Monica A. Perez

Motor skill training induces changes in the excitability of the leg cortical area in healthy humans

Training-induced changes in cortical excitability may play an important role in rehabilitation of gait ability in patients with neurological disorders. In this study, we investigated the effect of a 32-min period of motor skill, non-skill and passive training involving the ankle muscles on leg motor cortical excitability in healthy humans. Transcranial magnetic stimulation (TMS) at a range of intensities was applied to obtain a recruitment curve of the motor evoked potentials (MEPs) in the tibialis anterior (TA) muscle before and after training. We also explored the effect of training on inhibitory and facilitatory cortical circuits by using a paired-pulse TMS technique at intervals of 2.5xa0ms (short-interval intracortical inhibition, SICI) and 8xa0ms (intracortical facilitation, ICF). During motor skill training, subjects were instructed to make a cursor follow a series of target lines on a computer screen by performing voluntary ankle dorsi- and plantarflexion movements. Non-skill and passive training consisted of repeated voluntary and assisted dorsi- and plantarflexion movements, respectively. Recruitment curves increased significantly after 32xa0min of motor skill training but not after non-skill and passive training, suggesting that only skill motor training increases motor cortical excitability. Motor skill training was not accompanied by any changes in the recruitment curves of TA MEPs evoked by transcranial electrical stimulation, suggesting that the increased MEPs to TMS was likely caused by changes in excitability at a cortical site. SICI was decreased after 32xa0min of motor skill training but no changes were observed in ICF. We conclude that similar plastic changes as have previously been reported for the hand motor following motor skill training may also be observed for the leg motor area. The observed plastic changes appeared to be related to the degree of difficulty in the motor task, and may be of relevance for rehabilitation of gait disorders.

Changes in corticospinal drive to spinal motoneurones following visuo-motor skill learning in humans

We have previously demonstrated an increase in the excitability of the leg motor cortical area in relation to acquisition of a visuo‐motor task in healthy humans. It remains unknown whether the interaction between corticospinal drive and spinal motoneurones is also modulated following motor skill learning. Here we investigated the effect of visuo‐motor skill training involving the ankle muscles on the coupling between electroencephalographic (EEG) activity recorded from the motor cortex (Cz) and electromyographic (EMG) activity recorded from the left tibialis anterior (TA) muscle in 11 volunteers. Coupling in the time (cumulant density function) and frequency domains (coherence) between EEG–EMG and EMG–EMG activity were calculated during tonic isometric dorsiflexion before and after 32 min of training a visuo‐motor tracking task involving the ankle muscles or performing alternating dorsi‐ and plantarflexion movements without visual feedback. A significant increase in EEG–EMG coherence around 15–35 Hz was observed following the visuo‐motor skill session in nine subjects and in only one subject after the control task. Changes in coherence were specific to the trained muscle as coherence for the untrained contralateral TA muscle was unchanged. EEG and EMG power were unchanged following the training. Our results suggest that visuo‐motor skill training is associated with changes in the corticospinal drive to spinal motorneurones. Possibly these changes reflect sensorimotor integration processes between cortex and muscle as part of the motor learning process.

Patterned Sensory Stimulation Induces Plasticity in Reciprocal Ia Inhibition in Humans

Training of spinal cord circuits using sensorimotor stimulation has been proposed as a strategy to improve movement after spinal injury. How sensory stimulation may lead to long-lasting changes is not well understood. We studied whether sensory stimulation might induce changes in the strength of a specific spinal interneuronal circuit: spinally mediated reciprocal Ia inhibition. In healthy humans, the strength of reciprocal inhibition between ankle flexor and extensor muscles was assessed before and after 30 min of peroneal nerve stimulation at motor threshold intensity. Three stimulation protocols were assessed: patterned nerve stimulation (10 pulses at 100 Hz every 1.5 sec), uniform nerve stimulation (one pulse every 150 msec), and combined stimulation of the peroneal nerve and the motor cortex with transcranial magnetic stimulation. Short-latency reciprocal inhibition from ankle flexor to extensor muscles was measured by conditioning the soleus H-reflex with stimulation of the common peroneal nerve. The strength of the reciprocal inhibition was measured at baseline and for 20 min after each stimulation session. Patterned stimulation, with or without motor cortex stimulation, enhanced reciprocal inhibition for at least 5 min afterward. The uniform pattern of stimulation was ineffective. These results demonstrate the presence of short-term plasticity within spinal inhibitory circuits. We conclude that the pattern of sensory input is a crucial factor for inducing changes in the spinal circuit for reciprocal inhibition in humans. These findings may have implications for the use of repetitive patterned sensory stimulation in rehabilitative efforts to improve walking ability in patients with spinal injury.

