BPK 448 Midterm 2

What were the benefits for the subject from the first neurostep system?

5 weeks after implant, he no longer needed a knee brace. 10 weeks after implant, his gait had improved markedly. 6 months after implant, he regularly walked the length of his driveway and back (250m) without fatiguing. His balance control was greatly improved. Using Exercise Mode at home proved very useful. The nerve stimulation was never painful, nor unpleasant. He was appreciative of how much using the device had improved his mobility, balance and lifestyle. The battery ran out after 8 months; patient's condition slowly deteriorated again. -8 month long study (battery lasted this long). able to take home. got rid of knee brace in 5 weeks. Able to walk quite well after 10 weeks. after 6 months, walked length of driveway. 250m. to pick up mail and comeback (before couldnt walk more than 5 m). improvement in independence. Didnt need walker after. regained substantially balance control. Exercise mode - used magnet to apply inside of thigh over device, could turn it on if left magnet for 10sec but if left for 30 sec would turn into exercise mode. Foot would go through periodic flexion and extension (2sec on and off for 10 minutes 3x day). Nerve stimulation never painful. Liked to feel it cause knew was working. Problem: battery ran out eventually, requires surgery. Clinical trial didnt have replacement units. had agreement when become commercial would get one free whenever needed. Ended up getting walkaid.

What type of current stimulation is best recommended?

- "Zero Net Charge" is required to minimize electrode corrosion and tissue damage. Charge Balance Phase 2 ~ Phase 1. shape of pulse. big difference between monophasic and charged balanced biphasic (same initial pulse, which gets stimulation to happen, AP generated by 1st of biphasic, then followed by pulse of opposite polarity. Equal and opposite sign current immediately after each stimulation and neutralized charge left in body, important cause if not would just continue inject charge into body. Can be done in several ways) - charge imbalance biphasic - 2nd pulse lower amplitude, some residual charge activation - Charge balance biphasic with delay - delay pulse good for property electrode surfaces balanced biphasic (best) - Sharp breath negative pulse followed by short positive but much longer. Second pulse could cause anodal break excitation. Compensated biphasic - after delay open capacitor to allow it return and charge. Automatic way to reestablish neutrality.

What fibres size has the lowest threshold to electrical stimulation?

- Largest diameter fibers have lowest threshold (first to recruit) In human fibre diameter dont reach 20um. can i cat. Human largest are about 10. typical spectrum of fibres. Alpha motorneurons are largest fibres (afferents largest). Cutaneous group II r large, Pain and temp are a delta group 3 4 small myelinated or unmyelinated (smaller) practical consequence- it is easy to cause muscles to contract or to causes stimulation of larger fibres wihtout cause pain because pain fibres so much smaller and need larger stimulation to cause pain. Can see that pain fibres take 2-10x more current to be recruited. Doesnt mean stimulating through skin may not be painful (could be due to direct recruitment of pain receptors in skin) In people who have had SCI, may not have pain sensation anymore, stimulus may cause burns, need to make sure not happening.

How can functional output (voluntary movement) be augmented after SCI?

- focal functional electrical stimulation

How can residual descending input after SCI be augmented?

- pharmacological agents (clonadine, tizanidine, 5HT) - epidural spinal cord stimulation Residual descending input: - peripheral input: appropriate and inappropriate - Output: function and dysfunctional

How can general output be reduced after SCI?

- pharmacological agents (ex. baclofen, dantrolene) - surgical (ex. anterior rhizotomy, myelotomy)

Explain the physiological generation of Action Potentials. Is it possible to produce this through treatment?

-motor neuron generate AP in response to synaptic input (changes in membrane potential synaptically driven). If sufficient input, excitatory and inhibitory input, membrane potential will grow from resting to reach threshold (10mV) higher. Need to inject sufficient current. Current injection brings up to threshold, changes in gate channels. Opens up Na and K channels to generate AP. Trying to mimic this. If impale cell with microelectrode, will be injury to the cell, Need to mimic what motor neurons used to receive input -Followed by after hyperpolarization - cell is in refractory. Cannot fire again during this time - ionic channels (Na) not able to open again. K too high in concentration intracellularly, need to be kicked out to reestablish balance. Take advantage of this. - slow motor neurons slow at recovery after fire - fast motor neurons - can fire another AP sooner, greater dynamic range (intensity of firing) -direction and amplitude of synaptic inputs matters in bringing cell to fire and also controlling rate fires (how inhibited it is). Graph - small inihibitory inputs, graded with intensity of synaptic input, same with EPSP. EPSP of certain value can. cross threshold and develop AP. If want certain motor neurons not fire - should find a find to generate inhibitory inputs. If want fire need find way to generate excitatory inputs to open channels to start AP. SIgn of current injected will matter.

How can dysfunctional output (spasms) be reduced after SCI?

-peripheral neuroomy - chemical agent - botox - orthopaedic procedures (tenotomy)

What are the steps to applying an external system for foot drop?

1) Clean leg using water 2)Leg straight Find the head of fibula 3)First electrode just under the head of fibula 4)Second electrode over tibialis anterior -because peroneal nerve courses that way. The deep and superficial branches tend to separate around this area. electrode can and needs to recruit both nerve to get balance between inversion and eversion

What are the Physiological Mechanisms of Muscle Force Production and Control?

1. Orderly Recruitment of Motoneurons/Motor Units 2. Motor Unit Firing Rate Modulation -Muscles will contain numbers of motor units (100's) of different types. Individual axons control motor units are intermingled in the muscle. When produce force only some active. Except for maximum effort. 1) Development of force in muscle depends on orderly recruitment of motor units (motor neurons). 2) modulation of intensity with each motor neurons expected to fire - increased or decreased.

Where are the 10 body locations where Functional Electrical Stimulation may be applied?

10 body locations where FES may be applied to restore the use of paralyzed muscles - Skin surface - placing electrode on outside skin stimulate muscle - Intramuscular - introduced fibre wires through skin into muscle (could be permanent inside) - Epimysial - surface of muscle, on top of place where nerve enters muscle, high density nerve fibres associated with one muscle only. - peripheral nerves - collection of fibres that may supply one muscle or many could control multiple muscles - Ventral roots - only place where motor fibres selectively alone - Dorsal roots - opposite of SDR. stimulate dorsal root afferents to cause reflex recruitment of force - Motor nuclei - collections of motor neurons in columns of grey matter. - Spinal pattern generators - generate coordinated movement (ex. walking). stimulate to turn on group of motor neurons in desirable synergies - Deep brain - treat certain motor disorders like PD - Cortex - stimulate cortical neurons, cause output person cannot generate.

What type of system is the neuromuscular assist?

1st partially implanted peroneal nerve stimulator. Developed in 1968-1977 by McNeal, Perry and Waters at Rancho Los Amigos Hospital, CA Used Medtronic hardware. -The Neuromuscular Assist consisted of 3 parts: • external power source and RF transmitter • implanted receiver connected to bipolar electrode wrapped on the peroneal nerve • a heel switch worn inside the shoe. Implanted this device in 16 patients between Nov. 1971 and Jan. 1974 and performed a 2-year follow-up study. • Correction of foot drop was obtained in 13 of 16 subjects. • Failures were due to infection (1), peroneal palsy (1) or discontinued use (1). • Stimulation voltages were stable after 6 weeks and conduction velocity was normal throughout. • Dorsiflexion torque (supramaximal stimulation) remained above immediate post-operative values (Waters, 1977). -neuromuscular assist system - same basic components but electrodes implanted with wireless radio frequency. Heel switch. 2 year followup. Obtained correction of foot drop in 13/16 patients. infection due to surgical implantation. Peroneal palsy - palsy meaning partial paralysis cause by compression of peroneal nerve. stimulation voltages were stable after 6 weeks, CV normal throughout. stable voltages means that size of nerve fibres didnt change (if compressed, then would get smaller and require higher voltage to stimulate). (CV normal - same principle). Dorsiflexion torque with supramaximal stimulation - large enough to recruit every motor fibre, remained about immediate post operative values meaning no decline in force. Force should have gone up overtime with use.

What were the experimental results of STIMuSTEP?

21 STIMuSTEP procedures by 2008 • 18 CVA, 2 MS, 1 TBI • Functional results equivalent to ODFS • But - No skin irritation - More comfortable - More convenient • Aprox. 30 other cases in the Netherlands, France and Spain -21 patients provided by 2008. Functional result equivalent to odstock external system but advantages: no skin irritation, more comfortable, more convenient.

How could electrical stimulation of synergistic motorneuron pools in the spinal cord be beneficial?

3 motor neurons that together cause flexion extension and retraction of limb during walking. distinctly different motor neurons for each function. If way to electrically recruit those could generate entire patterns of motion but needs to be selective.

How can odstock be used for bilateral foot drop?

A single foot switch is used. Weight is taken off the switch: channel 1 is active. Weight returns on the switch: channel 2 is active. A delay added between the channels allows weight transfer for slower walkers. -Single channel system - Patient with bilateral dropped foot but were then having two channel system.(2 one channel systems linked together, single switch) 1 channel stimulated flexors in one leg and other channel other leg, linked timing of stimulation to the two events (heel rise (foot lift) start of flexion phase, and heel strike (signal to turn off stimulation in same leg) used also with delay programmed in to turn on flexors from other lags. Assumption constant speed walking (fixed delay estimated patient would benefit from). Orange extension. green area stimulation on during this time, gradually turned on then maintained then at heel strike, programmed extension. After heel strike, the turn off, leg starting to support weight. Stimulate flexors when going into extension. Period during EMG of gait when both extensor and flexors stimulated at same time, necessary to increase ankle stiffness during heel strike, (if didnt foot would slap the ground) too prevent foot slap ankle continues to be stimulated and to accept weight. Peroneals could be stimulated in both legs with timing

What is the nerve response to extracellular anode stimulation?

