François D. Roy

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

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

Peripheral sensory activation of cortical circuits in the leg motor cortex of man

Peripheral sensory afferents in the hand activate both excitatory and inhibitory intracortical circuits to potentially facilitate and prune descending motor commands. In this study, we characterized how afferent inputs modulate the excitability of cortical circuits in the leg area of the primary motor cortex by examining how stimulation of the tibial nerve (TN) at the ankle alters motor evoked potentials (MEPs) activated by transcranial magnetic stimulation (TMS). Resting MEPs in the tibialis anterior (TA) muscle were facilitated in response to heteronymous activation of the TN 45–50 ms earlier, whereas MEPs were inhibited at interstimulus intervals of 32.5–37.5 ms. Similar time‐dependent modulation occurred in the soleus (SOL) muscle with stimulation of the homonymous posterior tibial nerve (PTN) at the knee. To determine the site of this afferent‐evoked facilitation and inhibition (spinal or cortical), we compared the effects of afferent stimulation to responses evoked at subcortical sites. At interstimulus intervals where MEP facilitation was observed (near 50 ms), spinal H‐reflexes and responses evoked from corticospinal tract stimulation at the brainstem were predominantly depressed by the sensory stimulus suggesting that the observed MEP facilitation was cortical in origin. At interstimulus intervals where MEP depression was observed (near 35 ms), brainstem evoked responses were depressed to a similar degree and, in contrast to the hand, this suggests that spinal rather than cortical circuits mediate short‐latency afferent inhibition (SAI) of leg MEPs. When the MEP was facilitated by afferent inputs, short‐interval intracortical inhibition (SICI) was reduced and intracortical facilitation (ICF) was increased, but long‐interval intracortical inhibition (LICI) at a 100 ms interval was unchanged. In addition, sensory excitation increased the recruitment of early, middle and late descending corticospinal volleys as evidenced from increases in MEP facilitation at the corresponding I‐wave periodicity. We propose that sensory activation from the leg has a diffuse and predominantly facilitatory effect on the leg primary motor cortex.

Afferent Regulation of Leg Motor Cortex Excitability After Incomplete Spinal Cord Injury

An incomplete spinal cord injury (SCI) impairs neural conduction along spared ascending sensory pathways to disrupt the control of residual motor movements. To characterize how SCI affects the activation of the motor cortex by spared ascending sensory pathways, we examined how stimulation of leg afferents facilitates the excitability of the motor cortex in subjects with incomplete SCI. Homo- and heteronymous afferents to the tibialis anterior (TA) representation in the motor cortex were electrically stimulated, and the responses were compared with uninjured controls. In addition, we examined if cortical excitability could be transiently increased by repetitively pairing stimulation of spared ascending sensory pathways with transcranial magnetic stimulation (TMS), an intervention termed paired associative stimulation (PAS). In uninjured subjects, activating the tibial nerve at the ankle 45-50 ms before a TMS pulse in a conditioning-test paradigm facilitated the motor-evoked potential (MEP) in the heteronymous TA muscle by twofold on average. In contrast, prior tibial nerve stimulation did not facilitate the TA MEP in individuals with incomplete SCI (n = 8 SCI subjects), even in subjects with less severe injuries. However, we provide evidence that ascending sensory inputs from the homonymous common peroneal nerve (CPN) can, unlike the heteronymous pathways, facilitate the motor cortex to modulate the TA MEP (n = 16 SCI subjects) but only in subjects with less severe injuries. Finally, by repetitively coupling CPN stimulation with coincident TA motor cortex activation during PAS, we show that 7 of 13 SCI subjects produced appreciable (>20%) facilitation of the MEP following the intervention. The increase in corticospinal tract excitability by PAS was transient (<20 min) and tended to be more prevalent in SCI subjects with stronger functional ascending sensory pathways.

Short-interval intracortical inhibition with incomplete spinal cord injury

OBJECTIVE Short-interval intracortical inhibition (SICI) in leg and hand muscles was characterized in individuals with incomplete spinal cord injury (SCI) to understand how such inhibition limits corticospinal drive after spinal insult. METHODS We compared SICI during a voluntary contraction in 16 SCI and 14 control subjects, the latter group tested over a larger range of conditioning and test stimulus (CS and TS) intensities to best match the SCI data. RESULTS The average peak SICI in the tibialis anterior muscle was typically 3-4 times lower in the SCI subjects compared to controls. When matched for absolute TS intensity, in terms of maximum stimulator output, both U-shaped SICI recruitment curves were produced by similar CS intensities. SICI in the first dorsal interosseous muscle of the hand tended to be larger than in the ankle flexor. CONCLUSIONS Incomplete SCI reduces SICI compared to controls, but the absolute CS intensities that produce the U-shaped SICI recruitment curves are unchanged. SIGNIFICANCE These findings suggest that although the relative excitability profile of cortical SICI networks is unchanged after SCI, the effective inhibition of corticospinal tract output by these neurons is reduced.

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

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

Facilitation of corticospinal connections in able-bodied people and people with central nervous system disorders using eight interventions.

