The stomach is one of the major targets of the vagus nerve. Vagal cholinergic parasympathetic (efferent) neurons are located in the dorsal motor nucleus of the vagus (DMV) in the caudal brainstem. They do not directly innervate gastric effector cells, but instead a large portion of enteric neurons located in the myenteric plexus, which act as muscle motor neurons and function-specific pattern generators that can regulate specific motility and secretion programs in coordination with physiological needs and environmental conditions. Vagal sensory (afferent) neurons located in the nodose ganglia (NG) innervate all layers of the stomach wall, where they pick up mechanical and chemical signals to inform the brain and effectuate vago-vagal reflexes. The most abundant terminal structures, intraganglionic laminar endings (IGLEs), are in intimate contact with myenteric plexus neurons. Besides sensing gastric tension, they are likely also chemosensors and provide a link between the enteric nervous system and the brain. Transcriptomic analyses of vagal efferent and afferent neurons allowed making great progress on deciphering their respective coding logic, with a predominantly labeled line organization emerging as the general principle. Because of their distinct molecular fingerprints, separate populations of vagal efferents and afferents with unique morphologies and functions have become experimentally and therapeutically accessible. However, the full coding logic also depends on the organization of the peripheral interface with the enteric nervous system, as well as the central interface represented by 2nd and higher order sensory neurons and pre-autonomic neurons upstream of the DMV, which are only starting to be understood.

Ambulatory autonomic and sleep monitoring in real-world settings remains challenging. The Astroskin biometric system may offer a practical solution. Here, we evaluate the utility of Astroskin as a wearable research device compared to common industry standard approaches. We assessed the Astroskin under static and dynamic conditions, measuring peripheral blood oxygen saturation (SpO2) during hypobaric hypoxia; skin temperature and estimated core temperature under insulated thermal stress; heart rate (HR), systolic blood pressure (SBP), and respiratory rate and depth during Valsalva maneuvers and positional changes, and sleep staging during at-home sleep. Data were compared using Pearson's correlations, Bland-Altman plots for accuracy and precision, and two one-sided t-tests for equivalency. SpO2 (r = 0.93, p < 0.01; bias -2.95 ± 2.7%), skin temperature (r = 1.0, p < 0.01; bias -0.30 ± 0.43 °C), and HR (r = 0.71, p < 0.01; bias -1.77 ± 7.22 bpm) are strongly correlated, highly accurate, and equivalent to within 5% of the industry comparators. Estimated core temperatures also achieved high agreement with rectal temperature (r = 0.81, p < 0.01; bias +0.34 ± 0.2 °C; 1% equivalency). Respiratory parameters are optimized when derived directly from band stretch. SBP measurements approach industry standards with high accuracy and equivalency, but low precision (r = 0.56, p < 0.01; bias -2.13 ± 11.57 mmHg; 3% equivalency). Despite appropriate sleep detection (100% success), Astroskin's sleep staging algorithm was unpredictable (41% success). When staging was available, Astroskin differentiated sleep from wake with equivalency within 10%, including sensitive detection of arousals. The Astroskin is suitable for ambulatory monitoring, with accuracy optimized when systematic biases are corrected. Use for sleep assessment requires improved sleep staging success. Astroskin's practical, continuous, wearable approach underscores its potential for diverse applications.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder affecting a considerable proportion of the adult population. It is characterized by chronic intermittent hypoxia (CIH), resulting from recurrent partial (hypopnea) or complete obstruction (apnea) of the upper airway during sleep. Clinically, OSA produces fragmented sleep, loud snoring, excessive daytime somnolence, cognitive dysfunction, and nocturnal diaphoresis. Importantly, OSA is recognized as an independent risk factor for systemic hypertension and is associated with cardiac arrhythmias and stroke. The CIH contributes to these adverse outcomes by enhancing carotid body chemoreceptor sensitivity and promoting sympathetic overactivation, systemic inflammation, and oxidative stress. Syncope is a transient, fully reversible loss of consciousness caused by cerebral hypoperfusion. Although cardiac causes such as atrial fibrillation and brady-arrhythmias are well recognized, the vasovagal syncope (VVS) remains the most common etiology, triggered by exaggerated vagal activation. Emerging evidence suggests that OSA may contribute to VVS, as patients with unexplained syncope show a high prevalence of OSA and often improve with CPAP therapy. This minireview summarizes the potential mechanisms linking OSA to syncope, provides a brief overview of OSA pathophysiology, and discusses autonomic pathways that may underline syncope in this population, highlighting their relevance for clinical management.

