview of the current literature derived from morphological and functional data on the involvement of SCG in cardiac innervation, relevance of sidedness, sex differences, and pre- and postnatal differences in various species. X = Information not available Show less
This book contains two main messages. First, an attempt is made to explain the diverse beneficial findings on cognition and mental health in the literature of meditation practices by the factor of... Show moreThis book contains two main messages. First, an attempt is made to explain the diverse beneficial findings on cognition and mental health in the literature of meditation practices by the factor of breathing. In the respiratory vagal nerve stimulation model of contemplative practices (rVNS) specific respiratory patterns lead to changes in autonomic nervous system functioning that in turn produce changes in the central nervous system, which can be observed in a healthier cognitive and emotional balance. Second, there are two empirical chapters that show null-results on cognition with meditative movement (Tai Chi Chuan) and breathing interventions. The possible reasons for these lack of results are extensively discussed in this dissertation and put into a wider perspective within the scientific field. Show less
PurposeTo understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe.MethodsWe invited 84 European autonomic centers to... Show morePurposeTo understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe.MethodsWe invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders.ResultsForty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent (n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% (n = 27/29) established e-learning models. Both the 2020 joint EAN–EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020–2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year.ConclusionsThe COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design. Show less
Epileptic seizures are associated with changes in autonomic function. Ictal asystole, when it leads to syncope, can cause severe traumatic falls. We discovered a new indirect method, based on video... Show moreEpileptic seizures are associated with changes in autonomic function. Ictal asystole, when it leads to syncope, can cause severe traumatic falls. We discovered a new indirect method, based on video, EEG and ECG, to disentangle if vasodilatation was the dominant mechanism behind the syncope. In this group of patients, pacemaker implantation is less helpful. Autonomic manifestations of epilepsy can also help to detect seizures. Our literature review discovered that combining different modalities in one detection device provides higher sensitivity, and personalization of detection algorithms can decrease false alarm rate. We validated a wearable multimodal detection system (NightWatch) on children at home. NightWatch showed high sensitivity for the detection of potentially dangerous nocturnal seizures, reduces caregiver stress and saved costs from a societal perspective. Validation of an automated video detection system showed that this could provide a good alternative for children who cannot tolerate a wearable device.From different qualitative user studies, we concluded that caregivers’ needs for seizure detection vary greatly. Also, the success of device implementation is highly dependent on the protective behavior parents developed towards their child with epilepsy. This emphasizes the importance of tailored and user-centered approaches for seizure detection. Show less
Background: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear.... Show moreBackground: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear. Independent and cumulative dysregulations in physiological stress systems, in particular the hypothalamic-pituitaryadrenal axis (HPA-axis), immune inflammatory system, and autonomous nervous system (ANS), may contribute to this risk. However, findings have either been heterogeneous or absent thus far.Methods: Associations between individual markers and cumulative indices of the HPA-axis (cortisol awakening response and evening cortisol), immune-inflammatory system (C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-alpha), and the ANS (heart rate, respiratory sinus arrhythmia, and pre-ejection period) and the outcomes no suicide ideation with suicide attempt (SI-SA+), suicide ideation without suicide attempt (SI+SA-) and suicide ideation with suicide attempt (SI+SA+) were investigated in 1749 persons with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA).Results: High levels of CRP and IL-6 were associated with SI-SA+ and SI+SA+ respectively when compared to non-suicidal patients after adjusting for confounders and multiple testing. Also, cumulative immune inflammatory dysregulations were positively associated with SI+SA+, suggesting a dose-response effect. No significant associations were found between HPA-axis or ANS indicators and suicide-outcomes and between immune-inflammatory system markers or cumulative stress system dysregulations and SI+SA-.Conclusion: Although stress system markers could not differentiate between SI+SA-and non-suicidal patients, findings indicate that dysregulations of individual and cumulative immune-inflammatory markers are associated with suicide attempts in depressive and/or anxiety patients. Thus, immune-inflammatory system dysregulation may be involved in the pathophysiology of suicidal behavior, supporting further examination of the effects of anti-inflammatory interventions on suicidality. Show less
