Jonathan A. Norton

Changes in sensory-evoked synaptic activation of motoneurons after spinal cord injury in man

Following spinal cord injury (SCI), prolonged muscle spasms are readily triggered by brief sensory stimuli. Animal and indirect human studies have shown that a substantial portion of the depolarization of motoneurons during a muscle spasm comes from the activation of persistent inward currents (PICs). The brief (single pulse) sensory stimuli that trigger the PICs and muscle spasms in chronically spinalized animals evoke excitatory post-synaptic potentials (EPSPs) that are broadened to more than 500 ms, the duration of depolarization required to activate a PIC in the motoneuron. Thus, in humans, we investigated if post-synaptic potentials (PSPs) evoked from brief (<20 ms) sensory stimulation are changed after SCI and if they are broadened to > or =500 ms to more readily activate motoneuron PICs and muscle spasms. To estimate both the shape and duration of PSPs in human subjects we used peristimulus frequencygrams (PSFs), which are plots of the instantaneous firing frequency of tonically active single motor units that are time-locked to the occurrence of the sensory stimulus. PSFs in response to cutaneomuscular stimulation of the medial arch or toe of the foot, a sensory stimulus that readily triggers muscle spasms, were compared between non-injured control subjects and in spastic subjects with chronic (>1 year), incomplete SCI. In non-injured controls, a single shock or brief (<20 ms) train of cutaneomuscular stimulation produced PSFs consisting of a 300 ms increase in firing rate above baseline with an interposed period of reduced firing. Parallel intracellular experiments in motoneurons of adult rats revealed that a 300 ms EPSP with a fast intervening inhibitory PSP (IPSP) reproduced the PSF recorded in non-injured subjects. In contrast, the same brief sensory stimulation in subjects with chronic SCI produced PSFs of comparatively long duration (1200 ms) with no evidence for IPSP activation, as reflected by a lack of reduced firing rates after the onset of the PSF. Thus, unlike non-injured controls, the motoneurons of subjects with chronic SCI are activated by very long periods of pure depolarization from brief sensory activation. It is likely that these second-long EPSPs securely recruit slowly activating PICs in motoneurons that are known to mediate, in large part, the many seconds-long activation of motoneurons during involuntary muscle spasms.

Changes in Locomotor Muscle Activity After Treadmill Training in Subjects With Incomplete Spinal Cord Injury

Intensive treadmill training after incomplete spinal cord injury can improve functional walking abilities. To determine the changes in muscle activation patterns that are associated with improvements in walking, we measured the electromyography (EMG) of leg muscles in 17 individuals with incomplete spinal cord injury during similar walking conditions both before and after training. Specific differences were observed between subjects that eventually gained functional improvements in overground walking (responders), compared with subjects where treadmill training was ineffective (nonresponders). Although both groups developed a more regular and less clonic EMG pattern on the treadmill, it was only the tibialis anterior and hamstring muscles in the responders that displayed increases in EMG activation. Likewise, only the responders demonstrated decreases in burst duration and cocontraction of proximal (hamstrings and quadriceps) muscle activity. Surprisingly, the proximal muscle activity in the responders, unlike nonresponders, was three- to fourfold greater than that in uninjured control subjects walking at similar speeds and level of body weight support, suggesting that the ability to modify muscle activation patterns after injury may predict the ability of subjects to further compensate in response to motor training. In summary, increases in the amount and decreases in the duration of EMG activity of specific muscles are associated with functional recovery of walking skills after treadmill training in subjects that are able to modify muscle activity patterns following incomplete spinal cord injury.

