Vaughan G. Macefield

The firing rates of human motoneurones voluntarily activated in the absence of muscle afferent feedback.

1. To quantify the net influence of muscle afferent feedback on the firing rates of human motoneurones, the discharge frequencies of single motor axons in the common peroneal nerve were recorded during sustained voluntary efforts performed in the absence of feedback from the target muscle. These data were compared with the firing rates of single motor units in the intact tibialis anterior muscle. In five subjects, recordings were made from fifty‐two motor axons innervating tibialis anterior during acute deafferentation and paralysis of the dorsiflexor muscles produced by anaesthetic block of the nerve distal to the recording site. 2. Maximal sustainable firing rates were determined for twenty‐four motoneurons, twelve of which were classified as relatively low threshold (estimated recruitment level < or = 10% maximal) and six as high threshold. Mean firing rates of the low‐threshold motoneurones (21.7 +/‐ 2.7 Hz; +/‐ S.E.M.) were significantly higher than those of the high‐threshold motoneurones (14.0 +/‐ 4.4 Hz). The mean firing rate of the twenty‐four deafferented motoneurones during maximal efforts to contract the paralysed muscle was 18.6 +/‐ 1.9 Hz, significantly lower than the maximal firing rates of single motor units recorded from the normally innervated tibialis anterior muscle (28.2 +/‐ 0.6 Hz). 3. During half‐maximal efforts, the mean firing rate of eight deafferented motoneurones (10.8 +/‐ 1.1 Hz) was significantly lower than that of intact motor units (16.5 +/‐ 0.2 Hz). A similar finding was apparent during minimal efforts; the mean discharge frequency of seven deafferented motoneurones during weak voluntary efforts was 6.0 +/‐ 0.9 Hz, compared with 7.3 +/‐ 0.13 Hz for intact motor units. Overall, the range of motoneurone firing rates (from minimal to maximal levels of voluntary effort) was significantly affected by the acute deafferentation, but was shifted significantly to lower rates. 4. During sustained maximal voluntary efforts of at least 30 s duration the firing rate of deafferented motoneurones decreased over the first 5 s but was then maintained, i.e. there was no progressive decline as occurs with normally innervated motor units during fatiguing contractions. This observation supports a reflex origin for the normal decline in motoneurone discharge. 5. It is concluded that muscle afferents in the common peroneal nerve provide a net facilitation to the tibialis anterior motoneurone pool, reflexly increasing the motor output at all levels of voluntary drive by approximately one‐third.

Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally-charged images

The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.

The discharge behaviour of single vasoconstrictor motoneurones in human muscle nerves.

1. The discharge behaviour of fourteen single sympathetic vasoconstrictor efferents was studied using a tungsten microelectrode inserted percutaneously into a motor fascicle of the radial or peroneal nerve in eight awake supine subjects. Units were classified as vasoconstrictor because their firing properties correlated appropriately to changes in cardiac interval and arterial pressure. 2. On average, individual vasoconstrictor units discharged in only 21% of heart beats, with an overall mean frequency of 0.47 Hz. Usually only one spike was generated per cardiac cycle. Calculated from cardiac cycles in which a unit fired from two to seven spikes, the mean within‐burst firing rate was 18.8 +/‐ 2.5 Hz (mean +/‐ S.E.M.); but instantaneous frequencies above 50 Hz were occasionally observed. 3. Measured from a defined R‐wave of the ECG, the spike onset latency varied over 358 +/‐ 33 ms, suggesting considerable variation of synaptic delays in the baroreflex arc. This latency had a relatively uniform temporal relationship with the burst onset or peak latency, compatible with a fixed recruitment order of individual sympathetic neurones. 4. In view of the low average firing rate of individual units we suggest that the variable instantaneous firing rates may optimize the contractile responses of vascular smooth muscle.

Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury.