Always need to have 2 electordes in contact with body: 1 to inject current the other is to remove it. Closed circuit. Provide source of current and sink (loop flow through area of interest). Anode - locally under electrode hyperpolarization because accumulation outside and more negative inside, but if look to sides (cm's) to stimulation point, places where depolarization, not as much as hyperpolarization, but if current higher, then maybe AP could be generated at those points. transmembrane potential can be depolarization to cause AP. Anodal break excitation. Not common but possible. Try to place anode distant from anything excitable (not near nerves).

How can the odstock 2 channel system be used to treat bilateral foot drop?

Applications of 2 channel system: odstock foot drop system. For people who require more than just dorsiflexion on one foot. Linking activation of both legs out of phase to treat bilateral foot drop

How can appropriate peripheral input be augmented after SCI?

Augment with: - therapy - weight-bearing - transcutaneous stimulation - gait training (weight eliminated treadmill with therapist assistance vs. automated locomotor orthosis therapy)

What are the benefits, risks, and limitations of the partially implanted FES systems?

Benefits: More stable stimulation, Multichannel Risks:Requires surgery, Nerve damage Limitations: Must don/doff, May be inconvenient -partially - risk with surgery to death (some risk of full anesthesia), damage with improper nerve cuff

What are the benefits, risks, and limitations of the fully implanted FES systems?

Benefits: Most stable stimulation, Multichannel, Always ready, Invisible, Comfortable Risks: Requires surgery, Nerve damage Limitations: Battery life, Not commercially available yet -full implanted - more stable, big advantage not to have to strap on (big advantage for people who had stroke. to have something always ready to turn on without having to do anything big advantage. No external parts, more invisible and comfortable. -limitations - 3 devices need to put on and off, pain, discomfort. Fully impalnted - limited battery life, could be solved with rechargeable and connect once a week. May change. Still not commercially available.

What are the benefits, risks, and limitations of the ankle-foot orthosis?

Benefits: non-invasive, low cost Risks: Disuse atrophy, Skin damage, Peroneal palsy Limitations: Must don/doff Pain, discomfort Interferes with plantarflexion -risk of brace - no trivial, more atrophy, muscles not needed or used, skin damaged because of pressure extremes would be peroneal palsy

What are the benefits, risks, and limitations of the external FES systems?

Benefits:Non-invasive, Moderate cost Risks: Skin abrasion, Skin burns Limitations: Must don/doff Pain, discomfort -FES ext - damaged to skin because of electrodes, cuff around legs,

How can odstock help with tradalanberg gait?

Bilateral Gluteal muscles for correction of Trandalanberg Gait Lack of hip extension and abduction, affecting both sides. This causes the hip to drop when weight is taken through it, leading to instability while walking and a noticeable sway. Two switches are used. When weight is on a switch, the gluteal muscle on the same side is activated. -Trandalanberg gait - legs get into each other way because abductors are weak causing the legs to be adducted. Could stumble. Want to turn on gluteal muscles alternatively to improve posture.

How can the odstock system stimulate the calves to help with foot drop?

Calf stimulation provides push off at the end of the stance phase. Two switches are used: under the heel and under the 1st metatarsal head. Calf stimulation starts a short delay after flat foot and continues until the toes leave the ground. Dorsiflexion begins at toe off and ends at heel strike after an extension. -Patient may need stimulation of calf muscles (normally not problem, could be incomplete SCI or MS). 2 switches, one under heel and other under 1st metatarsal head to better determine the timing of heel strike and toe strike to stimulate at right time.

What did the clinical audit of the odstock determine?

Clinical Audit 120 stroke subjects • 9 stopped before 18 weeks - 3 lost to follow up - 2 unable to find electrode positions - 2 non related medical problems - 1 cognitive problems - 1 chose not to use the device -reason why: - unable find electrode position -cognitive, or need help - other had issues, one chose not to use -Stroke n = 111 • Total orthotic effect: Speed 27% increase PCI 31% decrease • Carry-over effect (training): Speed 14% increase PCI 19% decrease • Orthotic effect at 18 weeks: Speed 12% increase PCI15% decrease -with device on. after 18 weeks or more. on average speed went up 27% (enough to say walked faster) physiological cost index decreased substantially. walk faster and longer time (further).Carry over effect some improvement in speed, Having built up muscles with daily use, form of exercise. Patient could do better

How does the odstock improve ability to walk?

Device on each leg. no stimulation- unsteady, worrysome, bracing on walls, almost falls. walking stick, helper comes to help turn around (more prone to falling). Both feet have difficulty but can walk With stimulation - more confident, feet moving straighter, dont wobble as much, not hanging onto walls, turns out much quicker and easier. Improvement, walk faster and longer distances per day -• 6-8 new patients assessed each week - 80% go on to treatment • 5-8 patients start treatment each week • 56 follow-ups a week • 2200 have received treatment - Stoke 54%, MS 25%, SCI 8%, Other 13% - Compliance at 1 year 86% -Assessing 6-8 per week - 80% eligible for treatment (5-8 start each week) then followed up. Compliance - how many patients still using regularly everyday.

What are the different types of motor units used for? How can they be modified?

Different motor unit types are distinguished by mechanical and fatigue properties of muscle fibers (type S, slow; type FR, fast-twitch, fatigue resistant; type FInt, fast-twitch, fatigue intermediate; and type FF motor units, fast- twitch, fatigable) as well as myosin heavy chain (MHC) isoform expression (MHCSlow, MHC2A, MHC2X, MHC2B). -all muscle composed of several motor units types. Slow and fast - differ in myosin heavy chain isoforms. Have different kinetics. Time it takes to produce force and amount of force is different for each Slow type - smallest units, weakest, but will not fatigue. Will be able contribute small force for long time. fast contracting (fatiguing) - produce more force, 100x force compared to slow. Will fatigue in minutes of stimulation. Fatigues because oxygen (source of energy) depletes?. Fast type use glycogen in muscle (red muscle). Local stores of energy depleted when fast fibre types are needed, fatigue cant produce force same rate, take a day to recover. Intermediate muscle fibre types. FR - fast contracting resistant to fatigue (different myosin heavy chains which allow contract quickly but have higher supply oxygen from blood stream, less sources of glycogen). Although all these types genetically determined initially, all are modifiable and respond to exercise. With sustained driving frequencies not used to, can convert from one type to another type. training can favour certain types of fibres, Types S(low frequencies, used to working all the time, need activity or will atrophy) This will happen in paralyzed muscle, atrophy due to disuse, prevent atrophy by activate( reestablish drive to make fire, if fire like used to will rebuild). type f - less dependence on activity because can tolerate alot of activity. Will also atrophy is not used in reversible way. Activity determines viability of muscle fibres. Bone is not loadad - it will weaken

What problem can be posed by using EMG for an interface for a prosthetic?

EMG problem - only as good as remaining muscles that can be recorded from surface of skin. Higher amputation, fewer muscles left more functions required to be replaced. Going to the amputated nerves that supply voluntary action might be able to use to control electronic motors. Intrafascicular electrodes - place electrodes that can record signals.

What are the external functional electrical stimulation systems for foot drop?

External (Skin Surface Stimulation) Systems -A Foot Switch is placed in the shoe to sense and relay the 'Heel Strike' and 'Toe Lift' events -Surface Stimulation Electrodes are placed on the skin, distal to the knee, close to where the peroneal nerve courses subcutaneously. -The foot switch and electrodes are connected to a battery powered External Unit that stimulates the peroneal nerve to flex the ankle during swing. -First implemented in 1961 by Dr. Ted Liberson (1904- 1994), who is considered the Father of FES. -Completely external - electrodes on skin close to target muscles and nerves, Nerves mostly. Charge required to stimulate nerves lower then what needed stimulate muscles directly. Sensor can be foot switch. Foot switch - thin switch that sits under foot (heel), that is compressed when weight applied, switch closed - during that time stance phase, toe lift, weight comes off, switch opens (toe lift). Stimulation electrodes close to peroneal nerve. Battery powered unit size of cell phone hangs off belt or lower near the knee. - currently available devices havent changed much for external systems

What type of system is the Bioness? What is unique about it?

External FES Systems for Foot Drop: Bioness -L300 Foot Drop System has 3 parts that use wireless communication to "talk" to each other. 1. Comfortable, Lightweight Functional Stimulation Cuff The leg cuff is a small, light-weight device that fits just below the knee and contains electrodes which deliver stimulation where it helps you most. Available in two sizes: regular and small (for individuals with calf circumference approximately 12 inches or smaller). 2. Innovative Intelli-Sense Gait Sensor The gait sensor attaches to your shoe and lets the leg cuff know if your heel is on the ground or in the air. 3. Wireless, Portable Control Unit The hand-held remote control lets you adjust the level of stimulation and turn the unit on and off. The controller can be carried in your pocket, bag or purse. -FDA approved in 2006 1,000 sold in 1st year -Company in states developed in israel. Bioness - contemporary with walk aid. First to have wireless foot sensor (in shoes sole sensor). Has remote control. Easier then leaning over and controlling directly. Company sells a few 1000 per year. All using the same basic concepts and components from 50-60 years ago. State of the art with external systems. All include something needs to be directly placed. easier with large cuff because have a notch on front. (could sit on tibia) works well with people who tolerate and able to put on and off. Usually placed near nerves that cause direct activation of that muscle of reflex activation.

