Transsynaptic activation of human lumbar spinal motoneurons by transvertebral magnetic stimulation.

Noninvasive spinal stimulation has been increasingly used in research on motor control and neurorehabilitation. Despite advances in percutaneous electrical stimulation techniques, magnetic stimulation is not as commonly used as electrical stimulation. Therefore, it is still under discussion what neuronal elements are activated by magnetic stimulation of the human spinal cord. In this study, we demonstrated that transvertebral magnetic stimulation (TVMS) induced transsynaptic activation of spinal motoneuron pools in the lumbar cord. In healthy humans, paired-pulse TVMS was given over an intervertebral space between the L1-L2 vertebrae with an interpulse interval of 100 ms, and the stimulus-evoked electromyographic (EMG) responses were recorded in the lower limb muscles. The results show that the evoked EMG responses after the 2nd pulse were clearly suppressed compared with the widespread responses evoked after the 1st pulse in the muscles of the lower extremity, indicating that the transsynaptic activation of spinal motoneurons by the 2nd pulse was suppressed by the effects produced by the 1st pulse. The inconsistent modulation of response suppression to stimulus intensity across individuals suggests that the TVMS-evoked EMG responses are composed of the compound potentials mediated by the direct activation of motor axons and the transsynaptic activation of motoneuron pools through sensory afferents and that the recruitment order of those fibers by TVMS may be nonhomogeneous across individuals.

Corticospinal interface to restore voluntary control of joint torque in a paralyzed forearm following spinal cord injury in non-human primates.

The corticospinal tract plays a major role in the control of voluntary limb movements, and its damage impedes voluntary limb control. We investigated the feasibility of closed-loop brain-controlled subdural spinal stimulation through a corticospinal interface for the modulation of wrist torque in the paralyzed forearm of monkeys with spinal cord injury at C4/C5. Subdural spinal stimulation of the preserved cervical enlargement activated multiple muscles on the paralyzed forearm and wrist torque in the range from flexion to ulnar-flexion. The magnitude of the evoked torque could be modulated by changing current intensity. We then employed the corticospinal interface designed to detect the firing rate of an arbitrarily selected "linked neuron" in the forearm territory of the primary motor cortex (M1) and convert it in real time to activity-contingent electrical stimulation of a spinal site caudal to the lesion. Linked neurons showed task-related activity that modulated the magnitude of the evoked torque and the activation of multiple muscles depending on the required torque. Unlinked neurons, which were independent of spinal stimulation and located in the vicinity of the linked neurons, exhibited task-related or -unrelated activity. Thus, monkeys were able to modulate the wrist torque of the paralyzed forearm by modulating the firing rate of M1 neurons including unlinked and linked neurons via the corticospinal interface. These results suggest that the corticospinal interface can replace the function of the corticospinal tract after spinal cord injury.

Tuning of motor outputs produced by spinal stimulation during voluntary control of torque directions in monkeys.

Spinal stimulation is a promising method to restore motor function after impairment of descending pathways. While paresis, a weakness of voluntary movements driven by surviving descending pathways, can benefit from spinal stimulation, the effects of descending commands on motor outputs produced by spinal stimulation are unclear. Here, we show that descending commands amplify and shape the stimulus-induced muscle responses and torque outputs. During the wrist torque tracking task, spinal stimulation, at a current intensity in the range of balanced excitation and inhibition, over the cervical enlargement facilitated and/or suppressed activities of forelimb muscles. Magnitudes of these effects were dependent on directions of voluntarily produced torque and positively correlated with levels of voluntary muscle activity. Furthermore, the directions of evoked wrist torque corresponded to the directions of voluntarily produced torque. These results suggest that spinal stimulation is beneficial in cases of partial lesion of descending pathways by compensating for reduced descending commands through activation of excitatory and inhibitory synaptic connections to motoneurons.

Activation of human spinal locomotor circuitry using transvertebral magnetic stimulation.

