Ruma Goswami

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.

Forebrain neurocircuitry associated with human reflex cardiovascular control

Physiological homeostasis depends upon adequate integration and responsiveness of sensory information with the autonomic nervous system to affect rapid and effective adjustments in end organ control. Dysregulation of the autonomic nervous system leads to cardiovascular disability with consequences as severe as sudden death. The neural pathways involved in reflexive autonomic control are dependent upon brainstem nuclei but these receive modulatory inputs from higher centers in the midbrain and cortex. Neuroimaging technologies have allowed closer study of the cortical circuitry related to autonomic cardiovascular adjustments to many stressors in awake humans and have exposed many forebrain sites that associate strongly with cardiovascular arousal during stress including the medial prefrontal cortex, insula cortex, anterior cingulate, amygdala and hippocampus. Using a comparative approach, this review will consider the cortical autonomic circuitry in rodents and primates with a major emphasis on more recent neuroimaging studies in awake humans. A challenge with neuroimaging studies is their interpretation in view of multiple sensory, perceptual, emotive and/or reflexive components of autonomic responses. This review will focus on those responses related to non-volitional baroreflex control of blood pressure and also on the coordinated responses to non-fatiguing, non-painful volitional exercise with particular emphasis on the medial prefrontal cortex and the insula cortex.

Representation of somatosensory inputs within the cortical autonomic network.

Regions of the cortical autonomic network (CAN) are activated during muscle contraction. However, it is not known to what extent CAN activation patterns reflect muscle sensory inputs, top-down signals from the motor cortex, and/or motor drive to cardiovascular structures. The present study explored the functional representation of somatosensory afferent input within the CAN with an a priori interest in the insula and ventral medial prefrontal cortex (vMPFC) (n=12). Heart rate (HR) and functional MRI data were acquired during 1) 30s periods of electrical stimulation of the wrist flexors at sub-motor (SUB; Type I,II afferents) and 2) motor thresholds (MOT; Type I,II,III afferents), 3) volitional wrist flexion at 5% maximal voluntary contraction (MVC) to match the MOT tension (VOL5%), and 4) volitional handgrip at 35% MVC to elicit tachycardia (VOL35%). Compared with rest, HR did not change during SUB, MOT, or VOL5% but increased during VOL35% (p<0.001). High frequency HR variability was 29.42±18.87 ms(2) (mean±S.D.) at rest and 39.85±27.60 ms(2) during SUB (p=0.06). High frequency HR variability was decreased during VOL35% compared to rest (p≤0.005). SUB increased activity in the bilateral posterior insula, vMPFC, subgenual anterior cingulate cortex (ACC), mid-cingulate cortex (MCC), and posterior cingulate cortex. MOT increased activity in the left posterior insula and MCC. During VOL5%, activity increased in the right anterior-mid insula. VOL35% was associated with activity in the bilateral insula as well as vMPFC and subgenual ACC deactivation. These data suggest that the left posterior insula processes sensory input from muscle during passive conditions and specifically that Type I and/or II muscle afferent stimulation during SUB impacts the vMPFC and/or subgenual ACC, regions believed to be involved in brain default mode and parasympathetic activity.

Forebrain organization representing baroreceptor gating of somatosensory afferents within the cortical autonomic network.

Somatosensory afferents are represented within the cortical autonomic network (CAN). However, the representation of somatosensory afferents, and the consequent cardiovascular effects, may be modified by levels of baroreceptor input. Thus, we examined the cortical regions involved with processing somatosensory inputs during baroreceptor unloading. Neuroimaging sessions (functional magnetic resonance imaging [fMRI]) recorded brain activity during 30 mmHg lower-body negative pressure (LBNP) alone and combined with somatosensory stimulation (LBNP+SS) of the forearm (n = 14). Somatosensory processing was also assessed during increased sympathetic outflow via end-expiratory apnea. Heart rate (HR), blood pressure (BP), cardiac output (Q), and muscle sympathetic nerve activity (MSNA) were recorded during the same protocols in a separate laboratory session. SS alone had no effect on any cardiovascular or MSNA variable at rest. Measures of HR, BP, and Q during LBNP were not different compared with LBNP+SS. The rise in MSNA burst frequency was attenuated during LBNP+SS versus LBNP alone (8 vs. 12 bursts/min, respectively, P < 0.05). SS did not affect the change in MSNA during apnea. Activations within the insula and dorsal anterior cingulate cortex (ACC) observed during LBNP were not seen during LBNP+SS. Anterior insula and ACC activations occurring during apnea were not modified by SS. Thus, the absence of insular and dorsal ACC activity during LBNP+SS along with an attenuation of MSNA burst frequency suggest sympathoinhibitory effects of sensory stimulation during decreased baroreceptor input by a mechanism that includes conjoint insula-dorsal ACC regulation. These findings reveal that the level of baroreceptor input influences the forebrain organization of somatosensory afferents.

