Brain, Vol. 126, No. 4, 988-1000,
April 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg088
Changes in propriospinally mediated excitation of upper limb motoneurons in stroke patients
INSERM EMI E03 49, Neurophysiologie Clinique, Rééducation, Hôpital de la Salpêtrière, Paris, France
Correspondence to: Professor Emmanuel Pierrot-Deseilligny, Neurophysiologie Clinique, Rééducation, Hôpital de la Salpêtrière, 47 boulevard de l’Hôpital, 75651 Paris cedex 13, France E-mail: emmanuel.pierrot-deseilligny{at}chups.jussieu.fr
Received June 19, 2002. Revised September 26, 2002. Accepted November 19, 2002.
 |
Summary |
|---|
 Top Summary IntroductionMaterial and methodsResultsDiscussionReferences |
|---|
It has been argued that, in humans, a part of the descending command to upper limb motoneurons is transmitted through cervical propriospinal premotoneurons. We explored whether excitation of these putative propriospinal neurons projecting onto extensor carpi radialis (ECR) motoneurons was modified in patients recovering from stroke. Suppression of the voluntary on-going ECR EMG activity by stimulation of cutaneous afferents in the superficial radial nerve was used to estimate the component of the descending command passing through the propriospinal relay. The degree of suppression was assessed on both sides of 30 stroke patients (divided into two groups, whether recovery of wrist extension was poor or good by the time of the investigation) and of 34 age-matched controls. Single cutaneous volleys elicited a suppression which was symmetrical and of the same degree in patients and controls. In contrast, the amount of on-going EMG suppression produced by a train, which was symmetrical in normal subjects, was asymmetrical in most stroke patients: it indeed was significantly greater on the affected side of stroke patients with poor recovery of wrist extension than (i) in their non-affected side; (ii) in controls; and (iii) in the affected side of patients with good recovery. Cutaneous suppression of the H reflex, the motor evoked potential (MEP) and the on-going EMG was compared in three patients with poor recovery by the time of the first test; there was a small suppression of the H reflex on the affected side, but the asymmetry was much less than that of the on-going EMG and the MEP. In patients explored twice during the course of recovery, the asymmetry in the suppression of the on-going EMG tended to disappear, while recovery of wrist extension improved. This suggests that, when patients have not yet recovered, a relatively greater component of the descending command is mediated through the propriospinal relay. The findings are consistent with transiently increased efficacy of descending (possibly reticulospinal) projections onto propriospinal neurons, due to hyperexcitability of these neurons or unmasking and/or reorganization of the projections to them.
Keywords: recovery from stroke; cervical propriospinal neurons; corticospinal command
Abbreviations: Ant chor A= anterior choroidal artery; ECR = extensor carpi radialis; IPSP = inhibitory postsynaptic potential; ISI = interstimulus interval; MCA = middle cerebral artery; MEP = motor evoked potential; MT = motor threshold; MVC = maximum voluntary contraction; PT = perception threshold; TMS = transcranial magnetic stimulation
|
Introduction |
|---|
|
TopSummaryIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
The severe hemiparesis which follows stroke generally recovers partially. Discussions concerning changes in neural organization underlying ‘spontaneous’ or ‘rehabilitation-induced’ recovery have focused mainly on hemispheric mechanisms. Thus, plastic changes in the damaged contralateral hemisphere seem to be best suited for producing recovery from stroke (for a review see Hallett, 2001
). However, in patients with poor recovery, it has been suggested that the residual motor capacity could also involve projections from the ipsilateral undamaged hemisphere (Chollet et al., 1991) via bilateral cortico-reticulospinal connections (Benecke et al., 1991). This view was supported by the investigation of ipsilateral motor evoked potentials (MEPs) elicited in the affected arm by transcranial magnetic stimulation (TMS) (see Discussion) (Benecke et al., 1991; Turton et al., 1996). Involuntary synkinetic contractions, which generally are observed in patients with poor recovery, could also result from reticulospinal pathways taking over the descending command (Dewald et al., 1995).
The present investigation was undertaken to explore whether and to what extent spinal cervical propriospinal neurons might contribute to mediating the command for the residual movement of stroke patients. In the cat, the descending command for visually guided target reaching is mediated through a system of C3–C4 propriospinal neurons which transmit disynaptic excitation to forelimb motoneurons from the cortico-, rubro-, tecto- and reticulo-spinal tracts, and also receive feed-forward inhibition from the same tracts and feedback (mainly inhibitory) from cutaneous and muscle afferents (cf. Lundberg, 1999).
In humans, there is evidence for an analogous system of cervical premotoneurons onto which converge peripheral and corticospinal inputs (Fig. 5), and which transmit a part of the descending command to upper limb motoneurons, in parallel with the monosynaptic cortico-motoneuronal pathway. Several features of this system distinguish it from a segmental pathway (cf. Pierrot-Deseilligny, 1996; Pauvert et al., 1998; Nicolas et al., 2001): (i) the facilitation elicited from a given nerve has a diffuse pattern of distribution on virtually all upper limb muscles (except intrinsic hand muscles), including antagonists at the same joint; (ii) because the same inputs activate the putative propriospinal neurons and feedback inhibitory interneurons inhibiting them (Fig. 5), slightly increasing the afferent and/or the corticospinal input causes the facilitation to be reversed to inhibition; (iii) the low threshold of the afferent effects indicates an oligosynaptic linkage, but the central delay (3–6 ms) is much longer than that found in segmental pathways activated by low-threshold afferents; and (iv) the more caudal the motoneuron pool in the spinal cord, the greater the central delay of the excitation (and/or inhibition). This suggests a longer intraspinal pathway for caudal motoneurons, and implies interneurons located rostral to motoneurons, much as propriospinal neurons in the cat.
|
The existence of a functional cervical propriospinal pathway in higher primates has been challenged because of the rarity and weakness of propriospinally mediated corticospinal excitation in upper limb motoneurons of the macaque monkey (Maier et al., 1998
; Nakajima et al., 2000) or of humans (Maertens de Noordhout et al., 1999) in control conditions. In fact, this might be explained by the activation of inhibitory interneurons by artificial volleys applied to the pyramidal system (Alstermark et al., 1999; Nicolas et al., 2001). Thus, intracellular recordings from identified C3–C4 propriospinal neurons by Alstermark and Isa have documented their projections directly to upper limb motoneurons and the lateral reticular nucleus in the macaque monkey (see Rothwell, 2002).