What kind of system is the odstock? How has it changed?

External FES Systems for Foot Drop: Odstock -modernized hardware (function the same). Still has same components but eliminated the wire from foot switch to control unit (bluetooth). Show insole includes sensor and radio transmitter that sends signal by meter captured by control unit. Eliminates the wire. Wire is often a problem

What kind of system is the walk aide? What was different about it?

External FES Systems for Foot Drop: WalkAide The stimulation electrodes are attached under the strap of the control unit. A tilt sensor measures angle of the tibia in relation to gravity and starts stimulation. One-piece design allows one-hand application. For incomplete SCI, Stroke, MS patients. FDA approved in 2006. About 1,000 sold in 1st year -15 years earlier. Walkaide - version of device to stimulate externally, but completely eliminated wire and foot switch,. demonstrated by fact can walk barefoot. replaced foot switch by providing sensory feedback from different type of sensor (tilt sensor imbedded in control box - measuring angle of the tibia at all times.) Possible to follow extreme angles in walking to identify times of heel contact and foot lift which are correlated. with the extremes of that angle. Has become commercialized. Have also modernized the looks. This was FDA approved, 1st year sold about 1000 and about more than 1000 per year. Bought by company in states.

What can Functional Electrical Stimulation be used to do?

FES systems can be used to: -restore voluntary control of paralyzed muscles -patterned stimulation of muscle nerves -partially restore sensory-motor integration -afferent nerve stimulation can support force production -provide sensory cues -touch, vision, auditory perceptions -alleviate spasticity -afferent nerve stimulation can modify reflex gain -alleviate chronic pain e.g., with epidural stimulation (neuromodulation) - produce patterned stimulation that replicates what muscle would be doing in normal activation - return some sensation to people with sensory deficits - stimulating not just to maintain viability of muscle

Explain the activity dependent plasticity in muscle fibres.

Fast and slow muscle fibers are used in different ways and there are corresponding differences in the impulse traffic normally carried by their nerves. In early experiments, stimulating the nerve to a fast muscle for several weeks at 10 HZ—a pattern similar to that normally found in the nerves to slow muscles—was found to induce slow contractile characteristics. Salmons believes that aggregate amounts of activity, not the frequency per se, determine fiber type. Sustained high levels of use would induce slow, fatigue-resistant properties. Low or intermittent levels of use would allow fibers to retain, or revert to, a native fast, fatigue- susceptible state. There may be a threshold level of activity, or a series of thresholds triggering change. As successive thresholds are crossed, plastic changes occur in sequence. - plastic changes muscle undergo due to level of activity 3 thresholds: measure of total amount of stimulation per day, not dependent on pattern, but on how many AP motor neuron fire per day. Threshold 1 converts muscle fibres anaerobic to aerobic (F to s). threshold change myosin from 2x to 2a. threshold 3 convert all fibres to type 1 (2a to 1). 2a are ideal (fast but non fatiguing).

How does distance of stimulation affect threshold to nerve AP firing?

Fibers located closer to a stimulating electrode have lower thresholds. - how relatively far are target nerve fibres from electrode. Large nerve trunk, when stimulating from some distance may not catch fibres same way. Ones closer to electrode may be easier recruited. Range of responses. 4:15 - Go further away fibres require more current to be excited. threshold increases with distance

What type of device is neurostep?

Fully Implanted FES System -First pacemaker-like device All components were implanted in the thigh First to meet the acceptance criteria of Waters (1977) Designed and tested by Neurostream Technologies Spinoff company from the SFU Neurokinesiology Lab -could be basis for implanted full loop system. Features: 1st device completely implanted, includes control unit built by pacemaker company but with 2 nerve cuffs. implanted all components in thigh. Used 2 nerve cuffs. one to stimulate peroneal nerve only. then had 2nd nerve cuff to record from tibial nerve (info from sole of foot). both cuffs above the knee. -Pacemaker-like, fully implanted foot drop correction device. -All its components are inside the thigh. Requires no external parts. Includes a multi-channel stimulation cuff on the peroneal nerve and a nerve activity sensing cuff on the tibial nerve. Meets the criteria of Waters (1977). Developed in 2000-03 by Neurostream Technologies, a SFU spin-off company. First Pilot Feasibility Study patient was implanted in 2003 in Vancouver. -Two 30-mm NeurocuffsTM connected to the CP and Tibial nerves • Standard pacemaker primary battery and titanium encapsulation. • Circuitry includes proprietary amplifiers and a gait phase detection algorithm. -Implantable nerve signal sensing and stimulation device and method for treating foot drop and other neurological disorders. -did first pilot study in patient at SFU. patient had stroke years earlier. Use of nerve cuffs to record nerve activity in behaving animal or person, not available. -Neurocuff - nerve interface -Neurolink - implantable ASIC amplifier -innovations - advanced nerve cuffs, system that patented to close and surgeon friendly. interlocking members like piano hinge. monofilament suture surgeon pass through to close it. Cuff would not open. Important not to open or have gapping because EMG signals could contaminate recording inside). Chip amplifiers - implantable with necessary properties to record nerve signals of 10 uV -Piano-Hinge Closure System - Easy opening and secure closing, Thin flexible walls - laser fabrication - Modular 4-channel design -Nerve cuff built with laser and flat but flexible. We built it with 4 sets of pairs of wires. each pair of wires 2 exposed in centre, other exposed at both ends. Have balanced tripolar system ideal to record nerve signals. 4 channels that go around the nerve when closed . Little tubes that arise and separate channels. Only thing that touches nerve.

Who is Otto Bock?

Fully Implanted FES System: Neurostep Developed by Neurostream Technologies in 2001-2004 Neurostream was acquired by Victhom Human Bionics in 2004 -Otto Bock HealthCare acquired Victhom and Neurostream in 2011 -victhom did clincal trials (more extensive) then company acquired by ottobock (same company that bought actigait). bought both to control the market. intend to combine the 2. Used actigait external control and neurostep cuffs. -The Neurostep system underwent clinical trials in Vancouver, Quebec, India and UK. First subject implanted Dec 10, 2007 in Vancouver. Victhom received CE-mark approval in Feb. 2009 to sell the Neurostep System in Europe. -enter through posterior thigh, separate the hamstring, nerve cuff around the closing element. the lead from 2 cuffs connect onto control unit. Only thing changed, header (type of connector, made longer by putting 2 batteries in it). Signal travels up tibial nerve, sensed then at right time in step cycle toe off start stimulating. Actigait ankle flexors muscles step by step.

Is the H-reflex useful in treatment of atrophied muscles?

H reflex - ex. tibial nerve with gastroc. popliteal fossa, deliver electrical stimulation, cathode and reference somewhere else. Turning current up. First thing, afferent fibres (largest) recruited electrically, conduct APs in both direction, sensory nerve going to be conducting AP centrally towards cord. Group Ia fibres synchronously activated and come around and synapse onto motor neurons. Nice large EPSP sufficient to generate AP, synaptically in motonereuron (alpha - agonist, small) but loop delay because time take AP travel up cord across synapse and down. Shown as H-reflex. For low enough current, thats all that happens. If increase current, Hreflex will increase because more motor neruons will participate as increase more now will be Mwave (earlier because some motor neurons directly excited, and because distance shorter. Largest motorneruons, first ones to participate in Mwave (electrically easiest to recruit). As turn up current more and more, recruit motor neurons from both ends. Hreflex recruits smaller, Mwave recruits more starting with larger. Happens until Mwave takes over Hreflex, When crank up current, Mwave will have priority because AP travelling through muscle and antidromic AP travelling centrally, use up capacity of axon to transmit AP during the refractory preiod. By the time H-reflex come around they start not being able get through because some motor neurons blocked by being stimulated directly, As turn up M wave uses up all motor neurons With electrical stimulation of low intensity is a way to produce physiologically some force via the hreflex. If recruiting motor neurons synaptically around loop. As turn up intensity, will recruit directly. Range of values recruiting some motor neurons synaptically and some directly. Clinical applications to restore physiological function in muscles

How can odstock hamstring stimulation enhance foot drop cases?

Hamstring stimulation starts after a delay following heel strike and is ended by heel rise. An extension is added to take the stimulation through to mid swing. The hamstring activity is used to inhibit quadriceps tone, enabling greater knee flexion. Alternatively, hamstrings are used to discourage knee hyperextension at heel strike. To do this, the hamstrings are stimulated at or just before heel strike -patient would need to have hamstring stimulated in same leg. Reason: sometime to inhibit excessive quadriceps activation at the knee when the legs needs to be flexed during swing phase. After heel rise. Or to discourage knee hyper extension at heel strike. (can happen in patients who dont have sufficient strength in hamstring and overpowering strength in quads. Hyper extension causes leg to bend forward more than normal, painful, makes it difficult to walk and place heel). Time when stimulation occur: programmed delay at heel strike to start stimulate, stimulation would start at late stance phase to early swing phase (appropriate time for hamstring to be on)

What is the relationship between soma size of motor neurons and threshold to firing?

In order to produce force - 5 motor units out of the pool were followed. 1 -starts firing very early even before forces has arrived much. During increase effort increases then plateaus, last one to quit (typical of Type s. little motor unit , soma size small) SS 2 - comes in later, ramps up frequency then quits. FR 3 & 4 - recruit and derecruit in orderly way. FR 5 - highest threshold, only few AP then force to quit. FF - Smallest came first (threshold lowest meaning easiest to recruit), FF have much higher threshold

What will increasing stimulation into a motorneuron lead to?