Transvertebral magnetic stimulation (TVMS) of the human lumbar spinal cord can evoke bilateral rhythmic leg movements, as in walking, supposedly through the activation of spinal locomotor neural circuitry. However, an appropriate stimulus intensity that can effectively drive the human spinal locomotor circuitry to evoke walking-like movements has not been determined. To address this issue, TVMS was delivered over an intervertebral space of the lumbar cord (L1-L3) at different stimulus intensities (10-70% of maximum stimulator output) in healthy human adults. In a stimulus intensity-dependent manner, TVMS evoked two major patterns of rhythmic leg movements in which the left-right movement cycles were coordinated with different phase relationships: hopping-like movements, in which both legs moved in the same direction in phase, and walking-like movements, in which both legs moved alternatively in anti-phase; uncategorized movements were also observed which could not be categorized as either movement type. Even at the same stimulation site, the stimulus-evoked rhythmic movements changed from hopping-like movements to walking-like movements as stimulus intensity was increased. Different leg muscle activation patterns were engaged in the induction of the hopping- and walking-like movements. The magnitude of the evoked hopping- and walking-like movements was positively correlated with stimulus intensity. The human spinal neural circuitry required a higher intensity of magnetic stimulation to produce walking-like leg movements than to produce hopping-like movements. These results suggest that TVMS activates distinct neural modules in the human spinal cord to generate hopping- and walking-like movements.

[Artificial Neural Connection Restores Voluntary Motor Function After Stroke and Spinal Cord Injury].

Artificial neural connection (ANC) establishes an artificial neural pathway to connect distant neuromuscular substrates using a computer interface. Our series of studies have demonstrated three events achieved by ANC. 1)ANC compensated the voluntary motor pathways damaged by stroke and spinal cord injury (SCI). 2)ANC provided a novel function for the neuron to input its information into the ANC. 3)ANC induced plastic changes in the existing neural connectivity between the neural substrates connected by ANC. In the preset literature, we expound the neurophysiological mechanisms underlying the three events and introduce theoretical neural backgrounds in restoring and recovering impaired voluntary locomotor function after stroke and SCI.

Assessment of safety of self-controlled repetitive trans-vertebral magnetic stimulation.

OBJECTIVE: The aim of this study was to assess safety issues of self-controlled repetitive trans-vertebral magnetic stimulation (rTVMS) in humans. METHODS: We investigated effects of self-controlled rTVMS (≤20 Hz, ≤90% intensity) on vital signs and subjective sensations in 1690 trials of 30 healthy volunteers and 12 patients with spinal cord disorders. RESULTS: Healthy volunteers and the patients received 4595 ± 2345, and 4450 ± 2304 pulses in one day, respectively. No serious adverse events were observed in any participants, and only minor events were seen as follows. While blood pressure was unaffected in the patients, the diastolic blood pressure increased slightly after rTVMS in healthy volunteers. The peripheral capillary oxygen saturation increased after rTVMS in healthy volunteers. "Pain" or "Discomfort" was reported in approximately 10% of trials in both participants groups. Degree of the evoked sensation positively correlated with stimulus intensity and was affected by the site of stimulation. CONCLUSION: Self-controlled rTVMS (≤20 Hz and ≤90% intensity) did not induce any serious adverse effects in healthy volunteers and patients with spinal cord disorders. SIGNIFICANCE: Our results indicate that rTVMS can be used safely in physiological investigations in healthy volunteers and also as treatment for neurological disorders.

Abnormal changes in motor cortical maps in humans with spinal cord injury.