Putative propriospinal neurons activated by extensor carpi radialis (ECR) afferents and mediating the descending command to ECR motoneurons are inhibited specifically by tactile cutaneous afferents in the superficial radial nerve supplying the skin of the dorsal side of the hand (Nielsen and Pierrot-Deseilligny, 1991; Burke et al., 1994). We have taken advantage of this projection to investigate the component of the descending command passing through the propriospinal relay in stroke patients. A brief summary of some of the present results has appeared in abstract form (Mazevet et al., 1995), and preliminary results obtained with a different technique (see below) have been mentioned in a review (Pierrot-Deseilligny, 1996).
|
Material and methods |
|---|
|
TopSummaryIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
Patients
The investigation was carried out in 30 stroke patients aged 32–74 years (mean ± SEM 53.3 ± 2.3 years) and 34 age-matched healthy subjects (50.7 ± 2.9 years). All participants gave written informed consent to the experimental procedures, which were performed in accordance with the Declaration of Helsinki, and with the approval of the Ethics Committee of the Hôpital de la Salpêtrière. All subjects were self-proclaimed righthanders (attention was not paid to the consistency of right handedness, since there is no handedness-related asymmetry in the amount of cutaneous-induced suppression with the experimental paradigm used, see below).
Data concerning the sex, age, side of the hemiplegia, nature and location of the lesion, ECR strength at the time of the first test, and the time of this first test with respect to stroke are given in Table 1. All patients had unilateral focal lesion visualized on CT or MRI of the brain. Nineteen had suffered an infarct, and 11 a haemorrhage. Seventeen had a right and 13 a left hemiplegia. All had some sensory deficit associated with motor disorders. In none could cognitive or language deficits interfere with comprehension of the test protocol.
|
Clinical assessment
The strength of wrist extension (given in Table 1 at the time of the first test) was scored on a 1–5 scale adapted for hemiplegic patients (Held and Pierrot-Deseilligny, 1969
), where 2 represents the ability to maintain tonic wrist extension against gravity for only 20–30 s, 3 the ability to maintain it for 1–2 min, 4 an almost normal force and 5 a normal force. All recruited patients had ECR strength of at least 2–3 at the time of the first test in order to be able to perform the required tonic wrist extension. Wrist extension often was accompanied by associated synkinetic contractions of arm muscles. Patients were divided into two groups according to their recovery in ECR at the time of the first test.
Group A
By the time of the first test, 15 patients had recovered strength in the ECR of 
2–3, i.e. just sufficient to perform the tonic wrist extension against gravity, as required for participation in the study. In all 15 patients, wrist extension was accompanied by synkinetic contractions of arm muscles. Nine (patients 4, 6, 8, 14, 19, 20, 22, 24 and 25) were hospitalized for rehabilitation and were tested during the first 3 months following stroke, as soon as they were able to perform the ECR contraction, while the remaining six (patients 5, 12, 18, 26, 27 and 29) were explored 8–35 months after the stroke. Five of the former (8, 19, 20, 24 and 25) were tested a second time 1 month later when the strength of the ECR had improved and the synkinetic contractions had decreased (or disappeared). Patient 12 was tested the first time 21 months after the stroke when she was able to perform the required tonic wrist extension. She then continued to recover and was re-tested 6 months later when her ECR strength had reached a score of 4 without associated synkinetic contraction.
Group B
Fifteen patients had recovered an almost normal ECR strength (scored 
4) by the time of the test, with a minimum of synkinetic contractions, seven during the first months following stroke (3, 7, 9, 13, 16, 23 and 28), and the remaining eight (1, 2, 10, 11, 15, 17, 21 and 30) when tested much later (often several years after the stroke).
Electrophysiological tests
The subjects were seated comfortably in an armchair. The examined forearm and hand were lying in pronation on the arm of the chair with the shoulder abducted at 60° and the elbow semi-flexed (110–120°).
Symmetrical bilateral ECR voluntary contraction
Cutaneous-induced suppression was investigated during bilateral tonic contraction of the ECR, there being no handedness-related asymmetry in the superficial radial-induced modulation of the on-going EMG in normal subjects (Marchand-Pauvert et al., 1999). The contraction was adjusted to be just sufficient to maintain the wrist in neutral position against gravity (symmetrical amplitude of the hand and finger positions). In normal subjects and in the unaffected side of stroke patients, this corresponds to a contraction of 6–8% of maximal (tonic) voluntary contraction (MVC). To ensure the symmetry of the contractions, EMG activity of both sides was recorded at the same amplification, rectified and integrated, and displayed on an oscilloscope as a continuous line. Subjects were asked to adjust the contractions so that these lines were superimposed, and the test was interrupted when this was no longer the case. Finally, because the amount of suppression of the on-going EMG was expressed as a percentage of the control EMG activity integrated over 40 ms (see below, and thus the smaller this value, the greater the suppression expressed in this way), this value was corrected, using a factor of generally 0.8–1.2, to be the same on the two sides during the computation of results.
Modulation of the on-going EMG
Recording. On-going ECR EMG activity was recorded by surface electrodes 1 cm apart secured to the skin over the muscle belly. Voluntary on-going EMG activity was full-wave rectified and averaged (150 trials) against the conditioning stimuli for 10–50 (or 60) ms using a sampling rate of 1–5 kHz (e.g. 1 kHz in Fig. 2B and 5 kHz in Fig. 2D). Conditioned and unconditioned (i.e. trials in which the background EMG activity was measured) trials were alternated randomly (1 s) during short sequences of 30–100 s to avoid fatigue in patients with weakness. The data recorded in 3–10 sequences were averaged to produce a single run containing 150 conditioned responses. In Figs 1, 2 and 4A, showing data for single subjects, the amount of suppression, i.e. the difference between the grand average of conditioned values and the baseline EMG which was measured in the alternating 150 control trials and then integrated over 40 (or 50) ms to provide a measure of baseline EMG, is expressed as a percentage of this baseline. In Figs 3A–D, and 4B and C, representing data in all subjects investigated, the grand average of conditioned values is expressed as a percentage of the control EMG.
|
|
|
|
Stimulation. Shocks of 1 ms duration were delivered to the superficial radial nerve through bipolar surface electrodes (4 cm2 silver plates) placed on the skin of the inferior part of the radial edge of the forearm. In normal subjects and on the unaffected side of patients, this produced radiating par aesthesiae in the dorsal side of the hand and the first three fingers. To ensure the symmetry of the stimulation despite the sensory deficit generally observed on the affected side, the intensity of the conditioning stimulation was graded with respect to the motor response in thenar muscles due to a spread of the stimulation to the median nerve (Marchand-Pauvert et al., 2001). In most experiments, stimulus intensity was therefore adjusted at 0.5 x motor threshold (MT). In normal subjects (and on the unaffected side of patients), this corresponded to an intensity perceived at 2 x perception threshold (PT). Both single volleys and trains (three shocks at 300 Hz) were used at this intensity. In some preliminary experiments (Fig. 2A and B), single volleys just below the MT (0.95 x MT), corresponding to 4 x PT in normal subjects, were used.
