Intracortical brain-heart interplay: An EEG model source study of sympathovagal changes.

The interplay between cerebral and cardiovascular activity, known as the functional brain-heart interplay (BHI), and its temporal dynamics, have been linked to a plethora of physiological and pathological processes. Various computational models of the brain-heart axis have been proposed to estimate BHI non-invasively by taking advantage of the time resolution offered by electroencephalograph (EEG) signals. However, investigations into the specific intracortical sources responsible for this interplay have been limited, which significantly hampers existing BHI studies. This study proposes an analytical modeling framework for estimating the BHI at the source-brain level. This analysis relies on the low-resolution electromagnetic tomography sources localization from scalp electrophysiological recordings. BHI is then quantified as the functional correlation between the intracortical sources and cardiovascular dynamics. Using this approach, we aimed to evaluate the reliability of BHI estimates derived from source-localized EEG signals as compared with prior findings from neuroimaging methods. The proposed approach is validated using an experimental dataset gathered from 32 healthy individuals who underwent standard sympathovagal elicitation using a cold pressor test. Additional resting state data from 34 healthy individuals has been analysed to assess robustness and reproducibility of the methodology. Experimental results not only confirmed previous findings on activation of brain structures affecting cardiac dynamics (e.g., insula, amygdala, hippocampus, and anterior and mid-cingulate cortices) but also provided insights into the anatomical bases of brain-heart axis. In particular, we show that the bidirectional activity of electrophysiological pathways of functional brain-heart communication increases during cold pressure with respect to resting state, mainly targeting neural oscillations in the δ $$ \delta $$ , ß $$ \beta $$ , and γ $$ \gamma $$ bands. The proposed approach offers new perspectives for the investigation of functional BHI that could also shed light on various pathophysiological conditions.

Influence of sex on sympathetic vasomotor outflow responses to passive leg raising in young individuals.

The purpose of this study was to clarify sex differences in the inhibition of sympathetic vasomotor outflow which is caused by the loading of cardiopulmonary baroreceptors. Ten young males and ten age-matched females participated. The participants underwent a passive leg raising (PLR) test wherein they were positioned supine (baseline, 0º), and their lower limbs were lifted passively at 10º, 20º, 30º, and 40º. Each angle lasted for 3 min. Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. Baseline MSNA was lower in females compared to males. MSNA burst frequency was decreased during the PLR in both males (- 6.2 ± 0.4 bursts/min at 40º) and females (- 6.5 ± 0.4 bursts/min at 40º), but no significant difference was detected between the two groups (P = 0.61). These results suggest that sex has minimal influence on the inhibition of sympathetic vasomotor outflow during the loading of cardiopulmonary baroreceptors in young individuals.

Analysis of sympathetic responses to cognitive stress and pain through skin sympathetic nerve activity and electrodermal activity.

We explored the non-invasive evaluation of the sympathetic nervous system (SNS) by employing two distinct physiological signals: skin sympathetic nerve activity (SKNA), extracted from electrocardiogram (ECG) signals, and electrodermal activity (EDA), a well-studied marker in the context of the SNS assessment. Our investigation focused on cognitive stress and pain; two conditions closely associated with the SNS. We sought to determine if the information and dynamics of EDA could be derived from the novel SKNA signal. To this end, ECG and EDA signals were recorded simultaneously during three experiments aimed at sympathetic stimulation, Valsalva maneuver (VM), Stroop test, and thermal-grill pain test. We calculated the integral area under the rectified SKNA signal (iSKNA) and decomposed the EDA signal to its phasic component (EDAphasic). An average delay of more than 4.6 s was observed in the onset of EDAphasic bursts compared to their corresponding iSKNA bursts. After shifting the EDAphasic segments by the extent of this delay and smoothing the corresponding iSKNA bursts, our results revealed a strong average correlation coefficient of 0.85±0.14 between the iSKNA and EDAphasic bursts, indicating a noteworthy similarity between the two signals. We also reconstructed the EDA signals with time-varying sympathetic (TVSymp) and modified TVSymp (MTVSymp) methods. Then we extracted the following features from iSKNA, EDAphasic, TVSymp, and MTVSymp signals: peak amplitude, average amplitude (aSKNA), standard deviation (vSKNA), and the cumulative duration during which the signals had higher amplitudes than a specified threshold (HaSKNA). A strong average correlation of 0.89±0.18 was found between vSKNA and subjects' self-rated pain levels during the pain test. Our statistical analysis also included applying Linear Mixed-Effects Models to check if there were significant differences in features across baseline and different levels of SNS stimulation. We then assessed the discriminating power of the features using Area Under the Receiver Operating Characteristic Curve (AUROC) and Fisher's Ratio. Finally, using all the four EDA features, a multi-layer perceptron (MLP) classifier reached the classification accuracies 95.56%, 89.29%, and 67.88% for the VM, Stroop, and thermal-grill pain control and stimulation classes. On the other hand, the highest classification accuracies based on SKNA features were achieved using K-nearest neighbors (KNN) (98.89%), KNN (89.29%), and MLP (95.11%) classifiers for the same experiments. Our comparative analysis showed the feasibility of SKNA as a novel tool for assessing the SNS with accurate classification capability, with a faster onset of amplitude increase in response to SNS activity, compared to EDA.