Abstract The most obvious impairments associated with spinal cord injury (SCI) are loss of sensation and motor control. However, many subjects with SCI also develop persistent neuropathic pain below the injury which is often severe, debilitating and refractory to treatment. The underlying mechanisms of persistent neuropathic SCI pain remain poorly understood. Reports in amputees describing phantom limb pain demonstrate a positive correlation between pain intensity and the amount of primary somatosensory cortex (S1) reorganization. Of note, this S1 reorganization has also been shown to reverse with pain reduction. It is unknown whether a similar association between S1 reorganization and pain intensity exists in subjects with SCI. The aim of this investigation was to determine whether the degree of S1 reorganization following SCI correlated with on‐going neuropathic pain intensity. In 20 complete SCI subjects (10 with neuropathic pain, 10 without neuropathic pain) and 21 control subjects without SCI, the somatosensory cortex was mapped using functional magnetic resonance imaging during light brushing of the right little finger, thumb and lip. S1 reorganization was demonstrated in SCI subjects with the little finger activation point moving medially towards the S1 region that would normally innervate the legs. The amount of S1 reorganization in subjects with SCI significantly correlated with on‐going pain intensity levels. This study provides evidence of a link between the degree of cortical reorganization and the intensity of persistent neuropathic pain following SCI. Strategies aimed at reversing somatosensory cortical reorganization may have therapeutic potential in central neuropathic pain.

Somatotopic organization of the processing of muscle and cutaneous pain in the left and right insula cortex: A single-trial fMRI study

Abstract The insula is involved in processing noxious information. It is consistently activated by acute noxious stimuli, can elicit pain on stimulation, and lesions encompassing the insula can alter pain perception. Anatomical tracing, electrophysiological and functional brain imaging investigations have suggested that the insula is somatotopically organized with respect to noxious cutaneous inputs. It has also recently been revealed that the anterior insula displays differential activation during cutaneous compared with muscle pain. Given this difference, it is important to determine if an insula somatotopy also exists for muscle pain. Using high‐resolution functional magnetic resonance imaging (fMRI) we compared insula activation patterns in 23 subjects during muscle and cutaneous pain induced in the right leg and forearm. Group and frequency analyses revealed somatotopically organized signal increases in the posterior contralateral (left) and ipsilateral (right) anterior insula. Within the posterior contralateral insula, signal increases during both cutaneous and muscle forearm pain were located lateral and anterior to those evoked by leg pain, whereas in the ipsilateral anterior insula the pattern was reversed. Furthermore, within the ipsilateral anterior insula, muscle pain activated a region anterior to that activated by cutaneous pain. This somatotopic organization may be crucial for pain localization or other aspects of the pain experience that differ depending on both stimulation site and type of tissue activated. This study reveals that the insula is organized somatopically with respect to muscle and cutaneous pain and that this organization is further separated according to the tissue in which the pain originates.

Anatomical Changes in Human Motor Cortex and Motor Pathways following Complete Thoracic Spinal Cord Injury

A debilitating consequence of complete spinal cord injury (SCI) is the loss of motor control. Although the goal of most SCI treatments is to re-establish neural connections, a potential complication in restoring motor function is that SCI may result in anatomical and functional changes in brain areas controlling motor output. Some animal investigations show cell death in the primary motor cortex following SCI, but similar anatomical changes in humans are not yet established. The aim of this investigation was to use voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to determine if SCI in humans results in anatomical changes within motor cortices and descending motor pathways. Using VBM, we found significantly lower gray matter volume in complete SCI subjects compared with controls in the primary motor cortex, the medial prefrontal, and adjacent anterior cingulate cortices. DTI analysis revealed structural abnormalities in the same areas with reduced gray matter volume and in the superior cerebellar cortex. In addition, tractography revealed structural abnormalities in the corticospinal and corticopontine tracts of the SCI subjects. In conclusion, human subjects with complete SCI show structural changes in cortical motor regions and descending motor tracts, and these brain anatomical changes may limit motor recovery following SCI.

Vibration sensitivity of human muscle spindles and Golgi tendon organs.

The responses of the various muscle receptors to vibration are more complicated than a naïve categorization into stretch (muscle spindle primary ending), length (muscle spindle secondary endings), and tension (Golgi tendon organs) receptors. To emphasize the similarity of responses to small length changes, we recorded from 58 individual muscle afferents subserving receptors in the ankle or toe dorsiflexors of awake human subjects (32 primary endings, 20 secondary endings, and six Golgi tendon organs). Transverse sinusoidal vibration was applied to the distal tendon of the receptor‐bearing muscle, while subjects either remained completely relaxed or maintained a weak isometric contraction of the appropriate muscle. In relaxed muscle, few units responded in a 1:1 manner to vibration, and there was no evidence of a preferred frequency of activation. In active muscle the response profiles of all three receptor types overlapped, with no significant difference in threshold between receptor types. These results emphasize that when intramuscular tension increases during a voluntary contraction, Golgi tendon organs and muscle spindle secondary endings, not just muscle spindle primary endings, can effectively encode small imposed length changes. Muscle Nerve, 2007

