Professor Jane Butler

TEAM LEADER PROFILE

Principal Research Scientist, NeuRA Senior Research Fellow, NHMRC
Associate Professor, UNSW


Jane Butler (PhD) graduated in 1999 from UNSW, worked at the Miami Project to Cure Paralysis, University of Miami supported by a NHMRC post-doctoral fellowship, and has returned to Australia in 2002 to continue her research at NeuRA. She has a broad interest in the control of human motoneurones in health on disease with a focus on the control of respiration. Current studies include investigation of the behaviour of single motor units in respiratory muscles and respiratory neural control during normal breathing and in patients with respiratory disorders such as obstructive sleep apnoea, chronic obstructive pulmonary disease, and methods to improve respiratory function and health after spinal cord injury. She also studies the changes in the motor pathway that occur during normal movement and fatigue.

Projects Professor Jane Butler is currently involved with

CURRENT PROJECTS

Using Abdominal Functional Electrical Stimulation to improve bowel function in Multiple Sclerosis

There are currently over 20,000 people living with Multiple Sclerosis (MS) in Australia. Bowel and bladder problems, mainly in the form of constipation and urinary incontinence, affect more than half of these people. These problems have traditionally been managed using a combination of manual and pharmacological interventions. However, such solutions are usually only partially effective. Therefore, a non-invasive method of improving bowel and bladder function for people with MS is urgently needed.

The abdominal muscles play a major role during defecation and urination. Surface electrical stimulation of the abdominal muscles, termed Abdominal Functional Electrical Stimulation (Abdominal FES), has been shown to improve bowel function after spinal cord injury, with a case study suggesting this technique may also improve bowel function in MS. There is also limited evidence that Abdominal FES can improve bladder control.

We are currently undertaking the first significant study to investigate the effectiveness of Abdominal FES to improve the bowel and bladder function of people with MS. By making use of the most advanced motility testing system currently available, we hope to be able to definitively assess whether Abdominal FES could be a useful treatment solution for people with MS.

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Using Abdominal Functional Electrical Stimulation to improve bowel function in Multiple Sclerosis

Reducing mechanical ventilation duration for the critically ill: a pilot study

Approximately 33% of critically ill patients require mechanical ventilation to support respiration. During this time the major respiratory muscles, namely the diaphragm, abdominal and intercostal muscles, weaken. This vicious cycle leads to difficulty in separating patients from mechanical ventilation, increased mortality, and more readmissions to intensive care. Interventions that maintain respiratory muscle strength and reduce atrophy during mechanical ventilation are likely to reduce ventilation duration, complications and costs, and improve quality of life.

The abdominal muscles are the primary muscle group used during forced exhalation. We have shown that surface Functional Electrical Stimulation (FES) of the abdominal muscles, termed Abdominal FES, can improve respiratory function and assist weaning from mechanical ventilation in spinal cord injury. We hypothesise that Abdominal FES in critically ill patients will reduce diaphragm and abdominal muscle atrophy, with the long term goal of this project to demonstrate reduced mechanical ventilation duration.

We are currently conducting a pilot study at the Prince of Wales Hospital, Sydney, to investigate whether Abdominal FES is a feasible technique for reducing mechanical ventilation duration in critical illness. This work is being supported by our American project partners, Liberate Medical.

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Reducing mechanical ventilation duration for the critically ill: a pilot study

Abdominal Functional Electrical Stimulation to reduce respiratory complications after spinal cord in

While tetraplegia is often characterized by paralysis of all four limbs, paralysis also affects the major respiratory muscles, namely the diaphragm and abdominal and intercostal muscles. This reduces respiratory function, with associated respiratory complications, such as pneumonia and atelectasis. Such complications are a leading cause of illness and death for the tetraplegic population. Up to 68% of patients with tetraplegia have a respiratory complication in the first 6 weeks (i.e. the acute stage) of injury. A reduction in respiratory complications in acute tetraplegia would decrease illness and death, reduce rehabilitation time, improve quality of life, and result in a large cost saving for global health systems.

Surface electrical stimulation of the abdominal muscles, termed Abdominal Functional Electrical Stimulation (FES), can contract the abdominal muscles, even when paralysed. We have shown that the repeated application of Abdominal FES improves the respiratory function of people with tetraplegia. However, while respiratory function is a predictor of respiratory complications in tetraplegia, evidence that Abdominal FES reduces respiratory complications is only anecdotal. We will undertake the first prospective, multi-centre, randomised placebo controlled trial, to determine whether Abdominal FES reduces respiratory complications in acute tetraplegia.

Definitive evidence of the effectiveness of Abdominal FES to reduce respiratory complications in tetraplegia will drive the rapid worldwide translation of this low cost and easily applied technology for this vulnerable patient group. This will decrease illness and death, reduce rehabilitation time, improve quality of life, and result in a large cost saving for global health systems.

