Spinal Motoneuron Excitability Research Articles

F-waves responses derived from low-intensity electrical stimulation: A method to explore split-hand pathogenesis

ObjectivesThe “split-hand syndrome” is a common clinical sign in amyotrophic lateral sclerosis (ALS), being characterized by more severe atrophy of the hand muscles on the radial side of the hand compared to the ulnar side. We aimed to investigate possible physiological differences between relevant hand muscles using low-intensity F-wave stimulation to assess spinal motoneuron excitability. MethodsWe recruited 36 healthy volunteers. F-waves were recorded from the abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM), using 20 supramaximal stimuli followed by 20 stimuli at a low-intensity required to obtain M-waves with 10 % amplitude of maximal CMAP. We evaluated the following F-wave parameters: F-M latency, chronodispersion, persistence, amplitude, F/CMAP amplitude ratio and number of F-wave repeaters (with low-intensity). In 10 subjects, low-intensity stimulation F-waves were compared after 20 and 50 stimuli in each muscle. ResultsLow-intensity stimulation resulted in lower F-wave amplitude and persistence and higher F/CMAP amplitude ratios. There were no significant differences in F-wave latencies and chronodispersion. When comparing the three muscles, we found higher F-wave persistence and F/CMAP amplitude ratios when recording over the ADM and APB compared to the FDI. We also found a higher number of F-wave repeaters in the ADM with low-intensity stimulation. Results from 20 to 50 low-intensity stimuli were similar. DiscussionA small number of low-intensity stimuli is appropriate to study F-wave latencies and chronodispersion. We found differences in some physiological properties of the ADM spinal motoneuron pool compared to other hand muscles.

Effects of cerebellar transcranial direct current stimulation on the excitability of spinal motor neurons and vestibulospinal tract in healthy individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar cortical excitability in a polarity-dependent manner and affects inhibitory pathways from the cerebellum. The cerebellum modulates spinal reflex excitability via the vestibulospinal tract and other pathways projecting to the spinal motor neurons; however, the effects of ctDCS on the excitability of spinal motor neurons and vestibulospinal tract remain unclear. The experiment involved 13 healthy individuals. ctDCS (sham-ctDCS, anodal-ctDCS, and cathodal-ctDCS) was applied to the cerebellar vermis at 2mA with an interval of at least 3 days between each condition. We measured the maximal M-wave (Mmax) and maximal H-reflex (Hmax) in the right soleus muscle to assess the excitability of spinal motor neurons. We applied galvanic vestibular stimulation (GVS) for 200 ms at 100 ms before tibial nerve stimulation to measure Hmax conditioned by GVS (GVS-Hmax) and calculated the change rate of Hmax by GVS as the excitability of vestibulospinal tract. We measured the Mmax, Hmax, and GVS-Hmax before, during, and after ctDCS in the sitting posture. No main effects of tDCS condition, main effects of time, or interaction effects were observed in Hmax/Mmax or the change rate of Hmax by GVS. It has been suggested that ctDCS does not affect the excitability of spinal motor neurons and vestibulospinal tract, as measured by neurophysiological methods, such as the H-reflex, in healthy individuals in a sitting posture. Effect of ctDCS on other descending pathways to spinal motor neurons, the neurological mechanism of tDCS and the cerebellar activity during the experiment may have contributed to these results. Therefore, we need to investigate the involvement of the cerebellum in Hmax/Mmax and the change rate of Hmax by GVS under different neuromodulation techniques and postural conditions.

A preliminary study exploring the effects of transcutaneous spinal cord stimulation on spinal excitability and phantom limb pain in people with a transtibial amputation

Objective. Phantom limb pain (PLP) is debilitating and affects over 70% of people with lower-limb amputation. Other neuropathic pain conditions correspond with increased spinal excitability, which can be measured using reflexes andF-waves. Spinal cord neuromodulation can be used to reduce neuropathic pain in a variety of conditions and may affect spinal excitability, but has not been extensively used for treating PLP. Here, we propose using a non-invasive neuromodulation method, transcutaneous spinal cord stimulation (tSCS), to reduce PLP and modulate spinal excitability after transtibial amputation.Approach. We recruited three participants, two males (5- and 9-years post-amputation, traumatic and alcohol-induced neuropathy) and one female (3 months post-amputation, diabetic neuropathy) for this 5 d study. We measured pain using the McGill Pain Questionnaire (MPQ), visual analog scale (VAS), and pain pressure threshold (PPT) test. We measured spinal reflex and motoneuron excitability using posterior root-muscle (PRM) reflexes andF-waves, respectively. We delivered tSCS for 30 min d-1for 5 d.Main Results. After 5 d of tSCS, MPQ scores decreased by clinically-meaningful amounts for all participants from 34.0 ± 7.0-18.3 ± 6.8; however, there were no clinically-significant decreases in VAS scores. Two participants had increased PPTs across the residual limb (Day 1: 5.4 ± 1.6 lbf; Day 5: 11.4 ± 1.0 lbf).F-waves had normal latencies but small amplitudes. PRM reflexes had high thresholds (59.5 ± 6.1μC) and low amplitudes, suggesting that in PLP, the spinal cord is hypoexcitable. After 5 d of tSCS, reflex thresholds decreased significantly (38.6 ± 12.2μC;p< 0.001).Significance. These preliminary results in this non-placebo-controlled study suggest that, overall, limb amputation and PLP may be associated with reduced spinal excitability and tSCS can increase spinal excitability and reduce PLP.