KEY POINTS: The functional role of motor cortical reorganization following spinal cord injury (SCI) remains largely unknown. Here, we tested motor maps in a hand muscle at rest and during voluntary contraction of the hand with and without voluntary contraction of a proximal arm muscle. Motor map area in participants with SCI decreased during hand voluntary contraction and further decreased during additional contraction of a proximal arm muscle compared with rest. In contrast, motor map area in controls increased during the same motor tasks. Participants with SCI with more severe sensory deficits in the hand showed larger decreases in motor map area. Ten minutes of hand muscle-tendon vibration increased the motor map area during voluntary contraction in SCI participants. These novel findings suggest that abnormal changes in motor cortical maps during voluntary contraction after SCI can be reshaped by sensory input, knowledge that can have implications for rehabilitation. ABSTRACT: Motor cortical representations reorganize following cervical spinal cord injury (SCI). The functional role of this reorganization remains largely unknown. Using neuronavigated transcranial magnetic stimulation, we examined motor cortical maps during voluntary contraction in humans with chronic cervical SCI and age-matched controls. We constructed motor maps in the first dorsal interosseous (FDI) muscle at rest and during voluntary contraction of the FDI with and without voluntary contraction of the biceps brachi (BB). The role of sensory input into this reorganization was examined by muscle-tendon vibration. We found that, at rest, motor maps were larger in SCI (22.3 cm2 ) compared with control (12.6 cm2 , P < 0.001) participants. Motor map area increased during voluntary contraction of the FDI (120.7%) and further increased during contraction of the BB (143.9%) compared with rest in control subjects; however, motor map area decreased during voluntary contraction of the FDI (69.5%) and further decreased during contraction of the BB (55.5%) in individuals with SCI. SCI participants with larger decreases in map area during voluntary contraction of the FDI were those with larger sensory deficits in the hand and 10 min of hand muscle-tendon vibration increased motor map area. These results provide the first evidence of abnormal changes in motor cortical maps in humans with chronic SCI during voluntary contraction, suggesting that sensory input can help to reshape this reorganization.

Arm cycling increases the short-latency reflex from ankle dorsiflexor afferents to knee extensor muscles.

Low-intensity electrical stimulation of the common peroneal nerve (CPN) evokes a short latency reflex in the heteronymous knee extensor muscles (referred to as the CPN reflex). The CPN reflex is facilitated at a heel strike during walking, contributing to body weight support. However, the origin of the CPN reflex increase during walking remains unclear. We speculate that this increase originates from multiple sources due to a body of evidence suggesting the presence of neural coupling between the arms and legs. Therefore, we investigated the extent to which the CPN reflex is modulated during rhythmic arm cycling. Twenty-eight subjects sat in an armchair and were asked to perform arm cycling at a moderate cadence using a stationary ergometer while performing isometric contraction of the knee extensors, such that the CPN reflex was evoked. The CPN reflex was evoked by stimulating the CPN [0.9-2.0× the motor threshold (MT) in the tibialis anterior muscle] at the level of the neck of the fibula. The CPN-reflex amplitude was measured from the vastus lateralis (VL). The biphasic reflex response in the VL was evoked within 27-45 ms following CPN stimulation. The amplitude of the CPN reflex increased during arm cycling compared with that before cycling. The modulation of the CPN reflex during arm cycling was detected only for CPN stimulation intensity around 1.2× MT. Furthermore, CPN-reflex modulation was not observed during the isometric contraction of the arm or passive arm cycling. Our results suggest the presence of neural coupling between the CPN-reflex pathways and neural systems generating locomotive arm movement.NEW & NOTEWORTHY Whether locomotive arm movements contribute to the control of the reflex pathway from ankle dorsiflexor afferents to knee extensor muscles [common peroneal nerve (CPN)-reflex] is an unresolved issue. The CPN reflex in the stationary leg was facilitated only by arm cycling, and not by passive or isometric motor tasks. Our results suggest that the arm locomotor system modulates the reflex pathway from ankle dorsiflexor afferents to the knee extensor muscles.

[Toward to Understanding of Athletes' Brain].

Tokyo Olympic Games and the Paralympic Games in 2020 is coming up next year. The interest in sports has been growing ever especially in Japan. People marvels at the excellent performance in athletes. They spend same practices for many years. It is well known that practice causes strengthen of muscles and cardiovascular system. However it remains largely unclear how the brain structure and function in of these athletes differ from those of novices. Here, we reviews the recent findings that are trying to understand athlete's brain in neuroanatomical and physiological point of views.

