Professor Vaughan Macefield


Cardiovascular variability in Parkinson's disease and extrapyramidal motor slowing.

Brown R, Duma S, Piguet O, Broe GA, Macefield VG

Parkinson's disease (PD) is a degenerative neurological condition, associated with cardiovascular dysfunction. Many studies have utilised heart rate variability (HRV) to assess the autonomic nervous system in PD, but blood pressure variability (BPV) has received less attention. The purpose of the present study was to compare HRV and BPV between participants with established PD, extrapyramidal motor slowing (EPMS) (not reaching clinical criteria for PD), older healthy controls (OHC), and young healthy controls (YHC), in order to ascertain whether either of these measures can be used as an early marker of non-motor symptoms in PD.

Pain inhibits pain; human brainstem mechanisms.

Youssef AM, Macefield VG, Henderson LA

Conditioned pain modulation is a powerful analgesic mechanism, occurring when a painful stimulus is inhibited by a second painful stimulus delivered at a different body location. Reduced conditioned pain modulation capacity is associated with the development of some chronic pain conditions and the effectiveness of some analgesic medications. Human lesion studies show that the circuitry responsible for conditioned pain modulation lies within the caudal brainstem, although the precise nuclei in humans remain unknown. We employed brain imaging to determine brainstem sites responsible for conditioned pain modulation in 54 healthy individuals. In all subjects, 8 noxious heat stimuli (test stimuli) were applied to the right side of the mouth and brain activity measured using functional magnetic resonance imaging. This paradigm was then repeated. However, following the fourth noxious stimulus, a separate noxious stimulus, consisting of an intramuscular injection of hypertonic saline into the leg, was delivered (conditioning stimulus). During this test and conditioning stimulus period, 23 subjects displayed conditioned pain modulation analgesia whereas 31 subjects did not. An individual's analgesic ability was not influenced by gender, pain intensity levels of the test or conditioning stimuli or by psychological variables such as pain catastrophizing or fear of pain. Brain images were processed using SPM8 and the brainstem isolated using the SUIT toolbox. Significant increases in signal intensity were determined during each test stimulus and compared between subjects that did and did not display CPM analgesia (p<0.05, small volume correction). The expression of analgesia was associated with reduction in signal intensity increases during each test stimulus in the presence of the conditioning stimulus in three brainstem regions: the caudalis subdivision of the spinal trigeminal nucleus, i.e., the primary synapse, the region of the subnucleus reticularis dorsalis and in the dorsolateral pons in the region of the parabrachial nucleus. Furthermore, the magnitudes of these signal reductions in all three brainstem regions were significantly correlated to analgesia magnitude. Defining conditioned pain modulation circuitry provides a framework for the future investigations into the neural mechanisms responsible for the maintenance of persistent pain conditions thought to involve altered analgesic circuitry.

Skin Sympathetic Nerve Activity is Modulated during Slow Sinusoidal Linear Displacements in Supine Humans.

Bolton PS, Hammam E, Kwok K, Macefield VG

Low-frequency sinusoidal linear acceleration (0.08 Hz, ±4 mG) modulates skin sympathetic nerve activity (SSNA) in seated subjects (head vertical), suggesting that activation of the utricle in the peripheral vestibular labyrinth modulates SSNA. The aim of the current study was to determine whether SSNA is also modulated by input from the saccule. Tungsten microelectrodes were inserted into the common peroneal nerve to record oligounitary SSNA in 8 subjects laying supine on a motorized platform with the head aligned with the longitudinal axis of the body. Slow sinusoidal (0.08 Hz, 100 cycles) linear acceleration-decelerations (peak ±4 mG) were applied rostrocaudally to predominately activate the saccules, or mediolaterally to predominately activate the utricles. Cross-correlation histograms were constructed between the negative-going sympathetic spikes and the positive peaks of the sinusoidal stimuli. Sinusoidal linear acceleration along the rostrocaudal axis or mediolateral axis both resulted in sinusoidal modulation of SSNA (Median, IQR 27.0, 22-33% and 24.8, 17-39%, respectively). This suggests that both otolith organs act on sympathetic outflow to skin and muscle in a similar manner during supine displacements.

Increasing cutaneous afferent feedback improves proprioceptive accuracy at the knee in patients with sensory ataxia.