Acute intermittent hypoxia increases maximal motor unit discharge rates in people with chronic incomplete spinal cord injury.

Acute intermittent hypoxia (AIH) is an emerging technique for enhancing neuroplasticity and motor function in respiratory and limb musculature. Thus far, AIH-induced improvements in strength have been reported for upper and lower limb muscles after chronic incomplete cervical spinal cord injury (iSCI), but the underlying mechanisms have been elusive. We used high-density surface EMG (HDsEMG) to determine if motor unit discharge behaviour is altered after 15×60s exposures to 9% inspired oxygen, interspersed with 21% inspired oxygen (AIH), compared to breathing only 21% air (SHAM). We recorded HDsEMG from the biceps and triceps brachii of seven individuals with iSCI during maximal elbow flexion and extension contractions, and motor unit spike trains were identified using convolutive blind source separation. After AIH, elbow flexion and extension torque increased by 54% and 59% from baseline (P=0.003), respectively, whereas there was no change after SHAM. Across muscles, motor unit discharge rates increased by ∼4 pulses per second (P=0.002) during maximal efforts, from before to after AIH. These results suggest that excitability and/or activation of spinal motoneurons is augmented after AIH, providing a mechanism to explain AIH-induced increases in voluntary strength. Pending validation, AIH may be helpful in conjunction with other therapies to enhance rehabilitation outcomes after incomplete spinal cord injury, due to these enhancements in motor unit function and strength. KEY POINTS: Acute intermittent hypoxia (AIH) causes increases in muscular strength and neuroplasticity in people living with chronic incomplete spinal cord injury (SCI), but how it affects motor unit discharge rates is unknown. Motor unit spike times were identified from high-density surface electromyograms during maximal voluntary contractions and tracked from before to after AIH. Motor unit discharge rates were increased following AIH. These findings suggest that AIH can facilitate motoneuron function in people with incomplete SCI.

Dysregulation of persistent inward and outward currents in spinal motoneurons of symptomatic SOD1-G93A mice.

Persistent inward currents (PICs) and persistent outward currents (POCs) regulate the excitability and firing behaviours of spinal motoneurons (MNs). Given their potential role in MN excitability dysfunction in amyotrophic lateral sclerosis (ALS), PICs have been previously studied in superoxide dismutase 1 (SOD1)-G93A mice (the standard animal model of ALS); however, conflicting results have been reported on how the net PIC changes during disease progression. Also, individual PICs and POCs have never been examined before in symptomatic ALS. To fill this gap, we measured the net and individual PIC and POC components of wild-type (WT) and SOD MNs in current clamp and voltage clamp during disease progression (assessed by neuroscores). We show that SOD MNs of symptomatic mice experience a much larger net PIC, relative to WT cells from age-matched littermates. Specifically, the Na+ and Ca2+ PICs are larger, whereas the lasting SK-mediated (SKL) POC is smaller than WT (Na+ PIC is the largest and SKL POC is the smallest components in SOD MNs). We also show that PIC dysregulation is present at symptom onset, is sustained throughout advanced disease stages and is proportional to SOD MN cell size (largest dysregulation is in the largest SOD cells, the most vulnerable in ALS). Additionally, we show that studying disease progression using neuroscores is more accurate than using SOD mouse age, which could lead to misleading statistics and age-based trends. Collectively, this study contributes novel PIC and POC data, reveals ionic mechanisms contributing to the vulnerability differential among MN types/sizes, and provides insights on the roles PIC and POC mechanisms play in MN excitability dysfunction in ALS. KEY POINTS: Individual persistent inward currents (PICs) and persistent outward currents (POCs) have never been examined before in spinal motoneurons (MNs) of symptomatic amyotrophic lateral sclerosis (ALS) mice. Thus, we contribute novel PIC and POC data to the ALS literature. Male SOD MNs of symptomatic mice have elevated net PIC, with larger Na+ and Ca2+ PICs but reduced SKL POC vs. wild-type littermates. Na+ PIC is the largest and SKL POC is the smallest current in SOD cells. The PIC/POC dysregulation is present at symptom onset. PIC dysregulation is sustained throughout advanced disease, and is proportional to SOD MN size (largest dysregulation is in the largest cells, the most vulnerable in ALS). Thus, we reveal ionic mechanisms contributing to the vulnerability differential among MN types/sizes in ALS. Studying disease progression using SOD mice neuroscores is more accurate than using age, which could distort the statistical differences between SOD and WT PIC/POC data and the trends during disease progression.

