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Biomedical subjects

M R Dimitrijevic

Publications and source records attributed to M R Dimitrijevic.

At least 19 recordsLinked to original sources
PubMed2005

Motor control in the human spinal cord and the repair of cord function.

In this review we describe clinical and neurophysiological features of motor control in human spinal cord injury based on two models. First, motor control is considered in subjects with injury-induced complete division of the spinal cord from brain and brainstem structures, and second, in those in which the division is partial. We describe motor control in terms of segmental and plurisegmental reflex activity that dominates motor unit output to the muscles following complete separation from the brain motor structures by accidental injury. With incomplete separation of the spinal cord from brain structures, motor control is defined as the voluntary manipulation of reflex and automatic activity integrated with internal and external feedback signals. We review here motor control found after complete spinal cord injury with paradigm of single and regular-repeating stimuli applied to elicit cutaneous and muscle stretch reflex responses. We argue, that isolated spinal cord neural circuitry is capable of organizing characteristic reflex events that depend on the characteristics of the stimulus. Also, the profile of residual brain and brainstem, modified by the reduction in descending long spinal tract fibers arriving at their targets in the spinal gray matter, produces characteristic changes in motor output to the muscles that leads to the development of new neural strategies for control of segmental and plurisegmental neural circuitry. In the second part of this review, we discuss available treatment modalities for impaired cord function and briefly outline neurobiological interventions under development for repair of spinal cord injury.

Humans↗
PubMed2004

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.

Action Potentials↗
PubMed2003

Initiating extension of the lower limbs in subjects with complete spinal cord injury by epidural lumbar cord stimulation.

We provide evidence that the human spinal cord is able to respond to external afferent input and to generate a sustained extension of the lower extremities when isolated from brain control. The present study demonstrates that sustained, nonpatterned electrical stimulation of the lumbosacral cord--applied at a frequency in the range of 5-15 Hz and a strength above the thresholds for twitches in the thigh and leg muscles--can initiate and retain lower-limb extension in paraplegic subjects with a long history of complete spinal cord injury. We hypothesize that the induced extension is due to tonic input applied by the epidural stimulation to primary sensory afferents. The induced volleys elicit muscle twitches (posterior root muscle-reflex responses) at short and constant latency times and coactivate the configuration of the lumbosacral interneuronal network, presumably via collaterals of the primary sensory neurons and their connectivity with this network. We speculate that the volleys induced externally to the lumbosacral network at a frequency of 5-15 Hz initiate and retain an "extension pattern generator" organization. Once established, this organization would recruit a larger population of motor units in the hip and ankle extensor muscles as compared to the flexors, resulting in an extension movement of the lower limbs. In the electromyograms of the lower-limb muscle groups, such activity is reflected as a characteristic spatiotemporal pattern of compound motor-unit potentials.

Action Potentials↗
PubMed2000

Epidural electric stimulation of posterior structures of the human lumbar spinal cord: 1. muscle twitches - a functional method to define the site of stimulation.

OBJECTIVES: To describe an electrophysiological method for determining the relation between lumbar cord dorsal roots and cathode of epidural electrode for spinal cord stimulation (SCS). MATERIALS AND METHODS: Data has been collected from 13 subjects who have been under evaluation of effectiveness of SCS for control of spasticity. Induced muscle twitches from both quadriceps (Q), adductors (A), hamstrings (H), tibial anterior muscles (TA) and triceps surae muscles (TS) were simultaneously recorded with surface-electrode polyelectromyography (pEMG) and analyzed for amplitudes, latency times and recruitment order. RESULTS: Stimulation of dorsal lumbar cord structures evoked characteristic EMG events during muscle twitch responses. Their amplitudes varied with stimulus strength. Latency times were rather invariable regardless of stimulus strength. Two distinct recruitment orders were demonstrated depending on whether the stimulating cathode was placed over the upper (=response from quadriceps and/or adductor muscles) or the lower (=response from tibialis anterior and triceps surae) lumbar cord segments. The chances to stimulate upper lumbar cord segments are best around the 12th thoracic vertebra. CONCLUSIONS: pEMG recording of muscle twitches enables us to accurately differentiate between upper and lower lumbar cord segments. Furthermore, our findings regarding amplitude, latency and recruitment order strongly suggest that we stimulate posterior roots not posterior columns of the lumbar spinal cord.

