Basal parasympathetic deficits in C9orf72 hexanucleotide repeat expansion carriers relate to smaller frontoinsula and thalamus volume and lower empathy.

Diminished basal parasympathetic nervous system activity is a feature of frontotemporal dementia that relates to left frontoinsula dysfunction and empathy impairment. Individuals with a pathogenic expansion of the hexanucleotide repeat in chromosome 9 open reading frame 72 (C9orf72), the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, provide a unique opportunity to examine whether parasympathetic activity is disrupted in genetic forms of frontotemporal dementia and to investigate when parasympathetic deficits manifest in the pathophysiological cascade. We measured baseline respiratory sinus arrhythmia, a parasympathetic measure of heart rate variability, over two minutes in a sample of 102 participants that included 19 asymptomatic expansion carriers (C9+ asymp), 14 expansion carriers with mild cognitive impairment (C9+ MCI), 16 symptomatic expansion carriers with frontotemporal dementia (C9+ FTD), and 53 expansion-negative healthy controls (C9- HC) who also underwent structural magnetic resonance imaging. In follow-up analyses, we compared baseline respiratory sinus arrhythmia in the C9+ FTD group with an independent age-, sex-, and clinical severity-matched group of 26 people with sporadic behavioral variant frontotemporal dementia. The Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating-Sum of Boxes score was used to quantify behavioral symptom severity, and informant ratings on the Interpersonal Reactivity Index provided measures of participants' current emotional (empathic concern) and cognitive (perspective-taking) empathy. Results indicated that the C9+ FTD group had lower baseline respiratory sinus arrhythmia than the C9+ MCI, C9+ asymp, and C9- HC groups, a deficit that was comparable to that of sporadic behavioral variant frontotemporal dementia. Linear regression analyses indicated that lower baseline respiratory sinus arrhythmia was associated with worse behavioral symptom severity and lower empathic concern and perspective-taking across the C9orf72 expansion carrier clinical spectrum. Whole-brain voxel-based morphometry analyses in participants with C9orf72 pathogenic expansions found that lower baseline respiratory sinus arrhythmia correlated with smaller gray matter volume in the left frontoinsula and bilateral thalamus, key structures that support parasympathetic function, and in the bilateral parietal lobes, occipital lobes, and cerebellum, regions that are also vulnerable in individuals with C9orf72 expansions. This study provides novel evidence that basal parasympathetic functioning is diminished in FTD due to C9orf72 expansions and suggests that baseline respiratory sinus arrhythmia may be a potential non-invasive biomarker that is sensitive to behavioral symptoms in the early stages of disease.

Parasympathetic nervous system: A key role in control and mood disorders in patients with asthma.

BACKGROUND: Patients with severe asthma often have uncontrolled disease and experience mood disorders, particularly anxiety and depression. The autonomic nervous system (ANS) plays an important role in asthma, mainly through the parasympathetic ANS system (PANS), which favors bronchoconstriction and mental health status. OBJECTIVE: To evaluate the role of the activation of the PANS in uncontrolled asthma and related mood disorders. METHODS: This was a proof-of-concept cross-sectional study that analyzed demographic and clinical variables reflecting asthma severity and control, lung function, inflammation (from induced sputum), evaluation of quality of life, and the risk for anxiety and depression according to validated questionnaires. The PANS analysis was conducted based on heart rate variability: SD of the difference between consecutive normal-to-normal (NN) intervals (SDNN), root mean square of the successive differences (RMSSD), percentage of consecutive NN intervals (pNN50), total power (TP), and respiratory-related power (Pr). RESULTS: A total of 30 patients with asthma were grouped according to asthma control and the risk for anxiety and depression; 10 patients with uncontrolled asthma compared with the patients with controlled asthma showed significant differences (P < .05) in SDNN (26.5 [8.2] vs 42.7 [29.7]), RMSSD (14.1 [6.5] vs 24 [20]), pNN50 (0.6 [1.5] vs 6.2 [11.8]), TP (0.0005 [0.00046] vs 0.0014 [0.00085]), and Pr (0.0003 [0.00025] vs 0.0007 [0.00060]) respectively. A total of 13 patients at risk for anxiety and depression compared with the patients without showed reduced values (P < .05) for SDNN (26.5 [7.9] vs 45.6 [31.3]), pNN50 (0.75 [1.4] to 7.12 [12.6]), TP (0.0005 [0.00048] to 0.0012 [0.0008]), and Pr (0.0003 [0.00027] to 0.0008 [0.00062]). CONCLUSION: Our results suggest that PANS activity is depressed in patients with uncontrolled asthma and common mood disorders such as depression and anxiety, and the evaluation of heart rate variability may be a useful means for follow-up of asthma control and related mood disorders.