Differential responses to UCP1 ablation in classical brown versus beige fat, despite a parallel increase in sympathetic innervation.

In the cold, the absence of the mitochondrial uncoupling protein 1 (UCP1) results in hyper-recruitment of beige fat, but classical brown fat becomes atrophied. Here we examine possible mechanisms underlying this phenomenon. We confirm that in brown fat from UCP1-knockout (UCP1-KO) mice acclimated to the cold, the levels of mitochondrial respiratory chain proteins were diminished; however, in beige fat, the mitochondria seemed to be unaffected. The macrophages that accumulated massively not only in brown fat but also in beige fat of the UCP1-KO mice acclimated to cold did not express tyrosine hydroxylase, the norepinephrine transporter (NET) and monoamine oxidase-A (MAO-A). Consequently, they could not influence the tissues through the synthesis or degradation of norepinephrine. Unexpectedly, in the cold, both brown and beige adipocytes from UCP1-KO mice acquired an ability to express MAO-A. Adipose tissue norepinephrine was exclusively of sympathetic origin, and sympathetic innervation significantly increased in both tissues of UCP1-KO mice. Importantly, the magnitude of sympathetic innervation and the expression levels of genes induced by adrenergic stimulation were much higher in brown fat. Therefore, we conclude that no qualitative differences in innervation or macrophage character could explain the contrasting reactions of brown versus beige adipose tissues to UCP1-ablation. Instead, these contrasting responses may be explained by quantitative differences in sympathetic innervation: the beige adipose depot from the UCP1-KO mice responded to cold acclimation in a canonical manner and displayed enhanced recruitment, while the atrophy of brown fat lacking UCP1 may be seen as a consequence of supraphysiological adrenergic stimulation in this tissue.

Intra- and interday reliability of sympathetic transduction to blood pressure in young, healthy adults.