Adolescent↗
PubMed2000

Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 2. quantitative analysis by computer modeling.

OBJECTIVES: Analysis of the computed recruitment order of an ensemble of ventral and dorsal root fibers should enlighten the relation between the position of a bipolar electrode and the observed order of muscle twitches. MATERIAL AND METHODS: Thresholds of selected spinal root fibers are investigated in a two step procedure. First the electric field generated by the electrodes is computed with the Finite Element Method. In the second step the calculated voltage profile along each target neuron is used as input data for a cable model. For every electrode position the electrical excitability is analyzed for 12 large diameter ventral and dorsal root fibers of the second and fourth lumbar and first sacral segment. The predictions of the neural responses of any target fiber are based on the activating function concept and on the more accurate computer simulations of the electrical behavior of all nodes and internodes in the vicinity of the electrode. RESULTS: For epidural dorsal lumbosacral spinal cord stimulation we found the following rules. (i) The recruitment order of the spinal roots is highly related to the cathode level. (ii) Dorsal root fibers have the lowest threshold values, ventral root fibers are more difficult to excite and dorsal columns are not excitable within the clinical range of 10 V. (iii) For a cathode close to the level of the spinal cord entry of a target fiber thresholds are lowest and spike initiation is expected at the border between cerebrospinal fluid and white matter; excitation of L4 roots is not possible with 210 micros/10 V pulses when cathode is more than 2.2 cm cranial to their entry level (1.5 cm for S1 roots; standard data). (iv) Cathodes positioned (essentially) below the entry level cause spike initiation close to the cathode, in a region where the fibers follow the descending course within the cerebospinal fluid. (v) At rather low stimulation voltage twitches are expected in all investigated lower limb muscles for cathodes below L5 spinal cord level. CONCLUSIONS: Our simulations demonstrate a strong relation between electrode position and the order of muscle twitches which is based on the segmental arrangement of innervation of lower limb muscles. The proposed strategy allows the identification of the position of the electrode relative to spinal cord segments.

Electric Stimulation↗
PubMed2000

Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 3. Control Of spasticity.

OBJECTIVES: The purpose of this study was to evaluate the effect of spinal cord stimulation (SCS) on severe spasticity of the lower limbs in patients with traumatic spinal cord injury (SCI) under close scrutiny of the site and parameters of stimulation. MATERIALS AND METHODS: Eight SCI patients (four women, four men) were included in the study. Levels of spasticity before and during stimulation were compared according to a clinical rating scale and by surface electrode polyelectromyography (pEMG) during passive flexion and extension of the knee, supplemented by a pendulum test with the stimulating device switched either on or off over an appropriate period. RESULTS: Both the clinical and the experimental parameters clearly demonstrated that SCS, when correctly handled, is a highly effective approach to controlling spasticity in spinal cord injury subjects. The success of this type of treatment hinges on four factors: (1) the epidural electrode must be located over the upper lumbar cord segment (L1, L2, L3); (2) the train frequency of stimulation must be in the range of 50 - 100 Hz, the amplitude within 2 - 7 V and the stimulus width of 210 micross; (3) the stimulus parameters must be optimized by clinically assessing the effect of arbitrary combinations of the four contacts of the quadripolar electrode; and (4) amplitudes of stimulation must be adjusted to different body positions. CONCLUSIONS: Severe muscle hypertonia affecting the lower extremities of patients with chronic spinal cord injuries can be effectively suppressed via stimulation of the upper lumbar cord segment.

Adolescent↗
PubMed1998

Evidence for a spinal central pattern generator in humans.

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.