Stress-induced impairment of parasympathetic NO-mediated inhibition of sympathetic vasoconstriction in submucosal arteriole of rat rectum.

In the gastrointestinal tract, nitrergic inhibition of the arteriolar contractility has not been demonstrated. Here, we explored whether neurally-released nitric oxide (NO) inhibits sympathetic vasoconstrictions in the rat rectal arterioles. Changes in sympathetic vasoconstrictions and their nitrergic modulation in rats exposed to water avoidance stress (WAS, 10 days, 1 h per day) were also examined. In rectal submucosal preparations, changes in arteriolar diameter were monitored using video microscopy. In control or sham-treated rats, electrical field stimulation (EFS)-induced sympathetic vasoconstrictions were increased by the neuronal nitric oxide synthase (nNOS) inhibitor L-NPA (1 µM) and diminished by the cyclic guanosine monophosphate-specific phosphodiesterase 5 (PDE5) inhibitor tadalafil (10 nM). In phenylephrine-constricted, guanethidine-treated arterioles, EFS-induced vasodilatations were inhibited by the calcitonin gene-related peptide (CGRP) receptor antagonist BIBN-4096 (1 µM) but not L-NPA. Perivascular nNOS-immunoreactive nitrergic fibres co-expressing the parasympathetic marker vesicular acetylcholine transporter (VAChT) were intermingled with tyrosine hydroxylase (TH)-immunoreactive sympathetic fibres expressing soluble guanylate cyclase (sGC), a receptor for NO. In WAS rats in which augmented sympathetic vasoconstrictions were developed, L-NPA failed to further increase the vasoconstrictions, while tadalafil-induced inhibition of the vasoconstrictions was attenuated. Phenylephrine- or α,ß-methylene ATP-induced vasoconstrictions and acetylcholine-induced vasodilatations were unaltered by WAS. Thus, in arterioles of the rat rectal submucosa, NO released from parasympathetic nerves appears to inhibit sympathetic vasoconstrictions presumably by reducing sympathetic transmitter release. In WAS rats, sympathetic vasoconstrictions are augmented at least partly due to the diminished pre-junctional nitrergic inhibition of transmitter release without changing α-adrenoceptor or P2X-purinoctor mediated vasoconstriction and endothelium-dependent vasodilatation.

Adrenocortical and autonomic cross-system regulation in youth: A meta-analysis.

Childhood and adolescence are salient periods for the development of adrenocortical and autonomic arms of the stress response system (SRS), setting the stage for subsequent health and adaptive functioning. Although adrenocortical and autonomic systems theoretically function in highly coordinated ways, the strength of the relationship between these systems remains unclear. We leveraged a multivariate mixed effects meta-analytic approach to assess associations between adrenocortical, sympathetic, and parasympathetic functioning at rest and reactivity during stress-inducing tasks across 52 studies (N = 7,671; 5-20 years old). Results suggested a modest positive relation between adrenocortical and sympathetic systems as well as between adrenocortical and parasympathetic systems. Moderation analyses indicated the strength of associations varied as a function of several methodological and sociodemographic characteristics. Environmental effects on cross-system regulation were less clear, perhaps due to underrepresentation of adverse-exposed youth in the included studies. Collectively, our findings call for greater methodological attention to the dynamical, non-linear nature of cross-system functioning, as well as the role of experience in their organization across development.

