Taku Kitamura

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.

Robotic-assisted stepping modulates monosynaptic reflexes in forearm muscles in the human

Although the amplitude of the Hoffmann (H)-reflex in the forelimb muscles is known to be suppressed during rhythmic leg movement, it is unknown which factor plays a more important role in generating this suppression-movement-related afferent feedback or feedback related to body loading. To specifically explore the movement- and load-related afferent feedback, we investigated the modulation of the H-reflex in the flexor carpi radialis (FCR) muscle during robotic-assisted passive leg stepping. Passive stepping and standing were performed using a robotic gait-trainer system (Lokomat). The H-reflex in the FCR, elicited by electrical stimulation to the median nerve, was recorded at 10 different phases of the stepping cycle, as well as during quiet standing. We confirmed that the magnitude of the FCR H-reflex was suppressed significantly during passive stepping compared with during standing. The suppressive effect on the FCR H-reflex amplitude was seen at all phases of stepping, irrespective of whether the stepping was conducted with body weight loaded or unloaded. These results suggest that movement-related afferent feedback, rather than load-related afferent feedback, plays an important role in suppressing the FCR H-reflex amplitude.

Asymmetrical modulation of corticospinal excitability in the contracting and resting contralateral wrist flexors during unilateral shortening, lengthening and isometric contractions

Unilateral isometric muscle contractions increase motor-evoked potentials (MEPs) produced by transcranial magnetic stimulation not only in the contracting muscle but also in the resting contralateral homologous muscle. Corticospinal excitability in the M1 contralateral to the contracting muscle changes depending on the type of muscle contraction. Here, we investigated the possibility that corticospinal excitability in M1 ipsilateral to the contracting muscle is modulated in a contraction-type-dependent manner. To this end, we evaluated MEPs in the resting left flexor carpi radialis (FCR) during unilateral shortening, lengthening, and isometric muscle contractions of the right wrist flexors at 10, 20, and 30% of maximal isometric contraction force. To compare the effects of different unilateral contractions on MEPs between the contracting and resting sides, MEPs in the right FCR were recorded on two separate days. In a separate experiment, we investigated the contraction specificity of the crossed effect at the spinal level by recording H-reflexes from the resting left FCR during contraction of the right wrist flexors. The results showed that MEPs in the contracting right FCR were the smallest during lengthening contraction. By contrast, MEPs in the resting left FCR were the largest during lengthening contraction, whereas the H-reflex was similar in the resting left FCR during the three types of muscle contraction. These results suggest that different types of unilateral muscle contraction asymmetrically modulate MEP size in the resting contralateral homologous muscle and in the contracting muscle and that this regulation occurs at the supraspinal level.

The swimming test is effective for evaluating spasticity after contusive spinal cord injury

Spasticity is a frequent chronic complication in individuals with spinal cord injury (SCI). However, the severity of spasticity varies in patients with SCI. Therefore, an evaluation method is needed to determine the severity of spasticity. We used a contusive SCI model that is suitable for clinical translation. In this study, we examined the feasibility of the swimming test and an EMG for evaluating spasticity in a contusive SCI rat model. Sprague-Dawley rats received an injury at the 8th thoracic vertebra. Swimming tests were performed 3 to 6 weeks after SCI induction. We placed the SCI rats into spasticity-strong or spasticity-weak groups based on the frequency of spastic behavior during the swimming test. Subsequently, we recorded the Hoffman reflex (H-reflex) and examined the immunoreactivity of serotonin (5-HT) and its receptor (5-HT2A) in the spinal tissues of the SCI rats. The spasticity-strong group had significantly decreased rate-dependent depression of the H-reflex compared to the spasticity-weak group. The area of 5-HT2A receptor immunoreactivity was significantly increased in the spasticity-strong group. Thus, both electrophysiological and histological evaluations indicate that the spasticity-strong group presented with a more severe upper motor neuron syndrome. We also observed the groups in their cages for 20 hours. Our results suggest that the swimming test provides an accurate evaluation of spasticity in this contusive SCI model. We believe that the swimming test is an effective method for evaluating spastic behaviors and developing treatments targeting spasticity after SCI.

Short‐term effect of electrical nerve stimulation on spinal reciprocal inhibition during robot‐assisted passive stepping in humans

The purpose of this study was to investigate the effect of electrical stimulation to the common peroneal nerve (CPN) on the spinal reflex and reciprocal inhibition (RI) during robot‐assisted passive ground stepping (PGS) in healthy subjects. Five interventions were applied for 30 min in healthy subjects: PGS alone; strong CPN stimulation [50% of the maximal tibialis anterior (TA) M‐wave, functional electrical stimulation (FES)] alone; weak CPN stimulation [just above the MT for the TA muscle, therapeutic electrical stimulation (TES)] alone; PGS with FES; and PGS with TES. FES and TES were applied intermittently to the CPN at 25 Hz. The soleus (Sol) H‐reflex and RI, which was assessed by conditioning the Sol H‐reflex with CPN stimulation, were investigated before (baseline), and 5, 15 and 30 min after each intervention. The amplitudes of the Sol H‐reflex were not significantly different after each intervention as compared with the baseline values. The amounts of RI were significantly decreased 5 min after PGS with FES as compared with the baseline values, whereas they were significantly increased 5 and 15 min after PGS with TES. The other interventions did not affect the amount of RI. These results suggest that interventions that combined PGS with CPN stimulation changed the spinal RI in an intensity‐dependent manner.