Increasing current in a motoneuron above its threshold (recruitment) generates progressively increasing firing frequency (rate modulation). Bottom trace: current injected into motoneuron via a microelectrode. Middle trace: firing response of the cell, with the inset illustrating that the afterhyperpolarization (AHP) determines the time of occurrence of each action potential (spike). Upper panel: instantaneous firing rate for spikes in the middle panel. The relation between frequency and current is approximately linear. -With progressive increases in synaptic current injected directly into motor neuron, frequency of firing will ramp up proportional to the current. As depolarization becomes more sustained, motor neuron will be able to fire quicker. still only about 25/second. Rate at which fires can be modulated by intensity of current injected. Simple transducer. Brain drives harder, large synaptic currents to cause currents to cause higher firing.

What types of information did researchers look at in developing fully implanted systems?

Looked at information that cutaneous sensory nerve can carry about touch. Showed that when push on toe pad, holds then lets go, indentation and force and nerve signal that develops and immediately detects changes. Remains high during application of force then drops back. Raw electrode neurogram rectified and filter get a DC signal. Natural sensor that detects change in loading of the foot. Could be possible to used as second set of data. If apply larger forces causing larger indentations there is a response to each increment, asymetrical cause nerve sensors are asymetric but works over large range of forces. -Natural Sensors that may Detect Footlift and Footfall -based on that information. Implanted nerve cuffs in forelimb and hind limb in cats and able to record from median nerve, ulnar nerve and radial nerve for different times. Permanently implanted nerve cuffs. After cat recovered, able to record treadmill walking. (animals trained prior to implanttaion).

What were the 5 interfaces that were tested for use in neuromuscular FES control? Which one was successful?

Motor unit, neurogram, myogram, force, length Study: looked at signal from 5 different methods considered to provide permanent signals in pedal animal. Force trace given by implanted force transducer. Spring steal metal clip placed around a tendon (patellar ligament), force along tendon cause resistive elements to change resistance and given replication of force produced. Length - given by implanted gauge. Silicon elastic tubing filled with saline (conductor) and electrode at each end with sealed end. As length gauge stretched, distance between electrode increase, diameter decreases, resistance pathway increased. Increased with stretch, decreased with shortening. Motor unit - fine electrode placed permanently implanted in ventral root. Devices implanted in surgery. week later recording taken. Which of these experimental tools could become clinical to implanted people, ex. amputees, people require access to control signals. Compared properties all 5 then decided only 1 could be trusted to give stable consistent results for long time. Others would not last for long. The best choice was the neurogram because the ENG is small signal (few uV) Once place cuff around nerve, if nerve survives, cuff designed not to harm nerve. Once on will never drift, and signal will get better over 1st 3 months, increases resistance, and it will not decay further. Recording was stable overtime. EMG trying to record from moving muscles, wires inside muscle tend to break, drift, or be encapsulated (signal get smaller) distance between electrodes and fibres increase. Force - tendons dont like to have something forcing it to bend a bit. Tendon remodels all the time, signal over force transducer would be stable for few weeks then start to get smaller. Tendon remodelled around transducers, create new fibres growing around transducer, load was taken up by fibres that bypassed sensor, did not give reliable reading after few months. Mechanical devices screwed to bone creating tension. Fatigue and break. Nerve cuff considered to be one with promise.

What were the clinical results of the neurostep system?

Movement Produced with CP Nerve Stimulation - Combined stimulation of Channels 1 + 3 produced best foot dorsiflexion -could demonstrate that ankle could be dorsiflexed considerably. but now could lift the ankle. Force could be generated was initially low for first 3 weeks. as muscle built up with use (exercise) it would start developing more force which eventually reached levels for walking. -CP Nerve Stimulation: Increased Dorsiflexion Force -With application of NeurostepTM stimulation, disuse atrophy in the paralyzed muscles was reversed and ankle dorsiflexor force increased -CP Nerve Stimulation: Improved Fatigue Resistance -With application of NeurostepTM stimulation, fatigue resistance in the ankle dorsiflexors also improved markedly during the 2nd month. -how long it took for force to drop to 70% of the initial force. (seconds). initially 0 seconds. 2nd stimulation already less than 70% cause so fatiguable. after a month could be sustained for minute then minute and quarter with repeated stimulation. good level of resistance and fatigue. -monitoring pressure/force on both feet. Monitoring 8 or 9 steps. See that left leg (implanted leg). electroneurogram from tibial nerve cuff. If can see that rid of noise - dominant feature is gently rolling up and down. Able to filter information and control unit pulled out reliable timing information of heel contact and foot lift. Right foot force (underneath foot) non paralyzed. patient not walking symmetrically. spent more time on right foot. Double support for much time. Favouring the right foot (unparalyzed leg) but able to support it day 21. (early). Patient underwent exercise program (3 week). -10 weeks after patient was walking regularly and symmetrically (almost normal) no walker or people. cane to support. Without foot drop.

How did the walk aide assist a PD patient?

Multiple sclerosis subject without and with WalkAide FES -WalkAide Off Note foot drop, Circumduction, hip hiking. -WalkAide On Increased speed,improved symmetry, decreased effort. -Patient walking with walk aid. Walking around figure 8. Without aid can seen patient can walk but with difficulty and using the walking aid cart. With stimulation: patient walking fairly symmetrically, feet are moving parallel.

What is the orderly recruitment of motor unit?

NS controls all different types and engages which needed. Most typically with rare exceptions, the motor units in given muscle will be recruited in order of size and type. As requirement for more effort increases, % of motor units increase and type of units. All slow type I recruited (30% all fibres in muscle, some muscles have higher proportion) Force produced may be max of 15%. Then Type IIa recruited and only when needed Type IIx recruited - How does NS do it? - motor units intermingled - must be intrinsic property of each neuron that decides when it should fire to certain drive. Size of the Soma decides this. Small cells have largest electrical resistance - more volume more path for current to flow

What is the closed loop control of functional electrical stimulation?

Need sensors to monitor events during each step. - Sensed information is fed back to a control unit that detects the 'Heel Strike' and 'Toe Lift' events. -The control unit provides electrical stimulation in synchrony with the detected gait events. -This form of control is generally described as an event-triggered state machine' for walking -Has to be linked to some feature of gait that is monitoring and controlling timing of stimulation (closed loop). Need for one or more sensors that are watching for certain features during walking. Features: Start and end of each step: heel strike and toe lift, stance from swing phase. Control unit that is listening to sensory feedback from sensor indicating when events happening. Computer programmed deliver stimulation at certain times, after toe lift and before heel stroke. Could add timers to shift things with respect to actual time, but need to know when events happen (person might stop walking, stimulation could cause fall). State machine - simple device that has limited number of states (stimulate, dont stimulate, sleep, exercise mode (to build muscles)). State machine event triggered - heel strike and toe lift change the state of the machine, Change state from stimulating to not stimulating. General control strategies that are used in systems, need sensors and feature detection and control that stimulate sometime and not others. Machines will differ in components.

What can neuroprotheses do? How does it do it?

Neuroprosthetic systems can assist, augment, restore or replace functions that are lost or diminished because of injuries or diseases of the nervous system restore voluntary use of paralyzed skeletal muscles replace sensory modalities (touch, vision, hearing) restore sensory-motor integration (reflex pathways) alleviate chronic pain (gate control theory) modulate central pathways (neuromodulation) The principle of operation is delivery of controlled electrical stimulation to surviving motor pathways, sensory pathways and/or nuclei, in the PNS or the CNS -systems that generally use electricity to assist, or augment but if necessary restore or replace functions that are severely impaired or missing. - neuromodulation - assist, augment, or modify defective systems such as autonomic that can improve life. - finding out where to stimulate function and how to do it. Not many options: either central nuclei (not individual neurons), nuclei's that have a role or pathways (central or peripheral, motor or sensory)

What are the objectives of functional electrical stimulation for foot drop?

Objectives Activate the ankle flexor muscles that lift the foot as appropriate to enable walking. (Orthotic Effect) - Increase force and endurance in disused muscles. -Assist with activation of hip and knee flexor muscles -Help reduce extensor muscle spasticity. -Enable people with hemiplegia to walk with a more balanced, symmetric, energy efficient and faster gait. (Therapeutic Effect)

Explain Open Loop control of movement with Functional Electrical Stimulation. What is the problem with it? And the reason its a problem?

Open loop - signal decision to move now sent to command interface (control box), control system, electronic stimulator, electrodes to paralyzed muscle to cause contraction (movement) Problem: not guaranteed movement that want. Muscle notoriously nonlinear in behaviour - Problem: It is more difficult to achieve than it may sound. Reason: Muscle behaviour is complex; non-linear; velocity dependent; activation history-dependent. - refractory, stimulus rate, fusion of twitches, force of movement, activity history dependent. continuously fatiguing.

Why is positioning of the electrodes for the emetic FES external device important?

POSITIONING OF ELECTRODES AND THEIR INFLUENCE ON THE GAIT To obtain an optimal result, it is often necessary to adjust the positioning of the electrodes. It is important: - that the stimulation results in a straight lift of the foot, and - that after each step only the heel touches down first (not the whole foot, or part of it). -Incorrect positions of electrodes: If the ankle joint turns in, only the outer side of the foot touches the ground during walking. The result is an unsteady gait. The upper electrode should be moved a bit further out on the side of the leg. If the ankle joint turns out, only the inner side of the foot touches the ground during walking. The ankle joint is unnecessarily strained and the result is an unsteady gait. -Need to play around to avoid marked inversion or eversion because walking would be unsteady. Peroneal nerve carries nerves that supply inversion and eversion and forward motion, Shifting electrodes can catch different fibres. Tibialis anterior needs to be balance with inverters

What kind of system is Actigait?

