Autonomic Neuroscience-Basic & Clinical最新文献

Nociceptive and affective stimuli increase reflex sympathetic outflow to the pupils. To investigate effects of stimulus intensity, unpleasantness and distress on these pupillary reflexes, and to assess their stability, healthy participants immersed their hand in ice-water three times (for 20, 40 and 60 s; or 60, 40 and 20 s; or three times for 60 s) (N = 21 in each condition). Each ice-water immersion was preceded by a 90 s warm water immersion. To evaluate phasic sympathetic influences on pupil diameter, pupillary re-dilatation after 1 s of bright light was assessed during the last 10 s of each immersion. By-and-large, pain ratings and pupil diameter were greater during longer than shorter ice-water immersions, and ice-water immersions facilitated pupillary re-dilatation after the flash stimulus. However, mean pupil diameter during ice- and warm water immersions, minor ipsilateral amplification of the pupillary response, and ratings of pain unpleasantness and distress decreased across the experiment. Together, these findings suggest that nociceptive input increased sympathetic pupillary tone and amplified phasic increases in sympathetic activity after exposure to light. However, tonic sympathetic influences on pupil diameter and lateralization decreased across repeated immersions, possibly as novel or threatening aspects of the experience declined. Pupillary nociceptive and affective reflexes involve the locus coeruleus, an integral component of neural circuits that heighten cortical arousal and regulate pain. As these reflexes appear to reflect different aspects of sensory and affective processing, their combined assessment might increase the sensitivity and specificity of tests of locus coeruleus function in patients with suspected deficits.

Substance-P (SP) is a commonly used marker of nociceptive afferent axons, and it plays an important role in a variety of physiological functions including the regulation of motility, gut secretion, and vascular flow. Previously, we found that SP-immunoreactive (SP-IR) axons densely innervated the pyloric antrum of the flat-mount of the mouse whole stomach muscular layer. However, the regional distribution and morphology of SP-IR axons in the submucosa and mucosa were not well documented. In this study, the mouse antrum-pylorus-duodenum (APD) were transversely and longitudinally sectioned. A Zeiss M2 imager was used to scan the serial sections of each APD (each section montage consisted of 50–100 all-in-focus maximal projection images). To determine the detailed structures of SP-IR axons and terminals, we used the confocal microscope to scan the regions of interest. We found that 1) SP-IR axons innervated the muscular, submucosal, and mucosal layers. 2) In the muscular layer, SP-IR varicose axons densely innervated the muscles and formed varicose terminals which encircled myenteric neurons. 3) In the submucosa, SP-IR axons innervated blood vessels and submucosal ganglia and formed a network in Brunner’s glands. 4) In the mucosa, SP-IR axons innervated the muscularis mucosae. Some SP-IR axons entered the lamina propria. 5) The muscular layer of the antrum and duodenum showed a higher SP-IR axon density than the pyloric sphincter. 6) SP-IR axons were from extrinsic and intrinsic origins. This work provided a comprehensive view of the distribution and morphology of SP-IR axons in the APD at single cell/axon/varicosity scale. This data will be used to create a 3D scaffold of the SP-IR axon innervation of the APD.

The circadian system modulates all visceral organ physiological processes including urine storage and voiding. The “master clock” of the circadian system lies within suprachiasmatic nucleus of the hypothalamus while “peripheral clocks” are found in most peripheral tissue and organs, including the urinary bladder. Disruptions of circadian rhythms can cause organ malfunction and disorder or exacerbate pre-existing ones. It has been suggested that nocturia, which develops mostly in the elderly, could be a circadian-related disorder of the bladder. In the bladder, many types of gap junctions and ion channels in the detrusor, urothelium and sensory nerves are likely under strict local peripheral circadian control. The pineal hormone, melatonin, is a circadian rhythm synchroniser capable of controlling a variety of physiological processes in the body. Melatonin predominantly acts via the melatonin 1 and melatonin 2 G-protein coupled receptors expressed in the central nervous system, and many peripheral organs and tissues. Melatonin could be beneficial in the treatment of nocturia and other common bladder disorders. The ameliorating action of melatonin on bladder function is likely due to multiple mechanisms which include central effects on voiding and peripheral effects on the detrusor and bladder afferents. More studies are warranted to determine the precise mechanisms of circadian rhythm coordination of the bladder function and melatonin influences on the bladder in health and diseases.