Microneurographic recordings of muscle sympathetic nerve activity (MSNA) and the succeeding changes in beat-to-beat blood pressure (i.e., sympathetic transduction) provide important insights into the neural control of the circulation in humans. Despite its widespread use, the reliability of this technique remains unknown. Herein, we assessed the intra- and interday test-retest reliability of signal-averaging sympathetic transduction to blood pressure. Data were analyzed from 15 (9 M/6 F) young, healthy participants who completed two baseline recordings of fibular nerve MSNA separated by 60 min (intraday). The interday reliability was obtained in a subset of participants (n = 13, 9 M/4 F) who completed a follow-up MSNA study. Signal-averaging sympathetic transduction was quantified as peak change in diastolic (DBP) and mean arterial pressure (MAP) following a burst of MSNA. Analyses were also computed considering different MSNA burst sizes (quartiles of normalized MSNA) and burst patterns (singlets, couplets, triplets, and quadruplets+), as well as nonburst responses. Intraclass-correlation coefficients (ICCs) were used as the main reliability measure. Peak changes in MAP [intraday: ICC = 0.76 (0.30-0.92), P = 0.006; interday: ICC = 0.91 (0.63-0.97), P < 0.001] demonstrated very good to excellent reliability. Sympathetic transduction of MSNA burst size displayed moderate to very good reliability, though the reliability of MSNA burst pattern was poor to very good. Nonburst responses revealed poor intraday [ICC = 0.37 (-1.05 to 0.80), P = 0.21], but very good interday [ICC = 0.76 (0.18-0.93), P = 0.01] reliability. Intraday reliability measures were consistently lower than interday reliability. Similar results were obtained using DBP. Collectively, these findings provide evidence that the burst-triggering signal-averaging technique is a reliable measure of sympathetic transduction to blood pressure in young, healthy adults.NEW & NOTEWORTHY We found that signal-averaging sympathetic transduction to blood pressure displayed very good to excellent intra- and interday test-retest reliability in healthy, young adults. Reliability analyses according to muscle sympathetic burst size, burst pattern, and nonburst response were less consistent. Results were similar when using diastolic or mean arterial pressure in the transduction calculation. These findings suggest that the signal-averaging technique can be used with confidence to investigate sympathetic transduction to blood pressure in humans across time.

Autonomic dysfunction and treatment strategies in intracerebral hemorrhage.

AIMS: Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes. This review aims to provide insight and convenience for future clinical practice and research on autonomic dysfunction in ICH patients. DISCUSSION: We summarize the autonomic dysfunction in ICH from the aspects of potential mechanisms, clinical significance, assessment, and treatment strategies. The CAN structures mainly include insular cortex, anterior cingulate cortex, amygdala, hypothalamus, nucleus of the solitary tract, ventrolateral medulla, dorsal motor nucleus of the vagus, nucleus ambiguus, parabrachial nucleus, and periaqueductal gray. Autonomic dysfunction after ICH is closely associated with neurological functional outcomes, cardiac complications, blood pressure fluctuation, immunosuppression and infection, thermoregulatory dysfunction, hyperglycemia, digestive dysfunction, and urogenital disturbances. Heart rate variability, baroreflex sensitivity, skin sympathetic nerve activity, sympathetic skin response, and plasma catecholamine concentration can be used to assess the autonomic functional activities after ICH. Risk stratification of patients according to autonomic functional activities, and development of intervention approaches based on the restoration of sympathetic-parasympathetic balance, would potentially improve clinical outcomes in ICH patients. CONCLUSION: The review systematically summarizes the evidence of autonomic dysfunction and its association with clinical outcomes in ICH patients, proposing that targeting autonomic dysfunction could be potentially investigated to improve the clinical outcomes.

Differential control of sympathetic outflow to muscle and skin during physical and cognitive stressors.

PURPOSE: Sympathetic nerve activity towards muscle (MSNA) and skin (SSNA) regulates various physiological parameters. MSNA primarily functions in blood pressure and flow, while SSNA operates in thermoregulation. Physical and cognitive stressors have been shown to have effects on both types of sympathetic activity, but there are inconsistencies as to what these effects are. This article aims to address the discrepancies in the literature and compare MSNA and SSNA responses. METHODS: Microelectrode recordings were taken from the common peroneal nerve in 29 participants: MSNA (n = 21), SSNA (n = 16) and both MSNA and SSNA (n = 8). Participants were subjected to four different 2-min stressors: two physical (isometric handgrip task, cold pressor test) and two cognitive (mental arithmetic task, Stroop colour-word conflict test), the latter of which saw participants separated into responders and non-responders to the stressors. It was hypothesised that the physical stressors would have a greater effect on MSNA than SSNA, while the cognitive stressors would operate conversely. RESULTS: Peristimulus time histogram (PSTH) analysis showed the mental arithmetic task to significantly increase both MSNA and SSNA; the isometric handgrip task and cold pressor test to increase MSNA, but not SSNA; and Stroop test to have no significant effects on changing MSNA or SSNA from baseline. Additionally, stress responses did not differ between MSNA and SSNA in participants who had both sets of data recorded. CONCLUSIONS: This study has provided evidence to support the literature which claims cognitive stressors increase sympathetic activity, and provides much needed SSNA data in response to stressors.