Macefield VG, Norcliffe-Kaufmann L, Goulding N, Palma JA, Fuente Mora C, Kaufmann H

Hereditary sensory and autonomic neuropathy type III (HSAN III) features disturbed proprioception and a marked ataxic gait. We recently showed that joint angle matching error at the knee is positively correlated with the degree of ataxia. Using intraneural microelectrodes, we also documented that these patients lack functional muscle spindle afferents but have preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying more on proprioceptive cues provided by tactile afferents. We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape could improve proprioceptive accuracy in patients with a congenital absence of functional muscle spindles. Passive joint angle matching at the knee was used to assess proprioceptive accuracy in 25 patients with HSAN III and 9 age-matched control subjects, with and without taping. Angles of the reference and indicator knees were recorded with digital inclinometers and the absolute error, gradient, and correlation coefficient between the two sides calculated. Patients with HSAN III performed poorly on the joint angle matching test [mean matching error 8.0 ± 0.8° (±SE); controls 3.0 ± 0.3°]. Following application of tape bilaterally to the knee in an X-shaped pattern, proprioceptive performance improved significantly in the patients (mean error 5.4 ± 0.7°) but not in the controls (3.0 ± 0.2°). Across patients, but not controls, significant increases in gradient and correlation coefficient were also apparent following taping. We conclude that taping improves proprioception at the knee in HSAN III, presumably via enhanced sensory feedback from the skin.


Knellwolf TP, Hammam E, Macefield VG

Inter-individual responses to experimental muscle pain: Baseline anxiety ratings and attitudes to pain do not determine the direction of the sympathetic response to tonic muscle pain in humans.

Kobuch S, Fazalbhoy A, Brown R, Macefield VG

Consistent interindividual increases or decreases in muscle sympathetic nerve activity during experimental muscle pain.

Fazalbhoy A, Birznieks I, Macefield VG

We recently showed that long-lasting muscle pain, induced by intramuscular infusion of hypertonic saline, evoked two patterns of cardiovascular responses across subjects: one group showed parallel increases in muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate, while the other group showed parallel decreases. Given that MSNA is consistent day to day, we tested the hypothesis that individuals who show increases in MSNA during experimental muscle pain will show consistent responses over time. MSNA was recorded from the peroneal nerve, together with blood pressure and heart rate, during an intramuscular infusion of hypertonic saline causing pain for an hour in 15 subjects on two occasions, 2-27 weeks apart. Pain intensity ratings were not significantly different between the first (5.8 ± 0.4/10) and second (6.1 ± 0.2) recording sessions. While four subjects showed significant decreases in the first session (46.6 ± 9.2% of baseline) and significant increases in the second (159.6 ± 8.9%), in 11 subjects, there was consistency in the changes in MSNA over time: either a sustained decrease (55.6 ± 6.8%, n = 6) or a sustained increase (143.5 ± 6.1%, n = 5) occurred in both recording sessions. There were no differences in pain ratings between sessions for any subjects. We conclude that the changes in MSNA during long-lasting muscle pain are consistent over time in the majority of individuals, reflecting the importance of studying interindividual differences in physiology.

Single tactile afferents outperform human subjects in a vibrotactile intensity discrimination task.

Arabzadeh E, Clifford CW, Harris JA, Mahns DA, Macefield VG, Birznieks I

We simultaneously compared the sensitivity of single primary afferent neurons supplying the glabrous skin of the hand and the psychophysical amplitude discrimination thresholds in human subjects for a set of vibrotactile stimuli delivered to the receptive field. All recorded afferents had a dynamic range narrower than the range of amplitudes across which the subjects could discriminate. However, when the vibration amplitude was chosen to be within the steepest part of the afferent's stimulus-response function the response of single afferents, defined as the spike count over the vibration duration (500 ms), was often more sensitive in discriminating vibration amplitude than the perceptual judgment of the participants. We quantified how the neuronal performance depended on the integration window: for short windows the neuronal performance was inferior to the performance of the subject. The neuronal performance progressively improved with increasing spike count duration and reached a level significantly above that of the subjects when the integration window was 250 ms or longer. The superiority in performance of individual neurons over observers could reflect a nonoptimal integration window or be due to the presence of noise between the sensory periphery and the cortical decision stage. Additionally, it could indicate that the range of perceptual sensitivity comes at the cost of discrimination through pooling across neurons with different response functions.