Presynaptic control of group Ia afferents in relation to acquisition of a visuo-motor skill in healthy humans

Sensory information continuously converges on the spinal cord during a variety of motor behaviours. Here, we examined presynaptic control of group Ia afferents in relation to acquisition of a novel motor skill. We tested whether repetition of two motor tasks with different degrees of difficulty, a novel visuo‐motor task involving the ankle muscles, and a control task involving simple voluntary ankle movements, would induce changes in the size of the soleus H‐reflex. The slope of the H‐reflex recruitment curve and the H‐max/M‐max ratio were depressed after repetition of the visuo‐motor skill task and returned to baseline after 10 min. No changes were observed after the control task. To elucidate the mechanisms contributing to the H‐reflex depression, we measured the size of the long‐latency depression of the soleus H‐reflex evoked by peroneal nerve stimulation (D1 inhibition) and the size of the monosynaptic Ia facilitation of the soleus H‐reflex evoked by femoral nerve stimulation. The D1 inhibition was increased and the femoral nerve facilitation was decreased following the visuo‐motor skill task, suggesting an increase in presynaptic inhibition of Ia afferents. No changes were observed in the disynaptic reciprocal Ia inhibition. Somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve (TN) were also unchanged, suggesting that transmission in ascending pathways was unaltered following the visuo‐motor skill task. Together these observations suggest that a selective presynaptic control of Ia afferents contributes to the modulation of sensory inputs during acquisition of a novel visuo‐motor skill in healthy humans.

Short-term adaptations in spinal cord circuits evoked by repetitive transcranial magnetic stimulation: possible underlying mechanisms.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to induce adaptations in cortical neuronal circuitries. In the present study we investigated whether rTMS, through its effect on corticospinal pathways, also produces adaptations at the spinal level, and what the neuronal mechanisms involved in such changes are. rTMS (15xa0trains of 20xa0pulses at 5xa0Hz) was applied over the leg motor cortical area in ten healthy human subjects. At rest motor evoked potentials (MEPs) in the soleus and tibialis anterior muscles were facilitated by rTMS (at 1.2×MEPxa0threshold). In contrast, the soleus H-reflex was depressed for 1xa0s at stimulus intensities from 0.92 to 1.2×MEPxa0threshold. rTMS increased the size of the long-latency depression of the soleus H-reflex evoked by common peroneal nerve stimulation and decreased the femoral nerve facilitation of the soleus H-reflex. These observations suggest that the depression of the H-reflex by rTMS can be explained, at least partly, by an increased presynaptic inhibition of soleus Ia afferents. In contrast, rTMS had no effect on disynaptic reciprocal Ia inhibition from ankle dorsiflexors to plantarflexors. We conclude that a train of rTMS may modulate transmission in specific spinal circuitries through changes in corticospinal drive. This may be of relevance for future therapeutic strategies in patients with spasticity.

Impaired posture-dependent modulation of disynaptic reciprocal Ia inhibition in individuals with incomplete spinal cord injury

Posture influences the strength of spinal reflex circuits in healthy individuals. The purpose of this study was to determine the extent to which sitting and standing posture influences the strength of reciprocal Ia inhibition between ankle flexor and extensor muscles in individuals with incomplete spinal cord injury (SCI). Ten individuals with SCI and 15 healthy individuals participated in the study. Short-latency reciprocal inhibition was measured by conditioning the soleus H-reflex with stimulation of the common peroneal nerve. There was no significant difference in the strength of reciprocal Ia inhibition in sitting and standing positions in individuals with SCI. However, healthy individuals showed increased inhibition in a standing compared to a sitting position. The results suggest an impaired posture-dependent modulation of reciprocal Ia inhibition following SCI.

Reticulospinal Contributions to Gross Hand Function after Human Spinal Cord Injury

Multiple descending motor pathways likely contribute to the recovery of hand motor function following spinal cord injury (SCI). Reticulospinal neurons project to spinal motor neurons controlling hand muscles and extensively sprout into gray matter structures after SCI; therefore, it has been proposed that the reticulospinal tract is one of the descending motor pathways involved in recovery of hand function after injury. To test this hypothesis, we examined the StartReact response, an involuntary release of a planned movement via a startling stimulus that engages the reticulospinal tract, by measuring reaction times from electromyographic activity in an intrinsic finger muscle during three motor tasks requiring different degrees of hand dexterity: index finger abduction, a precision grip, and a power grip. Males and females with and without incomplete chronic cervical SCI were tested. We found that although SCI participants voluntarily responded to all tasks, reaction times were shorter during a startle cue while performing a power grip but not index finger abduction or precision grip. Control subjects had similarly shorter reaction times during a startle cue in all motor tasks. These results provide the first evidence for a contribution of the reticulospinal tract to hand control in humans with SCI during gross finger manipulations and suggest that this contribution is less pronounced during fine dexterous finger movements. SIGNIFICANCE STATEMENT It has been long proposed that brainstem pathways contribute to the recovery of hand function in humans with spinal cord injury (SCI). Here, we show that individuals with anatomically incomplete chronic cervical SCI responded to a startle stimulus, a test that engages the reticulospinal tract, while performing a power grip but not during index finger abduction or precision grip. Control subjects responded to a startle stimulus similarly across tasks. These observations suggest that reticulospinal outputs after SCI contribute to hand motor tasks involving gross finger movements. Interestingly, this contribution is less pronounced during fine dexterous finger movements.