The differences in the anatomy of the thoracolumbar and sacral autonomic outflow are quantitative.

PURPOSE: We have re-evaluated the anatomical arguments that underlie the division of the spinal visceral outflow into sympathetic and parasympathetic divisions. METHODOLOGY: Using a systematic literature search, we mapped the location of catecholaminergic neurons throughout the mammalian peripheral nervous system. Subsequently, a narrative method was employed to characterize segment-dependent differences in the location of preganglionic cell bodies and the composition of white and gray rami communicantes. RESULTS AND CONCLUSION: One hundred seventy studies were included in the systematic review, providing information on 389 anatomical structures. Catecholaminergic nerve fibers are present in most spinal and all cranial nerves and ganglia, including those that are known for their parasympathetic function. Along the entire spinal autonomic outflow pathways, proximal and distal catecholaminergic cell bodies are common in the head, thoracic, and abdominal and pelvic region, which invalidates the "short-versus-long preganglionic neuron" argument. Contrary to the classically confined outflow levels T1-L2 and S2-S4, preganglionic neurons have been found in the resulting lumbar gap. Preganglionic cell bodies that are located in the intermediolateral zone of the thoracolumbar spinal cord gradually nest more ventrally within the ventral motor nuclei at the lumbar and sacral levels, and their fibers bypass the white ramus communicans and sympathetic trunk to emerge directly from the spinal roots. Bypassing the sympathetic trunk, therefore, is not exclusive for the sacral outflow. We conclude that the autonomic outflow displays a conserved architecture along the entire spinal axis, and that the perceived differences in the anatomy of the autonomic thoracolumbar and sacral outflow are quantitative.

Evening but not morning aerobic training improves sympathetic activity and baroreflex sensitivity in elderly patients with treated hypertension.

The blood pressure-lowering effect of aerobic training is preceded by improving cardiovascular autonomic control. We previously demonstrated that aerobic training conducted in the evening (ET) induces a greater decrease in blood pressure than morning training (MT). To study whether the greater blood pressure decrease after ET occurs through better cardiovascular autonomic regulation, this study aimed to compare MT versus ET on muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) in treated patients with hypertension. Elderly patients treated for hypertension were randomly allocated into MT (n = 12, 07.00-10.00 h) or ET (n = 11, 17.00-20.00 h) groups. Both groups trained for 10 weeks, 3 times/week, cycling for 45 min at moderate intensity. Beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and MSNA (microneurography) were assessed at the initial and final phases of the study at baseline and during sequential bolus infusions of sodium nitroprusside and phenylephrine (modified-Oxford technique) to evaluate cardiac and sympathetic BRS. Mean blood pressure decreased significantly after ET but not after MT (-9 ± 11 vs. -1 ± 8 mmHg, P = 0.042). MSNA decreased significantly only after ET with no change after MT (-12 ± 5 vs. -3 ± 7 bursts/100 heart beats, P = 0.013). Sympathetic BRS improved after ET but not after MT (-0.8 ± 0.7 vs. 0.0 ± 0.8 bursts/100 heart beats/mmHg, P = 0.052). Cardiac BRS improved similarly in both groups (ET: +1.7 ± 1.8 vs. MT: +1.4 ± 1.9 ms/mmHg, Pphase  ≤ 0.001). In elderly patients treated for hypertension, only ET decreased mean blood pressure and MSNA and improved sympathetic BRS. These findings revealed that the sympathetic nervous system has a key role in ET's superiority to MT in blood pressure-lowering effect. KEY POINTS: Reducing muscle nerve sympathetic activity and increasing sympathetic baroreflex sensitivity plays a key role in promoting the greater blood pressure reduction observed with evening training. These findings indicated that simply changing the timing of exercise training may offer additional benefits beyond antihypertensive medications, such as protection against sympathetic overdrive and loss of baroreflex sensitivity, independent markers of mortality. Our new findings also suggest new avenues of investigation, such as the possibility that evening aerobic training may be beneficial in other clinical conditions with sympathetic overdrive, such as congestive heart failure and hypertrophic cardiomyopathy.