Parasympathetic regulation and support from family and friends predict prosocial development in U.S. Mexican-origin adolescents.

Both parasympathetic nervous system regulation and receipt of social support from close relationships contribute to prosocial development, although few studies have examined their combined influences in adolescence and particularly within racially and ethnically minoritized populations. In this longitudinal study of 229 U.S. Mexican-origin adolescents (48% female-identifying), youths reported on receipt of social support from family and friends from 10 to 16 years, had their baseline respiratory sinus arrhythmia (RSA) measured at 17 years, reported their prosocial behavior and completed the Mind in the Eyes test to assess cognitive empathy at 17 and 19 years, and reported their prosocial civic behavior (i.e., community activity) at 19 years. Family social support predicted prosocial behavior at 17 years, and friend social support predicted prosocial civic behavior at 19 years. Compared to youths with lower or higher baseline RSA, youths with moderate RSA reported more prosocial civic behavior, had greater cognitive empathy, and tended to report more general prosocial behavior at 19 years. The quadratic association between baseline RSA and cognitive empathy was stronger for youths with greater family social support. These findings are the first to extend the evidence that moderate baseline parasympathetic nervous system activity supports prosocial development into late adolescence and with the U.S. Mexican-origin community, and these findings address calls for more integrative biopsychosocial studies of prosociality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Exploring the efficacy of sense of Okayness (SOK) as an antidote for stress in older adults: the role of SOK elevation intervention, heart rate variability (HRV), and cognitive performance in stressful and relaxing situations.

Sense of Okayness (SOK) is an emerging concept that describes a person's ability to remain stable and unshaken in the face of life transitions and hardships. This quality enables effective stress regulation and heightened tolerance to uncertainty. To investigate the possible role of the parasympathetic nervous system (PNS) in mediating the relationship between SOK and stress regulation among older individuals, an analytical sample of N = 69 participants (74% women) with a mean age of 78.75 years (SD age = 6.78) was recruited for a standardized cognitive assessment and stress induction. Baseline heart rate variability (HRV), measured via electrocardiogram (ECG), and SOK assessments were conducted prior to stress induction, along with a baseline cognitive evaluation. Subsequently, participants were subjected to a psychosocial stress paradigm, followed by either a 30-minute SOK elevation intervention (n = 40) or a control condition with nature sounds (n = 29). A second cognitive assessment was administered post-intervention, with continuous HRV measurement through ECG. The results revealed significant HRV changes due to the experimental intervention, though no significant differences were observed between the SOK intervention and control groups. Interestingly, individuals with high trait SOK displayed more stable HRV trajectories, exhibiting a smaller decline during the stress intervention and a milder increase during both the stressor and SOK intervention phases. Overall, these findings do suggest a significant association between SOK, parasympathetic activity, and stress reactivity. These results prompt further investigation into whether personality patterns, such as a strong SOK, may be linked to reduced vagal reactivity and better coping in old age.

Desmopressin nasal spray inhibiting parasympathetic function on isolated tracheal smooth muscle.

Objectives: Nocturia with or without asthma is one of the aging diseases. Desmopressin has been used as a nasal spray for patients who are suffering from nocturia. This study determined the effects of desmopressin on isolated tracheal smooth muscle in vitro. Methods: We evaluated desmopressin's efficiency on isolated rat tracheal smooth muscle. Desmopressin was evaluated for the following effects on tracheal smooth muscle: (1) effect on resting tension; (2) effect on contraction brought on by parasympathetic mimetic 10-6 M methacholine; and (3) effect on electrically produced tracheal smooth muscle contractions. Results: As the concentration grew, desmopressin by itself had no impact on the trachea's baseline tension. Addition of desmopressin at doses of 10-5 M or above elicited a significant relaxation response to 10-6 M methacholine-induced contraction. Desmopressin could also inhibit spike contraction of the trachea induced by electrical field. Conclusion: According to this study, desmopressin at high quantities may prevent the trachea's parasympathetic activity. Due to its ability to block parasympathetic activity and lessen the contraction of the tracheal smooth muscle brought on by methacholine, Desmopressin nasal spray might help nocturia sufferers experience fewer asthma attacks.

