restoration of hand and arm by functional neuromuscular ... · neuromuscular applications) nerve...
TRANSCRIPT
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SPARC Workshop
Human Use - Cross-Cutting Technologies – Part II
Kevin L. Kilgore, Ph.D.
MetroHealth Medical CenterLouis Stokes Cleveland VAMC
Case Western Reserve University
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Nerve Block/Modulation• Temporary Block: reversible (within
seconds to minutes) arrest conduction of action potential along a neuron
• Modulation: increase or decrease the excitability of a neuron (or group of neurons)
• These features are particularly relevant to SPARC applications, because down-regulation is often as important as up-regulation (in contrast to most neuromuscular applications)
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Nerve Block/Modulation• Technologies available
• Kilohertz Frequency Alternating Current (KHFAC)
• Direct Current• Infrared (thermal) block• Optogenetics• Magnetic• Others…?
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KHFAC – Brief Tutorial• Illustrates the difficulties that we face in
applying “new” technologies to “not fully characterized” physiology• In contrast to motorneuron->skeletal
muscle• Illustrates the critical need for clinicians
and engineers to work directly together if SPARC initiatives are to be successful
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KHFAC – Back to the friendly confines of the somatic nervous system
Nerve Conduction Block Experimental Setup
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KHFAC Instant Reversibility
Proximal Prox Stim Block Distal Stim Distal
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KHFAC Graded Block
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Sine Wave Amplitude (Vpp)
Blo
ck E
ffec
tiven
ess
(%)
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Block in Sensory NerveAv
erag
ed C
AP
(uV)
30kHz HFAC Block
Time (ms)
8Vpp
6 Vpp
4Vpp
2 Vpp
0 Vpp
10 Vpp
Aβ Aγ Aδ
5uV
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Direct Effect of KHFAC on Neural Structures
• KHFAC can block conduction of action potentials (within 10ms in some cases)
• KHFAC block can be quickly reversible (within 1s)
• Block effect is strongly dependent on amplitude• At block threshold and above, activation always
occurs at startup (“onset response”)• There is a lot of unexplored territory in this field• Neural response to KHFAC is complex• Almost all of the basic work to date is in
myelinated nerves
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Typical stimulation frequency –neural response is simple and very well characterized
Amplitude (Vpp)
subthreshold activation NotSafe
20 Hz Stimulation
Dur
atio
n of
Del
iver
y
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Neural Response at ~5kHz and higher
The neural response to KHFAC is extremely complex.
This map only considers the amplitude-time domain!
Dur
atio
n of
Del
iver
y
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KHFAC Block
• You must know the dose you are delivering– What is the real output of the generator?
• You must know what the KHFAC is doing to the nerve fibers– Activated? Blocked? Nothing? Cooked?
• Requires a methodical approach– See Canning/Kollarik approach – start with the
simplest system possible and work up to the complete in-vivo system
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DC Block with No Onset ResponseWell known in the literature
Blocking Stimulus 50µA Amplitude100 ms
Single Fiber Recording
Mechanostimulator
Petruska, Hubscher, Johnson : Anodally focused polarization of peripheral nerve allows discrimination of myelinated and unmyelinated fiber input to brainstem nuclei. Exp Brain Res 1998.
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Considering Direct Current Nerve Block
CBDC Waveform
The current controlled waveform is a charge-balanced direct current waveform (CBDC) consisting of a cathodic blocking phase followed by a anodic recharge phase.
The total charge delivered was less than the Q value for Pt-Black and IrO2 electrodes. The length of the recharge was selected to return 100% of the charge at a current level of
10% of the cathodic DC.
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Nerve Block and Neuromodulation
• Features Relevant to SPARC• Downregulation of neural activity
• Availability and Human Use Status• KHFAC – human use• Other modalities – animal only
• Areas for Research and Development• Consistent and repeatable block• Chronic safety• Small fiber block (esp. C-fiber)• Targeted block of small fibers
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Nerve Cuff Electrodes• Features Relevant to SPARC
• Generally – activate whole nerve/fascicles• Generally >1mm diameter nerves
• Availability and Human Use Status• 10+ years of human use• Have been used on vagus
• Areas for Research and Development• Target <1mm diameter nerve branches• Activation of specific fibers sizes• Surgical techniques for electrode placement
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Implanted Electrodes in Proximity to Nerve
• Features Relevant to SPARC• Can target nerves of any size• Easy to implant• Poorly controlled selectivity
• Availability and Human Use Status• Widely used in humans and widely
available• Areas for Research and Development
• Usefulness and practicality for targeting small nerve branches
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Optrodes for Neural Activation
• Features Relevant to SPARC• High degree of specificity
• Availability and Human Use Status• Not yet available for human use
• Areas for Research and Development• Use as tool in animal models?• Groundwork for human use (safety,
practical designs)• Possible unique features, such as
activation and block; fiber type selectivity
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Non-invasive Neural Activation
• Features Relevant to SPARC• Non-invasive• Poor specificity
• Availability and Human Use Status• Low threshold for human use
• Areas for Research and Development• Possibility of activating autonomic neural
structures from skin surface
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Sensor Modalities• Blood Pressure/Bladder Pressure• Biomarkers of various sorts• pH• Ions• Cardiac output• Airway resistance• Glucose• More to come…
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Sensor Systems
• Features Relevant to SPARC• Most systems will require regulation to a
mean, not to an extreme• Availability and Human Use Status
• Few have extensive human use• Areas for Research and Development
• Identify important modalities• Chronic efficacy of sensors• Accuracy of sensor data• Incorporation into complete system
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Implant Systems• Stimulators• Stimulator/sensor systems• Modular systems
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Implant Systems
• Features Relevant to SPARC• In many cases, will require stimulation,
block, sensing, and signal processing• Availability and Human Use Status
• Some have extensive human use• Areas for Research and Development
• Identify system requirements• Regulatory requirements
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Cross-Cutting TechnologySummary
• Technologies for Activation• Technologies for Block/Modulation• Sensor Technologies• System Technologies• Signal Processing• Computational Modeling