Irritant Inhalation Evokes P Wave Morphological Changes in Spontaneously Hypertensive Rats via Reflex Modulation of the Autonomic Nervous System

Irritant inhalation is associated with increased incidence of atrial fibrillation (AF) and stroke. Irritant inhalation acutely regulates cardiac function via autonomic reflexes. Increases in parasympathetic and sympathetic reflexes may increase atrial susceptibility to ectopic activity and the initiation of arrhythmia such as AF. Both age and hypertension are risk factors for AF. We have shown that irritant-evoked pulmonary–cardiac reflexes are remodeled in spontaneously hypertensive (SH) rats to include a sympathetic component in addition to the parasympathetic reflex observed in normotensive Wistar-Kyoto (WKY) rats. Here, we analyzed P wave morphology in 15-week old WKY and SH rats during inhalation of the transient receptor potential ankyrin 1 agonist allyl isothiocyanate (AITC). P Wave morphology was normal during vehicle inhalation but was variably modulated by AITC. AITC increased RR intervals (RRi), PR intervals, and the P Wave duration. In SH rats only, AITC inhalation increased the occurrence of negative P waves. The incidence of AITC-evoked negative P waves in SH rats was dependent on RRi, increasing during bradycardic and tachycardic cardiac cycles. Inhibition of both parasympathetic (using atropine) and sympathetic (using atenolol) components of the pulmonary–cardiac reflex decreased the incidence of negative P waves. Lastly, the probability of evoking a negative P Wave was increased by the occurrence of preceding negative P waves. We conclude that the remodeled irritant-evoked pulmonary–cardiac reflex in SH rats provides a substrate for altered P Wave morphologies. These are likely ectopic atrial beats that could provide a trigger for AF initiation in structurally remodeled atria.

The 2021 Carl Ludwig Lecture. Unsympathetic autonomic regulation in heart failure: patient-inspired insights

Defined as a structural or functional cardiac abnormality accompanied by symptoms, signs or biomarkers of altered ventricular pressures or volumes, heart failure also is a state of autonomic disequilibrium. A large body of evidence affirms that autonomic disturbances are intrinsic to heart failure; that basal or stimulated sympathetic nerve firing or neural norepinephrine (NE) release more often than not exceed homeostatic need, such that an initially adaptive adrenergic or vagal reflex response, becomes maladaptive; and, that the magnitude of such maladaptation predicts prognosis. This Ludwig lecture develops two theses: that the elucidation and judiciously targeted amelioration of maladaptive autonomic disturbances offers opportunities to complement contemporary guideline-based heart failure therapy; and, that serendipitous single-participant insights, acquired in the course of experimental protocols with entirely different intent, can generate novel insight, inform mechanisms, and launch entirely new research directions. I précis 6 elements of our current synthesis of the causes and consequences of maladaptive sympathetic disequilibrium in heart failure, shaped by patient-inspired epiphanies: arterial baroreceptor reflex modulation; excitation stimulated by increased cardiac filling pressure; paradoxical muscle sympathetic activation as a peripheral neurogenic constraint on exercise capacity; renal sympathetic restraint of natriuresis; co-existing sleep apnea; and, augmented chemoreceptor reflex sensitivity, then conclude by envisaging translational therapeutic opportunities.

Acute Effects of Kinesiology Taping Stretch Tensions on Soleus and Gastrocnemius H-Reflex Modulations

This study examined the acute effects of stretch tensions of kinesiology taping (KT) on the soleus (SOL), medial (MG), and lateral (LG) gastrocnemius Hoffmann-reflex (H-reflex) modulation in physically active healthy adults. A cross-over within-subject design was used in this study. Twelve physically active collegiate students voluntarily participated in the study (age = 21.3 ± 1.2 years; height = 175.6 ± 7.1 cm; body weight = 69.9 ± 7.1 kg). A standard Y-shape of KT technique was applied to the calf muscles. The KT was controlled in three tension intensities in a randomised order: paper-off, 50%, and 100% of maximal stretch tension of the tape. The peak-to-peak amplitude of maximal M-wave (Mmax) and H-reflex (Hmax) responses in the SOL, MG, and LG muscles were assessed before taping (pre-taping), taping, and after taping (post-taping) phases in the lying prone position. The results demonstrated significantly larger LG Hmax responses in the pre-taping condition than those in the post-taping condition during paper-off KT (p = 0.002). Moreover, the ΔHmax/Mmax of pre- and post-taping in the SOL muscle was significantly larger during 50%KT tension than that of paper-off (p = 0.046). In conclusion, the stretch tension of KT contributes minor influence on the spinal motoneuron excitability in the triceps surae during rest.