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.

Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii.

Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and that these interneurons might be equivalent to those identified in animal experiments.

Cortical and reticular contributions to human precision and power grip.

KEY POINTS: The corticospinal tract contributes to the control of finger muscles during precision and power grip. We explored the neural mechanisms contributing to changes in corticospinal excitability during these gripping configurations. Motor evoked potentials (MEPs) elicited by cortical, but not by subcortical, stimulation were more suppressed during power grip compared with precision grip and index finger abduction. Intracortical inhibition was more reduced during power grip compared with the other tasks. An acoustic startle cue, a stimulus that engages the reticular system, suppressed MEP size during power grip to a lesser extent than during the other tasks at a cortical level and this positively correlated with changes in intracortical inhibition. Our findings suggest that changes in corticospinal excitability during gross more than fine finger manipulations are largely cortical in origin and that the reticular system contributed, at least in part, to these effects. ABSTRACT: It is well accepted that the corticospinal tract contributes to the control of finger muscles during precision and power grip in humans but the neural mechanisms involved remain poorly understood. Here, we examined motor evoked potentials elicited by cortical and subcortical stimulation of corticospinal axons (MEPs and CMEPs, respectively) and the activity in intracortical circuits (suppression of voluntary electromyography) and spinal motoneurons (F-waves) in an intrinsic hand muscle during index finger abduction, precision grip and power grip. We found that the size of MEPs, but not CMEPs, was more suppressed during power grip compared with precision grip and index finger abduction, suggesting a cortical origin for these effects. Notably, intracortical inhibition was more reduced during power grip compared with the other tasks. To further examine the origin of changes in intracortical inhibition we assessed the contribution of the reticular system, which projects to cortical neurons, and projects to spinal motoneurons controlling hand muscles. An acoustic startle cue, which engages the reticular system, suppressed MEP size during power grip to a lesser extent than during the other tasks and this positively correlated with changes in intracortical inhibition. A startle cue decreased intracortical inhibition, but not CMEPs, during power grip. F-waves remained unchanged across conditions. Our novel findings show that changes in corticospinal excitability present during power grip compared with fine finger manipulations are largely cortical in origin and suggest that the reticular system contributed, at least in part, to these effects.

A common neural element receiving rhythmic arm and leg activity as assessed by reflex modulation in arm muscles.

Neural interactions between regulatory systems for rhythmic arm and leg movements are an intriguing issue in locomotor neuroscience. Amplitudes of early latency cutaneous reflexes (ELCRs) in stationary arm muscles are modulated during rhythmic leg or arm cycling but not during limb positioning or voluntary contraction. This suggests that interneurons mediating ELCRs to arm muscles integrate outputs from neural systems controlling rhythmic limb movements. Alternatively, outputs could be integrated at the motoneuron and/or supraspinal levels. We examined whether a separate effect on the ELCR pathways and cortico-motoneuronal excitability during arm and leg cycling is integrated by neural elements common to the lumbo-sacral and cervical spinal cord. The subjects performed bilateral leg cycling (LEG), contralateral arm cycling (ARM), and simultaneous contralateral arm and bilateral leg cycling (A&L), while ELCRs in the wrist flexor and shoulder flexor muscles were evoked by superficial radial (SR) nerve stimulation. ELCR amplitudes were facilitated by cycling tasks and were larger during A&L than during ARM and LEG. A low stimulus intensity during ARM or LEG generated a larger ELCR during A&L than the sum of ELCRs during ARM and LEG. We confirmed this nonlinear increase in single motor unit firing probability following SR nerve stimulation during A&L. Furthermore, motor-evoked potentials following transcranial magnetic and electrical stimulation did not show nonlinear potentiation during A&L. These findings suggest the existence of a common neural element of the ELCR reflex pathway that is active only during rhythmic arm and leg movement and receives convergent input from contralateral arms and legs.

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.

Effects of repetitive transcranial magnetic stimulation on recovery of function after spinal cord injury.