From One's Heart to the Mind of Others: A Study in School-Aged Children.

Studies have shown a significant association between effective parasympathetic modulation of the heart and processes linked to social cognition. Particularly, Quintana and colleagues documented a relation between vagally-mediated heart rate variability (vmHRV) and performance on a theory of mind (ToM) task, namely, the Reading the Mind in the Eyes Test (RMET), in a sample of university students. The purpose of the present study was to test whether such result would extend to a sample of school-aged children (7-9 years old) using the child version of the RMET. In addition, the Eyes Test Revised was administered as it is more suitable to evaluate ToM during childhood. Results supported the positive association between vmHRV and ToM abilities, replicating and extending previous results obtained in young adults. The current study adds to the existing literature pointing to HRV as a putative biomarker of social cognition abilities.

Does Parasympathetic Nervous System Activity Exacerbate Depressive Symptoms in College Students Who Experienced Parent-Child Separation? A Longitudinal Examination.

Childhood separation caused by parental migration increases the risk of suffering depressive symptoms among college students. However, most studies in this field have focused on environmental factors and largely ignored the role of physiological reactivity to stress (e.g., parasympathetic nervous system activity) in this process. The present study examined the long-term effects of the parent-child separation experience on depressive symptoms in college students, and explored the moderating role of parasympathetic nervous system (PNS) activity in these relationships. The participants were 242 college students (Mage = 18.74 years, SD = 0.79; 32.2% male), including 149 college students who experienced parent-child separation and 93 college students without this experience. Using a three-wave longitudinal design, participants completed the measures of the parent-child separation experience, PNS activity (measured via respiratory sinus arrhythmia, RSA), and depressive symptoms at Time 1 (T1, before the COVID-19 lockdown). Their depressive symptoms were again measured at Time 2 (T2, during the COVID-19 lockdown) and Time 3 (T3, after the COVID-19 lockdown). The results showed that the parent-child separation experience positively predicted depressive symptoms in college students at three time points. Moreover, the parent-child separation experience positively predicted depressive symptoms at T2 among males with less and average RSA suppression but positively predicted depressive symptoms at T2 among females with greater RSA suppression. These findings indicate a long-term effect of parent-child separation on depressive symptoms in college students that still exist after they entered university, and that the effect varies depending on PNS activity and gender.

The effectiveness of an osteopathic manual technique compared with a breathing exercise on vagal tone as indicated by heart rate variability, a crossover study.

INTRODUCTION: Parasympathetic nervous system (PSNS) function can be inferred by heart rate variability (HRV) providing indications about an individual's health. Manual therapy may influence PSNS function, however the research outcomes in this regard are equivocal. This study explored the PSNS effect of a measured breathing technique with suboccipital balanced ligamentous tension, an osteopathic manipulative therapy technique. METHODS: Healthy adult participants in this crossover study (n = 18) were randomly allocated into two groups with differing order of interventions. A 1:1 breathing rate of 6 breaths per minute maintained for 5 min was compared to the osteopathic intervention. HRV was measured for 5 min before and after each intervention and analysed using the root mean square of successive differences (RMSSD) between normal heartbeats and high frequency normalised units (HFnu). RESULTS: The RMSSD data demonstrated no significant difference between groups or within groups (p > 0.05) over time. HFnu results showed a significant between-group difference over the four time points (p = 0.004) with a medium effect size (ηp2 = 0.240), and no significant within-group difference (p > 0.05). DISCUSSION: The osteopathic intervention raised HRV to a small extent, however measured breathing lowered HRV. In the group that received the osteopathic technique first, HFnu values continued to rise post-osteopathic treatment possibly indicating an increasing parasympathetic effect over time. Recommendations for future studies include changing the breathing ratio to ensure parasympathetic response, take into account potential delayed effects of interventions, consider outcome measures less variable than HRV, and longer follow up times. CONCLUSION: This study suggests parasympathetic stimulation may occur with the application of suboccipital balanced ligamentous tension and sympathetic stimulation from measured breathing.

