Milan R. Dimitrijevic

Evidence for a Spinal Central Pattern Generator in Humansa

Abstract: Non‐patterned electrical stimulation of the posterior structures of the lumbar spinal cord in subjects with complete, long‐standing spinal cord injury, can induce patterned, locomotor‐like activity. We show that epidural spinal cord stimulation can elicit step‐like EMG activity and locomotor synergies in paraplegic subjects. An electrical train of stimuli applied over the second lumbar segment with a frequency of 25 to 60 Hz and an amplitude of 5‐9 V was effective in inducing rhythmic, alternating stance and swing phases of the lower limbs. This finding suggests that spinal circuitry in humans has the capability of generating locomotor‐like activity even when isolated from brain control, and that externally controlled sustained electrical stimulation of the spinal cord can replace the tonic drive generated by the brain.

Central dysesthesia syndrome in spinal cord injury patients.

&NA; We have described 13 spinal cord injury patients with a complaint of diffuse, ongoing dysesthesias below the level of the lesion, which are burning in quality, and usually functionally limiting. Quantitative sensory and neurophysiological testing revealed relative preservation of the dorsal column functions in comparison to absence of spinothalamic system mediated functions. On the basis of these findings, we are speculating that such an imbalance between the spinothalamic and dorsal column systems is the main underlying mechanism of dysesthesias as a central nervous system misinterpretation of residual peripheral input.

Influence of concurrent tasks on gait: a dual-task approach

We studied the effect of concurrent tasks on motor control of gait with dual-task methodology. Ten healthy subjects were instructed to perform different cognitive and motor tasks during gait on a conductive walkway. Footswitch signals were recorded and stride time and double-support time were calculated. It was assumed that the former reflects gait-patterning mechanisms and the latter relates to balance control. Statistical analysis showed an increase in double-support time when a memory-retention task (digit-span) and a fine motor task (buttoning) were executed simultaneously during gait. During gait performance of the cognitive task declined compared to baseline conditions. Attentional demand of concurrent cognitive and motor tasks appeared to force subjects to modulate their gait strategy to ensure control of balance. Stride time was consistent across task conditions except when subjects performed fast finger-tapping during gait. Then all but one subject showed a decrease in stride time and an increase in stride-frequency that was repeatable on retest. Since different rhythmic movements are likely to share common neurobiological networks, we assumed that the modulation of stride-frequency was due to structural interference.

Stepping-like movements in humans with complete spinal cord injury induced by epidural stimulation of the lumbar cord: electromyographic study of compound muscle action potentials

Study design: It has been previously demonstrated that sustained nonpatterned electric stimulation of the posterior lumbar spinal cord from the epidural space can induce stepping-like movements in subjects with chronic, complete spinal cord injury. In the present paper, we explore physiologically related components of electromyographic (EMG) recordings during the induced stepping-like activity.Objectives: To examine mechanisms underlying the stepping-like movements activated by electrical epidural stimulation of posterior lumbar cord structures.Materials and methods: The study is based on the assessment of epidural stimulation to control spasticity by simultaneous recordings of the electromyographic activity of quadriceps, hamstrings, tibialis anterior, and triceps surae. We examined induced muscle responses to stimulation frequencies of 2.2–50 Hz in 10 subjects classified as having a motor complete spinal cord injury (ASIA A and B). We evaluated stimulus-triggered time windows 50 ms in length from the original EMG traces. Stimulus-evoked compound muscle action potentials (CMAPs) were analyzed with reference to latency, amplitude, and shape.Results: Epidural stimulation of the posterior lumbosacral cord recruited lower limb muscles in a segmental-selective way, which was characteristic for posterior root stimulation. A 2.2 Hz stimulation elicited stimulus-coupled CMAPs of short latency which were approximately half that of phasic stretch reflex latencies for the respective muscle groups. EMG amplitudes were stimulus-strength dependent. Stimulation at 5–15 and 25–50 Hz elicited sustained tonic and rhythmic activity, respectively, and initiated lower limb extension or stepping-like movements representing different levels of muscle synergies. All EMG responses, even during burst-style phases were composed of separate stimulus-triggered CMAPs with characteristic amplitude modulations. During burst-style phases, a significant increase of CMAP latencies by about 10 ms was observed.Conclusion: The muscle activity evoked by epidural lumbar cord stimulation as described in the present study was initiated within the posterior roots. These posterior roots muscle reflex responses (PRMRRs) to 2.2 Hz stimulation were routed through monosynaptic pathways. Sustained stimulation at 5–50 Hz engaged central spinal PRMRR components. We propose that repeated volleys delivered to the lumbar cord via the posterior roots can effectively modify the central state of spinal circuits by temporarily combining them into functional units generating integrated motor behavior of sustained extension and rhythmic flexion/extension movements. This study opens the possibility for developing neuroprostheses for activation of inherent spinal networks involved in generating functional synergistic movements using a single electrode implanted in a localized and stable region.