Window of analysis. Given a central delay of 4 ms for the cutaneous suppression and an extra peripheral conduction time of 4 ms for the superficial radial volley elicited at wrist level with respect to the radial Ia volley evoking the ECR H reflex at elbow level (Burke et al., 1994), the onset of the cutaneous-induced suppression should occur 8 ms later than the latency of the ECR H reflex. Since the latency of the ECR H reflex (measured during contraction) was on average 18 ms in the patient population, the suppression resulting from the cutaneous inhibition of propriospinal neurons might be expected to start 26 (18 + 8) ms after delivering the last cutaneous volley. Accordingly, the window of analysis started 26 ms after the single volley and 32 ms after the first shock of the train (i.e. 26 ms after the last shock). Vertical arrows in Fig. 1A indicate the expected onset of the effect elicited by each volley of the train. The duration of the window of analysis was limited to 10 ms in order to avoid late effects due to inhibition exerted at the cortical level (see Maertens de Noordhout et al., 1992). The suppression so assessed is illustrated by the grey area in Fig. 1A. Cortical inhibition probably accounts for the second phase of inhibition (starting 15 ms after the onset of the window of analysis, see Fig. 2A), and for the resulting long duration of the EMG suppression after a single volley (Burke et al., 1994).
Statistics. Variance analysis (Scheffé’s test) was used to show whether in each subject the cutaneous-induced suppression was significant in each side. An ANOVA (analysis of variance) was first used to determine the respective influences of the following factors on the amount of cutaneous-induced suppression obtained in each side of the subjects: (i) side (left and right) and (ii) status (patient affected and non-affected sides, control left and right sides). In a second step, the difference between the amount of EMG suppression elicited on each side was taken as dependent variable and the effects of ECR strength at the time of the first investigation (patients with strength of 2, 3, 4 and 5, and controls), location of the lesion [putaminal, middle cerebral artery (MCA), anterior choroidal artery (Ant chor A), parietal or other location], type of lesion (infarct versus haemorrhage) and duration of evolution (
3, >3 and 12, and >12 months) were investigated. Post hoc comparisons were made using the Bonferroni–Dunn test. A non-parametric test was used to compare results in the same patients at two moments of their recovery (Wilcoxon rank test).
Modulation of the H reflex and of the MEP
Absence of significant inhibition of the H reflex by the train in normal subjects. It has been argued that the superficial radial-induced suppression of the on-going ECR EMG in normal subjects can be attributed to a disfacilitation of ECR motoneurons, and not to inhibitory postsynaptic potentials (IPSPs) in motoneurons, because the same single cutaneous volley at 4 x PT suppresses the MEP, but has little effect on the ECR H reflex recorded during tonic ECR contraction (Burke et al., 1994). Similarly, as illustrated in Fig. 1A and B, trains of three shocks at 0.5 x MT in normal subjects produced a clear suppression of the on-going ECR EMG (Fig. 1A) but only a minor change in the ECR H reflex recorded during tonic contraction (Fig. 1B). Both on-going EMG and H reflex were assessed in the same subject during the same experiment within the same window of analysis, between the vertical dashed lines: starting at the 32 ms latency for the on-going ECR EMG (see above), and at the 14 ms interstimulus interval (ISI) for the H reflex (allowing 8 ms for the extra conduction time of the cutaneous volley and the central delay of the suppression, and 6 ms for the interval between the first and last shocks of the train).
Investigation of the modulation of the H reflex and of the MEP in patients
Comparison of the induced changes in the on-going EMG, the H reflex and the MEP was attempted in the initial studies in the patients of group A (those with the clearest asymmetrical suppression of the EMG, see below), who had no contra-indication to TMS; however, because of their weakness, the resulting long exploration was possible in only eight patients. In only three of them was the MEP of sufficient size on the affected side and/or the H reflex present on the unaffected side (even during contraction). All three patients had a weak ECR strength (3) by the time of the test, but later recovered to almost normal force. These studies were performed during steady tonic voluntary contractions of ECR, because (i) this ensured that the background conditions were the same as for the modulation of tonic EMG activity; (ii) it favoured the appearance of an ECR H reflex; (iii) it ensured that the MEPs reflected activity predominantly of ECR motoneurons; and (iv) the recruitment order of motoneurons by Ia and corticospinal inputs is then the same (see Discussion).
H reflex. This reflex, elicited by bipolar stimulation of the radial nerve in the spiral groove, was measured as the peak-to-peak amplitude of muscle action potentials. Because the sensitivity of H reflexes of small size varies with the amplitude of the unconditioned reflex, the size of the unconditioned reflex was adjusted to be at the same size on the two sides (15% of the maximal M wave, i.e. an amplitude when the sensitivity of the ECR H reflex no longer varies with the size of the control reflex, see Malmgren and Pierrot-Deseilligny, 1988; Crone et al., 1990)
MEP. The MEP was elicited by TMS delivered to the hemisphere contralateral to the test limb using a Magstim 200 (Magstim, Whitland, Dyfed, UK) with a 9 cm coil held at the vertex at the optimal position for the contralateral ECR. The optimal direction of the current flow in the coil was used for stimulation of each hemisphere: counter-clockwise for the left hemisphere, clockwise for the right. Because ECR MEPs (particularly on the affected side) often had a polyphasic shape, the waveform was full-wave rectified, averaged, and its area was measured over its entire duration. TMS intensity was adjusted to produce control MEPs of the same size on the two sides.
On-going EMG. This was recorded with a sampling rate of 5 kHz in these three subjects. To match the curves with those of Fig. 2F and G, each symbol in Fig. 2E is the mean of the 10 values recorded within 2 ms.