Does heart rate variability using the Newborn Infant Parasympathetic Evaluation index identify postsurgical pain levels and emergence delirium in toddlers? A prospective observational study.

PURPOSE: Children recovering from anesthesia commonly experience early postoperative negative behaviour, caused by pain and emergence delirium. Differentiating the two is challenging in young children. Perioperative pain influences the heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE) index and may also affect emergence delirium. We sought to investigate whether the perioperative NIPE index can discriminate between mild, moderate, or severe pain levels and can detect emergence delirium. METHODS: This prospective observational study enrolled children aged three years or younger undergoing elective adenotonsillectomy, tonsillectomy, or adenoidectomy. The NIPE index, the Faces, Legs, Activity, Cry, Consolability (FLACC) score, and the Pediatric Anesthesia Emergence Delirium (PAED) score were recorded in the postanesthesia care unit (PACU). The primary aim was to investigate the relationship between the postoperative NIPE index and postoperative pain severity. The secondary aims were to evaluate the association between the NIPE index and emergence delirium (PAED ≥ 10) and its delirium-specific (ED-I) and pain-specific (ED-II) components. RESULTS: Sixty-nine children were recruited. In the PACU, the mean (standard deviation [SD]) NIPE values in children experiencing moderate and severe pain were 50 (12) and 49 (14), respectively. These values were significantly lower than the mean (SD) value of 64 (13) observed in children with mild pain (mean difference moderate vs no/mild pain, -14; 95% confidence interval [CI], -17 to -11; P < 0.001, and mean difference severe vs no/mild pain, -17; 95% CI, -20 to -14; P < 0.001, respectively). The NIPE index was significantly lower in children experiencing pain-specific ED-II (mean [SD] NIPE instantaneous [NIPEi] for ED-II 49 [10] vs no ED-II 55 [13]; mean difference, -6; 95% CI, -11 to -2; P = 0.009). The NIPE index was unable to detect emergence delirium (mean [SD] NIPEi for ED, 54 [15] vs no ED, 51 [10]; mean difference, 3; 95% CI, -2 to 8; P = 0.23) or the delirium-specific component ED-I (mean [SD] NIPEi for ED-I, 55 [15] vs no ED-I, 51 [11]; mean difference, 4; 95% CI, 0 to 8; P = 0.06). CONCLUSION: The NIPE index can identify moderate and severe postoperative pain after adenotonsillectomy but not emergence delirium in children aged three years and younger. This discrimination can be valuable in the early postoperative phase when the differentiation between pain and emergence delirium is difficult. STUDY REGISTRATION: ClinicalTrials.gov ( NCT04909060 ); first submitted 26 May 2021.