Partially Implanted FES Systems: ActiGait -otto bock largest vendor powered prosthetic limbs. Device difference: common peroneal nerve stimulation above rather than below the knee just after branches of sciatic. (tibial and peroneal branch of sciatic above knee). able to place everything above the knee and used wire sensor from the heel contact. Awarded CE mark in 2006. Implanted over 20 then (clinical). -Otto Bock Healthcare purchased Neurodan in March 2005. ActiGait was awarded the CE mark in September 2006. Over 20 have been implanted to date. -hangs from belt. digital display. nerve cuff. transmitter outside and antenna inside body connect to nerve cuff. problems they had: nerve cuffs were too large for nerve - poor consistency in stimulation over time. Had to replace nerve cuff in several patients

What type of system is STIMuSTEP? How did it help a patient with a prior CVA 5 years ago?

Partially Implanted FES Systems: STIMuSTEP -commercial version of partially implanted system. location of implanted receiver inside under skin, lead wires running to two locations in 2 nerves. Stimulating 2 branches, deep and superficial of peroneal. Reason: to separately catch inversion and eversion components together with flexion. Control box placed so that it communicate with implant. This version had foot switch with wire connecting. -Device - communication antenna with 2 lead wires with dagger like electrode. Each electrode placed inside epinerium. so it stayed in nerve itself. tag provided sutured somewhere to keep from sliding out. Each dagger portion had 2 electrodes closely spaced. Need 2 electrode to sitmulale (source and sink). -Patient with device - placing external component, wire could catch on things. Walking confidently indoor or outdoor. Patient had CV event, using stimustep.

Which component of GAIT is used to power the bionic power harvester? Why is this machine beneficial? When does power generation increase?

Power goes into propelling the body during walking (extensors). Lots of power to stop forward motion of leg (hamstring in end swing phase). Power on knee joint quite considerable (watts). If could attach generated mounted on knee brace, could absorb energy and stop motion and generate electricity. -Generating lots of power (12 watt average). More downhill, less uphill. Brace on each leg (sum of both). Attached to thigh and lower leg. Gear embedded outside. Allows soldiers who carry a lot of electronics to not take so many batteries, avoided if soldiers could generate electricity used to recharge batteries -• Automatically adapts to terrain • 12 W generation level ground • 25 W generation downhill • 6 W generation uphill • Low profile gearbox • Integrated generator • Lightweight carbon fibre (900 g) • Sealed construction • Improved mobility • Foldable for transport • Integrated knee pad -Different power generations in different inclines and declines. Generating more power downhill

What are the problems with spastic hemiplegic walking?

Problems • Weakness • Slow, laborious, asymmetric, energy costly • Dropped foot stumbles • Poor balance • Worse in uneven terrain -How can we stabilize ankle so doesnt stumble and how do we help propel with less effort (energy costly). Need to hitch leg up by lifting on other leg then circumflexing at the hip to throw the leg forward (energy cossly)

What is the difference between the bipolar and monopolar electrode configuration?

Quasi monopolar - place 4 different electrode for 4 different channels. flexors and extensors of thigh and single return (ground) electrode so current flow out - 2 channel - current flow from source to sink, cathode to anode - volume of tissue stimulated 4-channel - current flows ground, could have unwanted stimulation somewhere else. may not be as selective. Closely spaced bipolar

What are the advantages of the Multi-Chambered Nerve Cuff - Long-term dynamics of the neurostep system?

Reason for ridges: patent provided an intimate seal with nerve without compressing the nerve. If cuff same size as nerve wouldnt allow the nerve to swell (which needs to happen after surgery). If nerve swells during next days, there is room for expansion (edema will be present). Nerve can fill up extra space, after edema recedes, nerve goes back to approximate size and permanentlly encapsulate in thin layer of connective tissue plus fluid. Provided a good seal (wanted good seal because activity neurons in region going to be seen by electrodes seen in one chamber compared to other distal chambers. (proximity) this seal would make reduce crosstalk between channels. if nerve sitting loosely, all channels would see the same thing). Good results. - day of implant - snug fit - 1 week later - edema - 6-12 months later - encapsulation - Improved Stimulation Selectivity - Improved Sensory Recording Selectivity -each channel can record from different subpopulation

How can inappropriate peripheral input be reduced after SCI?

Reduce with: - elimination of nociceptive stimuli - cooling/ischemia - dorsal rhizotomy - peripheral neurotomy - tendon lengthening

What are the Mechanics of ankle-foot orthoses (AFO)?

Rigid AFO Circumferential AFO Conventional AFO Ground Reaction AFO Hinged Ground Reaction AFO Patellar Tendon Bearing Orthosis (PTB Orthosis) Hinged AFO -Orthodic devices have improved: first was rigid, some hinged (allow plantarflexion for push off), ground reaction AFO - allows to stand more comfortably by leaning forward, leg taken up by front edge of orthoses, can unload extensor muscles (saves energies), Patellar tendon bearing orthoses - weihgt transferred more directly when necessary.

Explain the amplifier technology of the neurostep system.

SUB-μV NOISE AMPLIFIER TECHNOLOGY Gain @ 2.2 kHz = 91 dB Neurocuff TM Bandpass (- 6 dB) = 850-6000 Hz - nerve interface Input noise < 0.7 V rms. CMRR @ 250 Hz > 85 dB Power consumption < 12 mW @ 5V 2 x 2 mm ASIC -amplifier had to meet demanding criteria; amplifier has to resolve very tiny signals, Have intrinsic noise. Could have no more then 0.7 average noise because signal less then 10. Wanted signal to noise ratio to be decent. Also to not consumed alot of power. Limited at 12 mW. Battery driven by internally implanted device. Good quality sound amplification have a lot of power and transmitters. Fine if going to plug into wall. Big battery that can power can get away from implantable.

What were the results of the neurostep feasibility study?

Study approved by Health Canada and five research institutions. • Carried out in Vancouver, Jun 2003 to Feb 2004. • Subject was a 70 yr old male, 3 yr post-stroke with foot drop and severe hypotonia. • Managed with a knee brace in addition to AFO. • Could only walk 5-10 m without fatiguing. • Required a cane and contact guard assistance -patient had stroke 3 years earlier, foot drop severe hypotonia, knee hyperextension (painful). destabilized his walking. wearing knee brace to limit hyperextension. hated the brace. Before implantation, had the subject walking 10m. could only walk 5 m before fatigued and had to sit down. not able to walk well. with the help of wife or cane. -SURGICAL IMPLANTATION OF NEUROSTEP SYSTEM -A single 6-cm longitudinal incision in the posterior thigh was required. - The Common Peroneal (CP) and Tibial nerves were cleared over 6 cm -implanted cuff on common peroneal and tibial nerves above the knee (2 separate). had to place appropriate sized cuffs. ruler placed around each nerve to measure circumference then 7 different sizes to match. -SURGICAL IMPLANTATION OF NEUROCUFFS - Nerve circumferences were measured using a flexible silicone ruler. -Appropriately sized Neurocuffs were selected. -sealing the cuff - monofilament passed through closed filaments, mm left outside -The Neurocuff closing suture was sealed with a cautery tip. - The nerves were protected with a Teflon® heat shield strip. -teflon under nerve to protect tissue, approximated tip of cautery. touching tip would melt it and cause it to ball up and close. Surgical innovation. Device itself placed under skin -SURGICAL IMPLANTATION OF NEUROSTEP DEVICE -The Neurocuff lead cables were connected to the Neurostep Control Unit. The unit was placed in a subcutaneous pocket in the medial thigh and the incision was closed. The Neurostep was turned On or Off with a telemetry programming interface, or a magnet -control unit placed inside inner thigh under skin. could communicate with remote control. programmer to turn on or off.

What is the Odstock external system for functional electrical stimulation?

The Odstock Dropped Foot Stimulator ODFSIII -On/off switch, volume control, exercise model on box. Foot switch (full sized foot insole), electrodes directly adhered on skin, need to be right cause need to peel off. Need to do daily because would fall off if didnt. -target muscle and its nerve and skin. Active electrode more proximal, indifferent electrode more distal. Electric field lines converge onto other electrode. Charge density reach certain value for recruitment. 1 msec pulses, 20-50 mamps. Enough current to reach nerve cm under skin. Generate 20-50 V -20-50 mA x 1 ms pulses into 1 KOhm => 20-50 V

How can quadricep stimulation by odstock assist foot drop?

The quadriceps are stimulated throughout the stance phase to allow weight bearing. Dorsiflexion occurs in the swing phase -Weak quadriceps patient (ex. MS, incomplete SCI, (both foot drop and weak quads)) needs quads to support weight. Stimulate at the right time during stance phase

How Does Electrical Stimulation Differ from Exercise?

The recruitment order of motor units means that exercise effects are restricted to a population of fibers that is employed only infrequently under resting conditions but becomes active under exercise conditions. Changes in these fibers tend to be diluted at the whole muscle level by fibers whose activity is essentially unchanged. In contrast, electrical stimulation overrides the physiological recruitment order and can activate all the fibers in the muscle simultaneously. In addition, electrical stimulation can be applied continuously, 24 h a day, whereas exercise regimes are necessarily milder and more intermittent. For both reasons, the effects of stimulation are greater than those of voluntary endurance exercise. The effects of withdrawing activity are readily demonstrated. Human muscles have a heterogeneous fiber type composition, but the inactive muscles of individuals who have suffered a spinal cord injury become predominantly or exclusively fast - exercise is ideal in that it recruits motor units in natural order, not gonna change nature but gonna strengthen, electrical stimulate top down (from largest) easiest access to largest which toughest to voluntarily recruit. beneficial because gives way to bypass difficulty of recruiting things. Electrical stimulation can be applied continuously, exercise cant continuous because fatigue. Electrical will eventually cause fatigue. more efficient stimulate electrically (more per day). When withdrawal activity, all motor units go back to undifferentiated atrophied fast type

What size of pulse widths are recommended for electrical stimulation?