Various interstimulus intervals (ISIs). Modulations of the H reflex and of the MEP by the cutaneous train were investigated at various ISIs corresponding approximately to the window of analysis of the on-going EMG, using 2 ms steps. Dashed vertical lines in Fig. 2E–G indicate the expected onset of the effect of the last volley of the train: (i) 32 ms latency for the on-going EMG (Fig. 2E); (ii) 14 ms for the H reflex (Fig. 2G); and (iii) 12 ms ISI for the MEP (Fig. 2F). Indeed, because the onset of the MEP corresponds to the arrival of I waves at motoneuronal level, the onset of the suppression elicited by a single volley occurs at the 6 ms ISI (Mazevet et al., 1996; Marchand-Pauvert et al., 1999) (+6 ms between the first and last shocks of the train). For each ISI, 10–20 conditioned and unconditioned responses were alternated randomly, and the amount of suppression (conditioned – unconditioned responses) was expressed as a percentage of unconditioned responses (mean ± SEM). A non-parametric test was used to compare the asymmetry (measured at its maximum within the window of analysis) of results concerning the on-going EMG, the MEP and the H reflex (Kruskal–Wallis test).
|
Results |
|---|
|
TopSummaryIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
Suppression of the on-going ECR EMG by a cutaneous volley to the superficial radial nerve was employed to explore whether the component of the descending command for wrist extension mediated through putative propriospinal neurons is different in stroke patients and normal subjects. To ensure the symmetry of the stimulation despite the sensory deficit, the intensity of the conditioning stimulation was graded with respect to the motor response in thenar muscles due to a spread of the stimulation to the median nerve.
Suppression elicited by a single cutaneous volley at 0.95 x MT
In order to mimic experiments performed in normal subjects (Burke et al., 1994; Marchand-Pauvert et al., 1999), a single volley at 0.95 x MT (corresponding to 4 x PT in normal subjects) was used first. In Fig. 2A and B, the comparison is made between the amount of suppression of the on-going EMG on each side (continuous and dotted lines) of one normal subject (Fig. 2A) and one stroke patient (Fig. 2B). The amount of cutaneous-induced suppression, expressed with respect to the control baseline EMG (dashed horizontal line), was symmetrical in the two subjects and of the same order of magnitude. Similar results were obtained in 11 normal subjects and 21 patients explored in this way: in normal subjects, the suppression reduced the on-going EMG to 84.9 ± 2.5 and 86.9 ± 2.4% on the right and left side, respectively, and to 87.5 ± 2.1 and 89.7 ± 1.7% on the affected and unaffected side of stroke patients (ANOVA, effect of side and status: P = non-significant, NS).
Suppression elicited by a train at 0.5 x MT
The effects of a temporal summation elicited by a train of three shocks were investigated. Because the stimulation using a train of three shocks at 0.95 x MT was uncomfortable, the intensity of each shock in the train was reduced to 0.5 x MT. In Fig. 2C and D, the amount of suppression of the on-going EMG induced by the train is compared in the same normal subject (Fig. 2C) and patient (Fig. 2D) as in Fig. 2A and B. In the two subjects, the suppression was greater than with one shock (despite the reduction of the stimulus intensity), attesting that temporal summation between the three volleys of the train at the level of inhibitory interneurons was effective in inhibiting the presumed propriospinal neurons.
The central finding of the present investigation concerns the symmetry of the suppression. Indeed, whereas the suppression induced by the train was symmetrical in the normal subject (Fig. 2C), it was more profound on the affected than on the unaffected side of the patient with, as yet, poor recovery (Fig. 2D, continuous and dotted line, respectively; patient 12 at her first test). Similar results were obtained in most subjects, as shown in Fig. 3A and B, where the conditioned on-going EMG on each side (elicited by the train and expressed as a percentage of the control EMG) is plotted on vertical scales for 34 healthy subjects (Fig. 3A) and 30 stroke patients (Fig. 3B). Each thin line represents one subject. The mean value of the EMG suppression was not different between right and left sides of the controls nor between the unaffected side of the patients and either side of the controls. In contrast, there was a highly significant increase in the EMG suppression on the affected side of patients versus their unaffected side: ANOVA, effect of status (P < 0.0001); affected side versus unaffected side (P < 0.001); affected side versus either side of controls (P < 0.0001); unaffected side versus either side of controls (NS); effect of side (NS); side x status (NS).
In normal subjects (Fig. 3A), cutaneous-induced suppression generally was symmetrical, and mean values in the group were identical for the two sides (see filled circles in Fig. 3C). This may seem to contradict the slight handedness-related asymmetry with a trend to suppression greater on the dominant side described in a previous study (Pierrot-Deseilligny, 1996), but there are three important differences between the present investigation and the previous study: (i) the amount of suppression of the on-going EMG was investigated during bilateral and not unilateral voluntary wrist extension, and the former has been shown to reduce the handedness-related asymmetry (Marchand-Pauvert et al., 1999); (ii) the present investigation included self-proclaimed rather than objectively identified righthanders in order to match the population of stroke patients (in whom handedness was not tested specifically); and (iii) the conditioning stimulation was weaker in the present experiments (2 xPT instead of 3–4 xPT).
In Fig. 3C and D, the comparison is made between the mean results (±SEM) obtained with trains (filled circles) and single volleys (open squares) using a stimulus intensity adjusted at 0.5 x MT in normal subjects (Fig. 3C) and in patients (Fig. 3D): the asymmetry obtained with the train in stroke patients contrasted with the symmetry of the weak suppression elicited by single volleys, which was of the same magnitude in the two populations.
To look for clinical factors, other than ECR strength (see below), which could be correlated with an increase in the EMG suppression on the hemiplegic side of patients, a further ANOVA was done taking into account only the patients group. Neither the location, the type of the brain damage nor the duration of the illness at the first examination had an influence on the amount of radial-induced EMG suppression (ANOVA, location, type and duration: NS).
Changes in suppression of the on-going EMG throughout motor recovery
Figure 4 shows that the asymmetry of the suppression was correlated with the clinical assessment of wrist extension. In Fig. 4A, the comparison is made between the results observed in the six patients of group A (8, 12, 19, 20, 24 and 25) who were studied twice. Each triangle represents the difference between the amount of suppression on the affected and unaffected side (i.e. the asymmetry, cf. column 11 in Table 1), and the circles the mean values for the six subjects. The filled symbols show that, by the time of the first test when they had recovered just enough to perform the tonic wrist extension against gravity (ECR strength = 2–3), all six patients exhibited a significant asymmetry of EMG suppression. Open symbols illustrate that this asymmetry had almost completely disappeared by the time of the second test, when the strength of the wrist extensors approached normal (ECR strength = 4) (P < 0.03, Wilcoxon test). Accordingly, in these six subjects, the mean suppression on the affected side was considerably larger than in normal subjects in the first investigation (reducing the on-going EMG to 49.3 ± 7.3% of the control value), but approached normal values in the second investigation (74.7 ± 8.3%), even greater still than in normal subjects.