RéSUMé: OBJECTIF: Les enfants qui se remettent d'une anesthésie font fréquemment preuve d'un comportement négatif en début de période postopératoire. Ce comportement est causé par la douleur et le délire d'émergence, mais il est difficile de les distinguer chez les jeunes enfants. La douleur périopératoire a un impact sur l'indice d'évaluation parasympathique du nouveau-né et du nourrisson (NIPE) dérivé de la variabilité de la fréquence cardiaque et peut également affecter le délire d'émergence. Nous avons cherché à déterminer si l'indice NIPE périopératoire permettait de différencier des niveaux de douleur légers, modérés ou sévères et de détecter le délire d'émergence. MéTHODE: Cette étude observationnelle prospective a recruté des enfants de trois ans ou moins ayant bénéficié d'une adéno-amygdalectomie, d'une amygdalectomie ou d'une adénoïdectomie non urgente. L'indice NIPE, le score FLACC (Faces, Legs, Activity, Cry, Consolability) et le score PAED (Pediatric Anesthesia Emergence Delirium) ont été enregistrés en salle de réveil. L'objectif principal était d'étudier la relation entre l'indice NIPE postopératoire et la sévérité de la douleur postopératoire. Les objectifs secondaires étaient d'évaluer l'association entre l'indice NIPE et le délire d'émergence (PAED ≥ 10) et ses composantes spécifiques au délire (ED-I) et à la douleur (ED-II). RéSULTATS: Nous avons recruté soixante-neuf enfants. En salle de réveil, les valeurs NIPE moyennes (écart type [ET]) chez les enfants souffrant de douleurs modérées et sévères étaient respectivement de 50 (12) et de 49 (14). Ces valeurs étaient significativement inférieures à la valeur moyenne (ET) de 64 (13) observée chez les enfants présentant une douleur légère (différence moyenne modérée vs pas de douleur ou douleur légère, −14; intervalle de confiance [IC] à 95 %, −17 à −11; P < 0,001, et différence moyenne entre douleur sévère vs pas de douleur ou douleur légère, −17; IC 95 %, −20 à −14; P < 0,001, respectivement). L'indice NIPE était significativement plus faible chez les enfants présentant un ED-II spécifique à la douleur (moyenne [ET] NIPE instantanée [NIPEi] pour ED-II, 49 [10] vs pas de ED-II, 55 [13]; différence moyenne, −6; IC 95 %, −11 à −2; P = 0,009). L'indice NIPE n'a pas été en mesure de détecter le délire d'émergence (NIPEi moyen [ET] pour le délire d'émergence, 54 [15] vs pas de délire d'émergence, 51 [10]; différence moyenne, 3; IC 95 %, −2 à 8; P = 0,23) ou la composante spécifique au délire de l'ED-I (NIPEi moyen [ET] pour ED-I, 55 [15] vs pas d'ED-I, 51 [11]; différence moyenne, 4; IC 95 %, 0 à 8; P = 0,06). CONCLUSION: L'indice NIPE permet d'identifier une douleur postopératoire modérée et sévère après une adéno-amygdalectomie mais pas le délire d'émergence chez les enfants de trois ans et moins. Cette discrimination peut être utile dans la phase postopératoire précoce lorsqu'il est difficile de différencier la douleur et le délire d'émergence. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov ( NCT04909060 ); première soumission le 26 mai 2021.

The 24-h movement behaviours composition is associated with parasympathetic modulation in preschoolers.

AIM: To investigate the associations between 24-h movement behaviours and heart rate variability (HRV) in preschool children. METHODS: A total of 123 preschoolers (4.52 ± 0.25 years old; 62 girls) were assessed for physical activity (PA) and sedentary behaviour (SB) using an accelerometer (Actigraph WGT3x). Sleep duration (SD) was parent-reported. Children were laid down in a supine position for 10 min to assess HRV data. The R-R intervals recorded during the last 5 min of this period were analysed. We conducted compositional analysis in R studio, and the significance level was 95%. All ethical procedures were followed, and the study had the approval of the local ethical board. RESULTS: When considered as a composition, adjusted for age, body mass index and sex, the 24-h movement composition (PA, SB and SD) significantly predicted better parasympathetic modulation (Root mean square of the successive differences [RMSSD] [p = 0.04; r2 = 0.13]), but not high frequency (HF) (nu) (p = 0.51, r2 = 0.01), low frequency (nu) (p = 0.52, r2 = 0.02),or standard deviation (standard deviation of normal-to-normal intervals) (p = 0.55, r2 = 0.02), respectively. CONCLUSION: These results suggest the 24-h movement composition predicted the RMSSD time-domain index related to parasympathetic activity.

Normal baseline cardiac autonomic function and increased pupillary parasympathetic tone in patients with vasovagal syncope.