The threshold charge (amplitude x pulse width) injected into the tissue increases with the pulse width. To minimize charge injection, shorter pulses are recommended. Shorter excitation pulses are safer because they cause • less electrode corrosion and • less tissue damage. - Choice betwen short and long duration pulses. If can get away with shorter pulse width, charge need to pass is less (less corrosion of electrode - passing charge through electrode in contact with salty skin, metal in contact with electrolyte and current going through will cause it to dissolve. Copper one of best conductor but toxic. Silver too but toxic) Better electrodes are the noble metals (gold platinum. Very expensive, but safest). Damage to electrode and damage to tissue. to minimize damage, minimize pulse (0-200 better width range)

What are the two types of neuromuscular stimulation available for foot drop treatment?

Therapeutic Electrical Stimulation (TES) • Reverses disuse atrophy in paralyzed muscles Helps strengthen muscles, bones, circulation Requires intact lower motor neurons and muscles Functional Electrical Stimulation (FES) • Enables voluntary performance of motor activities through graded recruitment of paralyzed muscles • Requires intact lower motor neurons and muscles -to activate muscles weak or paralyzed and restore use of muscles at right times. requires application of therapeutic electrical stimulation. Maybe be no strength at all but potential to build up muscle again. over weeks, build up muscles strength. Requires flexors motoneurons that supply dorsiflexors still intact, if there compression neuropathy of peroneal nerve, prevents being able to do this. -therapeutic and Functional - difference is how used. same device produces electricity may be used, one is used for exercise others is for timed activation of muscles. Need to be set up that muscles stimulated when needed to pick up foot during swing phase. Need to be as automatic as possible.

What does electrical therapy require?

Therapeutic Electrical Stimulation (TES) of a paralyzed muscle REQUIRES: 1. intact motor innervation of the muscle - Need to make sure target muscles remains innervated. if muscle denervated will degenerate severely. Going to be very diminished, dont have nerve to stimulate. Stimulate the muscle directly. takes huge stimulation which may burn skin. Denervated muscle takes large current and long pulses. Normally want to stimulate motor axons. Want muscle to remain innervated (not paralyzed) paralyzed cause descending control disconnected.

What can therapeutic electrical stimulation on paralyzed muscles achieve?

Therapeutic Electrical Stimulation (TES) of paralyzed muscles can: • Prevent muscle atrophy or rescue disused atrophied muscles Increase muscle mass Increase muscle force Increase resistance to fatigue • Facilitate voluntary movement • Moderate spasticity • Increase blood flow, reduce edema, remove metabolic waste • Reduce pain, fibrous tissue growth, adhesions - prevent stimulation to what normally experience or if muscle already allowed to get to disuse atrophy, could reverse and rescue muscle from disuse state. Increase muscle mass, increase muscle force, increase resistance to fatigue. other things accomplished: person with weakness and incomplete paresis, strengthen muscle may allow enough strength to control muscle. Muscle that weak and spastic benefit from electrical stimulation, feedback loop re-established that make more normal. this effect will last longer 4:39 - increases blood flow (muscle pumping and demand for blood increasing), edema reduced (edema usually develops in lower limbs in bed ridden because large muscles in leg part of venous return system, pump venous blood back without contraction blood will pool and also lymph.) Removal of metabolic waste - reduce pain (pain can be associate with immobility, improper loading of joints, fibrosus tissue grow and attach adhere muscle not moving)

Hoes does the control of movement compensate for unpredictable muscle output?

To Compensate for Unpredictable Muscle Output, Control of Movement Mechanisms Include Sensory Feedback - invested in large number of receptors monitoring what happening. Sensors monitoring movements (inside muscles, skin surface). sensor activity feeds back to body both locally (reflex loops) brain and SC constantly adjust loop based on result of movement Central Feedback loop - Sensors take information from the movement and relay information back into the motor cortex (decision to move) and to the spinal cord Peripheral Feedback Loop - Sensors take information from the movement and relay information back into the spinal cord which modulates motor neuron pools, peripheral nerves, and the muscles to cause contraction

Does Functional Electrical Stimulation use sensory feedback for unpredictable muscle output?

To Compensate for Unpredictable Muscle Output, FES Control Mechanisms also Include Sensory Feedback - FES want the same - using sensory monitoring, sensors have power to inform control system and change. May inform person. Want to re-establish peripheral and central feedback that facilitate output. Central Feedback loop - Sensors feedback onto decision to move (command interface) and control circuitry Peripheral Feedback Loop - Sensors feedback onto control circuitry to multichannel stimulator and electrodes, peripheral nerves or muscles and then onto paralyzed muscles

What was the effect of constant frequency stimulation?

To determine long term consequences of continuous stimulation at different low frequencies, Salmons studied the response of rabbit fast muscles to 10, 5, and 2.5 HZ delivered for 10 months. There was a gradation in response to these patterns. After 10 months, muscle mass, maximum shortening velocity, maximum isometric tension, and power had all declined less at the lower frequencies than at 10 Hz. Continuous stimulation at 10 HZ transformed the myosin isoform composition completely from the fast to the slow pattern. 10/s x 60s/min x 60min/hr x 24 hr/day = 892,800 stimuli/day Even after 10 months of stimulation, however, the 2.5-HZ pattern had brought about only a partial transformation, with a disappearance of MHC2X, predominance of MHC2A, and slight induction of MHC1. At 5 HZ the results varied between one animal and another, resembling the 2.5-HZ response in some cases, and the 10-HZ response in others. - 3 different frequencies of stimulation 10, 5, 2.5 Hz. Rabbit tib. ant. Results were 2.5 Hz was the one that 2a predominated. 10Hz difficult to provide per day - The incomplete transformation seen at 2.5 HZ was similar to that seen after shorter periods of stimulation at 10 HZ. This suggests that the aggregate amount of activity is more important than the frequency. The variable response at 5 HZ is exactly what would be expected if this stimulation pattern placed the muscle close to the threshold for fast-to-slow transformation. Muscles stimulated at 2.5 HZ received least aggregate activity, but showed the highest levels of both oxidative and glycolytic activity. Muscles subjected to continuous stimulation at 10 HZ responded in a biphasic manner, an initial increase in oxidative activity being followed by a decline (shown in both mitochondrial volume and enzyme activity). - 2.5 Hz most parsimonious - least sitmulus with most benefit.

How can odstock be used to treat foot drop and weak gluteals?

To extend the hip, gluteal muscles are stimulated through the stance phase. To increase abduction, one electrode can be placed over the gluteus medialis. -treatment for weak gluteals. Dedicate 2nd channel during stance phase to stimulate. Ipsilateral in same leg in leg with foot drop

How can odstock stimulation of the triceps assist with gait?

Triceps is stimulated in the swing phase to reduce "associated reactions" while walking. -2nd channel to stimulate triceps and posterior deltiod on same side in order to promote swinging of the arm. (arm usually paralyzed on same side leg paralyzed). Promote natural swinging to maintain balance, conserve angular momentum and make walking more normal. Families of way to provide more function to patients individually prescribed. 2 channel system make possible to help them.

What is the response of extracellular nerve cathodal stimulation?

What happens along axon when current source is brought in proximity to one node along axon. See that (cathodic stimulation) relative depolarization of membrane under electrode but then hyperpolarizing some distance away in each direction (cm's). Accumulation of negative charge outside membrane and accumulation positive charge cause inside membrane negative. Amount of depolarization achieved going to be different for fibres of different diameter. Larger diameter more depolarization then smaller. Resistance of axon less for larger (easier for current to flow) and surface area larger, capacitive properties different. All combines to make easier to depolarization membrane with external source for large axons than smaller.

How does muscle length affect the H-reflex?

When length of muscle changes. When muscles change length: fibre change length , capacity produce force changes, sensitivity of spindles changes. Stimulation spindles electrically, length doesnt matter. - Lengthening muscle weaker Hreflex - could be that spindles firing because muscle being stretched. less available for spindle activation. refractory more of the time. H reflex may collide or occluded by many spindle afferents because afferent just fired. Passive isometric (□, ▪), shortening (○, •), and lengthening (Δ, Δ) recruitment curves of M wave and H reflex, normalized with corresponding maximal M wave, at angular velocity of 60°/s, for soleus of 1 subject, whose data best represent group data.

What are the key points between physiological and electrical recruitment of nerve fibres?

