Single vasoconstrictor nerve fibers in humans normally fire only once but have the capacity to fire as many as eight times, per cardiac interval. Our laboratory recently demonstrated that the mean firing frequency of individual vasoconstrictor fibers is more than doubled in the sympathoexcitation associated with congestive heart failure (Macefield VG, Rundqvist B, Sverrisdottir YB, Wallin BG, and Elam M. Circulation 100: 1708--1713, 1999). However, the propensity to fire only once per cardiac interval was retained. In the present retrospective study, we tested the hypothesis that vasoconstrictor fibers fire more than once per cardiac interval in response to transient sympathoexcitatory stimuli, providing one mechanism for further increase of an already augmented sympathetic discharge. Six patients with congestive heart failure (New York Heart Association functional class II--IV; left ventricular ejection range 13--37%, average 22%) were studied at rest and during premature ectopic heartbeats. Analyzed for a total of 60 premature beats, the average firing probability of 10 vasoconstrictor fibers increased from 61 to 80% in the prolonged cardiac interval (i.e., reduced diastolic pressure) after premature beats. The incidence of multiple within-burst firing increased markedly, with two spikes being more common than one. Our results illustrate two different mechanisms (increases in firing probability and multiple within-burst firing), and indirectly indicate a third mechanism (recruitment of previously silent fibers), for acute sympathoexcitatory responses.

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Background There is evidence of altered resting hypothalamic activity patterns and connectivity prior to a migraine, however it remains unknown if these changes are driven by changes in overall hypothalamic activity levels. If they are, it would corroborate the idea that changes in hypothalamic function result in alteration in brainstem pain processing sensitivity, which either triggers a migraine headache itself or allows an external trigger to initiate a migraine headache. We hypothesise that hypothalamic activity increases immediately prior to a migraine headache and this is accompanied by altered functional connectivity to pain processing sites in the brainstem. Methods In 34 migraineurs and 26 healthy controls, we collected a series comprising 108 pseudo-continuous arterial spin labelling images and 180 gradient-echo echo planar resting-state functional magnetic resonance volumes to measure resting regional cerebral blood flow and functional connectivity respectively. Images were pre-processed and analysed using custom SPM12 and Matlab software. Results Our results reflect that immediately prior to a migraine headache, resting regional cerebral blood flow decreases in the lateral hypothalamus. In addition, resting functional connectivity strength decreased between the lateral hypothalamus and important regions of the pain processing pathway, such as the midbrain periaqueductal gray, dorsal pons, rostral ventromedial medulla and cingulate cortex, only during this critical period before a migraine headache. Conclusion These data suggest altered hypothalamic function and connectivity in the period immediately prior to a migraine headache and supports the hypothesis that the hypothalamus is involved in migraine initiation.

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The established view is that vibrotactile stimuli evoke two qualitatively distinctive cutaneous sensations, flutter (frequencies < 60 Hz) and vibratory hum (frequencies > 60 Hz), subserved by two distinct receptor types (Meissner’s and Pacinian corpuscle, respectively), which may engage different neural processing pathways or channels and fulfil quite different biological roles. In psychological and physiological literature, those two systems have been labelled as Pacinian and non-Pacinian channels. However, we present evidence that low-frequency spike trains in Pacinian afferents can readily induce a vibratory percept with the same low frequency attributes as sinusoidal stimuli of the same frequency, thus demonstrating a universal frequency decoding system. We achieved this using brief low-amplitude pulsatile mechanical stimuli to selectively activate Pacinian afferents. This indicates that spiking pattern, regardless of receptor type, determines vibrotactile frequency perception. This mechanism may underlie the constancy of vibrotactile frequency perception across different skin regions innervated by distinct afferent types.

During voluntary contractions, muscle sympathetic nerve activity (MSNA) to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-min isometric dorsiflexion contractions (left leg) separated by 2-min rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5–10% of maximum). MSNA was recorded continuously (microneurography) from the left peroneal nerve and quantified from cardiac-synchronized, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34% (P < 0.01) during voluntary contractions but did not change significantly during electrically-evoked contractions (−8 ± 12%, P > 0.05). MSNA analyzed at 15-s intervals revealed that this effect of voluntary contraction appeared 15–30 s after contraction onset (P < 0.01), remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction.

2. Single cutaneous (n = 60), joint (n = 2) and muscle spindle (n = 34) afferents were recorded via tungsten microelectrodes inserted into the median and ulnar nerves at the wrist. Spiketriggered averaging was used to investigate synaptic coupling between these afferents and muscles acting on the digits. The activity of 37 % of FA I (7/19), 20 % of FA II (1/5) and 52 % of SA II afferents (11/21) evoked a reflex response. The discharge from muscle spindles, 15 SA I and two joint afferents did not modulate EMG activity.3. Two types of reflex responses were encountered: a single excitatory response produced by irregularly firing afferents, or a cyclic modulation evoked by regularly discharging afferents. Rhythmic stimulation of one FA I afferent generated regularly occurring bursts which corresponded to the associated cyclic EMG response.4. Selectively triggering from the first or last spike of each burst of one FA I afferent altered the averaged EMG profile, suggesting that afferent input modulates the associated EMG and not vice versa.5. The discharge from single FA I, FA II and SA II afferents can modify ongoing voluntary EMG in muscles of the human hand, presumably via a spinally mediated oligosynaptic pathway. Conversely, we saw no evidence of such modulation by SA I, muscle spindle or joint afferents.

2The established view is that vibrotactile stimuli evoke two qualitatively distinctive cutaneous sensations, 3 flutter (frequencies < 60 Hz) and vibratory hum (frequencies > 60 Hz), subserved by two distinct 4 receptor types (Meissner's and Pacinian corpuscle, respectively) which may engage different neural 5 processing pathways or channels and fulfill quite different biological roles. In psychological and 6 physiological literature those two systems have been labelled as Pacinian and non-Pacinian channels. 7However, we present evidence that low-frequency spike trains in Pacinian afferents can readily induce a 8 vibratory percept with the same low frequency attributes as sinusoidal stimuli of the same frequency 9 thus demonstrating a universal frequency decoding system. We achieved this using brief low-amplitude 10 pulsatile mechanical stimuli to selectively activate Pacinian afferents. This indicates that spiking pattern, 11 regardless of receptor type, determines vibrotactile frequency perception. This mechanism may underlie 12 the constancy of vibrotactile frequency perception across different skin regions innervated by distinct 13 afferent types. 14 15 Johansson, 1984). Observations that different receptor types are tuned to different stimulus features and 20 have distinct response profiles have led researchers to conclude that different receptor types are the 21 inputs to separate neural "channels" dedicated to processing of those features (Bolanowski, Gescheider, 22 operating range of one of the channels seems less likely. 132Recent psychophysical evidence demonstrated that there is interaction between the FAI and FAII inputs, 133by showing the assimilation effect, where a frequency in the range of one channel can influence 134 perceived frequency on the other channel (Kuroki, Watanabe, & Nishida, 2017). We suggest that our 135 data extends this, and represents evidence of the functional consequence of the recently discovered 136 extensive convergence of FAI-and FAII-derived inputs onto S1 cortical neurons (Carter, 262The amplitude of all pulsatile stimuli was 3 µm which was approximately 3 times the sensory threshold 263 found in our detection threshold experiment. At this amplitude, we expect only Pacinian (PC) afferents 264 to respond, as threshold for recruitment of FAI afferents, even at their preferred frequency, is no lower