No consistent startle modulation by reward

Previous studies have not clearly demonstrated whether motivational tendencies during reward feedback are mainly characterized by appetitive responses to a gain or mainly by aversive consequences of reward omission. In the current study this issue was addressed employing a passive head or tails game and using the startle reflex as an index of the appetitive-aversive continuum. A second aim of the current study was to use startle-reflex modulation as a means to compare the subjective value of monetary rewards of varying magnitude. Startle responses after receiving feedback that a potential reward was won or not won were compared with a baseline condition without a potential gain. Furthermore, startle responses during anticipation of no versus potential gain were compared. Consistent with previous studies, startle-reflex magnitudes were significantly potentiated when participants anticipated a reward compared to no reward, which may reflect anticipatory arousal. Specifically for the largest reward (20-cents) startle magnitudes were potentiated when a reward was at stake but not won, compared to a neutral baseline without potential gain. In contrast, startle was not inhibited relative to baseline when a reward was won. This suggests that startle modulation during feedback is better characterized in terms of potentiation when missing out on reward rather than in terms of inhibition as a result of winning. However, neither of these effects were replicated in a more targeted second experiment. The discrepancy between these experiments may be due to differences in motivation to obtain rewards or differences in task engagement. From these experiments it may be concluded that the nature of the processing of reward feedback and reward cues is very sensitive to experimental parameters and settings. These studies show how apparently modest changes in these parameters and settings may lead to quite different modulations of appetitive/aversive motivation. A future experiment may shed more light on the question whether startle-reflex modulation after feedback is indeed mainly characterized by the aversive consequences of reward omission for relatively large rewards.

Effect of Acute Heart Rate Variability Biofeedback on H-reflex Modulation: A Pilot Study

Heart rate variability biofeedback (HRV BFB) is paced breathing scheme that stimulates resonance in the cardiovascular system. This study aimed to investigate the effect of a single-session HRV BFB on Hoffman reflex (H-reflex) of the soleus muscle. Twelve healthy males (height: 173.7 ± 7.18 cm; weight: 72.7 ± 17.7 kg; age: 24.0 ± 5.02 yrs) completed a randomized-crossover intervention involving a 10-minute HRV BFB and normal breathing (CON) separated by 48 hours. Results revealed significantly lower 1a afferent activation after HRV BFB. Similarly, the HRV BFB also demonstrated lower proportion of activated motor neurons from 1a afferents. In conclusion, an acute HRV BFB influenced the reduction in motoneuron excitability at resting condition.

Paired motor cortex and spinal cord epidural stimulation strengthens sensorimotor connections and improves forelimb function after cervical spinal cord injury in rats

Associative plasticity occurs when two stimuli converge on a common neural target. We sought to use the strong convergence between motor and sensory systems in the spinal cord to restore movement after spinal cord injury (SCI). We developed a paired motor cortex and dorsal spinal cord stimulation protocol to target this interaction called spinal cord associative plasticity (SCAP). Subthreshold spinal cord stimulation strongly augments motor cortex evoked potentials at the time they are paired, but only when they arrive synchronously in the spinal cord. We tested the hypothesis that this paired stimulation effect depended on cortical descending motor and spinal cord proprioceptive afferents. Selective inactivation of either of these pathways fully abrogated the paired stimulation effect. We then found that repetitive pairing in awake rats increased spinal excitability for hours after pairing ended. To apply this protocol as therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was just as strong in rats with cervical SCI as in un-injured rats, demonstrating that spared connections after SCI are sufficient to support this plasticity. When 30 minutes of paired stimulation was done over 10 days, the effect of pairing was sustained for weeks. In addition, H-reflex modulation improved, showing decreased hyperreflexia that also persisted for weeks. Importantly, repetitive paired stimulation supported enhanced recovery of forelimb dexterity in rats after SCI with no augmentation of injury-induced neuropathic pain. We conclude that SCAP strengthens sensory-motor connections within the spinal cord, resulting in decreased hyperreflexia and improved forelimb function after SCI.Significance StatementDespite evidence that electrical stimulation of spared nervous system connections can facilitate recovery after SCI, strongly overlapping sensory and motor connections in the spinal cord have not been targeted for therapy. Here we demonstrate a robust paired stimulation paradigm that depends on corticofugal and proprioceptive afferent convergence in the spinal cord. The paradigm, termed SCAP for spinal cord associative plasticity, produced large-scale physiological changes in a preclinical model of cervical SCI. Importantly, SCAP caused lasting improvements in dexterity and decreased hyperreflexia in rats with SCI. Thus, we have determined the neural circuits that drive SCAP and have preclinical evidence for its efficacy to restore function after incomplete cervical SCI, the most common SCI in people.

Arm cycling increases short-latency reflex from ankle dorsiflexor afferents to knee extensor muscles

Low-intensity electrical stimulation of the common peroneal nerve (CPN) evokes a short latency reflex in the heteronymous knee extensor muscles (referred to as CPN-reflex). The CPN-reflex is facilitated at a heel strike during walking, contributing to body weight support. However, the origin of the CPN-reflex increase during walking remains unclear. We speculate that this increase originates from multiple sources due to a body of evidence suggesting the presence of neural coupling between the arms and legs. Therefore, we investigated the extent to which the CPN-reflex is modulated during rhythmic arm cycling. Twenty-eight subjects sat in an armchair and were asked to perform arm cycling at a moderate cadence using a stationary ergometer while performing isometric contraction of the knee extensors, such that the CPN-reflex was evoked. CPN-reflex was evoked by stimulating the CPN (0.9-2.0 × the motor threshold [MT] in the tibialis anterior muscle) at the level of the neck of the fibula. The CPN-reflex amplitude was measured from the vastus lateralis (VL). The biphasic reflex response in the VL was evoked within 27-45 ms following CPN stimulation. The amplitude of the CPN-reflex increased during arm cycling compared with that before cycling. The modulation of the CPN-reflex during arm cycling was detected only for CPN stimulation intensity around 1.2 × MT. Furthermore, CPN-reflex modulation was not observed during the isometric contraction of the arm or passive arm cycling. Our results suggest the presence of neural coupling between the CPN-reflex pathways and neural systems generating locomotive arm movement.