Sympathetic transduction of cardiac sympathetic nerve activity in healthy, conscious sheep.

Sympathetic transduction is the study of how impulses of sympathetic nerve activity (SNA) affect end-organ function. Recently, the transduction of resting bursts of muscle SNA (MSNA) has been investigated and shown to have a role in the maintenance of blood pressure through changes in vascular tone in humans. In the present study, we investigate whether directly recorded resting cardiac SNA (CSNA) regulates heart rate (HR), coronary blood flow (CoBF), coronary vascular conductance (CVC), cardiac output (CO) and mean arterial pressure. Instrumentation was undertaken to record CSNA and relevant vascular variables in conscious sheep. Recordings were performed at baseline, as well as after the infusion of a ß-adrenoceptor blocker (propranolol) to determine the role of ß-adrenergic signalling in sympathetic transduction in the heart. The results show that after every burst of CSNA, there was a significant effect of time on HR (n = 10, ∆: +2.1 ± 1.4 beats min-1 , P = 0.002) and CO (n = 8, ∆: +100 ± 150 mL min-1 , P = 0.002) was elevated, followed by an increase in CoBF (n = 9, ∆: +0.76 mL min-1 , P = 0.001) and CVC (n = 8, ∆: +0.0038 mL min-1  mmHg-1 , P = 0.0028). The changes in HR were graded depending on the size and pattern of CSNA bursts. The HR response was significantly attenuated after the infusion of propranolol. Our study is the first to explore resting sympathetic transduction in the heart, suggesting that CSNA can dynamically change HR mediated by an action on ß-adrenoceptors. KEY POINTS: Sympathetic transduction is the study of how impulses of sympathetic nerve activity (SNA) affect end-organ function. Previous studies have examined sympathetic transduction primarily in the skeletal muscle and shown that bursts of muscle SNA alter blood flow to skeletal muscle and mean arterial pressure, although this has not been examined in the heart. We investigated sympathetic transduction in the heart and show that, in the conscious condition, the size of bursts of SNA to the heart can result in incremental increases in heart rate and coronary blood flow mediated by ß-adrenoceptors. The pattern of bursts of SNA to the heart also resulted in incremental increases in heart rate mediated by ß-adrenoceptors. This is the first study to explore the transduction of bursts of SNA to the heart.

Remodelling the inguinal adipose sensory system to switch on the furnace: Electroacupuncture stimulation induces brown adipose thermogenesis.

Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the associated molecular mechanisms are lacking. We investigated body surface electroacupuncture stimulation (ES) at ST25 (targeted at the abdomen) induction of brown adipose thermogenesis and the neural mechanism of this process. Inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) were collected and the thermogenic protein expression levels were measured to evaluate iBAT thermogenesis capacity. The thermogenic centre activating region and sympathetic outflow were evaluated based on neural electrical activity and c-fos expression levels. iWAT sensory axon plasticity was analysed with whole-mount adipose tissue imaging. ES activated the sympathetic nerves in iBAT and the c-fos-positive cells induced sympathetic outflow activation to the iBAT from the medial preoptic area (MPA), the dorsomedial hypothalamus (DM) and the raphe pallidus nucleus (RPA). iWAT denervation mice exhibited decreased c-fos-positive cells in the DM and RPA, and lower recombinant uncoupling orotein 1 peroxisome proliferator-activated receptor, ß3-adrenergic receptor, and tyrosine hydroxylase expression. Remodelling the iWAT sensory axons recovered the signal from the MPA to the RPA and induced iBAT thermogenesis. The sympathetic denervation attenuated sensory nerve density. ES induced sympathetic outflow from the thermogenetic centres to iBAT, which mediated thermogenesis. iWAT sensory axon remodelling induced the MPA-DM-RPA-iBAT thermogenesis pathway.

A ganglionic intestinointestinal reflex activated by acute noxious challenge.