These longitudinal studies were performed on a limited number of patients, but further support came from a comparison of the amount of suppression of the on-going EMG in the two patient groups, A and B. Fig. 4B shows that in the 15 patients of group A, tested while they still had poor ECR recovery, there was greater suppression on the affected than on the unaffected side in almost all subjects, whereas in patients of group B, who had had a good recovery at the time of testing, there was no asymmetry. The level of ECR strength clearly influenced the amount of EMG suppression (ANOVA effect of factor strength P < 0.0001): the mean value of the difference between the amount of EMG suppression on the affected and unaffected side was 34 ± 5, 19 ± 5, 2.5 ± 3 and 7 ± 12% in patients with strengths of 2, 3, 4 and 5, respectively, and 0.6 ± 2% between the right and left side in control subjects. Patients with the lowest strengths (2 and 3) had deeper EMG suppression than controls (Bonferroni–Dunn test: strength 2 versus controls, P < 0.0001; strength 3 versus controls, P < 0.0001) and also than patients who had a good recovery and scored at 4 and 5 (Bonferroni–Dunn test: strength 2 versus strength 4, P < 0.0005; and strength 3 versus strength 4, P < 0.005). Results obtained in patients with a good recovery did not differ from those obtained in controls (NS).
Finally, it must be pointed out that the relevant factor for the EMG asymmetry is not the actual ECR strength developed during the test, since, in all cases, contraction was adjusted at the same level (i.e. just sufficient to maintain the wrist in a neutral position against gravity, with matching of the levels of rectified and integrated control EMG). In addition, in normal subjects, the amount of EMG suppression remained virtually identical for tonic contractions between 5 and 80% of MVC, when expressed as a percentage of the control EMG produced by a similar train at 0.5 x MT and assessed within the same window of analysis. This is illustrated in Fig. 1C, which shows mean values (±SEM) for 11 normal subjects.
Modulation of the H reflex and of the MEP
In Fig. 2E–G, the comparison is drawn between the modulation of the on-going EMG (Fig. 2E), the MEP (Fig. 2F) and the H reflex (Fig. 2G). Values obtained in the three patients of group A who could be so explored at the time of their first test were averaged and are illustrated (mean ± SEM). On the unaffected side (open circles), there was, as in normal subjects, a suppression of the EMG and of the MEP, whereas there was little change in the H reflex. On the affected side (filled circles), a slight, but significant suppression of the H reflex was present (Fig. 2G). However, the suppression of the on-going EMG (Fig. 2E) and of the MEP (Fig. 2F) was greater than that of the H reflex, and the resulting asymmetry between affected and unaffected sides for the two former responses (Fig. 2E and F) was much more marked than that of the H reflex (Fig. 2G) (P < 0.05, Kruskal–Wallis test). Figure 2F shows that the asymmetry in the MEP suppression started at the 12 ms ISI, i.e. at the expected time of the effect of the last volley (see Material and methods). However, suppression already existed at the 10 ms ISI. In accordance with results obtained in normal subjects using a single cutaneous volley (Mazevet et al., 1996), this suggests that the first shock(s) of the volley was efficient in eliciting the MEP suppression, particularly on the unaffected side, a point which is considered further in the Discussion.
|
Discussion |
|---|
|
TopSummaryIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
The major finding of this study is that the suppression of the on-going ECR EMG activity elicited by a train of stimuli to the cutaneous superficial radial nerve is symmetrical in healthy subjects, but asymmetrical in stroke patients who have not yet recovered wrist extensor strength. The EMG suppression was significantly more pronounced on the affected side than in normal subjects, but tended to return to normal values as motor function improved.
Symmetry of the contraction
The symmetry of the voluntary contraction is a prerequisite for a valid comparison of the results obtained on the two sides. As explained in Material and methods, this was achieved by matching the level of integrated rectified EMG activity recorded at the same amplification. However, on the affected side, a contraction matching a level of EMG activity of 6–8% of MVC on the unaffected side corresponded to a contraction of 50–80% of MVC in patients with the most severe weakness (patients of group A at the time of their first test), and of 20–50% of MVC in patients of group B. It is therefore important that, in normal subjects, the suppression of on-going EMG is identical for tonic contractions between 5 and 80% of MVC (Fig. 1C).
Pathway responsible for the cutaneous-induced inhibition
Evidence for disfacilitation in normal subjects
In normal subjects, volleys to cutaneous afferents in the superficial radial nerve suppress the on-going ECR EMG activity, and this occurs with a mean central delay of 4 ms (Burke et al., 1994). If the suppression was due to inhibition exerted directly on motoneurons, creating IPSPs in motoneurons, one would expect all motoneuron responses to be similarly reduced, whether evoked by cortical stimulation or by stimulation of homonymous Ia afferents (Berardelli et al., 1987). However, cutaneous volleys, either single volleys (Burke et al., 1994) or trains (Fig. 1B), had little suppressive effect on the H reflex of ECR, and this indicates that the inhibition is not exerted directly on motoneurons. Instead, it is presumably exerted on ‘premotoneurons’ which transmit a part of the voluntary drive to the ECR motoneuron pool, in parallel with the monosynaptic cortico-motoneuronal pathway. This view is supported by the finding that the same cutaneous volley suppressed the MEP elicited by magnetic (Burke et al., 1994) or electric (Mazevet et al., 1996) stimulation of the motor cortex, while sparing the initial part of the MEP due to the monosynaptic cortico-motoneuronal volley (an inhibition exerted on motoneurons should affect the entire corticospinal response, including the initial part due to the monosynaptic cortico-motoneuronal projection; Mazevet et al., 1996).
This interpretation implies that the sequence of motoneuron recruitment for the on-going EMG (from small motoneurons supplying slow units to large motoneurons supplying fast units) is similar for the H reflex and MEP. This has been demonstrated in the ECR during voluntary contraction for Ia (Aimonetti et al., 2000) and corticospinal (Bawa and Lemon, 1993) inputs. However, the post-spike afterhyperpolarization following the firing of units activated in the voluntary contraction might prevent them from being recruited into the H reflex or the MEP recorded during contraction, such that the H reflex and the MEP may involve units of higher threshold than those engaged in the voluntary contraction. Given that cutaneous volleys from the index finger can inhibit low threshold motoneurons and facilitate high threshold motoneurons innervating the human first dorsal interosseus (Garnett and Stephens, 1980), this could contribute to the discrepancy between the modulation of the EMG and the H reflex. Notwithstanding, this process should affect the MEP and the H reflex similarly, and the finding that the MEP and the on-going EMG undergo a similar degree of suppression (Burke et al., 1994) argues for a cutaneous-induced disfacilitation.
It must be pointed out that the superficial radial-induced disfacilitation of ECR motoneurons bears no relationship to the inhibition of the flexor carpi radialis H reflex described by Cavallari and Lalli (1998). The latter (i) has a much shorter latency (2 ms); (ii) alters the H reflex at rest, and thus results from IPSPs in motoneurons; (iii) is followed by a potent facilitation; and (iv) is not elicited by electrical stimuli but by natural stimuli to both palmar and dorsal sides of the finger (whereas the disfacilitation of ECR motoneurons is evoked specifically from the dorsal side; Nielsen and Pierrot-Deseilligny, 1991; Burke et al. 1994).