Locomotor-Related Networks in the Lumbosacral Enlargement of the Adult Spinal Cat: Activation Through Intraspinal Microstimulation

It is commonly accepted that locomotor-related neuronal circuitry resides in the lumbosacral spinal cord. Pharmacological agents, epidural electrical stimulation, and sensory stimulation can be used to activate these intrinsic networks in in vitro neonatal rat and in vivo cat preparations. In this study, we investigated the use of low-level tonic intraspinal microstimulation (ISMS) as a means of activating spinal locomotor networks in adult cats with complete spinal transections. Trains of low-amplitude electrical pulses were delivered to the spinal cord via groups of fine microwires implanted in the ventral horns of the lumbosacral enlargement. In contrast to published reports, tonic ISMS applied through microwires in the caudal regions of the lumbosacral enlargement (L7-S1) was more effective in eliciting alternating movements in the hindlimbs than stimulation in the rostral regions. Possible mechanisms of action of tonic ISMS include depolarization of locally oscillating networks in the lumbosacral cord, backfiring of primary afferents, or activation of propriospinal neurons

Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence

Intermuscular coherence analysis can be used to assess the common drive to muscles. Coherence in the β‐frequency band (15–35 Hz) is thought to arise from common cortical sources. Intermuscular coherence analysis is a potentially attractive tool for the investigation of motor cortical excitability changes because it is non‐invasive and can be done relatively quickly. We carried out this study to test the hypothesis that intermuscular coherence analysis was able to detect cortical excitability changes in healthy subjects following transcranial direct current stimulation (tDCS). tDCS has been shown to increase (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle potential evoked by TMS. We found that anodal tDCS caused an increase in motor evoked potential (MEP) size that was paralleled by an increase in β‐band intermuscular coherence. Similarly, the reduction in MEP size produced by cathodal tDCS was paralleled by a reduction in β‐band intermuscular coherence, while sham stimulation did not result in any change in either MEP amplitude or β‐band intermuscular coherence. The similar pattern of change observed for MEP and intermuscular coherence may indicate similar mechanisms of action, although this cannot be assumed without further investigation. These changes do suggest that at least some of the action of tDCS is on cortical networks, and that combined tDCS and intermuscular coherence analysis may be useful in the diagnosis of pathologies affecting motor cortical excitability.

Volitional Muscle Strength in the Legs Predicts Changes in Walking Speed Following Locomotor Training in People With Chronic Spinal Cord Injury

Background It is unclear which individuals with incomplete spinal cord injury best respond to body-weight–supported treadmill training. Objective The purpose of this study was to determine the factors that predict whether a person with motor incomplete spinal cord injury will respond to body-weight–supported treadmill training. Design This was a prognostic study with a one-group pretest-posttest design. Methods Demographic, clinical, and electrophysiological measurements taken prior to training were examined to determine which measures best predicted improvements in walking speed in 19 individuals with chronic (>7 months postinjury), motor-incomplete spinal cord injuries (ASIA Impairment Scale categories C and D, levels C1–L1). Results Two initial measures correlated significantly with improvements in walking speed: (1) the ability to volitionally contract a muscle, as measured by the lower-extremity manual muscle test (LE MMT) (r=.72), and (2) the peak locomotor electromyographic (EMG) amplitude in the legs (r=.56). None of the demographics (time since injury, age, body mass index) were significantly related to improvements in walking speed, nor was the clinical measure of balance (Berg Balance Scale). Further analysis of LE MMT scores showed 4 key muscle groups were significantly related to improvements in walking speed: knee extensors, knee flexors, ankle plantar flexors, and hip abductors (r=.82). Prediction using the summed MMT scores from those muscles and peak EMG amplitude in a multivariable regression indicated that peak locomotor EMG amplitude did not add significantly to the prediction provided by the LE MMT alone. Change in total LE MMT scores from the beginning to the end of training was not correlated with a change in walking speed over the same period. Limitations The sample size was limited, so the results should be considered exploratory. Conclusions The results suggest that preserved muscle strength in the legs after incomplete spinal cord injury, as measured by MMT, allows for improvements in walking speed induced by locomotor training.