This international collaboration brings together leading research and medical teams from: Neuroscience Research Australia, the Prince of Wales Hospital, and the Royal North Shore Hospital in Australia; The Indian Spinal Cord Injury Centre; Chang Mai University Hospital in Thailand and The Queen Elizabeth National Spinal Injuries Unit and the University of Glasgow in Scotland.

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Abdominal Functional Electrical Stimulation to reduce respiratory complications after spinal cord injury.

Determining new targets and approaches for treating sleep apnoea

We are running a range of projects to determine how existing treatments for sleep apnoea work so that we can optimise therapy and improve treatment success.

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Determining new targets and approaches for treating sleep apnoea

Defining the Causes and Developing New Treatments for People with Spinal Cord Injury and Sleep Apnoe

The prevalence of sleep apnoea in people with chronic quadriplegia is two to seven times higher than the general population. Optimal treatment approaches may also differ.

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Defining the Causes and Developing New Treatments for People with Spinal Cord Injury and Sleep Apnoea

Upper-Airway Reflexes and Muscle Control

We are conducting research to understand how important reflexes in the upper airway function to gain insight into the causes of obstructive sleep apnoea.

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Upper-Airway Reflexes and Muscle Control

Effect of Morphine on Obstructive Sleep Apnoea

The goal of this project is to investigate the effects of opioids on upper airway muscle activity, respiratory control, and breathing during sleep in patients with obstructive sleep apnoea.

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Effect of Morphine on Obstructive Sleep Apnoea

Sedatives and Sleep Apnoea

We are conducting several studies to examine the effects of common sleeping pills on the upper airway muscles and breathing during sleep.

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Sedatives and Sleep Apnoea

Investigations into the firing behaviour of human motoneurones in health and after neurological inju

This basic science project aims to examine the behaviour of human motoneurones during sustained activation to reveal their mechanisms of recovery after activation. We will take the fundamental findings from this study and compare the behaviour of motoneurones innervating muscles affected by neurological injury such as spinal cord injury and stroke.

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Investigations into the firing behaviour of human motoneurones in health and after neurological injury

Studies of voluntary and involuntary control of human breathing

Breathing is a complex motor task that needs to be coordinated at all times while we eat, speak, exercise and even during sleep. The breathing muscles are controlled automatically from the brainstem during normal breathing but can also be controlled voluntarily from the motor cortex. The way these two drives to the breathing muscles interact is still not well understood. While there is some evidence that there are at least two independent pathways, and that integration of the pathways occurs at the spinal cord, there is some uncertainty about whether these pathways may have some interaction in the brainstem. Our current experiments are looking at voluntary and involuntary drive to the breathing muscles to try to answer this fundamental question about the neural control of breathing. In addition we are looking at the potential cortical contributions to resting breathing in respiratory disorders.

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Studies of voluntary and involuntary control of human breathing

Control of the neural drive to human breathing muscles in disorders such as obstructive sleep apnoea

Obstructive sleep apnoea is a sleep disorder that affects more than 4% of the population and can lead to symptoms from daytime drowsiness to high blood pressure. People with sleep apnoea are often not breathing normally during sleep and may experience periods where the airway closes and they are unable to breathe. In severe sleep apnoea this can occur 50-60 times each hour. That is once each minute. The closure of the upper airway is thought to be due to a number of factors, one of which is that the neural drive to the airway muscles is insufficient in people with sleep apnoea. In our lab, we have made the first extensive recordings from the major muscle of the upper airway, genioglossus. We have shown that the neural drive to this muscle is very complex, more so than any limb muscle. At NeuRA, we have also pioneered new methods to image this muscle using fMRI and ultrasound. We are now planning to look at how changes in muscle architecture and mechanics relate to the neural drive to the muscle and whether that relationship is maintained in people with sleep apnoea.

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Control of the neural drive to human breathing muscles in disorders such as obstructive sleep apnoea

Control of the neural drive to human breathing muscles in health and disease

Our recent studies of the control of breathing muscles have shown a strong link between neural drive and mechanical action of the muscle. We showed that for a number of breathing muscles, the neural drive is directed to the muscles with the best mechanical effect for breathing. We termed this link between mechanics and neural drive ‘neuromechanical matching’. It is a new principle of muscle activation that allows for metabolically efficient activation of the muscles. This basic research finding is now leading to further studies in patients with respiratory disorders where muscle mechanics have changed. Chronic obstructive pulmonary disease is one such disease, where muscle mechanics are known to change. Our new studies will look at whether these patients have “adapted” to the changed muscle mechanics or whether their muscles may be activated inefficiently.

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Control of the neural drive to human breathing muscles in health and disease

Emotional breathing

Not only are the breathing muscles controlled automatically from the brainstem and motor cortex, but they can be activated in response to emotion, e.g. during laughing and crying. We plan to investigate the neural pathways involved in emotional breathing in healthy volunteers.