To investigate noxious stimulation-responsive neural circuits that could influence the gut, we recorded from intestinally directed (efferent) nerve filaments dissected from mesenteric nerves close to the small intestine in anesthetized rats. These exhibited baseline multiunit activity that was almost unaffected by vagotomy (VagX) and reduced only slightly by cutting the splanchnic nerves. The activity was halved by hexamethonium (Hex) treatment. When an adjacent gut segment received an intraluminal stimulus 2,4,6-trinitrobenzenesulfonate (TNBS) in 30% ethanol, mesenteric efferent nerve activity increased for more than 1 h. The increased activity was almost unaffected by bilateral vagotomy or splanchnic nerve section, indicating a lack of central nervous involvement, but it was 60% reduced by hexamethonium. Spike sorting discriminated efferent single and predominantly single-unit spike trains that responded to TNBS, were unaffected by splachnectomy but were silenced by hexamethonium. After noxious stimulation of one segment, the adjacent segment showed no evidence of suppression of gut motility or vasoconstriction. We conclude that luminal application of a noxious stimulus to the small intestine activates an entirely peripheral, intestinointestinal reflex pathway. This pathway involves enteric intestinofugal neurons that excite postganglionic sympathetic neurons via a nicotinic synapse. We suggest that the final sympathetic efferent neurons that respond to a tissue damaging stimulus are distinct from vasoconstrictor, secretomotor, and motility inhibiting neurons.NEW & NOTEWORTHY An intraluminal noxious chemical stimulus applied to one segment of small intestine increased mesenteric efferent nerve activity to an adjacent segment. This was identified as a peripheral ganglionic reflex that did not require vagal or spinal connections. Hexamethonium blocked most, but not all, ongoing and reflex mesenteric efferent activity. The prevertebral sympathetic efferent neurons that are activated likely affect inflammatory and immune functions of other gut segments.

Limb-specific muscle sympathetic nerve activity responses to the cold pressor test.

Recent studies have demonstrated that muscle sympathetic nerve activity (MSNA) responses to isometric exercise differs between active and inactive limbs. Whether limb-dependent responses are characteristic of responses to the cold pressor test (CPT) remains to be established. Therefore, we tested the hypothesis that CPT-induced MSNA responses differ between affected and unaffected limbs such that MSNA in the affected lower limb is greater than MSNA responses in the contralateral lower limb and the upper limb. Integrated peroneal MSNA (microneurography) was measured in young healthy individuals (n = 10) at rest and during three separate 3-min CPTs: the microneurography foot, opposite foot, and opposite hand. Peak MSNA responses were extracted for further analysis, as well as corresponding hemodynamic outcomes including mean arterial pressure (MAP; Finometer). MSNA responses were greater when the microneurography foot was immersed in ice water than when the opposite foot was immersed (38 ± 18 vs 28 ± 16 bursts/100hb: P < 0.01). MSNA responses when the opposite hand was immersed were greater than both the microneurography foot (46 ± 22 vs 38 ± 18 bursts/100hb: P < 0.01) and opposite foot (46 ± 22 vs 28 ± 16 bursts/100hb: P ≤0.01). Likewise, MAP responses were greater during the hand CPT than the microneurography foot (99 ± 9 vs 96 ± 8 mmHg: P < 0.01) and opposite foot CPT (99 ± 9 vs 96 ± 9 mmHg: P < 0.01). These data indicate that (a) upper limbs and (b) immersed limbs elicit greater MSNA responses to the CPT than lower and/or non-immersed limbs.

Glucose metabolism and autonomic function in healthy individuals and patients with type 2 diabetes mellitus at rest and during exercise.

Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P = 0.011). Resting MSNA was negatively correlated with haemoglobin A1c in all subjects (R = -0.45, P = 0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P < 0.05). In all subjects, the MSNA response to exercise was positively correlated with fasting blood glucose (R = 0.69, P < 0.001). Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters throughout diabetic and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in T2DM.

Input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs.