Changes in spinal motoneuron excitability during the improvement of fingertip dexterity by actual execution combined with motor imagery practice

Since there is an upper limit to skill improvement through the repetition of actual execution, we examined whether motor imagery could be used in combination with actual execution to maximize motor skill improvement. Fingertip dexterity was evaluated in 25 healthy participants performing a force adjustment task using a pinch movement with the left thumb and index finger. In the intervention condition, six sets of repetitions of combined actual execution and motor imagery were performed, while in the control condition, the same flow was performed, but with motor imagery replaced by rest. Changes in the excitability of spinal motoneurons during motor imagery compared to rest were compared in terms of the F/M amplitude ratio. Motor skill changes were compared before and after repeated practice and between the conditions, respectively, using the absolute amount of adjustment error between the target pinch force value and the delivered pinch force value (absolute error) as an index. The results showed that the repetition of exercise practice and motor imagery decreased the absolute error, which was greater than that of exercise practice alone in terms of motor skill improvement. The F/M amplitude ratio for motor imagery compared to rest did not increase. This suggests that motor imagery is involved in the degree of the increase of spinal motoneuron excitability based on the real-time prediction of motor execution and that there may be no need for an increase in excitability during motor skill control.

Segmental motor neuron dysfunction in amyotrophic lateral sclerosis: Insights from H reflex paradigms.

In amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre- and post-synaptic modulation of spinal motor neuron excitability by studying the H reflex, to understand spinal interneuron function in ALS. We evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H'RI ) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H'Pre ) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H'Pos ). Fifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H'RI 0.35 vs. 0.11, p = .036; H'Pre 1.0 vs. 5.0, p = .001; H'Pos 0.0 vs. 2.5, p = .031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition. Spinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS.

Synergic Effect of Isometric Resistance Training and Subthreshold Electrical Neuromuscular Stimulation on the Excitability of Spinal Motoneurons in Humans

Synergic Effect of Isometric Resistance Training and Subthreshold Electrical Neuromuscular Stimulation on the Excitability of Spinal Motoneurons in Humans

The severity of acute hypoxaemia determines distinct changes in intracortical and spinal neural circuits.

The purpose of this study was to examine how two common methods of continuous hypoxaemia impact the activity of intracortical circuits responsible for inhibition and facilitation of motor output, and spinal excitability. Ten participants were exposed to 2h of hypoxaemia at 0.13 fraction of inspired oxygen ( clamping protocol) and 80% of peripheral capillary oxygen saturation ( clamping protocol) using a simulating altitude device on two visits separated by a week. Using transcranial magnetic and peripheral nerve stimulation, unconditioned motor evoked potential (MEP) area, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and F-wave persistence and area were assessed in the first dorsal interosseous (FDI) muscle before titration, after 1 and 2h of hypoxic exposure, and at reoxygenation. The clamping protocols resulted in differing reductions in by 2h ( clamping protocol: 81.9±1.3%, clamping protocol: 90.6±2.5%). Although unconditioned MEP peak to peak amplitude and area did not differ between the protocols, SICI during clamping was significantly lower at 2h compared to clamping (P=0.011) and baseline (P<0.001), whereas ICF was higher throughout the clamping compared to clamping (P=0.005). Furthermore, a negative correlation between SICI and (rrm =-0.56, P=0.002) and a positive correlation between ICF and (rrm =0.69, P=0.001) were determined, where greater reductions in correlated with less inhibition and less facilitation of MEP responses. Although F-wave area progressively increased similarly throughout the protocols (P=0.037), persistence of responses was reduced at 2h and reoxygenation (P<0.01) during the clamping protocol compared to the clamping protocol. After 2h of hypoxic exposure, there is a reduction in the activity of intracortical circuits responsible for inhibiting motor output, as well as excitability of spinal motoneurones. However, these effects can be influenced by other physiological responses to hypoxia (i.e., hyperventilation and hypocapnia). NEW FINDINGS: What is the central question of this study? How do two common methods of acute hypoxic exposure influence the excitability of intracortical networks and spinal circuits responsible for motor output? What is the main finding and its importance? The excitability of spinal circuits and intracortical networks responsible for inhibition of motor output was reduced during severe acute exposure to hypoxia at 2 h, but this was not seen during less severe exposure. This provides insight into the potential cause of variance seen in motor evoked potential responses to transcranial magnetic stimulation (corticospinal excitability measures) when exposed to hypoxia.