It is controversial whether people with vasovagal syncope (VVS) have abnormal autonomic responses at baseline and whether specific diagnostic manoeuvres have a diagnostic value. We investigated whether the pupillary light reflex and cardiac autonomic tests can be used to identify autonomic dysfunction in volunteers with a medical history of VVS. The study groups included 128 healthy volunteers, of whom 31 reported a history of typical VVS. The right pupil was evaluated using an automated, commercial infra-red pupillometer under strict conditions. In addition to miosis and mydriasis kinetics, pupil diameters were measured. Heart rate variability at rest and heart rate changes to standing were quantified with high-resolution electrocardiography and designated software. The demographic and clinical characteristics of both groups were statistically similar. Average constriction velocity (ACV) was significantly higher in VVS patients following a univariate analysis (3.83 ± 0.59 vs. 3.56 ± 0.73 mm/s, p = 0.042) and after correcting for potential confounders (p = 0.049). All other pupillometric and heart rate indices were comparable between groups. Patients with a history of VVS depict pupillary parasympathetic overactivity in response to light stimuli, manifested as increased ACV. The prognostic implications of this finding and the significance of using this simple clinical tool to identify patients who are at risk for developing frequent episodes of VVS or physical injuries following a syncope merits further study.

Rhinorrhea and watery eyes in infancy and risk of attention-deficit hyperactivity disorder in school-age children.

Increased parasympathetic nervous system (PNS) activity is associated with attention-deficit/hyperactivity disorder (ADHD) inattentive symptoms, but not hyperactive-impulsive symptoms, and may contribute to inattentive subtype etiology. Guided by prior work linking infant rhinorrhea and watery eyes without a cold (RWWC) to PNS dysregulation, we examined associations between infant RWWC and childhood ADHD symptoms in a longitudinal cohort of Black and Latinx children living in the context of economic disadvantage (N = 301 youth: 158 females, 143 males). Infant RWWC predicted higher inattentive (relative risk [RR] 2.16, p < .001) but not hyperactive-impulsive (RR 1.53, p = .065) ADHD symptoms (DuPaul scale), administered to caregivers at child age 8-14 years. Stratified analyses revealed that these associations were present in females but not males, who were three times more likely to have higher ADHD current total symptoms if they had infant RWWC than if they did not. Additionally, associations between RWWC and inattention symptoms were observed only in females. RWWC may thus serve as a novel risk marker of ADHD inattentive-type symptoms, especially for females.

Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development.

Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of functional human parasymNs from Schwann cell progenitors. We employ these neurons (1) to assess human autonomic nervous system (ANS) development, (2) to model neuropathy in the genetic disorder familial dysautonomia (FD), (3) to show parasymN dysfunction during SARS-CoV-2 infection, (4) to model the autoimmune disease Sjögren's syndrome (SS), and (5) to show that parasymNs innervate white adipocytes (WATs) during development and promote WAT maturation. Our model system could become instrumental for future disease modeling and drug discovery studies, as well as for human developmental studies.

Childhood psychological maltreatment and social anxiety in college students: The roles of parasympathetic nervous system activity and parent-child separation experience.

BACKGROUND: Childhood psychological maltreatment is a risk factor for social anxiety in adulthood. Parent-child separation, as one of the most serious adversities in early life, may exacerbate the risk of psychological maltreatment and influence the interactions between childhood psychological maltreatment and biological sensitivity to stress in relation to social anxiety. However, there has been a dearth of work on this issue. OBJECTIVE: This study investigated the interactive effects between childhood psychological maltreatment and parasympathetic nervous system (PNS) activity on social anxiety in college students by comparing those who experienced parent-child separation versus those who did not. Potential sex differences in the aforementioned associations were tested as an exploratory aim. PARTICIPANTS AND SETTING: Data were obtained from 264 college students (Mage = 18.45 years, SD = 0.69), including 156 students who experienced parent-child separation and 108 students without this experience. METHODS: Participants completed measures of childhood psychological maltreatment and social anxiety and reported their parent-child separation experience. The data of PNS activity, measured by respiratory sinus arrhythmia (RSA) reactivity, were obtained during the Trier Social Stress Test (TSST) in the lab. RESULTS: Childhood psychological maltreatment was positively associated with college students' social anxiety. RSA reactivity moderated the relationship between childhood psychological maltreatment and college students' social anxiety, and the moderating role of RSA reactivity varied with parent-child separation experience and sex. CONCLUSIONS: Parent-child separation experience influenced the biosocial interactions between childhood psychological maltreatment and PNS activity in relation to individuals' social anxiety, and this effect persisted in adulthood.