Spike-timing-dependent plasticity in lower-limb motoneurons after human spinal cord injury

Recovery of lower-limb function after spinal cord injury (SCI) likely depends on transmission in the corticospinal pathway. Here, we examined whether paired corticospinal-motoneuronal stimulation (PCMS) changes transmission at spinal synapses of lower-limb motoneurons in humans with chronic incomplete SCI and aged-matched controls. We used 200 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation (TMS) over the leg representation of the motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the tibialis anterior (TA) muscle 2 ms before antidromic potentials evoked in motoneurons by electrical stimulation of the common peroneal nerve (PCMS+) or when antidromic potentials arrived 15 or 28 ms before corticospinal volleys (PCMS-) on separate days. Motor evoked potentials (MEPs) elicited by TMS and electrical stimulation were measured in the TA muscle before and after each stimulation protocol. After PCMS+, the size of MEPs elicited by TMS and electrical stimulation increased for up to 30 min in control and SCI participants. Notably, this was accompanied by increases in TA electromyographic activity and ankle dorsiflexion force in both groups, suggesting that this plasticity has functional implications. After PCMS-, MEPs elicited by TMS and electrical stimulation were suppressed if afferent input from the common peroneal nerve reduced TA MEP size during paired stimulation in both groups. In conclusion, PCMS elicits spike-timing-dependent changes at spinal synapses of lower-limb motoneurons in humans and has potential to improve lower-limb motor output following SCI.NEW & NOTEWORTHY Approaches that aim to enhance corticospinal transmission to lower-limb muscles following spinal cord injury (SCI) are needed. We demonstrate that paired corticomotoneuronal stimulation (PCMS) can enhance plasticity at spinal synapses of lower-limb motoneurons in humans with and without SCI. We propose that PCMS has potential for improving motor output in leg muscles in individuals with damage to the corticospinal tract.

Interhemispheric Connectivity during Bimanual Isometric Force Generation

Interhemispheric interactions through the corpus callosum play an important role in the control of bimanual forces. However, the extent to which physiological connections between primary motor cortices are modulated during increasing levels of bimanual force generation in intact humans remains poorly understood. Here we studied coherence between electroencephalographic (EEG) signals and the ipsilateral cortical silent period (iSP), two well-known measures of interhemispheric connectivity between motor cortices, during unilateral and bilateral 10%, 40%, and 70% of maximal isometric voluntary contraction (MVC) into index finger abduction. We found that EEG-EEG coherence in the alpha frequency band decreased while the iSP area increased during bilateral compared with unilateral 40% and 70% but not 10% of MVC. Decreases in coherence in the alpha frequency band correlated with increases in the iSP area, and subjects who showed this inverse relation were able to maintain more steady bilateral muscle contractions. To further examine the relationship between the iSP and coherence we electrically stimulated the ulnar nerve at the wrist at the alpha frequency. Electrical stimulation increased coherence in the alpha frequency band and decreased the iSP area during bilateral 70% of MVC. Altogether, our findings demonstrate an inverse relation between alpha oscillations and the iSP during strong levels of bimanual force generation. We suggest that interactions between neural pathways mediating alpha oscillatory activity and transcallosal inhibition between motor cortices might contribute to the steadiness of strong bilateral isometric muscle contractions in intact humans.

Altered corticospinal function during movement preparation in humans with spinal cord injury.

In uninjured humans, transmission in the corticospinal pathway changes in a task‐dependent manner during movement preparation. We investigated whether this ability is preserved in humans with incomplete chronic cervical spinal cord injury (SCI). Our results show that corticospinal excitability is altered in the preparatory phase of an upcoming movement when there is a need to suppress but not to execute rapid index finger voluntary contractions in individuals with SCI compared with controls. This is probably related to impaired transmission at a cortical and spinal level after SCI. Overall our findings indicate that deficits in corticospinal transmission in humans with chronic incomplete SCI are also present in the preparatory phase of upcoming movements.