Aryan Salmanpour

Sympathetic neural activation: an ordered affair

Is there an ordered pattern in the recruitment of postganglionic sympathetic neurones? Using new multi‐unit action potential detection and analysis techniques we sought to determine whether the activation of sympathetic vasomotor neurones during stress is governed by the size principle of recruitment. Multi‐unit postganglionic sympathetic activity (fibular nerve) was collected from five male subjects at rest and during periods of elevated sympathetic stress (end‐inspiratory apnoeas; 178 ± 37 s(mean ± S.D.)). Compared to baseline (0.24 ± 0.04 V), periods of elevated stress resulted in augmented sympathetic burst size (1.34 ± 0.38 V, P < 0.05). Increased burst size was directly related to both the number of action potentials within a multi‐unit burst of postganglionic sympathetic activity (r= 0.88 ± 0.04, P < 0.001 in all subjects), and the amplitude of detected action potentials (r= 0.88 ± 0.06, P < 0.001 in all subjects). The recruitment of larger, otherwise silent, neurons accounted for approximately 74% of the increase in detected action potentials across burst sizes. Further, action potential conduction velocities (inverse of latencies) were increased as a function of action potential size (R2= 0.936, P= 0.001). As axon diameter is positively correlated with action potential size and conduction velocity, these data suggest that the principle of ordered recruitment based on neuronal size applies to postganglionic sympathetic vasomotor neurones. This information may be pertinent to our understanding of reflex‐specific recruitment strategies in postganglionic sympathetic nerves, patterns of vasomotor control during stress, and the malleability of sympathetic neuronal properties and recruitment in health and disease.

Relationship between size and latency of action potentials in human muscle sympathetic nerve activity

We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

Spike detection in human muscle sympathetic nerve activity using a matched wavelet approach

Sympathetic nerve recordings associated with blood pressure regulation can be recorded directly using microneurography. A general characteristic of this signal is spontaneous burst activity of spikes (action potentials) separated by silent periods against a background of considerable Gaussian noise. During measurement with electrodes, the raw muscle sympathetic nerve activity (MSNA) signal is amplified, band-pass filtered, rectified and integrated. This integration process removes information regarding action potential content and their discharge properties. This paper proposes a new method for detecting action potentials from the raw MSNA signal to enable investigation of post-ganglionic neural discharge properties. The new method is based on the design of a mother wavelet that is matched to an actual mean action potential template extracted from a real raw MSNA signal. To detect action potentials, the new matched wavelet is applied to the MSNA signal using a continuous wavelet transform following a thresholding procedure and finding of a local maxima that indicates the location of action potentials. The performance of the proposed method versus two previous wavelet-based approaches was evaluated using (1) real MSNA recorded from seven healthy participants and, (2) simulated MSNA. The results show that the new matched wavelet performs better than the previous wavelet-based methods that use a non-matched wavelet in detecting action potentials in the MSNA signal.

Recruitment pattern of sympathetic neurons during breath-holding at different lung volumes in apnea divers and controls

We tested the hypothesis that breath-hold divers (BHD) attain higher level of sympathetic activation than controls due to the duration of breath-hold rather than a different recruitment strategy. In 6 control subjects and 8 BHD we measured muscle sympathetic neural activity (MSNA) prior to and during functional residual capacity (FRC) and total lung capacity (TLC) breath-holding. On a subset of subjects we applied a new technique for the detection of action potentials (APs) in multiunit MSNA. Compared with controls, BHD group had lower burst AP content (13±7 vs. 6±3AP/burst; P=0.05) and number of active clusters (5±1 vs. 3±1clusters/burst; P=0.05) at baseline. However, the overall sympathetic AP/unit-time was comparable between the groups (131±105 vs. 173±152AP/min; P=0.62) due to increased burst frequency in BHD group (20±4bursts/min) vs. controls (13±3bursts/min) (P=0.039). The achieved level in total MSNA during FRC breath-holds was higher in divers (2298±780 vs. 1484±575a.u./min; P=0.039). Total MSNA at the end of TLC breath-hold was comparable between the groups (157±50 (controls) vs. 214±41s (BHD); P=0.61). FRC and TLC breath-holds increased AP frequency, burst AP content and active clusters/bursts in both groups but the response magnitude was determined by the type of the breath-hold. The divers used fewer number of APs/burst and active clusters/burst. In both groups breath-holds resulted in similar increases in MSNA which were reached both by an increase in firing frequency and by recruitment of previously silent, larger (faster conducting) sympathetic neurons, and possibly by repeated firing within the same burst.