Background: Voluntary contractions (VOL), functional electrical stimulation (FES), and transcranial magnetic stimulation (TMS) can facilitate corticospinal connections. Objective: To find the best methods for increasing corticospinal excitability by testing eight combinations: (1) VOL, (2) FES, (3) FES + VOL, (4) TMS, (5) TMS + VOL, (6) paired associative stimulation (PAS) consisting of FES + TMS, (7) PAS + VOL, and (8) double-pulse TMS + VOL. Methods: Interventions were applied for 3 × 10 minutes in 15 able-bodied subjects, 14 subjects with stable central nervous system lesions (e.g., chronic stroke, and incomplete spinal cord injury) and 16 subjects with progressive central nervous system conditions (e.g., secondary progressive multiple sclerosis). Motor-evoked potentials (MEP), M-waves, and H-reflexes were monitored over a 1-hour period. Results: Three interventions (PAS, PAS + VOL, and double-pulse TMS + VOL) caused 15% to 20% increases (P < 0.05) in the MEP at a stimulus level that initially produced a half-maximal response (MEPhalf) during a contraction. Interventions were less effective in both clinical groups than in the able-bodied group. Interventions with VOL were more effective in increasing the MEPhalf than those without (P = 0.022). When more modalities were combined, the MEP increases were larger (P = 0.022). Conclusions: (1) Short-term application of FES, TMS, and VOL can facilitate corticospinal pathways, particularly when methods are combined. (2) The effects may depend on the total activation of neural pathways, which is reduced in central nervous system disorders.

Training to Enhance Walking in Children With Cerebral Palsy: Are We Missing the Window of Opportunity?

The objective of this paper is to (1) identify from the literature a potential critical period for the maturation of the corticospinal tract (CST) and (2) report pilot data on an intensive, activity-based therapy applied during this period, in children with lesions to the CST. The best estimate of the CST critical period for the legs is when the child is younger than 2 years of age. Previous interventions for walking in children with CST damage were mainly applied after this age. Our preliminary results with training children younger than 2 years showed improvements in walking that exceeded all previous reports. Further, we refined techniques for measuring motor and sensory pathways to and from the legs, so that changes can be measured at this young age. Previous activity-based therapies may have been applied too late in development. A randomized controlled trial is now underway to determine if intensive leg therapy improves the outcome of children with early stroke.

Post-activation depression in the human soleus muscle using peripheral nerve and transcutaneous spinal stimulation

Transcutaneous stimulation of the human lumbar spine can be used to elicit root-evoked potentials (REPs). These sensory-motor responses display notable similarities to the monosynaptic H-reflex. The purpose of this study was to compare post-activation depression of the soleus REP to that of the H-reflex, when conditioned by either an H-reflex or an REP. Paired pulses were delivered 25-200ms apart and the recovery was characterized using three levels of stimulation. In all conditions, post-activation depression was reduced during contraction as compared to rest (P<0.001). REP doublets, delivered using an inter-pulse interval of 150ms, recovered to 68±8% of control during plantarflexion and 20±6% of control at rest. During contraction, recovery of a second REP was 65% of the corresponding recovery for a second H-reflex. The recovery of an H-reflex was equivalent, when conditioned by either an H-reflex or an REP, even though the spinal stimulus activated and/or engaged more afferent and efferent fibers. Our results suggest that the additional elements activated by the spinal stimulus did not affect the recovery of the H-reflex. However, the transcutaneous spinal stimulus produced more inhibition when it was assessed using two low-intensity REPs (P<0.05) suggesting that the pathway mediating the spinally-evoked response was more susceptible to being inhibited.

External Sensors for Detecting the Activation and Deactivation Times of the Major Muscles Used in Walking

Functional electrical stimulation (FES) can improve walking in individuals with mobility impairments. We evaluated accelerometers, force sensitive resistors, segment angles, and segment angular velocities to identify which sensor best determines the activation and deactivation times of the main muscles used during walking. This sensor(s) can be used in the future in conjunction with FES systems to improve walking. Able-bodied subjects walked at various speeds. Threshold levels were set for each sensor that minimized the difference between the times of activating and deactivating the electromyogram (EMG) of six muscles and the times of sensor threshold crossings as a percent of the step cycle. Mobility-impaired subjects walked at their preferred speed with and without FES to correct foot drop. Thresholds were set for these subjects so that sensor signals would cross at times that matched those of able-bodied subjects. Segment angles were generally the most effective sensor signals. Using segment angles of the thigh, shank, and foot, activation and deactivation times of the six muscles could be determined to within 6% of the step cycle. The shank segment angle produced the lowest overall error and was among the top three sensors for 10 of the 12 events (activation and deactivation of six muscle groups). A segment angle sensor was implemented using a complementary filter (accelerometer/gyroscope combination). Using this sensor improved rule-based timing of FES in subjects with foot drop as compared to accelerometers alone.

Reduced postactivation depression of soleus H reflex and root evoked potential after transcranial magnetic stimulation

Postactivation depression of the Hoffmann (H) reflex is associated with a transient period of suppression following activation of the reflex pathway. In soleus, the depression lasts for 100-200 ms during voluntary contraction and up to 10 s at rest. A reflex root evoked potential (REP), elicited after a single pulse of transcutaneous stimulation to the thoracolumbar spine, has been shown to exhibit similar suppression. The present study systematically characterized the effect of transcranial magnetic stimulation (TMS) on postactivation depression using double-pulse H reflexes and REPs. A TMS pulse reduced the period of depression to 10-15 ms for both reflexes. TMS could even produce postactivation facilitation of the H reflex, as the second reflex response was increased to 243 ± 51% of control values at the 75-ms interval. The time course was qualitatively similar for the REP, yet the overall increase was less. While recovery of the H reflex was slower in the relaxed muscle, the profile exhibited a distinct bimodal shape characterized by an early peak at the 25-ms interval, reaching 72 ± 23% of control values, followed by a trough at 50 ms, and then a gradual recovery at intervals > 50 ms. The rapid recovery of two successively depressed H reflexes, ∼ 25 ms apart, was also possible with double-pulse TMS. The effect of the TMS-induced corticospinal excitation on postactivation depression may be explained by a combination of pre- and postsynaptic mechanisms, although further investigation is required to distinguish between them.