Evidence of subclinical brain influence in clinically complete spinal cord injury: discomplete SCI

Previous studies of the neurocontrol of movement in spinal cord injury (SCI) subjects revealed that even those without volitional movement may retain some degree of preservation of distal brain influence. We previously defined a discomplete lesion as one which is clinically complete but which is accompanied by neurophysiological evidence of residual brain influence on spinal cord function below the lesion. In order to document the nature and extent of such neurocontrol, we recorded surface EMGs from multiple muscle groups to study patterns of motor unit activity in response to tendon vibration, activation of muscles below the lesion by reinforcement maneuvers above the lesion and by voluntary suppression of plantar withdrawal reflexes. We analyzed data from this brain motor control assessment (BMCA) procedure in order to describe the frequency of occurrence and characteristics of residual control in discomplete SCI subjects, comparing with findings in (clinically and neurophysiologically) complete and in (clinically and neurophysiologically) incomplete SCI subjects. From a group of 139 SCI subjects seen for management of spasticity, 88 had clinically complete lesions. Of these, 74 (84%) were discomplete as defined by responses to the above maneuvers. The selection of management and intervention strategies, whether physiological, pharmacological, behavioral or surgical, should give consideration to the high likelihood that clinically complete subjects may be neurophysiologically incomplete.

Focal depression of cortical excitability induced by fatiguing muscle contraction: a transcranial magnetic stimulation study

Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the motor cortex were recorded in separate sessions to assess changes in motor cortex excitability after a fatiguing isometric maximal voluntary contraction (MVC) of the right ankle dorsal flexor muscles. Five healthy male subjects, aged 37.4±4.2 years (mean±SE), were seated in a chair equipped with a load cell to measure dorsiflexion force. TMS or TES was delivered over the scalp vertex before and after a fatiguing MVC, which was maintained until force decreased by 50%. MEPs were recorded by surface electrodes placed over quadriceps, hamstrings, tibialis anterior (TA), and soleus muscles bilaterally. M-waves were elicited from the exercised TA by supramaximal electrical stimulation of the peroneal nerve. H-reflex and MVC recovery after fatiguing, sustained MVC were also studied independently in additional sessions. TMS-induced MEPs were significantly reduced for 20 min following MVC, but only in the exercised TA muscle. Comparing TMS and TES mean MEP amplitudes, we found that, over the first 5 min following the fatiguing MVC, they were decreased by about 55% for each. M-wave responses were unchanged. H-reflex amplitude and MVC force recovered within the 1st min following the fatiguing MVC. When neuromuscular fatigue was induced by tetanic motor point stimulation of the TA, TMS-induced MEP amplitudes remained unchanged. These findings suggest that the observed decrease in MEP amplitude represents a focal reduction of cortical excitability following a fatiguing motor task and may be caused by intracortical and/or subcortical inhibitory mechanisms.

Posterior root-muscle reflexes elicited by transcutaneous stimulation of the human lumbosacral cord