Physiological characteristics of low-threshold mechanoreceptors in joints, muscle and skin in human subjects

1. The development of microneurography, in which an insulated tungsten microelectrode is inserted into an accessible peripheral or cranial nerve in awake human subjects, has allowed detailed analyses of the signalling capacities of single mechanoreceptive afferents from the skin, muscles and joints. For example, we know much about how the two classes of rapidly adapting (Meissner and Pacinian) and two classes of slowly adapting (Merkel and Ruffini) cutaneous mechanoreceptors encode forces applied normal or tangential to the skin of the hand and the similarities and differences in glabrous versus non‐glabrous skin (and receptors associated with hairs). We also know about stretch‐ and force‐sensitive endings in muscle (the muscle spindle and Golgi tendon organ, respectively) and how they behave during passive or active movements or during isometric contractions. In addition, we have characterized the firing properties of mechanoreceptors in the joint capsules of the fingers. However, we know little about sensory nerves in the periosteum, other than that nociceptors and Pacinian corpuscles exist.

The discharge behaviour of single sympathetic neurones supplying human sweat glands

Firing properties of single sudomotor axons were studied via tungsten microelectrodes inserted percutaneously into cutaneous fascicles of the peroneal nerve in awake subjects. Sweating was induced by radiant heat and measured by changes in skin electrical resistance within the innervation territory on the dorsum of the foot. Eight units were classified as sudomotor neurones because spike-triggered averaging revealed a time-locked relationship between the unitary discharge and the subsequent decrease in skin resistance (1.12 +/- 0.05 s), but no relationship to skin blood flow (measured by a laser-doppler probe). Sudomotor units usually fired only one (maximum six) spike(s) in a sympathetic burst. The mean firing rate was 0.62 Hz, but instantaneous frequencies above 50 Hz could be generated. R-wave triggered histograms and coherence analysis revealed significant coupling between the firing of three sudomotor neurones and the ECG. Moreover, the firing of four sudomotor neurones showed a weak but significant correlation with the spontaneous fluctuations in cardiac interval, diastolic pressure, or the rate of fall in arterial pressure. We conclude that the discharge of human sudomotor neurones is modulated by baroreceptor input.

Firing properties of single vasoconstrictor neurones in human subjects with high levels of muscle sympathetic activity

1 Single‐unit recordings were made from 19 postganglionic muscle vasoconstrictor axons via tungsten microelectrodes in the peroneal nerve in seven healthy subjects with many multi‐unit sympathetic discharges at rest (‘high group’, 75 ± 5 multi‐unit bursts per 100 heart beats, mean ± s.e.m.). The results were compared with previous data from 14 units in subjects with 21 ± 2 multi‐unit bursts per 100 heart beats (‘low group’). 2 In the ‘high group’ the units fired spontaneously in 35 ± 4 % of all cardiac intervals. One unit only ever fired once per cardiac interval, 14 units (74 %) generated maximally two to three spikes, and four units (21 %) up to four to five spikes. Of those cardiac intervals in which a unit fired, a single spike occurred in 78 %, two spikes in 18 %, three spikes in 4 % and four spikes in less than 1 % of cardiac intervals. Measured as the inverse of all interspike intervals, the mean rate was 0.33 ± 0.04 Hz and the mean intraburst frequency 22.2 ± 1.6 Hz. Most results were similar to those in the ‘low group’, but in the ‘low group’ heart rate was higher (64.5 vs. 50.4 beats min−1) and mean firing frequency was higher (0.49 ± 0.06 Hz). 3 During increases of multi‐unit burst activity evoked by sustained inspiratory‐capacity apnoea the firing probability of nine units in the ‘high group’ increased from 33 ± 6 to 56 ± 3 % of the cardiac intervals. Simultaneously, the incidence of single spikes decreased and the incidence of multiple spikes per cardiac interval increased, resulting in an increase of mean firing frequency from 0.23 ± 0.04 Hz at rest to 1.04 ± 0.14 Hz during the apnoea. 4 We conclude that single muscle vasoconstrictor neurones usually fire only a solitary spike during sympathetic bursts both in subjects with a high and in subjects with a low number of bursts at rest. Presumably, differences in the numbers of bursts are due mainly to differences in firing probability and recruitment of sympathetic fibres. During acute increases of multi‐unit activity, both increases in discharge frequency and recruitment of additional neurones contribute to the increased intensity of an individual sympathetic burst.