Reprogramming the Nervous System through a Wearable Neurostimulation Device
Lead Research Organisation:
Newcastle University
Department Name: Institute of Neuroscience
Abstract
Brain cells communicate with each other via connections called synapses. The strength of these connections changes as the brain learns, or as circuits are rewired to allow recovery after injury. We now know that an important factor in remodelling synapses is the timing of activity. When a synapse is active at the same time as the cell it connects to, this connection is strengthened.
Over the last ten years, neuroscientists have shown that certain brain circuits can be remodelled by delivering pairs of stimuli at the correct time ? an example would be a magnetic stimulus to the motor cortex, paired with electrical stimulation of a nerve in the arm. However, this work has all been done in a laboratory setting. Changes in synapses are often only short-lived, because the stimuli are only applied for a short time.
In this project, we will develop a novel electronic device capable of delivering precisely timed stimuli. It will also be capable of measuring activity in muscle, and limb movement, so that stimuli can be timed relative to the naturally-occurring activity of the nervous system. This device will be miniaturised and wearable, allowing it to work continually as the subject carries out their normal daily activities. We expect that this will lead to long term changes in neural connections.
We will initially test the device in healthy subjects. We will attempt to rewire connections in the spinal cord believed to be important in reducing tremor, and connections in the motor cortex which may constrain our ability to activate muscles independently. Once we have developed effective paradigms, we will then test them in patients. Initially, we will target people with pathological tremor, focal task-specific dystonias and stroke. In tremor, we predict that it will be possible to reduce tremor amplitude, thereby partially alleviating the severe disability which pathological tremor can produce. In stroke and dystonias, we hope to reduce abnormal co-activation of different muscles controlling the upper limb; this would allow patients to carry out activities of daily living more independently. If successful, this approach could open up a new range of therapeutic options for a wide range of neurological disease.
Over the last ten years, neuroscientists have shown that certain brain circuits can be remodelled by delivering pairs of stimuli at the correct time ? an example would be a magnetic stimulus to the motor cortex, paired with electrical stimulation of a nerve in the arm. However, this work has all been done in a laboratory setting. Changes in synapses are often only short-lived, because the stimuli are only applied for a short time.
In this project, we will develop a novel electronic device capable of delivering precisely timed stimuli. It will also be capable of measuring activity in muscle, and limb movement, so that stimuli can be timed relative to the naturally-occurring activity of the nervous system. This device will be miniaturised and wearable, allowing it to work continually as the subject carries out their normal daily activities. We expect that this will lead to long term changes in neural connections.
We will initially test the device in healthy subjects. We will attempt to rewire connections in the spinal cord believed to be important in reducing tremor, and connections in the motor cortex which may constrain our ability to activate muscles independently. Once we have developed effective paradigms, we will then test them in patients. Initially, we will target people with pathological tremor, focal task-specific dystonias and stroke. In tremor, we predict that it will be possible to reduce tremor amplitude, thereby partially alleviating the severe disability which pathological tremor can produce. In stroke and dystonias, we hope to reduce abnormal co-activation of different muscles controlling the upper limb; this would allow patients to carry out activities of daily living more independently. If successful, this approach could open up a new range of therapeutic options for a wide range of neurological disease.
Technical Summary
Recent work has shown that precisely timed stimulation of the central and peripheral nervous system can produce long lasting changes in neural connectivity. However, such experiments are carried out in a laboratory setting, with stimuli given for only brief periods. Additionally, stimuli are usually timed only relative to other stimuli. In this application, we seek to test a new paradigm for the generation of plastic changes. We will firstly modify an existing design for an autonomous implanted circuit (the ?Neurochip?, developed by A. Jackson) to make it appropriate for use as a wearable device in human subjects. The device will record muscle activity or limb acceleration and deliver non-invasive stimuli, with timing that can be flexibly reconfigured for different uses. We will then test the potential of this device to modify neural connections in a variety of neurological conditions in human subjects.
We have recently obtained data in monkey showing that spinal circuits are important in reducing the amplitude of physiological tremor. We will use the wearable Neurochip to give afferent inputs, timed relative to tremor oscillations measured via accelerometry. The phase of stimulation will be chosen based on our monkey data, as most likely to lead to Hebbian-like strengthening of synaptic pathways and an enhancement of the ability of the spinal circuitry to reduce tremor. This stimulation will be given continually over several days whilst subjects go about their usual activities. We predict that tremor amplitude will be reduced over this time, and that the changes will outlast the stimulation period. If successful, we will then test whether similar approaches can reduce pathological tremor in patients.
Focal task-specific dystonias occur when patients make abnormal patterns of muscle co-activation associated with a specific task. We will test whether the wearable Neurochip is capable of improving the fractionated control of hand muscles in normal subjects. Effective paradigms will then be applied to patients with dystonias; success will be measured by a reduction in aberrant co-activation, as well as on clinical measures of disease severity.
Following stroke, patients often experience impaired upper limb control, which includes co-contraction similar to the focal dystonias. We will also test the ability of the wearable Neurochip to improve rehabilitation in these patients.
We have recently obtained data in monkey showing that spinal circuits are important in reducing the amplitude of physiological tremor. We will use the wearable Neurochip to give afferent inputs, timed relative to tremor oscillations measured via accelerometry. The phase of stimulation will be chosen based on our monkey data, as most likely to lead to Hebbian-like strengthening of synaptic pathways and an enhancement of the ability of the spinal circuitry to reduce tremor. This stimulation will be given continually over several days whilst subjects go about their usual activities. We predict that tremor amplitude will be reduced over this time, and that the changes will outlast the stimulation period. If successful, we will then test whether similar approaches can reduce pathological tremor in patients.
Focal task-specific dystonias occur when patients make abnormal patterns of muscle co-activation associated with a specific task. We will test whether the wearable Neurochip is capable of improving the fractionated control of hand muscles in normal subjects. Effective paradigms will then be applied to patients with dystonias; success will be measured by a reduction in aberrant co-activation, as well as on clinical measures of disease severity.
Following stroke, patients often experience impaired upper limb control, which includes co-contraction similar to the focal dystonias. We will also test the ability of the wearable Neurochip to improve rehabilitation in these patients.