A major goal of rehabilitation strategies after spinal cord injury (SCI) is to enhance the recovery of function. One possible avenue to achieve this goal is to strengthen the efficacy of the residual neuronal pathways. Noninvasive repetitive transcranial magnetic stimulation (rTMS) has been used in patients with motor disorders as a tool to modulate activity of corticospinal, cortical, and subcortical pathways to promote functional recovery. This article reviews a series of studies published during the last decade that used rTMS in the acute and chronic stages of paraplegia and tetraplegia in humans with complete and incomplete SCI. In the studies, rTMS has been applied over the arm and leg representations of the primary motor cortex to target 3 main consequences of SCI: sensory and motor function impairments, spasticity, and neuropathic pain. Although some studies demonstrated that consecutive sessions of rTMS improve aspects of particular functions, other studies did not show similar effects. We discuss how rTMS parameters and postinjury reorganization in the corticospinal tract, motor cortical, and spinal cord circuits might be critical factors in understanding the advantages and disadvantages of using rTMS in patients with SCI. The available data highlight the limited information on the use of rTMS after SCI and the need to further understand the pathophysiology of neuronal structures affected by rTMS to maximize the potential beneficial effects of this technique in humans with SCI.

Polarity specific effects of transcranial direct current stimulation on interhemispheric inhibition.

Transcranial direct current stimulation (tDCS) has been used as a useful interventional brain stimulation technique to improve unilateral upper-limb motor function in healthy humans, as well as in stroke patients. Although tDCS applications are supposed to modify the interhemispheric balance between the motor cortices, the tDCS after-effects on interhemispheric interactions are still poorly understood. To address this issue, we investigated the tDCS after-effects on interhemispheric inhibition (IHI) between the primary motor cortices (M1) in healthy humans. Three types of tDCS electrode montage were tested on separate days; anodal tDCS over the right M1, cathodal tDCS over the left M1, bilateral tDCS with anode over the right M1 and cathode over the left M1. Single-pulse and paired-pulse transcranial magnetic stimulations were given to the left M1 and right M1 before and after tDCS to assess the bilateral corticospinal excitabilities and mutual direction of IHI. Regardless of the electrode montages, corticospinal excitability was increased on the same side of anodal stimulation and decreased on the same side of cathodal stimulation. However, neither unilateral tDCS changed the corticospinal excitability at the unstimulated side. Unilateral anodal tDCS increased IHI from the facilitated side M1 to the unchanged side M1, but it did not change IHI in the other direction. Unilateral cathodal tDCS suppressed IHI both from the inhibited side M1 to the unchanged side M1 and from the unchanged side M1 to the inhibited side M1. Bilateral tDCS increased IHI from the facilitated side M1 to the inhibited side M1 and attenuated IHI in the opposite direction. Sham-tDCS affected neither corticospinal excitability nor IHI. These findings indicate that tDCS produced polarity-specific after-effects on the interhemispheric interactions between M1 and that those after-effects on interhemispheric interactions were mainly dependent on whether tDCS resulted in the facilitation or inhibition of the M1 sending interhemispheric volleys.

Selective activation of ipsilateral motor pathways in intact humans.

It has been proposed that ipsilateral motor pathways play a role in the control of ipsilateral movements and recovery of function after injury. However, the extent to which ipsilateral motor pathways are engaged in voluntary activity in intact humans remains largely unknown. Using transcranial magnetic stimulation over the arm representation of the primary motor cortex, we examined ipsilateral motor-evoked potentials (iMEPs) in a proximal arm muscle during increasing levels of unilateral and bilateral isometric force in a sitting position. We demonstrate that iMEP area and amplitude decreased during bilateral contraction of homonymous (elbow flexor) muscles and increased during bilateral contraction of heteronymous (elbow flexor and extensor) muscles compared with a unilateral contraction, regardless of the level of force tested. To further understand the neuronal inputs involved in the bilateral effects, we examined the contribution from neck afferents projecting onto ipsilateral motor pathways. Medial (away from the muscle tested) and lateral (toward the muscle tested) rotation of the head enhanced bilateral iMEP effects from homonymous and heteronymous muscles, respectively. In contrast, head flexion and extension exerted nonspecific bilateral effects on iMEPs. Intracortical inhibition, in the motor cortex where iMEPs originated, showed modulation compatible with the changes in iMEPs. We conclude that ipsilateral projections to proximal arm muscles can be selectively modulated by voluntary contraction of contralateral arm muscles, likely involving circuits mediating asymmetric tonic neck reflexes acting, at least in part, at the cortical level. The pattern of bilateral actions may represent a strategy to engage ipsilateral motor pathways in a motor behavior.