Background: Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)).... Show moreBackground: Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)). Suchdysregulationshave rarely beensimultaneously examined across different stress systems.Methods: In the Netherlands Study of Depression and Anxiety (n=2789), we investigated whether current or remitted depressive and/or anxiety disorders (based on the CIDI semi-structured interview), including specific symptom profiles, were associated with separate markers and cumulative indexes of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), immune system (C-reactive protein, interleukin-6, tumor necrosis factor-alpha), and ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period).Results: Depressive andanxiety disorderswere significantlyassociated with changes in three biological stress systemsincluding HPA-axis hyperactivity, increased inflammatory activity, and a higher ANS tone, particularly for integrative and cumulative indexes of these stress systems (pFDR <.05) vs. controls. The strongest associations were seen with current disorders andcumulative indexes of the HPA-axis (13=.124, pFDR=.001), the immune system (13 =.057, pFDR=.032), and total cumulative index across stress systems (13=.102, pFDR=.004). Atypical, energy-related depression severity was linked to immune system markers (pFDR<0.001), melancholic depression severity to HPA-axis markers (pFDR=.032), and anxiety arousal severity to both HPA-axis and immune system markers (pFDR<0.05). Findings were partially explained by poorer lifestyle, more chronic diseases, or (especially for ANS-function) antidepressant use. Limitations: Cross-sectional analyses limit examination of temporal associations.Conclusion: Patients withdepressive and anxiety disorders showed consistent dysregulation across biological stress systems, particularly for current episodes.To understand stress system functionality in affective disorders, an integrated approach capturing cumulative stress indices within and across biological stress systems is important. Show less
Background: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. Although dysregulated biological stress systems may underlie the enduring effect of CT, the relation between... Show moreBackground: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. Although dysregulated biological stress systems may underlie the enduring effect of CT, the relation between CT and separate and cumulative activity of the major stress systems, namely, the hypothalamic-pituitary-adrenal (HPA)-axis, the immune-inflammatory system, and the autonomic nervous system (ANS), remains inconclusive.Methods: In the Netherlands Study of Depression and Anxiety (NESDA, n = 2778), we determined whether self-reported CT (as assessed by the Childhood Trauma Interview) was associated with separate and cumulative markers of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), the immune-inflammatory system (C-reactive protein, interleukin-6, tumor necrosis factor-alpha), and the ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period) in adulthood.Results: Almost all individuals with CT (n = 1330) had either current or remitted depressive and/or anxiety disorder (88.6%). Total-sample analyses showed little evidence for CT being significantly associated with the separate or cumulative stress systems' activity in adulthood. These findings were true for individuals with and without depressive and/or anxiety disorders. To maximize contrast, individuals with severe CT were compared to healthy controls without CT. This yielded slight, but significantly higher levels of cortisol awakening response (AUCg, beta =.088, p =.007; AUCi, beta =.084, p =.010), cumulative HPA-axis markers (beta =.115, p =.001), Creactive protein (beta =.055, p =.032), interleukin-6 (beta =.053, p =.038), cumulative inflammation (beta =.060, p =.020), and cumulative markers across all systems (beta =.125, p =.0003) for those with severe CT, partially explained by higher rates of smoking, body mass index, and chronic diseases.Conclusion: While our findings do not provide conclusive evidence on CT directly dysregulating stress systems, individuals with severe CT showed slight indications of dysregulations, partially explained by an unhealthy lifestyle and poorer health. Show less
Zandstra, T.; Kies, P.; Man, S.C.; Maan, A.; Bootsma, M.; Vliegen, H.; ... ; Jongbloed, M. 2020
Background: QT interval variability (QTV) and heart rate turbulence (HRT) are measures of cardiac autonomic function, which, when abnormal, are correlated with ventricular arrhythmias and worse... Show moreBackground: QT interval variability (QTV) and heart rate turbulence (HRT) are measures of cardiac autonomic function, which, when abnormal, are correlated with ventricular arrhythmias and worse clinical outcome. This study aims to evaluate QTV and HRT in patients with a systemic right ventricle (RV) and to assess correlations with clinical characteristics.Methods: In a retrospective cohort study, QTV and HRT were derived from 24-h Holter registrations of patients with a systemic RV and healthy controls. QTV and HRT were compared between groups. In patients, the association between QTV, HRT, and clinical characteristics was assessed.Results: Holter recordings from 40 patients (mean age 40 years, 16 females) and 37 healthy controls (mean age 42 years, 21 females) were analyzed. Groups were comparable in terms of age and sex. QTV was increased in patients compared with controls (p < 0.001), HRT did not differ significantly between the groups. Increased QTV and decreased HRT correlated with medication use, especially of diuretics, and with clinical events, particularly supraventricular arrhythmias. Increased QTV correlated with reduced systemic RV function. Decreased HRT was independently associated with a larger number of past clinical events (estimate -0.33, 95% CI -0.63 to -0.02, p = 0.037). QTV was higher in women in both patients and controls (p = 0.041 and p = 0.034, respectively).Conclusions: QTV and HRT are associated with clinical factors and events in patients with a systemic RV. Further studies are mandatory to confirm their prognostic value. (C) 2020 Published by Elsevier Ltd on behalf of Japanese College of Cardiology. Show less