Stroke is a pathophysiological condition which results in alterations in cerebral blood flow (CBF). The mechanism by which the brain maintains adequate CBF in presence of fluctuating cerebral perfusion pressure (CPP) is known as cerebral autoregulation (CA). Disturbances in CA may be influenced by a number of physiological pathways including the autonomic nervous system (ANS). The cerebrovascular system is innervated by adrenergic and cholinergic nerve fibers. The role of the ANS in regulating CBF is widely disputed owing to several factors including the complexity of the ANS and cerebrovascular interactions, limitations to measurements, variation in methods to assess the ANS in relation to CBF as well as experimental approaches that can or cannot provide insight into the sympathetic control of CBF. CA is known to be impaired in stroke however the number of studies investigating the mechanisms by which this occurs are limited. This literature review will focus on highlighting the assessment of the ANS and CBF via indices derived from the analyses of heart rate variability (HRV), and baroreflex sensitivity (BRS), and providing a summary of both clinical and animal model studies investigating the role of the ANS in influencing CA in stroke. Understanding the mechanisms by which the ANS influences CBF in stroke patients may provide the foundation for novel therapeutic approaches to improve functional outcomes in stroke patients.

Dynamic cerebral autoregulation (CA) characterizes the cerebral blood flow (CBF) response to abrupt changes in arterial blood pressure (ABP). CA operates at frequencies below 0.15 Hz. ABP regulation and probably CA are modified by autonomic nervous activity. We investigated the CBF response and CA dynamics to mild increase in sympathetic activity.

Twelve healthy volunteers underwent oscillatory lower body negative pressure (oLBNP), which induced respiratory-related ABP oscillations at an average of 0.22 Hz. We recorded blood velocity in the internal carotid artery (ICA) by Doppler ultrasound and ABP. We quantified variability and peak wavelet power of ABP and ICA blood velocity by wavelet analysis at low frequency (LF, 0.05–0.15 Hz) and Mayer waves (0.08–0.12 Hz), respectively. CA was quantified by calculation of the wavelet synchronization gamma index for the pair ABP–ICA blood velocity in the LF and Mayer wave band.

oLBNP increased ABP peak wavelet power at the Mayer wave frequency. At the Mayer wave, ABP peak wavelet power increased by >70 % from rest to oLBNP (p < 0.05), while ICA blood flow velocity peak wavelet power was unchanged, and gamma index increased (from 0.49 to 0.69, p < 0.05). At LF, variability in both ABP and ICA blood velocity and gamma index were unchanged from rest to oLBNP.

Despite an increased gamma index at Mayer wave, ICA blood flow variability was unchanged during increased ABP variability. The increased synchronization during oLBNP did not cause less stable CBF or less active CA. Sympathetic activation seems to improve the mechanisms of CA.

Background

Abnormalities in the regulation of physiological arousal and interoceptive processing are implicated in the expression and maintenance of specific psychiatric conditions and symptoms. We undertook a cross-sectional characterisation of patients accessing secondary mental health services, recording measures relating to cardiac physiology and interoception, to understand how physiological state and interoceptive ability relate transdiagnostically to affective symptoms.

Methods

Participants were patients (n = 258) and a non-clinical comparison group (n = 67). Clinical diagnoses spanned affective disorders, complex personality presentations and psychoses. We first tested for differences between patient and non-clinical participants in terms of cardiac physiology and interoceptive ability, considering interoceptive tasks and a self-report measure. We then tested for correlations between cardiac and interoceptive measures and affective symptoms. Lastly, we explored group differences across recorded clinical diagnoses.

Results

Patients exhibited lower performance accuracy and confidence in heartbeat discrimination and lower heartbeat tracking confidence relative to comparisons. In patients, greater anxiety and depression predicted greater self-reported interoceptive sensibility and a greater mismatch between performance accuracy and sensibility. This effect was not observed in comparison participants. Significant differences between patient groups were observed for heart rate variability (HRV) although post hoc differences were not significant after correction for multiple comparisons. Finally, accuracy in heartbeat tracking was significantly lower in schizophrenia compared to other diagnostic groups.

Conclusions

The multilevel characterisation presented here identified certain physiological and interoceptive differences associated with psychiatric symptoms and diagnoses. The clinical stratification and therapeutic targeting of interoceptive mechanisms is therefore of potential value in treating certain psychiatric conditions.

Background

Guillain–Barre syndrome (GBS) presents an annual incidence of 1.2–2.3 per 100,000. Sympathetic and parasympathetic nervous systems' peripheral control of visceral organs is affected by GBS aberrant immune response. Associated cardiovascular, gastrointestinal, sudomotor, pupillary, and other systems disturbances cause significant morbidity and mortality. This study aims to evaluate the dysautonomia spectrum in GBS patients, its relationship with patient outcomes, and compare it with those without autonomic disturbances.

Methods

We performed an ambispective review study of patients with GBS and dysautonomia admitted to the Institute of Neurology from 2017 to 2021. We recorded demographics, comorbidities, nerve conduction studies, clinical course, hospital complications, and functional outcomes.