Influence of hyperglycemia during and after pregnancy on postpartum vascular function

Endothelial dysfunction is commonly observed in women with a previous diagnosis of gestational diabetes mellitus (GDM). Whether arterial stiffness is also related to pregnancy and/or postpartum glucose intolerance has not been determined. We examined the influence of GDM during pregnancy and hyperglycemia in the postpartum period on arterial function. Thirty postpartum women were stratified into one of three groups: 1) normoglycemic pregnancy, normoglycemic postpartum (NORM), 2) GDM during pregnancy, normoglycemic postpartum (GDM-N); and 3) GDM during pregnancy, hyperglycemic postpartum (GDM-H). Ten never-pregnant controls were also recruited (Control). All measures were made at 2 mo postpartum or in the early follicular phase in Control women. Arterial stiffness was assessed by pulse wave velocity (PWV) and brachial and carotid artery distensibility. Endothelial function was determined by flow-mediated dilation (FMD). PWV was not different between the four groups. Distensibility of the brachial and carotid arteries was lower in GDM-N women (brachial: 1.1 × 10(-3) mmHg(-1) ± 3.6 × 10(-4); carotid: 2.0 × 10(-3) ± 3.3 × 10(-4)) and GDM-H (brachial: 1.4 × 10(-3) mmHg(-1) ± 4.1 × 10(-4); carotid: 1.8 × 10(-3) mmHg(-1) ± 5.0 × 10(-4)) compared with NORM women (brachial: 3.4 × 10(-3) mmHg(-1) ± 7.0 × 10(-4); carotid: 3.9 × 10(-3) ± 7.4 × 10(-4)). However, only brachial artery distensibility returned to Control levels by 2 mo postpartum in the NORM women. FMD was lower in previously GDM women (GDM-N: 4.1% ± 2.3; GDM-H: 4.4% ± 0.9) compared with NORM women (10.8% ± 1.3; P < 0.01). These findings suggest that the vascular function of women in the early postpartum period is influenced by GDM during pregnancy and the persistence of clinical and/or subclinical hyperglycemia after delivery.

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.

Dynamic responsiveness of the vascular bed as a regulatory mechanism in vasomotor control

The dynamics of blood supply to a vascular bed depend on lumped mechanical properties of that bed, namely the compliance (C), resistance (R), viscoelasticity (K), and inertance (L). While the study of regulatory mechanisms has so far placed the emphasis largely on R, it is not known how the remaining properties contribute collectively to the play of dynamics in vasomotor control. To examine this question and to establish some benchmark values of these properties, simultaneous measurements of pressure and flow waveforms in the vascular bed of the forearm were obtained from three groups: young healthy individuals, older hypertensives with controlled blood pressure, and older hypertensives with uncontrolled blood pressure. The values of R and C were found to vary within a wide range in each of the three groups to the extent that neither R nor C could be used independently as an indicator of health or age of the subjects tested. However, higher level dynamic properties of the bed, such as the time constants and damping index, which depend on combinations of C,K, and L, and which may reflect measures of the dynamic responsiveness or “sluggishness” of the system, were found to be maintained over a wide range of pulse pressures. These findings support a hypothesis that the pulsatile dynamics of blood supply to a vascular bed are adapted to the individual baseline values of R and C in different subjects with the effect of optimizing the level of dynamic responsiveness to changes in pressure or flow, and that this dynamic property of the vascular bed may be a protected and/or regulated property.

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.