Understanding the sensory nervous system's precise innervation of visceral organs remains a major challenge in systems neuroscience, particularly for designing neuromodulatory therapies. Here, we introduce a digital twin of the rodent stomach that combines high-resolution structural images and nerve-specific mapping onto a common coordinate scaffold. Using a pipeline developed within the NIH SPARC (Stimulate Peripheral Activity to Relieve Conditions) framework, we used immunohistochemistry (fluorescence and chromogenic) and anterograde tracing to label Calcitonin gene-related peptide (CGRP) axons and tracer-labeled spinal afferents in the whole stomach flat-mounts, digitized the axons, and registered axon data from nerve tracing experiments. These datasets were integrated into a standard scaffold, enabling cross-specimen alignment and annotation. The scaffold promotes integration of topographically anatomical and physiological metadata into the scaffold to enable simulation of neuromodulatory input effects, advances research on targeted nerve stimulation to improve organ function, and supports iterative development of closed-loop bioelectronic devices. The scaffold is publicly available via the SPARC Portal and supports modular extension to other species and organ systems. Our methodology contributes to a better understanding of the visceral afferent nervous system and multi-organ connectome, as well as establishing a reproducible computational framework for mapping and manipulating autonomic pathways in visceral organs, with applications spanning basic neuroanatomy to translational clinical intervention.

Exercise training induces physiological adaptations that have traditionally been interpreted mainly through changes in skeletal muscle, cardiovascular, metabolic, immune, and endocrine systems. Recent evidence from Kindel and colleagues shows that ventromedial hypothalamic steroidogenic factor-1 neurons are activated by exercise and are required for endurance gains. Here, we highlight complementary evidence from the autonomic nervous system. Our recent stereological study of rat stellate ganglia showed side-specific structural remodelling after treadmill training, including right-left asymmetry in neuronal number and divergent changes in neuronal soma size. Together, these observations suggest that exercise-associated adaptation may involve neural plasticity across central and peripheral autonomic circuits. This perspective raises testable questions about whether central hypothalamic and autonomic ganglionic adaptations act independently, sequentially, or as part of a coordinated body-brain-autonomic feedback system relevant to cardiac sympathetic regulation.

There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3 years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.

Urodynamics remain the gold standard for objectively evaluating bothersome lower urinary tract symptoms (LUTS) and offer indirect insight into the autonomic innervation of the lower urinary tract (LUT). Disruptions to the autonomic nervous system (ANS), particularly sympathetic and parasympathetic denervation, are frequently encountered in urological and neurological practice due to their common manifestation as LUTS. This narrative review synthesises current evidence on urodynamic features observed during bladder filling and voiding and their relationship to autonomic innervation in health and disease, drawing on established principles of LUT neural physiology. It contrasts normal urodynamic patterns with characteristic findings reported in neurological disorders associated with ANS disruption, such as multiple system atrophy, Parkinson's disease, diabetic and amyloid neuropathies, and spinal cord injury, to infer autonomic pathway integrity. These findings include changes in cystometric capacity, bladder compliance, filling sensations, and bladder neck appearance, the presence of detrusor overactivity or incontinence, and voiding phase abnormalities, including detrusor underactivity and bladder outflow obstruction. Together, these findings may provide insight into autonomic regulation across both health and disease. Urodynamics do not directly measure neural activity, and interpretation may be influenced by overlapping somatic effects, variable diagnostic thresholds, and non-neurogenic or co-existing pathology, but they remain an indispensable clinical tool for understanding LUT function and ANS involvement.

This systematic review aims to assess the current use of heart rate variability (HRV) analysis in clinical research, focusing on the diseases studied, the common indices used, and the physiological insights gained. A search was conducted in PubMed, articles published in recent years (2019-2025) in English or Spanish involving humans and pathophysiological interpretations were reviewed. After screening and verifying quality criteria, 99 articles were included in the review. HRV was most frequently applied in mental, behavioral, or neurodevelopmental disorders; diseases of the nervous system, and diseases of the circulatory system. Across studies, interpretations clustered around Treatment/Stimulus effects and Etiology/Mechanisms, with comparatively fewer works focused on Diagnostic/Screening or Severity/Staging. Approximately 58% of articles justified a targeted selection of HRV indices aligned with their clinical hypotheses, whereas the rest relied on batteries of indices. This review highlights the diverse use and interpretation of HRV across clinical contexts, pointing to a lack of standardized protocols. The heterogeneity of recording durations, maneuver use, and spectral units provided, together with under-reporting of nonlinear prerequisites, all limit cross-study comparability and clinical translation. We outline a tentative roadmap for clinically oriented HRV work that emphasizes, where appropriate, measurement standardization, analytic rigor and transparency, and clinical translation, ideally supported by preregistration, harmonized reporting, and open, validated resources. Future research should focus on developing standardized and updated guidelines for HRV analysis to improve its clinical utility and to encourage interdisciplinary collaboration in selecting and interpreting HRV indices based on research objectives and clinical hypotheses.