Subcortical control of precision grip after human spinal cord injury.

The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients. Regardless of whether cortical and cervicomedullary stimulation was used, suppression of the MEP was only evident 1-3 ms after its onset. Long-term (∼5 years) use of the GABAb receptor agonist baclofen by SCI patients reduced MEP size during precision grip to similar levels as uninjured humans. Index finger sensory function correlated with MEP size during precision grip in SCI patients. Intracortical inhibition decreased during precision grip and spinal motoneuron excitability remained unchanged in all groups. Our results demonstrate that the control of precision grip in humans involves premotoneuronal subcortical mechanisms, likely disynaptic or polysynaptic spinal pathways that are lacking after SCI and restored by long-term use of baclofen. We propose that spinal GABAb-ergic interneuronal circuits, which are sensitive to baclofen, are part of the subcortical premotoneuronal network shaping corticospinal output during human precision grip.

Leg automaticity is stronger than arm automaticity during simultaneous arm and leg cycling.

Recent studies indicate that human locomotion is quadrupedal in nature. An automatic rhythm-generating system is thought to play a crucial role in controlling arm and leg movements. In the present study, we attempted to elucidate differences between intrinsic arm and leg automaticity by investigating cadence variability during simultaneous arm and leg (AL) cycling. Participants performed AL cycling with visual feedback of arm or leg cadence. Participants were asked to focus their attention to match the predetermined cadence; this affects the automaticity of the rhythm-generating system. Leg cadence variability was only mildly affected when the participants intended to precisely adjust either their arm or leg cycling cadence to a predetermined value. In contrast, arm cadence variability significantly increased when the participants adjusted their leg cycling cadence to a predetermined value. These findings suggest that different neural mechanisms underlie the automaticities of arm and leg cycling and that the latter is stronger than the former during AL cycling.

Speed-dependent contribution of callosal pathways to ipsilateral movements.

Transcallosal inhibitory interactions between primary motor cortices are important to suppress unintended movements in a resting limb during voluntary activation of the contralateral limb. The functional contribution of transcallosal inhibition targeting the voluntary active limb remains unknown. Using transcranial magnetic stimulation, we examined transcallosal inhibition [by measuring interhemispheric inhibition (IHI) and the ipsilateral silent period (iSP)] in the preparatory and execution phases of isotonic slower self-paced and ballistic movements performed by the ipsilateral index finger into abduction and the elbow into flexion in intact humans. We demonstrate decreased IHI in the preparatory phase of self-paced and ballistic index finger and elbow movements compared to rest; the decrease in IHI was larger during ballistic than self-paced movements. In contrast, in the execution phase, IHI and the iSP increased during ballistic compared to self-paced movements. Transcallosal inhibition was negatively correlated with reaction times in the preparatory phase and positively correlated with movement amplitude in the execution phase. Together, our results demonstrate a widespread contribution of transcallosal inhibition to ipsilateral movements of different speeds with a functional role during rapid movements; at faster speeds, decreased transcallosal inhibition in the preparatory phase may contribute to start movements rapidly, while the increase in the execution phase may contribute to stop the movement. We argue that transcallosal pathways enable signaling of the time of discrete behavioral events during ipsilateral movements, which is amplified by the speed of a movement.