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Emotional breathing

Control of coughing and expiratory muscles in spinal cord injury

Respiratory complications are the major cause of death for people with spinal cord injuries. People with a high level spinal cord injury are 150 times more likely to die from pneumonia than the general population. This is because after high level spinal cord injury, people have a reduced ability to cough and to clear secretions from the lungs. The major group of muscles that produce a cough are the abdominal muscles. If the abdominal muscles are paralysed after spinal cord injury then the strength of the cough will be severely reduced. In our lab, we are looking at ways to improve cough in people with spinal cord injury by using surface functional electrical stimulation of the abdominal muscles. We have shown that this type of stimulation can improve cough significantly. We are now looking for ways to further improve cough through muscle training as well as ways to develop a portable stimulator that would allow independent activation of a cough.

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Control of coughing and expiratory muscles in spinal cord injury

The effect of respiratory muscle training on respiratory health after spinal cord injury

After cervical spinal cord injury (SCI), the respiratory muscles are partly or completely paralysed. This has two major clinical consequences: a decreased ability to get air into the lungs and a decreased ability to cough and remove secretions. This results in a lifetime of recurrent respiratory tract infections (2/year/person) that often progress to pneumonia with frequent and extended hospital admissions. People with cervical SCI are 150 times more likely to die from respiratory complications than the general population, as many as 28% die within the first year after injury. For those that survive the first year, a cervical SCI has a lifetime cost of $9.5million, a large proportion of which is attributed to respiratory-related complications. A recent longitudinal study of people with cervical SCI showed that respiratory muscle weakness is associated with incidental pneumonia. Respiratory muscle weakness also causes dyspnoea (breathlessness) and sleep-disordered breathing, which is 4-10 times more prevalent in people with SCI than the able-bodied population. Therefore, there is an urgent need to identify a simple and cost-effective treatment for respiratory muscles weakness to prevent respiratory complications after SCI, improve quality of life and reduce the burden on the healthcare system.

Our primary aim is to determine definitively the effectiveness of training on respiratory muscle strength, respiratory physiology and health outcomes. To do this we will conduct a randomised controlled trial 2 times bigger than the largest previous study, of respiratory muscle resistive load training in individuals with acute and chronic cervical SCI. The project will provide critical new knowledge about the efficacy of a simple and inexpensive respiratory muscle training regime, which can be applied immediately in the hospital and community, to minimise respiratory morbidity in people with SCI. This project also provides a unique opportunity to investigate other consequential effects of long-term respiratory muscle training that have never been studied in people with SCI. These include effects on cough efficacy, sleep-disordered breathing, breathlessness, respiratory morbidity, respiratory health and neural drive to the diaphragm, as well as quality of life.

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The effect of respiratory muscle training on respiratory health after spinal cord injury

RESEARCH TEAM

Claire Boswell-Ruys

DR CLAIRE BOSWELL-RUYS Postdoctoral fellow

DR RACHEL MCBAIN Postdoctoral fellow

DR CHAMINDA LEWIS PhD student

PUBLICATIONS

Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after Spinal Cord Injury.

Butler JE, Godfrey S, Thomas CK

Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury.

Zopiclone Increases the Arousal Threshold without Impairing Genioglossus Activity in Obstructive Sleep Apnea.

Carter SG, Berger MS, Carberry JC, Bilston LE, Butler JE, Tong BK, Martins RT, Fisher LP, McKenzie DK, Grunstein RR, Eckert DJ

To determine the effects of the nonbenzodiazepine sedative zopiclone on the threshold to arousal with increasing respiratory effort and genioglossus muscle activity and to examine potential physiological factors mediating disparate effects of zopiclone on obstructive sleep apnea (OSA) severity between patients. In a group of patients with predominantly severe OSA, zopiclone increased the arousal threshold without reducing genioglossus muscle activity or its responsiveness to negative pharyngeal pressure. These properties may be beneficial in some patients with OSA with certain pathophysiological characteristics but may worsen hypoxemia in others.

Time course of human motoneuron recovery after sustained low-level voluntary activity.

Héroux ME, Butler AA, Gandevia SC, Taylor JL, Butler JE

Motoneurons often fire repetitively and for long periods. In sustained voluntary contractions the excitability of motoneurons declines. We provide the first detailed description of the time course of human motoneuron recovery after sustained activity at a constant discharge rate. We recorded the discharge of single motor units (MUs, n = 30) with intramuscular wire electrodes inserted in triceps brachii during weak isometric contractions. Subjects (n = 15) discharged single MUs at a constant frequency (∼10 Hz) with visual feedback for prolonged durations (3-7 min) until rectified surface electromyogram (sEMG) of triceps brachii increased by ∼100%. After a rest of 1-2, 15, 30, 60, 120, or 240 s, subjects briefly resumed the contraction with the target MU at the same discharge rate. Each MU was tested with three to four rest periods. The magnitude of sEMG was increased when contractions were resumed, and the target motoneuron discharged at the test frequency following rest intervals of 2-60 s (P = 0.001-0.038). The increased sEMG indicates that greater excitatory drive was needed to discharge the motoneuron at the test rate. The increase in EMG recovered exponentially with a time constant of 28 s but did not return to baseline even after a rest period of ∼240 s. Thus the decline in motoneuron excitability from a weak contraction takes several minutes to recover fully.

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