Baroreflex mechanisms regulating the occurrence of neural spikes in human muscle sympathetic nerve activity

This study tested the hypothesis that the discharge patterns of action potentials (APs) within bursts of postganglionic muscle sympathetic nerve activity (MSNA) are subject to arterial baroreflex control but in a manner that varies inversely with AP size. MSNA data were collected over 5 min of supine rest in 15 young and healthy individuals (8 males; 24 ± 4 yr of age; means ± SD). The baroreflex threshold and sensitivity diagrams were constructed for both the integrated sympathetic bursts and for the AP clusters. For the integrated bursts, a strong linear relationship between burst probability and diastolic blood pressure (DBP) was observed (P < 0.05). There was little relationship between integrated burst strength (amplitude) and DBP. On average, 12 AP clusters were observed across individuals. Larger APs tended to appear in the larger bursts. Linear regression analysis was used to study the baroreflex threshold (probability of AP cluster occurrence vs. DBP) as well as the baroreflex sensitivity (AP cluster size vs. DBP). A significant reflex threshold relationship was observed in 75-100% of AP clusters across all individuals. In contrast, significant reflex sensitivity relationships were observed in only 9 of 15 individuals and for limited APs. Overall, the slope of the AP baroreflex threshold relationship was greater for the small-medium sized AP clusters than that of the larger APs. Therefore, within each burst, the small-medium sized APs are governed by the baroreflex mechanism. However, the large APs, which tend to appear in the large integrated bursts, are weakly associated with a baroreflex control feature. The variable impact of baroreflex control over AP occurrence provides a plausible explanation for the overall weak baroreflex control over integrated burst strength, a feature that is determined by both the number and size of the AP complement.

Sympathetic neural recruitment patterns during the Valsalva maneuver

Sympathetic nerve activity is an important regulator of blood pressure and blood flow in humans. Our understanding about how sympathetic neurons are recruited during baroreflex stress is limited. This paper investigates the sympathetic neural recruitment patterns during the Valsalva maneuver. Using microneurography, muscle sympathetic nerve activity was recorded in seven healthy subjects during baseline and the Valsalva maneuver. A new algorithm for detection and classification of action potentials was employed to study the differences between the recruitment of sympathetic neurons during baseline and the Valsalva maneuver. The data suggests that the Valsalva maneuver increases the number of spikes per sympathetic bursts and also recruits at least one additional new cluster of larger, faster conducting neurons. Also, action potentials latencies (i.e., inverse of conduction velocity) were shifted downward for all action potential clusters during this maneuver.

Myogenic activity in autoregulation during low frequency oscillations

Lower body negative pressure (LBNP) was applied in eight human subjects to trigger low frequency oscillations in order to study the nature of functional coupling between the hemodynamic and autonomic nervous systems, with particular focus on how the myogenic response fits within this coupling. To this end muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were measured at baseline and during LBNP and were then examined in both the time and frequency domains. At the height of low frequency oscillations (~0.1Hz) there was a strong coupling between all the five indices, marked by perfect alignment of their oscillatory frequencies. Results in the time domain show that a fall in MAP is followed by a fall in TPR at 1.58s SD 0.69), a rise in heart rate at 2.64s (SD 0.98), a rise in cardiac output at 3.72s (SD 0.60), a peak in MSNA at 5.71s (SD 1.27) and, finally, a rise in TPR at 7.13s (SD 1.02). A possible interpretation of the latter is that a drop in MAP first triggers a drop in TPR via a myogenic response before the expected rise in TPR via a rise in MSNA. In other words, following a drop in arterial pressure, myogenic response controls vessel diameter before this control is taken over by MSNA. These findings provide a possible resolution of a longstanding conceptual argument against attributing a significant role for the myogenic response in blood flow autoregulation.

Performance analysis of stationary and discrete wavelet transform for action potential detection from sympathetic nerve recordings in humans

Accurate investigation of the sympathetic nervous system is important in the diagnosis and study of various autonomic and cardiovascular control and disorders. Sympathetic function associated with blood pressure regulation in humans can be evaluated by recording muscle sympathetic nerve activity (MSNA), which is characterised by synchronous neuronal discharges separated by periods of neural silence dominated by colored gaussian noise. In this paper two common methods for detecting filtered action potential in MSNA recordings is compared. These methods are based on stationary wavelet transform (SWT) and discrete wavelet transform (DWT). The performance analysis are evaluated using simulated MSNA using templates extracted from real MSNA recorded from three healthy subjects.

Detection and classification of raw action potential patterns in human Muscle Sympathetic Nerve Activity

The Muscle Sympathetic Nerve Activity (MSNA) consists of synchronous neural discharges separated by periods of neural silence dominated by heavy background noise. During measurement with electrodes, the raw MSNA signal is amplified, band-pass filtered, rectified and integrated. This integration process removes much neurophysiological information. In this paper a method for detecting a raw action potential (before the pre-amplifier) and filtered action potential (after the bandpass filter) is presented. This method is based on stationary wavelet transform (SWT) and a peak detection algorithm. Also, the detected action potentials were clustered using the k-means method and the cluster averages were calculated. The action potential detector and classification algorithm are evaluated using real MSNA recorded from three healthy subjects.

Detection of single action potential in multi-unit postganglionic sympathetic nerve recordings in humans: A matched wavelet approach

Sympathetic nerve activity associated with blood pressure regulation can be recorded directly using microneurography. Action potentials (APs) in the sympathetic nerve signal are dominated by colored gaussian noise. This paper proposes a novel method for detecting APs from muscle sympathetic nerve activity (MSNA) in multi-unit postganglionic recordings. The new method is based on designing a new mother wavelet matched to an actual AP template extracted from a real raw MSNA signal. To detect action potentials, the new matched wavelet was applied to the MSNA signal using a continuous wavelet transform following a thresholding procedure and detecting local maxima to estimate AP arrival times. The performance of the proposed method was evaluated using real MSNA recorded from six healthy participants and compared with two previous wavelet-based methods using a simulated MSNA signal.