Toshiki Tazoe

Modulations of interlimb and intralimb cutaneous reflexes during simultaneous arm and leg cycling in humans

OBJECTIVE We investigated to what extent intralimb and interlimb cutaneous reflexes are altered while simultaneously performing arm and leg cycling (AL cycling) under different kinematic and postural conditions. METHODS Eleven subjects performed AL cycling under conditions in which the arm and leg crank ipsilateral to the stimulation side were moved synchronously (in-phase cycling) or asynchronously (anti-phase cycling) while sitting or standing. Cutaneous reflexes following superficial radial or superficial peroneal nerve stimulation (2.0-2.5 times radiating threshold, 5 pulses at 333 Hz) were recorded at 4 different pedal positions from 12 muscles in the upper and lower limbs. Cutaneous reflexes with a peak latency of 80-120 ms were then analyzed. RESULTS The magnitude of interlimb and intralimb cutaneous reflexes in the arm and leg muscles was significantly modulated depending on the crank position for the relevant limb (phase-dependent modulation). A significant correlation between the magnitude of the cutaneous reflex and background EMG was observed in the majority of muscles during static contraction, but not during AL cycling (task-dependent modulation). No significant difference was found in comparisons of the magnitude of intralimb and interlimb cutaneous reflexes obtained during in- and anti-phase AL cycling. Qualitatively, the same results were obtained during AL cycling while sitting or standing. In addition, the modulation of cutaneous reflexes in arm muscles was identical among in-phase, anti-phase and isolated arm cycling. Results were the same for leg muscles. CONCLUSIONS Cutaneous reflexes in arm muscles are little influenced by rhythmic movement of the legs and vice versa during AL cycling. It is likely that neural components that control interlimb reflexes are loosely coupled during AL cycling while sitting or standing. SIGNIFICANCE Our results provide a better understanding of the coordination between the upper and lower limbs during rhythmic movement.

Disinhibition of upper limb motor area by voluntary contraction of the lower limb muscle

It is well known that monosynaptic spinal reflexes and motor evoked potentials following transcranial magnetic stimulation (TMS) are reinforced during phasic and intensive voluntary contraction in the remote segment (remote effect). However, the remote effect on the cortical silent period (CSP) is less known. The purpose of the present study is to determine to what extent the CSP in the intrinsic hand muscle following TMS is modified by voluntary ankle dorsiflexion and to elucidate the origin of the modulation of CSP by the remote effect. CSP was recorded in the right first dorsal interosseous while subjects performed phasic dorsiflexion in the ipsilateral side under self-paced and reaction-time conditions. Modulation of the peripherally-induced silent period (PSP) induced by electrical stimulation of the ulnar nerve was also investigated under the same conditions. In addition, modulation of the CSP was investigated during ischemic nerve block of the lower limb and during application of vibration to the tibialis anterior tendon. The duration of CSP was significantly shortened by phasic dorsiflexion, and the extent of shortening was proportional to dorsiflexion force. Shortening of the CSP duration was also observed during tonic dorsiflexion. In contrast, the PSP duration following ulnar nerve stimulation was not altered during phasic dorsiflexion. Furthermore, the remote effect on the CSP duration was seen during ischemic nerve block of the lower limb and the pre-movement period in the reaction-time paradigm, but shortening of the CSP was not observed during tendon vibration. These findings suggest that phasic muscle contraction in the remote segment results in a decrease in intracortical inhibitory pathways to the corticospinal tract innervating the muscle involved in reflex testing and that the remote effect on the CSP is predominantly cortical in origin.

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.

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.

Modulation of interhemispheric interactions across symmetric and asymmetric bimanual force regulations

The corpus callosum is essential for neural communication between the left and right hemispheres. Although spatiotemporal coordination of bimanual movements is mediated by the activity of the transcallosal circuit, it remains to be addressed how transcallosal neural activity is involved in the dynamic control of bimanual force execution in human. To address this issue, we investigated transcallosal inhibition (TCI) elicited by single‐pulse transcranial magnetic stimulation (TMS) in association with the coordination condition of bimanual force regulation. During a visually‐guided bimanual force tracking task, both thumbs were abducted either in‐phase (symmetric condition) or 180° out‐of‐phase (asymmetric condition). TMS was applied to the left primary motor cortex to elicit the disturbance of ipsilateral left force tracking due to TCI. The tracking accuracy was equivalent between the two conditions, but the synchrony of the left and right tracking trajectories was higher in the symmetric condition than in the asymmetric condition. The magnitude of force disturbance and TCI were larger during the symmetric condition than during the asymmetric condition. Right unimanual force tracking influenced neither the force disturbance nor TCI during tonic left thumb abduction. Additionally, these TMS‐induced ipsilateral motor disturbances only appeared when the TMS intensity was strong enough to excite the transcallosal circuit, irrespective of whether the crossed corticospinal tract was activated. These findings support the hypotheses that interhemispheric interactions between the motor cortices play an important role in modulating bimanual force coordination tasks, and that TCI is finely tuned depending on the coordination condition of bimanual force regulation.