Communication between the gastrointestinal tract and the central nervous system, known as the gut-brain axis, is fundamental to physiology and is implicated in a range of pathological conditions. A critical component of this axis is the sensory information conveyed from the gut to the brain through spinal afferent pathways. Understanding the location and types of spinal afferents present in the GI tract and their mechanisms of activation is essential to advance our knowledge of gut-brain communication in health and disease. Though generally trailing knowledge of gut vagal afferents, major advances have been made in understanding spinal sensory pathways through recent critical adaptations of neuroanatomical tracing, neurogenetics and molecular profiling techniques, revealing an unforeseen diversity in the morphology of their endings in the gut wall and novel classifications based on molecular identity. Moreover, spinal afferents have been implicated in multiple physiological functions besides their well-known role in nociception, including potential roles in nutrient sensing and regulating gut motility. Among spinal afferent endings in the gut mucosal layer, much has been learnt about how enterochromaffin (EC) cells communicate with spinal (and vagal) afferents. Evidence now suggests that EC cells release substances (like serotonin), which activate the terminals of spinal (and vagal) afferent endings via a paracrine, not synaptic, transmission. Here, we review the latest findings regarding spinal afferent endings and point to outstanding questions and future directions for research into this complex and clinically relevant area of neuroscience.

Sixty-two children (18 with inflammatory bowel disease [IBD], 28 with irritable bowel syndrome [IBS], 18 healthy controls) underwent pre- and postprandial electrogastrography and autonomic assessment with the Composite Autonomic Symptom Score-31 (COMPASS-31) and Composite Autonomic Severity Scale (CASS). No between-group differences in EGG parameters were observed. Children with IBS showed increased postprandial normogastria. Higher autonomic symptom burden correlated with lower postprandial power dominant frequency, and symptomatic dysautonomia was associated with reduced postprandial power dominant frequency. These exploratory findings suggest a link between autonomic symptoms and postprandial gastric activity and warrant confirmation in larger cohorts.

Chronic kidney disease (CKD) impairs cardiac baroreflex sensitivity (cBRS), contributing to poor blood pressure (BP) control and heightened cardiovascular risk. Emerging evidence indicates that isometric handgrip (IHG) exercise may enhance cBRS in healthy individuals; however, its effects in CKD remain unclear. Therefore, this study tested the hypothesis that a single IHG session increases cBRS and reduces beat-to-beat BP variability (BPV) in CKD patients. In 21 patients (61 ± 12 yr; stages III-IV), beat-to-beat BP (finger photoplethysmography), heart rate (HR, electrocardiography), and respiration were continuously measured before and 10-, 20-, and 30-min post IHG vs. sham exercise in a crossover design. cBRS was assessed via the sequence technique and cardiac autonomic modulation via time- and frequency-domain HR variability (HRV). BPV was quantified using time domain indexes. cBRS increased following IHG exercise (10-min: Δ20 ± 4%; 20-min: Δ23 ± 5%; 30-min: Δ17 ± 5%; all P < 0.004 vs rest). This increase was significantly different from sham at 10-min and 20-min (all P < 0.006 vs sham), but not at 30-min post-IHG (P = 0.074). HR decreased throughout recovery (all P = 0.001 vs rest). Systolic BP decreased 30-min following IHG exercise (Δ-5 ± 2 mmHg; P = 0.047 vs. rest). Time-domain HRV increased during recovery (P = 0.005) whereas BPV remained unchanged following IHG exercise. After sham, all variables remained similar to rest, except systolic BP was significantly higher 20-min after sham. A single IHG session increased cBRS and vagal modulation, with a modest reduction in systolic BP and no change in BPV, in CKD patients. Overall, these findings suggest that IHG may serve as a non-pharmacological intervention for cardiovascular regulation in CKD.

We tested the validity of the Polar H10 chest strap against criterion electrocardiography (ECG) for heart rate variability (HRV) and cardiac autonomic reflex assessment in young adults and examined associations between supine HRV and other cardiovagal markers. Forty-three healthy adults (18-39 years, 44% male) completed an 8-min protocol: 3 min supine rest (HRV assessed in minute 2 after 1-min stabilization), 1 min paced deep breathing (minute 4; 0.1 Hz), 1 min supine washout, and 3 min active standing (30:15 ratio assessed post-transition; HRV assessed in minute 6 after 1-min post-transition stabilization). Simultaneous RR intervals were recorded via ECG and H10. Agreement was evaluated for time-domain HRV (mean RR interval, root-mean square of successive differences [RMSSD], and standard deviation of normal RR intervals) and reflex tests (deep breathing expiratory [E] to inspiratory [I] ratio, E - I difference, heart rate response; orthostatic 30:15 ratio). Excellent agreement was observed between devices for all metrics (concordance correlation ≥0.99; mean absolute percentage error < 1%; and narrow 95% limits of agreement (widest = -1.5 to 1.7 ms). Supine RMSSD shared 39-53% of variance with deep breathing outcomes, 34% with standing RMSSD, and < 1% with the 30:15 ratio. The H10 provides measurements effectively interchangeable with laboratory ECG for time-domain HRV and standard cardiovagal reflex tests in healthy young adults. Supine RMSSD shares approximately half or less of the variance with other cardiovagal markers, reinforcing the importance of incorporating complementary reflex and orthostatic tests for comprehensive cardiac autonomic assessment.