The empirical research in this thesis focused on individual differences in subjective- and physiological reactivity to flight-related stimuli. The results of these studies are mixed, making them... Show moreThe empirical research in this thesis focused on individual differences in subjective- and physiological reactivity to flight-related stimuli. The results of these studies are mixed, making them difficult to fit into existing theoretical models. The relationship between emotional response systems is likely affected by many intervening variables, including higher order cognitive processes. Pre-treatment individual differences in subjective distress reactivity and physiological reactivity to flight related stimuli, and pre-treatment use of cognitive coping strategies were not prognostic of short- and long-term post-treatment clinical course. In the course of therapy, individual reactivity became more strongly related to treatment outcome. The magnitude of change in the use of maladaptive coping strategies during therapy was indicative of long-term persistence of flight anxiety and long-term flying behaviour. Subjective distress reactivity, pre-exposure and during actual flight, was prognostic for short- and long-term treatment outcomes. Adding measurements of physiological reactivity improved the prediction of treatment outcome. The magnitude of synchronous change in subjective and physiological reactivity did not increase with higher intensity of phobic stimuli, and was not related to outcome. Subjective and physiological measurements of fear activation provided partly independent information. Prognosis for clinical course of aviophobia therefore could benefit from including physiological reactivity measurements. Show less
Suurland, J.; Heijden, K.B. van der; Huijbregts, S.C.J.; Goozen, S.H.M. van; Swaab, H. 2017
Nonreciprocal action of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increases susceptibility to emotional and behavioral problems in children exposed to adversity. Little is... Show moreNonreciprocal action of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increases susceptibility to emotional and behavioral problems in children exposed to adversity. Little is known about the PNS and SNS in interaction with early adversity during infancy. Yet this is when the physiological systems involved in emotion regulation are emerging and presumably most responsive to environmental influences. We examined whether parasympathetic respiratory sinus arrhythmia (RSA) and sympathetic pre-ejection period (PEP) response and recovery at six months, moderate the association between cumulative prenatal risk and physical aggression at 20 months (N = 113). Prenatal risk predicted physical aggression, but only in infants exhibiting coactivation of PNS and SNS (i.e., increase in RSA and decrease in PEP) in response to stress. These findings indicate that coactivation of the PNS and SNS in combination with prenatal risk is a biological marker for the development of aggression. Show less
Kinderen die op jonge leeftijd een hoge mate van agressief gedrag laten zien hebben een verhoogd risico op problemen later in de ontwikkeling. Blootstelling aan risicofactoren tijdens de prenatale... Show moreKinderen die op jonge leeftijd een hoge mate van agressief gedrag laten zien hebben een verhoogd risico op problemen later in de ontwikkeling. Blootstelling aan risicofactoren tijdens de prenatale periode is in verband gebracht met de ontwikkeling van agressief gedrag. Echter, de mate waarin deze risicofactoren de ontwikkeling van het kind beïnvloeden hangt deels af van de eigenschappen van het individuele kind, waaronder het vermogen tot zelfregulatie. In dit proefschrift is onderzocht hoe zelfregulatie, gemeten op fysiologisch, emotioneel en cognitief niveau, en prenatale risicofactoren de kwetsbaarheid voor agressief gedrag in de vroege kinderleeftijd vergroten en in hoeverre prenatale risicofactoren samenhangen met vroege zelfregulatie. Geconcludeerd kan worden dat 1) kinderen in de voorschoolse leeftijd met een verhoogde mate van agressief gedrag gekenmerkt worden door een specifieke combinatie van tekorten in zelfregulatie op emotioneel en cognitief niveau, 2) de impact van prenatale risicofactoren op de ontwikkeling van fysieke agressie in de peuterleeftijd afhankelijk is van fysiologische zelfregulatie in de babytijd, en 3) blootstelling aan prenatale risicofactoren voorspellend is voor fysiologische zelfregulatie in de babytijd. Deze bevindingen suggereren dat (preventieve) interventieprogramma’s ter voorkoming van agressief gedrag zich moeten richten op zowel beïnvloeden van prenatale omstandigheden als zelfregulatie in de vroege kindertijd. Show less