Effect of spinal cord injury and its lesion level on stretch reflex modulation by cold stimulation in humans.

OBJECTIVE To determine how short-latency stretch reflex amplitude in the soleus muscle is modulated by cold stimulation in able-bodied individuals and individuals with complete spinal cord injury. METHODS An initial 100-s baseline period was followed by 50-s cold stimulation periods. Stretch reflex of the right soleus muscle was elicited for 10-s intervals, while cold stimulation was applied to the left thigh. RESULTS Peak-to-peak amplitude of the stretch reflex increased significantly during cold stimulation up to 127 ± 21% of the baseline in the able-bodied group (n=9, P<0.01). Similarly, stretch reflex increased up to 125 ± 11% in a group with injury level at or below thoracic 10 (n=4), although this increase was not significant. On the other hand, stretch reflex decreased significantly down to 78 ± 20% in a group with injury level at or above thoracic 6 (n=8, P<0.05). CONCLUSIONS Effect of afferent inputs induced by cold stimulation on stretch reflex modulation is different depending on the extent of central nervous systems participating in the modulation. SIGNIFICANCE Our findings provide a better understanding of some basic changes in afferent-efferent spinal reflex pathways which are probably not monosynaptic in nature.

Velocity-dependent suppression of the soleus H-reflex during robot-assisted passive stepping.

The amplitude of the Hoffmann (H)-reflex in the soleus (Sol) muscle is known to be suppressed during passive stepping compared with during passive standing. The reduction of the H-reflex is not due to load-related afferent inputs, but rather to movement-related afferent inputs from the lower limbs. To elucidate the underlying neural mechanisms of this inhibition, we investigated the effects of the stepping velocity on the Sol H-reflex during robot-assisted passive stepping in 11 healthy subjects. The Sol H-reflexes were recorded during passive standing and stepping at five stepping velocities (stride frequencies: 14, 21, 28, 35, and 42 min(-1)) in the air. The Sol H-reflexes were significantly inhibited during passive stepping as compared with during passive standing, and reduced in size as the stepping velocity increased. These results indicate that the extent of H-reflex suppression increases with increasing movement-related afferent inputs from the lower limbs during passive stepping. The velocity dependence suggests that the Ia afferent inputs from lower-limb muscles around the hip and knee joints are most probably related to this inhibition.

Hypoventilation during passive leg movement in spinal cord-injured humans

We examined ventilatory response during passive walking-like exercise in the standing posture in complete spinal cord-injured humans and found that ventilatory equivalent for O2 uptake, which would be related to the sensation of breathlessness, was lower during passive exercise than during quiet standing.

Corticospinal Excitability Is Modulated as a Function of Postural Perturbation Predictability

Recent studies demonstrated that the corticospinal pathway is one of the key nodes for the feedback control of human standing and that the excitability is flexibly changed according to the current state of posture. However, it has been unclear whether this pathway is also involved in a predictive control of human standing. Here, we investigated whether the corticospinal excitability of the soleus (SOL) and tibialis anterior (TA) muscles during standing would be modulated anticipatorily when perturbation was impending. We measured the motor-evoked potential (MEP) induced by transcranial magnetic stimulation over the motor cortex at six stimulus intensities. Three experimental conditions were set depending on predictabilities about perturbation occurrence and onset: No perturbation, No Cue, and Cue conditions. In the Cue condition, an acoustic signal was given as timing information of perturbation. The slope of the stimulus–response relation curve revealed that the TA-MEP was enhanced when postural perturbation was expected compared to when the perturbation was not expected (No Perturbation vs. No Cue, 0.023 ± 0.004 vs. 0.042 ± 0.007; No Perturbation vs. Cue, 0.023 ± 0.004 vs. 0.050 ± 0.009; Bonferroni correction, p = 0.01, respectively). In addition, two-way analysis of variance (intensity × condition) revealed the main effect of condition (F(1,13) = 6.31, p = 0.03) but not intensity and interaction when the MEP amplitude of the Cue and No Cue conditions was normalized by that in No Perturbation, suggesting the enhancement more apparent when timing information was given. The SOL-MEP was not modulated even when perturbation was expected, but it slightly reduced due to the timing information. The results of an additional experiment confirmed that the acoustic cue by itself did not affect the TA- and SOL-MEPs. Our findings suggest that a prediction of a future state of standing balance modulates the corticospinal excitability in the TA, and that the additional timing information facilitates this modulation. The corticospinal pathway thus appears to be involved in mechanisms of the predictive control as well as feedback control of standing posture.

Unusual blood pressure response during standing therapy in tetraplegic man

We report a case of an individual with cervical spinal cord injury who showed a unique blood pressure response during passive standing and passive walking-like leg movement, i.e., hypertension with standing and hypotension with leg movement.