When the motoneurons in a pool are physiologically recruited, the SMALLER neurons tend to be recruited FIRST. When external electrical stimulation is applied to a nerve, the LARGEST axons tend to be recruited FIRST. This contradicts the "size principle" of orderly recruitment. HOWEVER... In paralyzed muscles, this anomaly may be unimportant, because disuse causes atrophy and conversion into fast-type motor units Thereafter, exercising paralyzed muscles with electrical stimulation can convert fast-type fibers into slow-type, thus rebuilding force capacity and increasing fatigue resistance (when compared to disused, atrophied, fast-fatiguing paralyzed muscle) - First motor units to be stimulated are the largest which are the hardest to voluntarily recruit. (good for athletes) Using electrical stimulation to rebuild or reuse muscles that has been affected by injury. Now need to think about what happen to motor units in long run. - Once a muscle no longer activated normally (paralyzed) going to quickly atrophy massively (disuse) only because not being used. Nothing wrong with it. If muscle paralyzed not activatied within 6 weeks, motor fibre types convert from slow type to fast type. (default) immature fast type motor units (same as fetus). Only through pattern activation some units will gain identity of slow type. Low frequency stimulation everyday of low frequency. To become slow type requires molecular change. Myosin chagnes from fast type to slow type. All four types present are expressed as function of activational pattern. Pattern changes cause of paralysis, all revert to fast type. Going to be fast type and incredibly weak fast type, same time lost mass and degeneration in muscle fibres. By the time person paralyzed, within few weeks all slow type convert away. Now have to train muscle to become something, opportunity to train toward slow type by imparting slow type pattern. Gained: stimulation over weeks (more than 6 weeks), can restore capacity of muscle to resist fatigue, main objective. Condition the muscle to be fatigue resistant again.

Explain the pros and cons of ankle foot orthosis as a treatment for drop foot.

ankle-foot orthosis (AFO) -AFO Pros Allows toe clearance for walking, Non-invasive, Inexpensive -AFO Cons Uncomfortable - can be heavy, hot Interferes with plantarflexion Promotes muscle disuse atrophy Metabolic cost is still high Is not always available Requires donning & doffing Cosmetically objectionable Can cause skin pressure sores Can cause peroneal nerve palsy -Orthosis - brace on ankle that can have many shapes. Objective is to lift foot and hold at angle that gonna be easier to clear the ground when swinging. Advantages: does the job, non-invasive (external device), fairly inexpensive. Disadvantages: uncomfortable , painful, because clamps ankle, impairs ability to propel (plantarflexion), but not cant push against ground, more energy costly, promotes disuse atrophy of flexors (further), metabolic cost higher (lift and throw leg plus something heavy hanging on end of it, not always available when need (middle of night), Can cause injuries because clamped onto leg (pressure sores where attached, nerve compression damage, peroneal nerve (lateral and distal to knee where top part clamps down), Person who has had CNS disorder could have lost sensation and not able to tell there is damage to skin or nerve

How does resistance affect which neuron will fire first?

both have large dendritic trees. Extended together. Dendrites extend past each other. Common synaptic drive. Soma size is large. Soma input resistance is low for large cell. Small cell resistance is high. If you have synaptic current delivered similarly to all motor neurons, voltage change proportional to synaptic current times the resistance of that cell. Resistance of small cell larger - more difficult current flow through. EPSP produced by current will be large in small motor neuron and small in large motor neuron. Therefore in order to make large motor neuron fire take larger current to reach its threshold. EPSP small change in large cell because injected current has lots of places to flow out. Small motor neruon - current more impactful with any patch of membrane causing large EPSP. Threshold to generate AP high for large neuron and low for small neruons because easier EPSP of sufficient size generate in smaller motor nueron Cannot replicate this because cant inject current the way CNS does

How does The Motoneuron's Firing Rate Controls the Motor Unit's Force Output?

calcium then needs to be taken away. Development of tension can be reestablished by another AP arriving and create another event. Calcium movement creates fusion in slow like muscle fibre that generates. Generation of force reaches peak then take twice as long. - If another AP arrives before 1st depleted - summation of force. Does not have time go back to 0. Rate stimulated cannot be higher then 3-4 per second because start seeing fusion. 20 sufficient summation. 30 and higher fusion and greater increasing forces but eventually calcium. saturated so force equals maximum. - nonlinear response - frequency of firing follows linear fashion, - Stimulus rates below 20 pps result in unfused force profile, while rates above 30 pps provide near titanic forces - very little force regulations available between 30 and 70 pps

What is the emetic external functional electrical stimulation system?

device requires regulatory approvals, country needs to approve it. Permission needs to be obtained. Clinical trials need to be done. 2 velcro straps carrying electrodes: source and sink, cathode and anode. connected to control unit , battery, foot switch (fits under heel), wire running out of shoe to side of leg, wires running to electrodes. Now wireless. Wires could catch on things when walking. Devices have to be placed correctly so electrodes in right place or else wont work right -Used daily by over 3500 patients in Denmark. Commercially available in Europe (AT, CH, DE, DK, NL) -The Footlifter consists of a small electronic unit (50x62x20 mm, weight 75 g), a heel switch and two stimulation electrodes. -OPERATING INSTRUCTIONS The Control Unit and surface electrodes are attached to two Velcro straps. The felt cushions of the electrodes must be moistened with saline solution. -Electrodes attached to cushions moistened with saline for good electrical contact. Can dry up. Current flow not the same, doesnt work quite right -The heel switch is placed in a heel cushion with the cable along the inside of the leg. -The heel cushion is placed inside the shoe with the cable along the inside of the leg. -Another heel cushion (without a heel switch) is placed in the other shoe to prevent uneven back strain. -The control switch is set for automatic cyclic stimulation. The stimulation amplitude is slowly increased until the foot is lifted. Foot motion must be as straight as possible since incorrect pulling of the ankle joint may result in swelling and pain. Incorrect movements can be adjusted by moving the black electrode to either side. -amplitude turn up until foot starts to lift, need to make sure foot lifts straight forward rather than lateral or medial. Ankle can be adjusted by moving to either side.

How was full implantation tested in cats?

distinct burst of activity. and EMG to compare. Can see that stance and swing phase obviously defined by EMG. but also in nerve signal (mainly sensory) can also see modulation of activity. Can see that at start there is a burst in the median (On and OFF response). can count timing of nerve signal to follow the step cycle. In order to see if can use in closed loop and control signal to apply electrical stimulation . Did experiment where transiently blocked activity of median nerve (extensor nerve of wrist). When blocked median nerve by injecting lidocaine (1 hour) during walking the heel would yield. Paw would collapse not being able to extend. Situation where cat limping for hour cause couldnt support wrist activity. Electrodes in palmaris longus - stimulation to cause wrist to extend. -Closed the loop, recording EMG from radial and median nerves. Would identify the time of foot contact and foot lift from EMG. used as feedback signal to control output and predict from those records when palmaris longus should be on then stimulated the muscle during those times. When did that - cat walked almost normally again

What are the neuromuscular interfaces for prosthesis control?

double amputee - could be farming or electrical accident. Severe burns can lead to amputations. Having some remnant musculature allowed fitting prosthetic arm driven by EMG. Voluntary activation from muscles can be used to drive movement. Cable driven prosthetic - cable around body, moving back can cause arm to move. Operating one joint at a time.

How can Excitation of Nerve Fibers using Extracellular Stimulation occur?

how do we generate an AP part way through an axon. Introduce nearby source of voltage or current nearby or change field nearby. Done with stimulator. ex. handheld unit (2 electrodes) 1 cathode (source of current injected somehow in body inside or outside on skin and reaches target axons, because excess ions flowing it will relatively depolarize membrane, if strong enough will cause new AP. Electrode somehow able to support current and will start AP in both directions - electrical stimulation usually causes bidirectional generation of action potentials

What is the relationship between strength and duration of electrical stimulation?

how to deliver stimulation: to stimulate nerves or muscles dont use DC (constant voltage). Nerve fibre cant follow change that step and hold, needs a brief change (rapid change then reverses). DC can get single AP then not able to generate more, Need AC (series of AP like stimuli, EPSP like), each pulse needs to be quite brief. Current that pulse of brief duration has to be in order to stimulate another fibre varies inversely to duration because area of pulse (duration * amplitude) is what matters (measure of charge injected) Hyperbolic function - any values on this curve work to stimulate nerve. ex. 100ms duration and small, or could be half duration and twice amplitude, or longer duration and less amplitude). Takes time to build up transfer in charge. Exponentially reaches value. Does mean that ultimately pulse that too brief doesnt get enough time for charge to build up cause shut down too quickly. Asymptote is basically DC. Meaning is pulse that has twice the amplitude of the asymptote (one that has long duration). rheobase current value that pulse of infinite duration would have (asymptote) (fixed parameter. - (chronaxie) twice the rheobase value is the pulse amplitude of pulse whos duration Factors affecting the rheobase value for a muscle include: electrode position on skin, skin resistance, subcutaneous fat layer, edema, denervation/renervation 3:58.

What is needed for motor units to change which type is firing?

intrinsic properties of motor neurons - linear relationship between synaptic current and frequency motor neuron generates response. FR require more current to fire start firing at higher frequency, respond with higher dynamic range. After all recruited need to drive synaptic current to higher values. Reason recruited in orderly way - as you drive up synaptic current, synaptic drive sent to all motor neurons, larger wont reach threshold until much higher (determines when start participating) - descending input distributed to dendritic trees form synapse with every motor neurons in pools - by the time recruiting all fibres, smoothly forms sigmoidal S type shape. Saturates when all unit producing all force can. Explains why when we want to produce certain force under normal conditions we can. depends on fact that motor units contribution are a change of types that come in to take over when others are saturated. Type s only produce a little then other take over

What are the limitations to electrical stimulation?

limitations: SCI - functional parts above, disabled parts of body that need to try and re-engage in way person can control. take stimulator 2 channels 2 electrode per channel , calf and thigh can be stimulated separated for thigh, provide control so person can generate.

