Abstract
The purpose of this study was to investigate if FET produces a greater
increase in cortical excitability than either electrical stimulation (ES) or
voluntary (VOL) training alone in able-bodied volunteers. Cortical excitability
was assessed with transcranial magnetic stimulation (TMS) by constructing a
stimulus-response input-output curve with motor evoked responses of the finger
flexor muscles. A 20-minute FET session produced an 83% increase in the maximum
height of the input-output curve, whereas ES and VOL produced no increase in
cortical excitability. These results suggest that the combination of ES and
voluntary exercise might lead to better recovery than either ES or voluntary
exercise alone. Furthermore, FET might enhance motor recovery following stroke
by increasing cortical excitability, thus promoting cortical plasticity.
1. INTRODUCTION
The observation of carry-over effects with Functional Electrical
Stimulation has led to the development of electrical stimulation (ES) as a
therapeutic intervention for the treatment of stroke [1;2]. One treatment,
Functional Electrical Therapy (FET) combines intensive voluntary exercise with
patterned ES of specific muscle groups to mimic the normal activation of
able-bodied humans [1-3].
Results from recent clinical studies have shown promise for the use of
FET in the acute phase stroke rehabilitation of upper-limb motor function [1,3].
However, the physiological mechanisms that promote this recovery remain
unknown. Both aspects of FET, motor training and ES, have independently been shown
to produce cortical reorganisation [e.g. 4;5]. The combination of ES and
voluntary motor training (VOL) also produces changes in cortical excitability
in the tibialis anterior [6-8]. This suggests that one of the primary benefits
of FET might be that it promotes functional motor recovery by strengthening
corticospinal circuitry.
The apparent carry-over effects of
2. METHODS
Eight subjects with no known history of neuromuscular
disorder volunteered to participate in this study. All of the experiments were
conducted in accordance with the Declaration of Helsinki. The experimental
protocol was approved by the local ethical committee and all subjects gave
their written informed consent prior to their participation.
The setup for upper-limb FET is fully described by
Popovic et al. [3]. Clinically, upper-limb
FET for grasp function is conducted with a four-channel stimulator programmed
to control hand opening and closing (finger flexion/extension and thumb
abduction/adduction). In this study, we used a reduced version of FET where the
stimulation was restricted to finger flexion/extension alone. The excitability
of the finger flexor area in the motor cortex was examined after 20 minutes of
training.
2.1.
Electrical Muscle Stimulation
The
stimulation was applied using disposable self-adhesive surface electrodes with
the cathodes positioned over the respective motor points of the flexor muscles
(Flexor Digitorum Profundus (FDP) and Flexor Digitorum Super-ficialis (FDS))
and the Extensor Digitorum Communis (EDC). A common anode was placed on the
lateral surface of the forearm just proximal to the wrist. The electrode
positions were carefully selected to ensure that the opening and closing
movements of the hand were as natural as possible. The stimulation pattern was
designed to mimic the activity of fingers that is typical of slow grasping and
releasing. The pulse duration, frequency, and amplitude (current) were set to
minimize discomfort during stimulation yet produce a finger flexion/extension
movement that would allow the subject to grasp and lift a 50 cl bottle of water
without voluntary assistance (e.g.: f=50 Hz, T=200 μs, I=6–13 mA.
2.2.
Transcranial Magnetic Simulation
Transcranial magnetic stimuli (Magstim Rapid2, Magstim
Company,
2.3.
Peripheral Nerve Simulation
Peripheral nerve stimulation was used to normalize the magnetic evoked
potentials so that intra-subject comparisons could be made between MEPs
measured during different test sessions. A compound action potential in the
finger flexors was elicited with monopolar electrical stimulation of the median
nerve. The EMG responses representing the direct motor stimulation (M-wave)
were monitored as the stimulation intensity was increased from a subliminal
level until there was no further increase in the peak-to-peak amplitude of the
M-wave with increasing intensity. The stimulation amplitude was then increased
by approximately 15%. This supra-maximal stimulation level was used to elicit
the maximal M-wave (Mmax) to which the MEPs were normalized.
2.4.
Experimental Protocol
Each
subject participated in three training sessions involving 20 minutes of hand
grasp exercise where they lifted a 50 cl water bottle. The three training
sessions involved FET, ES alone, and VOL alone. The experiments were conducted
in three different sessions with at least 24 hours between each session.
A stimulus-response input-output curve was constructed before and after
each training session by measuring MEPs with a series of single pulse magnetic stimuli
delivered at a random inter-stimulus interval of 1-1.5 s and pseudo-random
stimulus intensity. The MEPs were quantified as the peak-to-peak amplitude, and
expressed as a percentage of the Mmax. The normalized MEPs were then
plotted against the stimulus intensity.