Afferent inputs to mid- and lower-lumbar spinal segments are necessary for stepping in spinal cats

Afferent inputs are known to modulate the activity of locomotor central pattern generators, but their role in the generation of locomotor patterns remains uncertain. This study sought to investigate the importance of afferent input for producing bilateral, coordinated hindlimb stepping in adult cats. Following complete spinal transection, animals were trained to step on the moving belt of a treadmill until proficient, weight‐bearing stepping of the hindlimbs was established. Selective dorsal rhizotomies of roots reaching various segments of the lumbosacral enlargement were then conducted, and hindlimb stepping capacity was reassessed. Depending on the deafferented lumbosacral segments, stepping was either abolished or unaffected. Deafferentation of mid‐lumbar (L3/L4) or lower‐lumbar (L5‐S1) segments abolished locomotion. Locomotor capacity in these animals could not be restored with the administration of serotonergic or adrenergic agonists. Deafferentation of L3, L6, or S1 had mild effects on locomotion. This suggested that critical afferent inputs pertaining to hip position (mid‐lumbar) and limb loading (lower‐lumbar) play an important role in the generation of locomotor patterns after spinal cord injury.

Electromyography in Children's Laryngeal Mobility Disorders: A Proposed Grading System

OBJECTIVES To describe a consecutive series of children with laryngeal mobility disorders assessed by laryngeal electromyography (LEMG), to propose a grading system for LEMG findings, and to determine whether the LEMG grades correlate with requirement for tracheostomy. DESIGN Retrospective, observational, uncontrolled study. SETTING A single pediatric otolaryngology practice. PATIENTS Children who had LEMG performed and a minimum follow-up of 3 months. MAIN OUTCOME MEASURES Demographic characteristics, diagnoses, surgical procedures, number of LEMG procedures, and complications were obtained. The LEMG results from the thyroarytenoid and posterior cricoarytenoid muscles were graded 0 to 4 according to amplitude and relation to the phase of respiration. A correlation analysis between the need for tracheostomy and the baseline LEMG score as well as a multivariable analysis to determine the predictors of requirement for tracheostomy were performed. RESULTS Between April 28, 2008, and November 2, 2011, 43 LEMG procedures were performed on 23 patients (13 girls; mean [SD] age, 1.5 [2.85] years). Eight required tracheostomy. Among the 23 patients, 16 had laryngeal paralysis (11 bilateral, 5 unilateral), 4 had laryngeal dyskinesia, and 3 had miscellaneous conditions. Fourteen had secondary large airway lesions, and 14 had a nonairway diagnosis that affected respiration. The overall LEMG results correlated negatively with requirement for tracheostomy (r = -0.4; P < .05) and were 86.36% accurate compared with endoscopy. No predictors for tracheostomy were identified. CONCLUSIONS The LEMG grading was accurate and correlated with the requirement for tracheostomy. Combined with endoscopy, the grading may help better characterize laryngeal mobility disorders.

Utility of neurophysiology in the diagnosis of tethered cord syndrome

OBJECT The diagnosis of tethered cord syndrome (TCS) remains difficult, and the decision to operate is even more complex. The objective of this study was to examine how detailed examination of neurophysiological test results can affect the diagnosis for patients undergoing a surgical cord release. METHODS Patients undergoing tethered spinal cord releases were matched by age and sex with control patients undergoing scoliosis correction in the absence of spinal cord pathology. The latency and width of the P37 peak of the posterior tibial nerve somatosensory evoked potential (SSEP) and the motor evoked potential (MEP) latencies were examined. Immediate changes as a result of the surgical procedure were reported. RESULTS The width of the P37 response differed significantly between TCS and control patients and changed significantly during the surgical procedure. Nonsignificant trends were seen in SSEP and MEP latencies. CONCLUSIONS The width of the P37 response may be a useful marker for TCS and may play a role in presurgical decision making.