Continuous epidural stimulation of lumbar posterior root afferents can modify the activity of lumbar cord networks and motoneurons, resulting in suppression of spasticity or elicitation of locomotor‐like movements in spinal cord–injured people. The aim of the present study was to demonstrate that posterior root afferents can also be depolarized by transcutaneous stimulation with moderate stimulus intensities. In healthy subjects, single stimuli applied through surface electrodes placed over the T11–T12 vertebrae with a mean intensity of 28.6 V elicited simultaneous, bilateral monosynaptic reflexes in quadriceps, hamstrings, tibialis anterior, and triceps surae by depolarization of lumbosacral posterior root fibers. The nature of these posterior root–muscle reflexes was demonstrated by the duration of the refractory period, and by modifying the responses with vibration and active and passive movements. Stimulation over the L4–L5 vertebrae selectively depolarized posterior root fibers or additionally activated anterior root fibers within the cauda equina depending on stimulus intensity. Transcutaneous posterior root stimulation with single pulses allows neurophysiological studies of state‐ and task‐dependent modulations of monosynaptic reflexes at multiple segmental levels. Continuous transcutaneous posterior root stimulation represents a novel, non‐invasive, neuromodulative approach for individuals with different neurological disorders. Muscle Nerve, 2006

Motor control after spinal cord injury: Assessment using surface EMG

The brain motor control assessment (BMCA) protocol is a comprehensive multichannel surface EMG recording used to characterize motor control features in persons with upper motor neuron dysfunction. Key information is contained in the overall temporal pattern of motor unit activity, observed in the EMG (RMS) envelope. In paralysis, a rudimentary form of suprasegmental control of tonic and phasic reflexes can be demonstrated. EMG patterns evoked by voluntary and passive maneuvers and by volitional modulation of reflex responses reveal features of motor control not apparent in the clinical examination. Such subclinical findings may explain paradoxically different responses in apparently similar SCI subjects, and may be used to monitor spontaneous or induced changes. The recording protocol, examples of EMG patterns, and their prevalence in 40 spinal cord injured (SCI) subjects are presented, and compared with 5 healthy subjects.

Modification of cervical dystonia by selective sensory stimulation

Cervical dystonia is often refractory to all forms of therapy. Many patients, however, are able to transiently abolish their spasms following a specific gesture that presumably enhances sensory input. Such observations prompted us to develop a protocol to determine if various forms of sensory stimulation could modify the motor control patterns in cervical dystonia. Surface EMG recordings of multiple neck and trunk muscles were obtained in 11 consecutive cervical dystonia patients. Baseline patterns of voluntary and involuntary muscle activation were established during a series of motor and non-motor tasks. The tasks were repeated during the application of vibratory or electrical stimulation to select muscle groups or to cutaneous and mixed nerves. Analysis of the results was made on the basis of paper and computer recordings of the data. Sensory stimulation decreased involuntary muscle activity and reduced spasms in 5 subjects. However, objective or subjective improvement usually occurred only after specific stimuli were applied to specific anatomical sites. In these cases, the protocol identified the site at which a specific sensory stimulus could be applied to control the dystonia. We conclude that selective sensory stimulation can beneficially modify cervical dystonia in some patients. Such findings warrant further investigation of the use of sensory stimulation for control of cervical dystonia.

Facilitation of motor evoked potentials by somatosensory afferent stimulation

The effect of an electrically induced peripheral afferent volley upon electrical and magnetic motor evoked potentials (MEPs) from muscles of the upper and lower extremities was studied in 16 healthy volunteers. A standard conditioning-test (C-T) paradigm was employed whereby the test stimulus (transcranial electric or magnetic) was applied at random time intervals, from 10 msec prior to 90 msec after the conditioning stimulus (peripheral nerve stimulus). MEP amplitude facilitation was observed for the majority of the upper extremity muscles tested at two distinct periods, one occurring at short, and the other at long C-T intervals. This bimodal trend of MEP facilitation was found to be equally as prominent in the lower extremity muscles tested. The period of short C-T interval facilitation is consistent with modifications in the spinal excitability of the segmental motoneuron pool. On the other hand, the period of long C-T interval facilitation is suggested to be due to alterations in excitability of the motor cortex as a result of the arrival of the orthodromic sensory volley. Although most pronounced in muscles innervated by the nerve to which the conditioning stimulus was applied, this bimodal facilitatory effect was also observed in adjacent muscles not innervated by the stimulated nerve. Qualitatively, the conditioned MEPs from the upper and lower extremities responded similarly to both electrical and magnetic trans-cranial stimulation. In addition, our study demonstrates that the C-T paradigm has potential for use in the assessment of spinal and cortical sensorimotor integration by providing quantitative information which cannot be obtained through isolated assessment of sensory and/or motor pathways.(ABSTRACT TRUNCATED AT 250 WORDS)