2.5.
Analysis
Data analysis was conducted offline. The normalized stimulus-response
input-output curve data were modeled with a three-parameter sigmoid equation:
where a, b and x0,
describe the height, slope, and center point of the curve, respectively. The
parameters were estimated by fitting this equation to the MEP data with a Marquardt-Levenberg
nonlinear least squares algorithm. The percent change from the pre-training to
post-training was calculated for each parameter. A one-way repeated measures
ANOVA was used to test for statistically significant differences as a result of
training and a Scheffé multiple-comparison test was used to test for difference
between training conditions. All statistical tests were conducted with a significance
level of 0.05.
3. RESULTS
A set of stimulus-response input-output curves for a single subject is illustrated
in Figure 1A-C. For the FET condition, the maximum height of the curve is
increased and there is a clear left-shift with respect to the pre-training
curve. In contrast, there is only a small change in the ES curve and no change
in VOL. In this case, parameter a increased
by 127%, 24% and 6% for FET, ES and VOL respectively. Across all subjects, only
parameter a showed a significant increase
with training (a: P=0.001; b: P=0.88; x0: P=0.94). The results for parameter a are illustrated in Figure 1D. Training
for 20 min produced a change in parameter a
of 83%, ‑1.5%, and 1% for FET, ES, and VOL, respectively. The Scheffé
multiple-comparison post-hoc test indicated that the FET group was significantly
different from the ES and VOL groups (P<0.05).
Figure 1. A-C) Stimulus-response input-output curves for finger flexor
MEPs normalized to Mmax. Responses after training (solid lines) are
shown superimposed on pre-training curves (dashed lines). D) Mean percent
change in parameter a (input-output
curve maximum) across all subjects.
4. DISCUSSION AND
CONCLUSIONS
A single session of FET training for 20 min in healthy subjects produced
changes in TMS-assessed cortical excitability. This observation provides
evidence for the suggestion that one of the methods by which FET enhances motor
recover following stroke is to increase cortical plasticity. For the upper limb
this phenomenon seems to be significantly greater for FET than either ES or
voluntary exercise applied alone. However, it is surprising that no significant
changes were found with either the ES or VOL conditions alone. Based on these
results more investigation into the effects of FET on cortical excitability is
warranted to improve its effectiveness in acute post-stroke rehabilitation.
References
[1] Popovic,D.B., Popovic,M.B., Sinkjaer,T.,
Ste-fanovic,A., Schwirtlich,L., Therapy of paretic arm in hemiplegic subjects
augmented with a neural pros-thesis: a cross-over study, Can. J. Physiol Pharmacol.,
82 (2004) 749-756.
[2] Gritsenko V., Prochazka A., A
functional electric stimulation-assisted excersise therapy system for
hemiplegic hand function, Arch. Phys. Med. Rehabil. 85 (2004) 881-885.
[3] Popovic,M.B., Popovic,D.B., Sinkjaer,T.,
Ste-fanovic,A., Schwirtlich,L., Clinical evaluation of Functional Electrical
Therapy in acute hemiplegic subjects, J. Rehabil. Res. Dev., 40 (2003) 443-453.
[4] Karni,A., Meyer,G., Jezzard,P.,
Adams,M.M., Turner,R., Ungerleider,L.G., Functional MRI evi-dence for adult
motor cortex plasticity during motor skill learning, Nature, 377 (1995)
155-158.
[5] Ridding,M.C., McKay,D.R.,
Thompson,P.D., Miles,T.S., Changes in corticomotor representations induced by
prolonged peripheral nerve stimulation in humans, Clin. Neurophysiol., 112
(2001) 1461-1469.
[6] Khaslavskaia,S., Sinkjaer,T.,
Motor cortex excit-ability following repetitive electrical stimulation of the
common peroneal nerve depends on the volun-tary drive, Exp. Brain Res., (2005).
[7] Kido,T.A., Stein,R.B.,
Short-term effects of functional electrical stimulation on motor-evoked
potentials in ankle flexor and extensor muscles, Exp. Brain Res., 159 (2004)
491-500.
[8] Knash,M.E., Kido,A.,
Gorassini,M., Chan,K.M., Stein,R.B., Electrical stimulation of the human common
peroneal nerve elicits lasting facilitation of cortical motor-evoked
potentials, Exp. Brain Res., 153 (2003) 366-377.
Acknowledgements
This study was funded by grants from the Danish
National Research Council and Det Obelske Familiefond.