Changing our thinking about walking

The act of walking seems so simple when we perform it; we just put one leg in front of the other, and most of us are able to do other things at the same time. Watching children who are learning to walk, however, provides us with some insights into how complicated the whole process is and the tremendous level of sensori-motor integration required for safe walking. For a number of years we have known that infants can step on a moving treadmill belt before they can walk independently (Yang & Gorassini, 2006). Adults with complete spinal cord injuries can also be trained to step on a moving treadmill belt (Yang & Gorassini, 2006) and this has provided some of the strongest evidence to date for the existence of human spinal central pattern generators (Dietz, 2003). However, for over-ground walking a spinal pattern generator does not appear to be sufficient. Supraspinal control is needed to provide both the drive for locomotion as well as the coordination to negotiate a complex environment. In this issue of The Journal of Physiology, Petersen et al. (2010) describe a series of recordings made on children while they walk on a treadmill at a self-selected pace and while they perform a static ankle dorsiflexion. Using the technique of intramuscular coherence they examined changes in common drive from the motor cortex to the tibialis anterior muscle. This method is an elegant approach to studying nervous system function. Surface EMG recordings that are entirely non-invasive can be used to obtain information concerning the neural drive that produces an action. Most commonly, recordings for coherence analysis have been made from pairs of muscles, such as in our study of incomplete spinal cord-injured subjects (Norton & Gorassini, 2006). Recordings from two sites of the same muscle, as used in this study of children, are more suited to this analysis than pairs of muscles. Neural drive to two portions of a muscle is likely to be higher than to two independent muscles, even if they act synergistically. Care must be taken to avoid cross-talk between the electrode pairs but this group have previously shown techniques that avoid this problem (Hansen et al. 2005). Although many techniques exist for assessing the neural control of movement, such as reflex studies and motor-evoked potentials, a big advantage of the coherence approach is that it does not perturb the system. This method assesses the control of the movement as it happens, rather than the prior state or readiness of the system (Nielsen, 2002). There are shortcomings, however; in particular we are left to wonder about the remaining non-coherent activity. How much is lost as an artifact of the analysis technique and how much represents non-coherent neural drive is uncertain. We do not know the true maximum coherence if all drive came from a single corticospinal origin. For instance, at 24 Hz the highest level of coherence is well under 0.5 and in many instances and frequencies the coherence is below 0.1, potentially leaving up to 90% of the drive at that frequency of unknown origin. What is remarkable in the study by Petersen et al. (2010) is the relationship between the age of the subject and the coherence in the β-band during static contractions and γ-band during walking. These clear age-related differences indicate that the neural drive to the movement changes with age and could be considered as a marker for skill level in these relatively young children. By kinematic measures, these children appeared to have increased their skill level, as evidenced by reduced movement variability. Previous studies have shown changes in coherence with visuo-motor skill learning for this muscle (Perez et al. 2006) and others (Semmler et al. 2004). Changes in motor unit synchrony during development have also been reported (James et al. 2008) but this is the first study to examine the changes during a functional, lower-limb task such as walking without overt motor training. It is yet to be determined whether the developmental increase in coherence relates to a maturation of functional coordination within the corticospinal tract or this neural drive displacing non-cortical drive to the muscle.

Neuromonitoring During Surgery for Paediatric Spinal Deformity in Canada (2007)

BACKGROUND Neuromonitoring during paediatric (and adult) spinal deformity surgery helps to reduce the risk of both permanent and short term neurological damage. A shortage of neurophysiologists and technicians limits the availability of this service. Not all surgeons believe neuromonitoring offers neuroprotection during spinal surgery. This study aimed to document the degree to which paediatric patients undergoing spinal deformity correction surgery have their spinal cord function monitored. METHODS A questionnaire was sent electronically to all of the surgical members of the Canadian Paediatric Spinal Deformity Study Group. RESULTS Results were received from 9/9 centres indicating that monitoring was performed in 7/9 centres, with one further centre awaiting staffing. Whilst half of those centres that do monitor only monitor sensory and motor evoked potentials, the remaining centres also use EMG and EEG to assess the state of the patient intraoperatively. CONCLUSIONS Despite a shortage of staff, most paediatric spinal deformity surgeons in Canada who wish to, are able to neurophysiologically monitor their surgical cases. Neuromonitoring appears to be becoming a standard of care, at least for paediatric spinal deformity surgery. There is an urgent need for the establishment of national standards for both technologists and interpreters, as well as training programmes for both these groups.