Results

We included 214 patients, mean age 46.44 ± 16.49 years, 51 (31 %) presented dysautonomia, hypertension in most of the patients 39 (84.8 %), hypotension 35 (76.1 %), tachycardia 35 (76.1 %), enteric dysmotility 35 (76.1 %), and need for vasopressor 27 (58.7 %) were common characteristics. Twenty (39.2 %) with a demyelinating form and twenty (39.2 %) with an axonal motor form. The bivariate analysis report factors associated with dysautonomia, were lower cranial nerves (VII, IX, X) involvement (p = 0.002), need for mechanical ventilation (p = 0.0001) and intensive care (p = 0.0001), higher mEGOS (p = 0.05), EGRIS (p = 0.004), GBS disability score (p = 0.004), and delirium presence (p = 0.001). Kaplan-Meier survival analysis showed that dysautonomic patients needed more days for the independent walk (p = 0.004). There was no associated mortality.

Conclusions

Autonomic dysfunction in GBS significantly affects the peripheral nervous system. With consequently worse functional results. Further investigation needs to clarify whether more aggressive treatment is beneficial in this category of GBS.

Patients with long COVID suffer from many neurological manifestations that persist for 3 months following infection by SARS-CoV-2. Autonomic dysfunction (AD) or dysautonomia is one complication of long COVID that causes patients to experience fatigue, dizziness, syncope, dyspnea, orthostatic intolerance, nausea, vomiting, and heart palpitations. The pathophysiology behind AD onset post-COVID is largely unknown. As such, this review aims to highlight the potential mechanisms by which AD occurs in patients with long COVID. The first proposed mechanism includes the direct invasion of the hypothalamus or the medulla by SARS-CoV-2. Entry to these autonomic centers may occur through the neuronal or hematogenous routes. However, evidence so far indicates that neurological manifestations such as AD are caused indirectly. Another mechanism is autoimmunity whereby autoantibodies against different receptors and glycoproteins expressed on cellular membranes are produced. Additionally, persistent inflammation and hypoxia can work separately or together to promote sympathetic overactivation in a bidirectional interaction. Renin-angiotensin system imbalance can also drive AD in long COVID through the downregulation of relevant receptors and formation of autoantibodies. Understanding the pathophysiology of AD post-COVID-19 may help provide early diagnosis and better therapy for patients.

To identify autonomic neuropathy (AN) phenotypes, we used principal component analysis on data from participants (N = 209) who underwent standardized autonomic testing including quantitative sudomotor axon reflex testing, and heart rate and blood pressure at rest and during tilt, Valsalva, and standardized deep breathing. The analysis identified seven clusters: 1) normal, 2) hyperadrenergic features without AN, 3) mild AN with hyperadrenergic features, 4) moderate AN, 5) mild AN with hypoadrenergic features, 6) borderline AN with hypoadrenergic features, 7) mild balanced deficits across parasympathetic, sympathetic and sudomotor domains. These findings demonstrate a complex relationship between adrenergic and other aspects of autonomic function.

Introduction

ICU patients with SARS-CoV-2-related pneumonia are at risk to develop a central dysautonomia which can contribute to mortality and respiratory failure. The pupillary size and its reactivity to light are controlled by the autonomic nervous system. Pupillometry parameters (PP) allow to predict outcomes in various acute brain injuries. We aim at assessing the most predictive PP of in-hospital mortality and the need for invasive mechanical ventilation (IV).

Material and methods

We led a prospective, two centers, observational study. We recruited adult patients admitted to ICU for a severe SARS-CoV-2 related pneumonia between April and August 2020. The pupillometry was performed at admission including the measurement of baseline pupillary diameter (PD), PD variations (PDV), pupillary constriction velocity (PCV) and latency (PDL).

Results

Fifty patients, 90 % males, aged 66 (60–70) years were included. Seven (14 %) patients died in hospital. The baseline PD (4.1 mm [3.5; 4.8] vs 2.6 mm [2.4; 4.0], P = 0.009), PDV (33 % [27; 39] vs 25 % [15; 36], P = 0.03) and PCV (3.5 mm.s⁻¹ [2.8; 4.4] vs 2.0 mm.s⁻¹ [1.9; 3.8], P = 0.02) were significantly lower in patients who will die. A PD value <2.75 mm was the most predictive parameter of in-hospital mortality, with an AUC = 0.81, CI 95 % [0.63; 0.99]. Twenty-four (48 %) patients required IV. PD and PDV were significantly lower in patients who were intubated (3.5 mm [2.8; 4.4] vs 4.2 mm [3.9; 5.2], P = 0.03; 28 % [25; 36 %] vs 35 % [32; 40], P = 0.049, respectively).

Conclusions

A reduced baseline PD is associated with bad outcomes in COVID-19 patients admitted in ICU. It is likely to reflect a brainstem autonomic dysfunction.