Objective: Attenuated activity of stress-regulating systems has consistently been reported in boys with conduct problems. Results in studies of girls are inconsistent, which may result from the... Show moreObjective: Attenuated activity of stress-regulating systems has consistently been reported in boys with conduct problems. Results in studies of girls are inconsistent, which may result from the high prevalence of comorbid post-trauma symptoms. Therefore, the aim of the present study is to investigate post-trauma symptoms as a potential mediator in the relation between stress-regulation systems functioning and conduct problems in female adolescents. Methods: The sample consisted of 78 female adolescents (mean age 15.4; SD 1.1) admitted to a closed treatment institution. The diagnosis of disruptive behaviour disorder (DBD) was assessed by a structured interview-the diagnostic interview schedule for children version IV (DISC-IV). To assess post-trauma symptoms and externalizing behaviour problems, self-report questionnaires, youth self report (YSR) and the trauma symptom checklist for Children (TSCC) were used. The cortisol awakenings response (CAR) measured hypothalamic-pituitary-adrenal (HPA) axis activity, whereas autonomous nervous system (ANS) activity was assessed by heart rate (HR), pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA). Independent t-tests were used to compare girls with and without DBD, while path analyses tested for the mediating role of post- trauma symptoms in the relation between stress regulating systems and externalizing behaviour. Results: Females with DBD (n = 37) reported significantly higher rates of post-trauma symptoms and externalizing behaviour problems than girls without DBD (n = 39). Path analysis found no relation between CAR and externalizing behaviour problems. With regard to ANS activity, positive direct effects on externalizing behaviour problems were present for HR (standardized β = 0.306, p = 0.020) and PEP (standardized β = -0.323, p = 0.031), though not for RSA. Furthermore, no relation-whether direct or indirect-could be determined from post-trauma symptoms. Conclusions: Present findings demonstrate that the neurobiological characteristics of female externalizing behaviour differ from males, since girls showed heightened instead of attenuated ANS activity. While the prevalence of post-trauma symptoms was high in girls with DBD, it did not mediate the relation between stress parameters and externalizing behaviour. Clinical implications and future directions are discussed. Show less
This dissertation comprises an empirical study and a meta-analytical study on autonomic nervous system (ANS) functioning and attachment representations in maltreating parents. For the empirical... Show moreThis dissertation comprises an empirical study and a meta-analytical study on autonomic nervous system (ANS) functioning and attachment representations in maltreating parents. For the empirical study we recruited a sample of 45 mothers with substantiated abuse and neglect and 45 non-maltreating control mothers. Mothers listened to infant cry sounds of varying pitches while their heart rate, vagal tone, pre-ejection period, skin conductance, and salivary α-amylase were measured. Maltreating mothers showed a blunted ANS response to the cry sounds, as well as a lack of coherence between ANS components, compared to the non-maltreating group. During a second appointment we conducted the Adult Attachment Interview. More maltreating mothers had an Unresolved/disoriented (U/d) attachment representation and maltreating mothers showed lower coherence of mind. In turn, U/d attachment was associated with a decrease in skin conductance during an attachment-related computer paradigm, while coherence of mind was associated with higher skin conductance during the paradigm. A meta-analysis of 11 studies (N = 524)showed that (risk for) child maltreatment was associated with higher levels of baseline ANS activity, while a second meta-analysis (k = 11, N = 503) showed no differences in ANS stress reactivity between maltreating parents/at-risk adults and non-maltreating/low-risk comparison groups. Show less
The brain is increasingly recognized as the regulator of body homeostasis and as possible treatment target for cardiovascular disease. This thesis further reveals the role of the autonomic nervous... Show moreThe brain is increasingly recognized as the regulator of body homeostasis and as possible treatment target for cardiovascular disease. This thesis further reveals the role of the autonomic nervous system (ANS) in the control of lipid metabolism and inflammation, and identified pathological consequences of disturbed regulation. Part I focuses on regulation of lipid metabolism by the ANS, with special attention for brown adipose tissue (BAT) as an emerging pharmacological target for therapy. We describe novel targets that modulate BAT, both directly (e.g. CB1R) and via the brain (e.g. MC4R, GLP-1R) to show that BAT activation improves dyslipidemia, glucose tolerance and T2D and even atherosclerosis. In addition, we identified the biological clock as an important regulator of BAT function and showed the consequences of disturbed circadian rhythmicity for lipid metabolism. Part II of this thesis describes studies on the regulation of inflammation by the ANS, with focus on the anti-inflammatory reflex. During this reflex, binding of acetylcholine to _7nAChR and subsequent intracellular signaling results in transcriptional repression of pro-inflammatory genes. We investigated the effects of hematopoietic _7nAChR deficiency and the consequences of selective parasympathetic and sympathetic denervation of the spleen for this reflex, and for inflammation and atherosclerotic plaque development. Show less
Kraima, A.C.; Schaik, J. van; Susan, S.; Velde, C.J.H. van de; Hamming, J.F.; Lakke, E.A.J.F.; DeRuiter, M.C. 2015