Does EMG suppression reflect disfacilitation on the affected side of patients?
In the three subjects illustrated in Fig. 2G, the H reflex on the affected side (filled circles) was more suppressed than on the unaffected side (open circles). The question then arises of whether this might reflect a change in segmental spinal pathways potentially activated by the conditioning volley, given the modifications of excitability that have been described in several segmental circuits in stroke patients. However, here again, an inhibition transmitted through segmental pathways to motoneurons should affect the MEP and the H reflex to the same extent. The finding that asymmetry of the on-going EMG and the MEP between affected and unaffected sides (Fig. 2E and F) was significantly more marked than that of the H reflex (Fig. 2G) argues in favour of disfacilitation in stroke patients.
In fact, the small inhibition of the H reflex recorded on the affected side may be explained because experiments were performed during contraction. In normal subjects, disfacilitation reduces the peak of monosynaptic Ia excitation in single units and, accordingly, during contraction, would prevent the less excitable motoneurons firing in the control reflex from being recruited by the test volley (Burke et al., 1994). Yet, this would be offset (at least in part) by the availability for the H reflex of motoneurons no longer engaged in the contraction, now the most excitable of the subliminal fringe of descending excitation. Thus, disfacilitation produces a decrease in excitation for each individual motoneuron, but the H reflex is modified only slightly because the reflex can now access motoneurons no longer active in the contraction to compensate for the failure to recruit less excitable motoneurons. Because the H reflex at 15% of Mmax recruits more motoneurons than the voluntary contraction at 6–8% of MVC, such a compensation is incomplete. This explains that there was some trend to inhibition of the H reflex when using either a single cutaneous volley (see Fig. 3A of Burke et al., 1994) or a train (Fig. 1B), and the stronger the disfacilitation, the more incomplete this compensation can be and, thus, the greater the trend to inhibition of the reflex (filled circles in Fig. 2G).
Which interneurons?
Similar evidence for disfacilitation (i.e. suppression of the on-going EMG and of the MEP, but not of the monosynaptic reflex) has been found in biceps and triceps brachii of normal subjects. The average central delay of this superficial radial-induced suppression is longer the more caudal the motoneuron pool in the spinal cord: 3.2 ms in biceps (C5–C6), 4.2 ms in ECR (C6–C8), 4.9 ms in triceps (C7–T1) (Burke et al., 1994; Pierrot-Deseilligny, 1996). As mentioned in the Introduction, this suggests that the excitatory premotoneurons inhibited by the superficial radial volley are located rostral to the motoneurons, much as are the putative propriospinal neurons. It is argued that the disfacilitation seen in stroke patients is also due to inhibition of these neurons, although similar investigations in biceps and triceps so far have not been performed.
Possible mechanism underlying the increased suppression in stroke patients
Cutaneous volleys activate feedback inhibitory interneurons, which in turn inhibit presumed propriospinal neurons (see Fig. 5). Increased suppression of the on-going EMG in patients with poor recovery may result from an increased part of the descending command passing through the putative propriospinal relay (the greater this component, the greater can be the cutaneous-induced disfacilitation). However, alternative possibilities must be considered. (i) Feedback inhibitory interneurons receive an excitatory corticospinal drive (Nicolas et al., 2001), and an increase in this drive could facilitate the transmission in the inhibitory pathway and enhance the EMG suppression. However, the finding that the cutaneous inhibition was symmetrical (and of the same magnitude as in normal subjects) when using a single shock (open squares in Fig. 3C and D) provides evidence against increased corticospinal activation of inhibitory interneurons (a possibility that would be unlikely, given the corticospinal lesion). (ii) Increased excitability of inhibitory interneurons due to changes in their input from other sources, and/or decreased presynaptic inhibition of cutaneous afferents synapsing with presumed propriospinal neurons would be possible; but, again, this should also produce asymmetrical suppression when using single volleys.
In fact, the corticospinal lesion is more likely to have caused decreased corticospinal drive on feedback inhibitory interneurons. The greater suppression observed on the affected side with the train could thus be the net result of two opposing effects: decreased corticospinal drive on inhibitory interneurons due to the lesion, and a greater component of the descending command relayed through the propriospinal system. The finding that the suppression of the MEP became asymmetrical only when the last volley could act (12 ms ISI in Fig. 2F), while there was a symmetrical suppression elicited by the first shock(s) (10 ms ISI in Fig. 2F), gives some support to this view, even though it is difficult to draw conclusions from the limited data.
Possible mechanisms underlying increased excitation of propriospinal neurons
The origin of any such increased excitation could be an increased excitability of the putative propriospinal neurons, i.e. an increased excitability either to the peripheral input related to the contraction (see Marchand-Pauvert et al. 1999) or to other descending (reticulospinal) inputs. There could also be unmasking (and/or reorganization) of connections from the ipsilateral undamaged hemisphere (see Benecke et al., 1991; Chollet et al., 1991; Turton et al., 1996; Cramer et al., 1997; Honda et al., 1997; Cao et al., 1998; and the wiring diagram in Fig. 5). A good candidate would be the connections from the ipsilateral premotor cortex to the reticular formation, which, in turn, gives rise to bilateral reticulospinal projections (Benecke et al., 1991). Data obtained with TMS of the ipsilateral undamaged hemisphere in patients with poor recovery from stroke are consistent with this view. Indeed, MEPs elicited by stimulation of the undamaged hemisphere in the ipsilateral affected arm are more likely and have a lower threshold than in normal subjects, but have a longer latency than those elicited in the contralateral unaffected arm (Benecke et al., 1991; Turton et al., 1996). Rearrangement of the damaged hemisphere with mediation through indirect contralateral cortico-reticulo spinal pathways could also contribute to the transmission of the cortical command down to the spinal cord (Turton and Lemon, 1999).
In any case, if data in the cat (cf. Lundberg, 1999) apply to humans, the potent reticulospinal projections onto proprio spinal neurons could account for the residual motor possibilities of patients with poor recovery, whether due to unmasking and/or reorganization of these projections, or to hyperexcitability of these neurons themselves. This view is supported by the fact that patients with poor recovery had associated involuntary synkinetic movements. In this respect, it has been shown that propriospinal neurons have divergent projections onto motoneurons of muscles operating at different joints in the cat (Alstermark et al., 1990), and there is indirect evidence for similar divergent projections of presumed propriospinal neurons in humans (Mazevet and Pierrot-Deseilligny, 1994; Pierrot-Deseilligny, 1996). This creates a hard-wired spinal network appropriate for the co-activation of several muscles, as would be required in complex movements such as reaching. However, if a greater part of the descending command were mediated through this system, isolated movements would be difficult, especially if the absence of corticospinal drive on inhibitory interneurons prevented the sharpening of the focus in this intrinsically diffuse system. Thus, only stereotyped synkinetic movements would be performed, much as is the case in patients with poor motor recovery.