Action Potentials↗
PubMed1997

Assessment of corticospinal function in spinal cord injury using transcranial motor cortex stimulation: a review.

Other than clinical examination, few methods exist for assessing the functional condition of descending long tracts of the spinal cord in humans. This review covers neurophysiological examination of the corticospinal system using transcranial electrical and magnetic motor cortex stimulation. The neurophysiological basis for the motor evoked potentials (MEPs) and the differences between the two methods are discussed followed by a review of their use in individuals with spinal cord injury (SCI). Transcranial motor cortex stimulation is used to monitor descending spinal cord tract condition during spinal surgeries and could be useful for assessing central nervous system trauma, especially in the unconscious multitrauma patient. In the chronic phase of SCI, recordings of MEPs have enabled the estimation of central conduction times that relate to the condition of axons passing through the injured segment of the spinal cord. They were found to correlate well with clinical examination scores but as predictors of outcome, the reports have been mixed. The use of transcranial motor cortex stimulation to modify segmental reflexes and in combination with volitional attempts have also provided evidence of conduction across the lesion in paralyzed SCI subjects. However, MEPs can be absent in some SCI individuals who may be able to volitionally activate muscles below the level of the spinal cord lesion. Such findings are useful in elucidating the neural mechanisms underlying the performance of a volitional movement and may serve to guide and monitor the effects of future treatments for paralysis in SCI and other neurological disorders.

Animals↗
PubMed1997

Motor control physiology below spinal cord injury: residual volitional control of motor units in paretic and paralyzed muscles.

We have described motor control in people with different degrees of SCI by using surface polyelectromyographic recordings during single- and multijoint volitional motor tasks. We have shown that neurobiologic conditions of the injured spinal cord can be expressed in two main categories: "new anatomy" and "reduced anatomy". The evidence for a variety of definite features of motor control elicited by volitional effort for the performance of a present or even clinically absent motor task suggests that we can benefit from animal experimental neurobiologic studies while we are progressing toward the application of this new knowledge for the restoration of impaired spinal cord function in humans. Reports on the successfully enhanced regenerating capabilities of the axons and improved connectivity within neuronal circuits after SCI encourage us to intensify our efforts in parallel with studies on the recovery processes found in experimentally induced lesions in animals, as well as in accidentally induced SCI in humans.

Adolescent↗
PubMed1996

Effect of fatiguing maximal voluntary contraction on excitatory and inhibitory responses elicited by transcranial magnetic motor cortex stimulation.

Vertex transcranial magnetic stimulation (TMS) elicited tibialis anterior motor evoked potentials (MEPs) and silent periods (SPs) that were recorded during and following isometric maximal volitional contraction (MVC). During MVC in 6 healthy subjects, MEP amplitudes in the exercised muscle showed an increasing trend from an initial value of 4539 +/- 809 muV (mean +/- SE) to 550 +/- 908 muV (P < 0.13) while force and EMG decreased (P < 0.01). Also, SP duration increased from 165 +/- 37 ms to 231 +/- 32 ms (P < 0.01). Thus, during a fatiguing MVC both excitatory and inhibitory TMS-induced responses increased. TMS delivered during repeated brief 10% MVC contractions before and after a fatiguing MVC in 5 subjects, showed no change in MEP amplitude but SP duration was prolonged after MVC. This SP prolongation was focal to the exercised muscle. Silent periods recorded after pyramidal tract stimulation were unchanged following the MVC. These results suggest that MEP and SP might have common sources of facilitation during an MVC and that inhibitory mechanisms remain focally augmented following a fatiguing MVC.

Adult↗
PubMed1995

Early and late motor evoked potentials reflect preset agonist-antagonist organization in lower limb muscles.