Although Gaussian white noise (GWN) inputs offer a theoretical framework for identifying higher-order nonlinearity, an actual application to the data of the neural arc of the carotid sinus baroreflex did not succeed in fully predicting the well-known sigmoidal nonlinearity. In the present study, we assumed that the neural arc can be approximated by a cascade of a linear dynamic (LD) component and a nonlinear static (NS) component. We analyzed the data obtained using GWN inputs with a mean of 120 mmHg and standard deviations (SDs) of 10, 20, and 30 mmHg for 15 min each in anesthetized rats (n = 7). We first estimated the linear transfer function from carotid sinus pressure to sympathetic nerve activity (SNA) and then plotted the measured SNA against the linearly predicted SNA. The predicted and measured data pairs exhibited an inverse sigmoidal distribution when grouped into 10 bins based on the size of the linearly predicted SNA. The sigmoidal nonlinearity estimated via the LD-NS model showed a midpoint pressure (104.1 ± 4.4 mmHg for SD of 30 mmHg) lower than that estimated by a conventional stepwise input (135.8 ± 3.9 mmHg, P < 0.001). This suggests that the NS component is more likely to reflect the nonlinearity observed during pulsatile inputs that are physiological to baroreceptors. Furthermore, the LD-NS model yielded higher R2 values compared with the linear model and the previously suggested second-order Uryson model in the testing dataset.NEW & NOTEWORTHY We examined the input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs. A linear dynamic-static nonlinear model yielded higher R2 values compared with a linear model and captured the well-known sigmoidal nonlinearity of the neural arc, indicating that the nonlinear dynamics contributed to determining sympathetic nerve activity. Ignoring such nonlinear dynamics might reduce our ability to explain underlying physiology and significantly limit the interpretation of experimental data.

Aging and sympathetic transduction to blood pressure in humans: methodological and physiological considerations.

Recent reports suggest that quantification of signal-averaged sympathetic transduction is influenced by resting muscle sympathetic nerve activity (MSNA) and burst occurrence relative to the average mean arterial pressure (MAP). Herein, we asked how these findings may influence age-related reductions in sympathetic transduction. Beat-to-beat blood pressure and MSNA were recorded during 5 min of rest in 27 younger (13 females: age, 25 ± 5 yr; BMI, 25 ± 4 kg/m2) and 26 older (15 females: age, 59 ± 5 yr; BMI, 26 ± 4 kg/m2) healthy adults. All MSNA bursts were signal averaged together. Beat-to-beat MAP values were then split into low (T1), middle (T2), and high (T3) tertiles, and signal-averaged transduction was calculated within each tertile. Resting MSNA was higher in older adults and MAP was similar between groups. Older adults exhibited blunted overall MAP transduction (younger, Δ1.5 ± 0.6 vs. older, Δ0.9 ± 0.7 mmHg; P = 0.005), which was irrespective of relation to prevailing MAP. A greater proportion of bursts occurred above the average MAP in older adults (P < 0.001), and a larger proportion of these bursts were associated with depressor responses (P = 0.005). Nonetheless, assessment of bursts above the average MAP associated with pressor responses revealed similar age-associated reductions in transduction (younger, Δ2.6 ± 1.6 vs. older, Δ1.7 ± 0.8 mmHg; P = 0.016). These findings indicate an age-related increase in burst occurrence above the average resting MAP, which alone does not explain blunted transduction, thereby supporting the physiological underpinnings of age-related decrements in sympathetic transduction to blood pressure.NEW & NOTEWORTHY The current study demonstrated that aging is associated with a greater prevalence of sympathetic bursts occurring above the average blood pressure, which offers both methodologically and physiologically relevant information regarding aging and sympathetic control of blood pressure. These data support age-related reductions in sympathetic transduction via a reduced pressor response to sympathetic bursts irrespective of the prevailing absolute blood pressure value, along with increases in sympathetic outflow necessary to maintain blood pressure.

Noncontact Evaluation Method for Autonomic Nervous System Activity during Exercise Using RGB Camera.