Changes in neural mechanisms during the course of recovery
Asymmetry between the cutaneous-induced suppression of the on-going EMG on the affected and unaffected sides was observed only in patients with poor recovery of wrist extension (Fig. 4B and C). Moreover, in those patients who were tested twice, the initial asymmetry seen at the stage of poor recovery tended to disappear with further recovery. Although these data were obtained for only six patients in group A, the finding still suggests that the take-over of the transmission of the descending command by propriospinal neurons could be merely a transient compensatory response following the interruption of the contralateral corticospinal pathway by the lesion. With good recovery, plastic changes occur in the contralateral damaged hemisphere, with extension and relocation of the upper limb area (Weiller et al., 1993; Rossini et al., 1998). By that time, contralateral corticospinal projections presumably are rearranged, as shown by the reappearance of MEPs elicited by stimulation of the contralateral damaged hemisphere with a latency decline highly correlated with the quality of the motor recovery (Turton et al., 1996), and the previously enhanced propriospinal mediation decreases.
|
Acknowledgements |
|---|
We wish to thank Professor D. Burke, Professor R. Lemon and Dr L. Mazières for reading and commenting upon the manuscript, and Annie Rigaudie for excellent technical assistance. This work was supported by grants from Assistance Publique Hôpitaux de Paris (PHRC 95/078), Ministère de la Recherche (UPRES EA 2393), Institut National pour la Santé et la Recherche Médicale (CRI INSERM 96037) and Institut pour la Recherche sur la Moelle Épinière (IRME).
|
References |
|---|
|
TopSummaryIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
Aimonetti JM, Vedel JP, Schmied A, Pagni S. Distribution of presynaptic inhibition on type-identified motoneurones in the extensor carpi radialis pool in man. J Physiol 2000; 522: 125–35.
Alstermark B, Kümmel H, Pinter MJ, Tantisira B. Integration in descending motor pathways controlling the forelimb in the cat. 17. Axonal projection and termination of C3–C4 propriospinal neurones in the C6–Th1 segments. Exp Brain Res 1990; 81: 447–61.[CrossRef][Web of Science][Medline]
Alstermark B, Isa T, Ohki T, Saito T. Disynaptic pyramidal excitation in forelimb motoneurones mediated via C3–C4 propriospinal neurons in the Macaca fuscata. J Neurophysiol 1999; 82: 3580–5.
Bawa P, Lemon RN. Recruitment of motor units in response to transcranial magnetic stimulation in man. J Physiol 1993; 471: 445–64.
Benecke R, Meyer BU, Freund HJ. Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation. Exp Brain Res 1991; 83: 419–26.[Web of Science][Medline]
Berardelli A. Day BL, Marsden CD, Rothwell JC. Evidence favouring presynaptic inhibition between antagonist muscle afferents in the human forearm. J Physiol 1987; 39: 71–83.
Burke D, Gracies JM, Mazevet D, Meunier S, Pierrot-Deseilligny E. Non-monosynaptic transmission of the cortical command for voluntary movement in man. J Physiol 1994; 480: 191–202.
Cao Y, D’Olhaberriague L, Vikingstad EM, Levine SR, Welch KM. Pilot study of functional MRI to assess cerebral activation of motor function after poststroke hemiparesis. Stroke 1998; 29: 112–22.
Cavallari P, Lalli S. Changes in excitability of the flexor carpi radialis H-reflex following tactile stimulation of the index fingertip. Exp Brain Res 1998; 120: 345–51.[CrossRef][Web of Science][Medline]
Chollet F, DiPiero V, Wise RJ, Brooks DJ, Dolan RJ, Frackowiak RS. The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. Ann Neurol 1991; 29: 63–71.[CrossRef][Web of Science][Medline]
Cramer SC, Nelles G, Benson RR, Kaplan JD, Parker RA, Kwong KK, et al. A functional MRI study of subjects recovered from hemiparetic stroke. Stroke 1997; 28: 2518–27.
Crone C, Hultborn H, Mazières L, Morin C, Nielsen J, Pierrot-Deseilligny E. Sensitivity of monosynaptic test reflexes to facilitation and inhibition as a function of the test reflex size: a study in man and the cat. Exp Brain Res 1990; 81: 35–45.[Web of Science][Medline]
Dewald JP, Pope PS, Given JD, Buchanan TS, Rymer WZ. Abnormal muscle coactivation patterns during isometric torque generation at the elbow and shoulder in hemiparetic subjects. Brain 1995; 118: 495–510.
Garnett R, Stephens JA. The reflex responses of single motor units in human first dorsal interosseus muscle following cutaneous afferent stimulation. J Physiol 1980; 303: 351–64.
Hallett M. Plasticity of the human motor cortex and recovery from stroke. Brain Res Rev 2001; 36: 169–74.[CrossRef][Medline]
Held JP, Pierrot-Deseilligny E. Rééducation motrice des affections neurologiques. Paris: J.B. Baillères; 1969.
Honda M, Nagamine T, Fukuyama H, Yonekura Y, Kimura J, Shibasaki H. Movement-related cortical potentials and regional cerebral blood flow change in patients with stroke after motor recovery. J Neurol Sci 1997; 146: 117–26.[CrossRef][Web of Science][Medline]
Lundberg A. Descending control of forelimb movements in the cat. Brain Res Bull 1999; 50: 323–4.[CrossRef][Web of Science][Medline]
Maertende Noordhout A, Rothwell JC, Day BL, Dressler D, Nakashima K, Thompson PD, et al. Effect of digital nerve stimuli on responses to electrical or magnetic stimulation on the human brain. J Physiol 1992; 447: 535–48.
Maertende Noordhout A, Rapisarda G, Bogacz D, Gérard P, de Pasqua V, Pennisi G, et al. Corticomotoneuronal synaptic connections in normal man. An electrophysiological study. Brain 1999; 122: 1327–40.
Maier M, Illert M, Kirkwood PA, Nielsen J, Lemon RN. Does a C3–C4 propriospinal system transmit corticospinal excitation in the primate? An investigation in the macaque monkey. J Physiol 1998; 511: 191–212.