What are the different types of muscle fibres?

main types motor units - 1 and 2. 1 is oxidative, 2 glycolytic, 2a resistance to fatigue 2b and 2x fatiguing. 2a ideal because larger faster and resists fatigue. How do we try to convert muscles to 2a with electrical stimulation - Type 1 Slow-twitch Non-fatigable Oxidative Small size, force First to recruit - Type 2 Fast-twitch Fast-fatiguing Glycolytic Large size, force Last to recruit Type 2A, Type 2B, Type 2X - In human muscles the fiber types are comingled. They can be distinguished at a microscopic level by using histochemical or immunohistochemical techniques that show differences in the content of metabolic enzymes, the pH lability of myofibrillar ATPase, or antibodies specific to particular protein isoforms. The classification scheme is based on variation in myosin heavy chains (MHC). The isoforms present are MHC1, 2A, 2X and 2B. This scheme is reasonably robust and reflects corresponding differences in the fiber contractile speeds. The contractile speed of a muscle is closely allied to its function. It governs the power of a contraction: Power = Force x Shortening Velocity Fast twitch contractile speed is needed in activities such as rapid breathing during sprinting, or coughing. It calls for rapid delivery of energy from available stores, provided through anaerobic pathways. Brief bursts of intense activity must be interspersed with quiescent periods, needed to replenish energy reserves. A slow time course of twitch contraction and relaxation is better suited to low-level use, such as quiet breathing. Tension can be maintained with less frequent activation than would be required of a fast muscle. The rate of utilization of chemical energy is low enough to be supported by oxidative metabolism. Slowness eliminates the requirement for short-term energy reserves and recovery periods needed to replenish them. Type 1 fibers are slow-contracting and fatigue-resistant. Type 2A fibers are fast-contracting and fatigue-resistant. Type 2B and 2X fibers are fast-contracting and susceptible to fatigue.

How did electrical stimulation improve resistance in atrophied muscles?

measures of endurance. interested in increasing force and endurance. Stimulating common peroneal nerve for ankle dorsiflexion. Stimulate for 2 sec followed by 2 sec no stimulation followed by stimulation for 3.5 minutes. Measure of endurance derived from amplitude of force at end of 3.5 minutes in last spindles compared to force when muscle fresh. Considerable decline in force due to repetitive stimulation. Demonstrated that progressively decline in force from first to last stimulus (40% of original value) but with progressive stimulation 45 minute stimulation daily during 6 weeks, improvement fatigue resistant 60%. 8 hours a daily got endurance to 80%. similar to normal conditions. - Endurance index, the fraction of force that is still being generated after 3.5 min of intermittent stimulation, increased progressively in subjects that received increasing durations of daily intermittent stimulation. - Looked at what ideal way to stimulate. How many minutes per day. first 6 weeks only 15 minutes per day. At 6 weeks switched to 45 minutes per day the 2 hours, then 8 hours. At 8 hours got to perform like normal muscle. to maintain reduced to 45min per day, began to see some decline. Some stimulation per day will still be needed. but not only was force improved but resistant to fatigue improved

What is the difference between tonic and phasic to respiratory motorneurons?

motor units types normally receive very different types of physiological drive. Respiratory muscles there cant be both tonic and phasic motor neurons. can see that respiratory tonic neurons always active but modulated, increases during inspiration. Phasic only fire at beginning of inspiration. Try to provide something similar to what motor neuron used to if paralyzed

Can an AP be initiated at different points in an axon?

normally motor neurons generate AP at axon hillock. Passive electronic arrival of EPSP, AP generate travels down axon. leaves behind refractory area. Releases neurotransmitters. Doesnt mean AP only fire at axon hillock. Can happen at other points in axon in resting neuron. If happens at different point in axon it will propagate in either direction, Except in region that refractory.

Explain the effect of therapeutic electrical stimulation on atrophied quads.

showed that electrical stimulation to quads for 6 weeks at 25 pulses per second daily could double the maximal torque at knee within 6 weeks. Sometimes more than double. Quite a consistent finding with atrophied muscles

Explain the path of normal movement control from the decision to move.

somewhere in mind decision to move message sent to motor cortex passes to every level eventually muscle contract cause movement. - Decision to move - Motor Cortex - Spinal Cord Nuclei - Motorneuron pools - Peripheral Nerves - Muscles - Movement

Explain the 4-channel stimulation electrode neurocuff.

there is a centre electrode through which stimulate. then stimulation proved in middle two end electrodes source for current flow, could be used for recording and stimulation (dual purpose)

What is the traditional way to control prosthetic limbs? What are the neuromuscular interfaces for FES control?

traditional way to control prosthetic limb is body power. For decades has been capacity to use EMG signals to control degrees of freedom provided by prosthetic limb Interfaces: Ventral root microelectrodes ENG nerve cuff electrodes intrafascicular electrodes EMG

Is calcium important to force generation?

transduction involved calcium to activate ATP and cause conformational change in crossbridges, increases attachment, and generation of force. Stimulus reach membrane (neuromuscular synapse) causes membrane potential change in muscle. Starts very soon but takes time to develop, remains ongoing causing a release of calcium, event not very fast, takes some milliseconds. Eventually availability of calcium intracellular allow crossbridges form, actin myosin slide past each other and produce force, Can take up to 100ms (slow and 20-30ms (fast)/

What neuron size is better excited through external nerve stimulation?

with electrical recruitment, with larger cross-sectional area , resistane lower, AP threshold lower for large neuron (more exctiable) hen both experience same current flow.

What is the pathology of hemiplegia: foot drop?

• A consequence of a brain lesion, such as after a stroke, traumatic brain injury, multiple sclerosis, or cerebral palsy. • Motor cortex output connections to the spinal cord are disrupted. • The ankle dorsiflexor muscles are paralyzed and cannot lift the foot. • Disused shin muscles undergo atrophy. • Hip and knee flexor muscles are weak. • Spasticity develops in extensor muscles. • Contractures limit ankle range of motion. Need to generate power for standing and walking. How does disability affect this?. Hemiplegia - complete or not complete (substantially) in one side (leg). Because of stroke, CP, traumatic brain injury, MS (could be reversed, episodic) others are permanent. Most effected are ankle dorsiflexors and all flexors in leg. extensors might still be under voluntary control but spastic, effort of dorsiflexion even greater because extensors resisting. Disuse atrophy of flexors (hip and knee too). Contractures are common.

What was the limitations of neuromuscular assist?

• Dr. Waters, one of the original developers of the NMA system, reported the following limitations with the device (1977): • Intact cognition and patient motivation were required to wear and operate the equipment on a daily basis, and • It was difficult to obtain balanced dorsiflexion with a single channel of stimulation. • Dr. Waters predicted in 1977 that broad acceptance of a foot drop correction system would require a fully implanted system as was the case for the heart pacemaker. • He anticipated that multi-channel peroneal stimulation would be necessary in order to obtain more balanced dorsiflexion. • In the following 30 years, several commercial FES devices for foot drop became available but none met these criteria. -2 things required: intact cognition and patient motivation. Difficult to obtained balanced dorsiflexion with single channel stimulation. Also true with external system. With implanted electrode cant move around. Single channel system difficult cause foot would move out cause tib ant domination. Predicted that broadd acceptance of corrective footdrop system would require full implantation. Fully implanted - patient doesnt have to be able to place external component. Multichannel stimulation would be necessary in order to balance the motion

What does a partially implanted functional electrical stimulation system work?

• Stimulation Electrodes are permanently implanted near, inside, or around the peroneal nerve to provide greater stimulation stability. • The Sensor remains external. - EitheraFootSwitch,or - anInclinometerthatmeasuresshankangle. • The foot switch and electrodes are connected to a battery powered External Unit • The External Unit communicates transcutaneously via RF to activate the peroneal nerve implanted electrodes. -partially implanted refers to where the control unit and battery are whether internally or externally. Stimulation electrodes permanently implanted - more secure stimulation cause electrodes in right place no need to reposition, when electrodes inside, the amount of current needing to be delivered to target nerve is much less and stimulation much more precise with fewer side effects (ex. surface stimulation unwanted effect - can produce pain and sores, or discomfort (pin and needles)) When permanently implant electrodes do not cause pain. Stimulate large nerve fibres directly before stimulate small nerve fibres that carry pain information. Sensor is outside the body (foot switch or inclinometer or tilt sensor). The battery is outside. Radio frequency wireless communication used to transmit control signals to electrodes inside the body

Give a summary of the effects of electrical stimulation.

• The response to long-term stimulation of skeletal muscle is evidence of an adaptive capacity that enables it to modify its properties to suit the type of work demanded of it. • The impulse activity delivered by the motor nerve is a major determinant of adult fiber type composition. • The myosin heavy chain transitions from 2B to 2X to 2A to 1 are governed by a series of threshold levels of activity. The MHC2A-to-1 transition is particularly important because of its profound effect on the contractile speed of the muscle, and therefore the power available. • The effects of long-term electrical stimulation are similar to those of endurance exercise, but they are more profound, because stimulation bypasses volitional limitations and the physiological recruitment order. • It makes little difference whether a given pattern of increased impulse activity is delivered in a single session or divided over more than one session during the day. The changes are, however, completely reversible; both after cessation of stimulation and under conditions of disuse the muscle reverts to a native, fast state. • The long-term influence of stimulation on muscle phenotype depends primarily on the aggregate number of impulses delivered, not on the frequency. However, a pattern consisting of high-frequency bursts will elicit a higher mean force, and this elevates protein synthesis. A muscle subjected to such pattern will have greater mass and cross-sectional area and develop greater force than a muscle subjected to an equivalent continuous low-frequency pulse train. • A limit of 40,000 impulses per day, however delivered, is the suggested maximum if Type 2A characteristics are to be retained.