A single transcranial magnetic stimulus can evoke two involuntary muscle responses in lower limb muscles of healthy humans. The purpose of the present study was to find out if these responses, when evoked during the processing period of a simple or choice reaction time task, such as ankle dorsiflexion, have specific characteristics related to the task. During the auditory reaction time, a transcranial magnetic stimulus was delivered to observe changes in the excitability of the central nervous system. A dual-cone coil was used, which effectively stimulated the fairly deep-lying lower limb motor cortex. Stimuli were delivered in a random order with 20-300-ms delays from the auditory go-signal. Motor evoked potentials (MEP) in right and left anterior tibial and soleus muscles were analyzed while early MEPs were observed invariably in both muscles; late MEPs occurred consistently only in soleus muscles. Both early and late MEP amplitudes were larger in simple reaction time trials than in choice reaction time trials. The late MEP appeared earlier in the simple reaction time task than in the choice reaction time task, reflecting faster central processing of simple reaction time tasks. The amplitude of the soleus late MEP in the simple reaction time task followed closely the amplitude of anterior tibial early MEP, suggesting a preset agonist-antagonist organization. This relationship was not present in the choice reaction time task.

Adult↗
PubMed1995

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.

Adult↗
PubMed1993

Surface and epidural lumbosacral spinal cord evoked potentials in chronic spinal cord injury.

Nine patients were examined in the chronic stage of spinal cord injury (12 to 56 months postinjury). Surface lumbosacral spinal cord evoked potentials (LSEPs) were obtained using electrodes placed over the S1, L2, L4, and T12 vertebral levels, referenced to a T6 surface electrode. Epidural LSEPs were obtained using a multielectrode lead placed percutaneously into the epidural space for evaluation of the efficacy of spinal cord stimulation for modification of pain and spasticity. The LSEPs resulting from supramaximal stimulation of the tibial nerve at the popliteal fossa were composed of propagating and stationary action potential components. Based on the surface LSEP amplitudes and latencies established in healthy subjects, the data was divided into normal (less than 2 SD), marginal (between 2 and 2.5 SD), and abnormal (greater than 2.5 SD) categories. Comparison of surface and epidural LSEPs at the T12 vertebral level for the normal group (n = 6, 4 incomplete and 2 complete) revealed a mean epidural/surface amplitude ratio of 9.44 and a latency for the major negative component of 15.2 +/- 0.6 ms for the epidural versus 14.8 +/- 0.6 ms for the surface LSEP. In cases where the lead was progressively removed and LSEPs recorded (n = 4) the propagating components rapidly attenuated and increased in duration while the stationary components attenuated but did not change in duration. The LSEPs for the marginal group (n = 2, 1 incomplete and 1 complete) showed similar epidural/surface amplitude ratios. In the abnormal case (n = 1, complete) surface LSEPs were absent but epidural LSEPs were present but with stationary and propagating components of low amplitude. This study demonstrates the ability of the epidural LSEP to provide more information than the surface LSEP of the functional condition of the lumbosacral spinal cord, particularly regarding the character of the propagating action potentials and in cases when the surface LSEPs appear to be of very low amplitude or absent.

Adolescent↗
PubMed1993

Features of motor control in patients with proximal childhood spinal muscle atrophy (pilot study).

The differences in the motor performance during different tasks between 19 subjects suffering from SMA and 10 healthy controls were observed. The simultaneous EMG activity of twelve lower limbs and lower trunk muscles was recorded with surface electrodes. EMG data were automatically reduced and compared with data evaluated from performed by physiotherapist manual testing of muscle strength. Results showed characteristic differences between healthy and spinal muscular atrophy (SMA) subjects: 1. SMA patients display generally more activity occurring in numerous muscle groups and more spinal levels are activated. 2. SMA patients reveal a disturbed functional relation between the posterior and anterior compartments of muscles. 3. EMG activity in SMA patients is spreading out also to the contralateral muscle groups even during slight, unilateral singlejoint movements. Oligosegmental, plurisegmental and brain sources are probably responsible for mentioned phenomena. The reciprocal influences between reduced number of motoneurons (in SMA) and function of central movement generators results in different mode of movement execution in SMA patients.

Adolescent↗
PubMed1992

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.

Adult↗