For efficient exercise, motor functions, heart rate, oxygen uptake (which are controlled by autonomic nervous system activity), heat acclimation-related functions, such as sweating, and thermoregulation must work properly during exercise. In this research, a noncontact method of measuring capillary contraction and dilation, one of the autonomic nervous system activities, using only a commercial web camera was developed. The absorption rate by haemoglobin in blood differs for each wavelength of light. When the capillaries in the face contract or dilate, the colour component of the light reflected from the face changes. The focus of this study was on the changes in the green and blue values of the face image. Green light reaches the dermis, where capillaries are located, while blue light reaches only the epidermis. The G/B ratio, the green value divided by the blue value, shows the changes in capillary contraction and dilation. An experiment was conducted to validate the G/B ratio method. Ten subjects (23 ± 1.6 years of age) participated in the experiment, and face movement and heart rate were measured during an aerobic bike exercise test. The results showed that, when the heart rate increased, the G/B ratio decreased immediately after the start of exercise. After the exercise stopped, the heart rate decreased immediately, and the G/B ratio increased. The G/B ratio revealed that the sympathetic nervous system became dominant during exercise, causing facial capillaries to dilate, and that the parasympathetic nervous system became dominant after exercise, causing facial capillaries to constrict.

The Changes of Cardiovascular Neurotransmitter Levels under Low-Intensity Focused Ultrasound Stimulation of the Vagus Nerve.

BACKGROUND: Our previous study has shown that stimulation of the vagus nerve with low-intensity focused ultrasound could modulate blood pressure (BP), but the underlying mechanisms remain unclear. This study investigated the changes of cardiovascular neurotransmitter levels to indirectly evaluate the responses of the autonomic nervous system and renin-angiotensin system under low-intensity focused ultrasound stimulation (FUS) of the vagus nerve. METHODS: Cardiovascular neurotransmitter levels of epinephrine (EPI), norepinephrine (NE), and angiotensin II (ANGII) were measured and compared before and after the FUS in seven spontaneously hypertensive rats; and were also measured and compared between a target stimulation group (FUS, n = 6) and non-target stimulation group (Control, n = 5) after stimulation to exclude the influence of potential confounding factors. RESULTS: The t-test results showed that the levels of EPI, NE, and ANGII were significantly decreased (P < 0.05) after stimulation compared to before stimulation. Additionally, the levels of NE and EPI were significantly lower (P < 0.05) in the FUS group than in the Control group after stimulation, indicating that the activities of the sympathetic nervous system and renin-angiotensin system of the vagus nerve might be inhibited by FUS of the vagus nerve. CONCLUSION: These findings reveal the mechanism of BP lowing in response to FUS of the vagus nerve.Clinical Relevance-This study revealed the mechanism of BP lowering in response to focused ultrasound stimulation of the vagus nerve through analyzing the changes of cardiovascular neurotransmitter levels.

Plasticity in Preganglionic and Postganglionic Neurons of the Sympathetic Nervous System during Embryonic Development.

Sympathetic preganglionic neurons (SPNs) are the final output neurons from the central arm of the autonomic nervous system. Therefore, SPNs represent a crucial component of the sympathetic nervous system for integrating several inputs before driving the postganglionic neurons (PGNs) in the periphery to control end organ function. The mechanisms which establish and regulate baseline sympathetic tone and overall excitability of SPNs and PGNs are poorly understood. The SPNs are also known as the autonomic motoneurons (MNs) as they arise from the same progenitor line as somatic MNs that innervate skeletal muscles. Previously our group has identified a rich repertoire of homeostatic plasticity (HP) mechanisms in somatic MNs of the embryonic chick following in vivo synaptic blockade. Here, using the same model system, we examined whether SPNs exhibit similar homeostatic capabilities to that of somatic MNs. Indeed, we found that after 2-d reduction of excitatory synaptic input, SPNs showed a significant increase in intracellular chloride levels, the mechanism underlying GABAergic synaptic scaling in this system. This form of HP could therefore play a role in the early establishment of a setpoint of excitability in this part of the sympathetic nervous system. Next, we asked whether homeostatic mechanisms are expressed in the synaptic targets of SPNs, the PGNs. In this case we blocked synaptic input to PGNs in vivo (48-h treatment), or acutely ex vivo, however neither treatment induced homeostatic adjustments in PGN excitability. We discuss differences in the homeostatic capacity between the central and peripheral component of the sympathetic nervous system.