Effects of Leg Pedaling on Early Latency Cutaneous Reflexes in Upper Limb Muscles

The functional coupling of neural circuits between the upper and lower limbs involving rhythmic movements is of interest to both motor control research and rehabilitation science. This coupling can be detected by examining the effect of remote rhythmic limb movement on the modulation of reflex amplitude in stationary limbs. The present study investigated the extent to which rhythmic leg pedaling modulates the amplitude of an early latency (peak 30-70 ms) cutaneous reflex (ELCR) in the upper limb muscles. Thirteen neurologically intact volunteers performed leg pedaling (60 or 90 rpm) while simultaneously contracting their arm muscles isometrically. Control experiments included isolated isometric contractions and discrete movements of the leg. ELCRs were evoked by stimulation of the superficial radial nerve with a train of rectangular pulses (three pulses at 333 Hz, intensity 2.0- to 2.5-fold perceptual threshold). Reflex amplitudes were significantly increased in the flexor carpi radialis and posterior deltoid and significantly decreased in the biceps brachii muscles during leg pedaling compared with that during stationary isometric contraction of the lower leg muscles. This effect was also sensitive to cadence. No significant modulation was seen during the isometric contractions or discrete movements of the leg. Additionally, there was no phase-dependent modulation of the ELCR. These findings suggest that activation of the rhythm generating system of the legs affects the excitability of the early latency cutaneous reflex pathways in the upper limbs.

Effects of remote muscle contraction on transcranial magnetic stimulation-induced motor evoked potentials and silent periods in humans

OBJECTIVE To determine to what extent tonic contraction of the testing muscle modulates the effect of remote muscle contraction on motor evoked potentials (MEPs) and cortical silent periods (CSPs) in resting and active proximal and distal muscles following transcranial magnetic stimulation (TMS). In addition, we tested whether the remote effect on MEP was observable when the test MEP was small. METHODS While performing tonic abductions of the first dorsal interosseous (FDI), flexor carpi radialis, or anterior deltoid muscles, subjects made phasic dorsiflexions of the right ankle at various forces. MEPs and CSPs were induced by separately optimized TMS intensities and locations in the left motor cortex and recorded electromyographically. RESULTS Phasic dorsiflexion increased MEP amplitude and shortened CSP duration in a dorsiflexion intensity-dependent manner in all muscles tested. At test MEPs <10% of Mmax, remote effects on MEP amplitude and CSP duration were significantly attenuated while the testing muscle was active. CONCLUSIONS Phasic contraction of remote muscles potentiates excitatory- and suppresses inhibitory intracortical neuronal pathways converging on corticospinal tract cells innervating the upper limb muscles even when they are active. However, the magnitude of the remote effect on MEP amplitude strongly depends on the test MEP amplitude. SIGNIFICANCE Although remote effects on MEP amplitude and CSP duration are observed even when the test muscle is active, the magnitude of the remote effect strongly depends on TMS intensity.

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.

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.

Gain modulation of the middle latency cutaneous reflex in patients with chronic joint instability after ankle sprain

OBJECTIVE To investigate the neural alteration of reflex pathways arising from cutaneous afferents in patients with chronic ankle instability. METHODS Cutaneous reflexes were elicited by applying non-noxious electrical stimulation to the sural nerve of subjects with chronic ankle instability (n=17) and control subjects (n=17) while sitting. Electromyographic (EMG) signals were recorded from each ankle and thigh muscle. The middle latency response (MLR; latency: 70-120 ms) component was analyzed. RESULTS In the peroneus longus (PL) and vastus lateralis (VL) muscles, linear regression analyses between the magnitude of the inhibitory MLR and background EMG activity showed that, compared to the uninjured side and the control subjects, the gain of the suppressive MLR was increased in the injured side. This was also confirmed by the pooled data for both groups. The degree of MLR alteration was significantly correlated to that of chronic ankle instability in the PL. CONCLUSIONS The excitability of middle latency cutaneous reflexes in the PL and VL is modulated in subjects with chronic ankle instability. SIGNIFICANCE Cutaneous reflexes may be potential tools to investigate the pathological state of the neural system that controls the lower limbs in subjects with chronic ankle instability.