Malmgren K, Pierrot-Deseilligny E. Evidence for non-monosynaptic Ia excitation of human wrist flexor motoneurones, possibly via propriospinal neurones. J Physiol 1988; 405: 747–64.
Marchand-Pauvert V, Mazevet D, Pierrot-Deseilligny E, Pol S, Pradat-Diehl P. Handedness-related asymmetry in transmission in a system of human cervical premotoneurones. Exp Brain Res 1999; 125: 323–34.[CrossRef][Web of Science][Medline]
Marchand-Pauvert V, Mazevet D, Pradat-Diehl P, Alstermark B, Pierrot-Deseilligny E. Interruption of a relay of corticospinal excitation by a spinal lesion at C6–C7. Muscle Nerve 2001; 24: 1554–61.[CrossRef][Web of Science][Medline]
Mazevet D, Pierrot-Deseilligny E. Pattern of descending excitation of presumed propriospinal neurones at the onset of voluntary movement in man. Acta Physiol Scand 1994; 150: 27–38.[Web of Science][Medline]
Mazevet D, Meunier S, Pol S, Pierrot-Deseilligny E. Recovery from hemiplegia through propriospinal neurones [abstract]. Electroencephalogr Clin Neurophysiol 1995; 97: S.212.
Mazevet D, Pierrot-Deseilligny E, Rothwell JC. A propriospinal-like contribution to electromyographic responses evoked in wrist extensor muscles by transcranial stimulation of the motor cortex in man. Exp Brain Res 1996; 109: 495–9.[Web of Science][Medline]
Nakajima K, Maier MA, Kirkwood PA, Lemon RN. Striking differences in transmission of corticospinal excitation to upper limb motoneurones in two primate species. J Neurophysiol 2000; 84: 698–709.
Nicolas G, Marchand-Pauvert V, Burke D, Pierrot-Deseilligny E. Corticospinal excitation of presumed cervical propriospinal neurones and its reversal to inhibition in humans. J Physiol 2001; 533: 903–19.
Nielsen J, Pierrot-Deseilligny E. Pattern of cutaneous inhibition of the propriospinal-like excitation to human upper limb motoneurones. J Physiol 1991; 434: 169–82.
Pauvert V, Pierrot-Deseilligny E, Rothwell JC. Role of spinal premotoneurones in mediating corticospinal input to forearm motoneurones in man. J Physiol 1998; 508: 301–12.
Pierrot-Deseilligny E. Transmission of the cortical command for human voluntary movement through cervical propriospinal premotoneurons. Prog Neurobiol 1996; 48: 489–517.[CrossRef][Web of Science][Medline]
Rossini PM, Caltagirone C, Castriota-Scanderbeg A, Cicinelli P, Del Gratta C, Demartin M, et al. Hand motor cortical area reorganization in stroke: a study with fMRI, MEG and TCS maps. Neuroreport 1998; 9: 2141–6.[Web of Science][Medline]
Rothwell JC. Spinal interneurones: re-evaluation and controversy. Adv Exp Med Biol 2002; 508: 259–63.[Web of Science][Medline]
Turton A, Lemon RN. The contribution of fast corticospinal input to the voluntary activation of proximal muscles in normal subjects and in stroke patients. Exp Brain Res 1999; 129: 559–72.[CrossRef][Web of Science][Medline]
Turton A, Wroe S, Trepte N, Fraser C, Lemon RN. Contralateral and ipsilateral EMG responses to transcranial magnetic stimulation during recovery of arm and hand function after stroke. Electroencephalogr Clin Neurophysiol 1996; 101: 316–28.[CrossRef][Medline]
Weiller C, Ramsay SC, Wise RJ, Friston KJ, Frackowiak RS. Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction. Ann Neurol 1993; 33: 181–9.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. V. Roberts, C. M. Stinear, G. N. Lewis, and W. D. Byblow Task-Dependent Modulation of Propriospinal Inputs to Human Shoulder J Neurophysiol, October 1, 2008; 100(4): 2109 - 2114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. B.C. Swayne, J. C. Rothwell, N. S. Ward, and R. J. Greenwood Stages of Motor Output Reorganization after Hemispheric Stroke Suggested by Longitudinal Studies of Cortical Physiology Cereb Cortex, August 1, 2008; 18(8): 1909 - 1922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Lewek, T. G. Hornby, Y. Y. Dhaher, and B. D. Schmit Prolonged Quadriceps Activity Following Imposed Hip Extension: A Neurophysiological Mechanism for Stiff-Knee Gait? J Neurophysiol, December 1, 2007; 98(6): 3153 - 3162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Iglesias, V. Marchand-Pauvert, G. Lourenco, D. Burke, and E. Pierrot-Deseilligny Task-related changes in propriospinal excitation from hand muscles to human flexor carpi radialis motoneurones J. Physiol., August 1, 2007; 582(3): 1361 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Martin, S. C. Gandevia, and J. L. Taylor Muscle fatigue changes cutaneous suppression of propriospinal drive to human upper limb muscles J. Physiol., April 1, 2007; 580(1): 211 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H. Dobkin Behavioral, Temporal, and Spatial Targets for Cellular Transplants as Adjuncts to Rehabilitation for Stroke Stroke, February 1, 2007; 38(2): 832 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Kline, B. D. Schmit, and D. G. Kamper Exaggerated interlimb neural coupling following stroke Brain, January 1, 2007; 130(1): 159 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. I.E. Renner, H. Woldag, and H. Hummelsheim Central Compensation at Short Muscle Range Is Differentially Affected in Cortical Versus Subcortical Strokes Stroke, August 1, 2006; 37(8): 2076 - 2080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Ward, J. M. Newton, O. B. C. Swayne, L. Lee, A. J. Thompson, R. J. Greenwood, J. C. Rothwell, and R. S. J. Frackowiak Motor system activation after subcortical stroke depends on corticospinal system integrity Brain, March 1, 2006; 129(3): 809 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Jankowska and S. A. Edgley How Can Corticospinal Tract Neurons Contribute to Ipsilateral Movements? A Question With Implications for Recovery of Motor Functions Neuroscientist, February 1, 2006; 12(1): 67 - 79. [Abstract] [PDF]
|
|
|
|
|
|
S. Sasaki, T. Isa, L.-G. Pettersson, B. Alstermark, K. Naito, K. Yoshimura, K. Seki, and Y. Ohki Dexterous Finger Movements in Primate Without Monosynaptic Corticomotoneuronal Excitation J Neurophysiol, November 1, 2004; 92(5): 3142 - 3147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Dobkin Editorial Comment--Functional MRI: A Potential Physiologic Indicator for Stroke Rehabilitation Interventions Stroke, May 1, 2003; 34 (5): e26 - e28. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||