Partial Resistance to Thyroid Hormone-Induced Tachycardia and Cardiac Hypertrophy in Mice Lacking Thyroid Hormone Receptor ß.

Background: Thyroid hormones regulate cardiac functions mainly through direct actions in the heart and by binding to the thyroid hormone receptor (TR) isoforms α1 and ß. While the role of the most abundantly expressed isoform, TRα1, is widely studied and well characterized, the role of TRß in regulating heart functions is still poorly understood, primarily due to the accompanying elevation of circulating thyroid hormone in TRß knockout mice (TRß-KO). However, their hyperthyroidism is ameliorated at thermoneutrality, which allows studying the role of TRß without this confounding factor. Methods: Here, we noninvasively monitored heart rate in TRß-KO mice over several days using radiotelemetry at different housing temperatures (22°C and 30°C) and upon 3,3',5-triiodothyronine (T3) administration in comparison to wild-type animals. Results: TRß-KO mice displayed normal average heart rate at both 22°C and 30°C with only minor changes in heart rate frequency distribution, which was confirmed by independent electrocardiogram recordings in freely-moving conscious mice. Parasympathetic nerve activity was, however, impaired in TRß-KO mice at 22°C, and only partly rescued at 30°C. As expected, oral treatment with pharmacological doses of T3 at 30°C led to tachycardia in wild-types, accompanied by broader heart rate frequency distribution and increased heart weight. The TRß-KO mice, in contrast, showed blunted tachycardia, as well as resistance to changes in heart rate frequency distribution and heart weight. At the molecular level, these observations were paralleled by a blunted cardiac mRNA induction of several important genes, including the pacemaker channels Hcn2 and Hcn4, as well as Kcna7. Conclusions: The phenotyping of TRß-KO mice conducted at thermoneutrality allows novel insights on the role of TRß in cardiac functions in the absence of the usual confounding hyperthyroidism. Even though TRß is expressed at lower levels than TRα1 in the heart, our findings demonstrate an important role for this isoform in the cardiac response to thyroid hormones.

Efficacy and safety of trigeminal parasympathetic pathway stimulation for dry eye: A systematic review and meta-analysis.

This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified.

Effects of transcutaneous auricular vagus nerve stimulation at left cymba concha on experimental pain as assessed with the nociceptive withdrawal reflex, and correlation with parasympathetic activity.

The aim of this study was to clarify the effects of transcutaneous auricular vagus nerve stimulation (taVNS) to the left cymba concha on the pain perception using nociceptive withdrawal reflex (NWR), which is known to be associated with chronic pain, and to investigate whether there is a relationship between taVNS-induced suppression of the NWR and parasympathetic activation. We applied either 3.0 mA, 100 Hz taVNS for 120 s on the left cymba concha (taVNS condition) or the left earlobe (Sham condition) for 20 healthy adults. NWR threshold was measured before (Baseline), immediately after (Post 0), 10 min (Post 10) and 30 min after (Post 30) stimulation. The NWR threshold was obtained from biceps femoris muscle by applying electrical stimulation to the sural nerve. During taVNS, electrocardiogram was recorded, and changes in autonomic nervous activity measured by heart rate variability (HRV) were analyzed. We found that the NWR thresholds at Post 10 and Post 30 increased compared with baseline in the taVNS group (10 min after: p = .008, 30 min after: p = .008). In addition, increased parasympathetic activity by taVNS correlated with a greater increase in NWR threshold at Post 10 and Post 30 (Post 10: p = .003; Post 30: p = .001). The present results of this single-blinded study demonstrate the pain-suppressing effect of taVNS on NWR threshold and suggest that the degree of parasympathetic activation during taVNS may predict the pain-suppressing effect of taVNS after its application.