Sex differences concerning the effects of ankle muscle fatigue on static postural control and spinal proprioceptive input at the ankle.

The main aim of this study was to determine sex differences in postural control changes with ankle muscle fatigue during a standing forward leaning (FL) task under different vision conditions. The secondary aim was to examine sex differences in the effect of fatigue on soleus (SOL) H-reflex amplitude, a measure of motoneuron excitability with activation of Ia afferents. Fifteen healthy young adult males (mean age: 28.0 years) and 16 healthy young adult females (mean age: 26.1 years) were asked to perform four consecutive FL tasks [30 s; two with eyes open (EO) and two with eyes closed (EC)] before, and immediately following a fatiguing exercise consisting of alternating ankle plantarflexion (6 s) and dorsiflexion (2 s) maximal isometric contractions, and at 5 and 10 min of recovery. Center of pressure (COP) sway variables (mean position, standard deviation, ellipse area, average velocity, and frequency), an ankle co-contraction index, and a ratio of SOL H-reflex to the maximum amplitude of the compound muscle action potential (M-max) were obtained during the FL tasks. A rating of perceived fatigue (RPF) was also documented at the different time points. Time to task failure (reduction of 50% in maximal voluntary isometric contraction torque of ankle plantar flexors) and the increase in RPF value were not significantly different between males and females. Both sex groups showed similar and significant increases (p < 0.05) in mean COP sway velocity with no significant changes in co-contraction indices. No significant effects of fatigue and related interactions were found for SOL H/M-max ratio. The absence of a significant sex difference in postural control change (sway and co-contraction) with fatigue could be explained by similar perceived (RPF) and performance fatigability (exercise duration) between males and females in the present study. Fatigue did not lead to significant changes in SOL spinal motoneuron excitability with activation of Ia afferents.

Cytoplasmic TDP-43 accumulation drives changes in C-bouton number and size in a mouse model of sporadic Amyotrophic Lateral Sclerosis

An altered neuronal excitability of spinal motoneurones has consistently been implicated in Amyotrophic Lateral Sclerosis (ALS) leading to several investigations of synaptic input to these motoneurones. One such input that has repeatedly been shown to be affected is a population of large cholinergic synapses terminating mainly on the soma of the motoneurones referred to as C-boutons. Most research on these synapses during disease progression has used transgenic Superoxide Dismutase 1 (SOD1) mouse models of the disease which have not only produced conflicting findings, but also fail to recapitulate the key pathological feature seen in ALS; cytoplasmic accumulations of TAR DNA-binding protein 43 (TDP-43). Additionally, they fail to distinguish between slow and fast motoneurones, the latter of which have more C-boutons, but are lost earlier in the disease.To circumvent these issues, we quantified the frequency and volume of C-boutons on traced soleus and gastrocnemius motoneurones, representing predominantly slow and fast motor pools respectively. Experiments were performed using the TDP-43ΔNLS mouse model that carries a transgenic construct of TDP-43 devoid of its nuclear localization signal, preventing its nuclear import. This results in the emergence of pathological TDP-43 inclusions in the cytoplasm, modelling the main pathology seen in this disorder, accompanied by a severe and lethal ALS phenotype.Our results confirmed changes in both the number and volume of C-boutons with a decrease in number on the more vulnerable, predominantly fast gastrocnemius motoneurones and an increase in number on the less vulnerable, predominantly slow soleus motoneurones. Importantly, these changes were only found in male mice. However, both sexes and motor pools showed a decrease in C-bouton volume. Our experiments confirm that cytoplasmic TDP-43 accumulation is sufficient to drive C-bouton changes.

ОТ АКТИВНОСТИ К БЕЗДЕЙСТВИЮ И СНОВА К АКТИВНОСТИ. СИГНАЛЬНЫЕ ПРОЦЕССЫ В ПОСТУРАЛЬНОЙ МЫШЦЕ В ПЕРЕХОДНЫЙ ПЕРИОД

Experiments with tail-suspended rats exposed to Kepler's parabolic flight and human subjects in dry immersion showed repeatedly decreases, sometimes to the point of full inhibition, of the soleus m. electrical activity. Stopping the activity, closely resembling the temporal physiological rest that in rat's m. soleus is normally 8-10 hours a day, is much longer in experiments and can be characterized as a state of inactivity. Already after 24 hours of inactivity, expression of key muscle ubiquitin Е3 ligases increases with parallel reductions in protein synthesis and translational capacity. Expression of the slow isoform of myosin heavy chains reduces also. Purpose of the review is to summarize the data on dynamics of molecular events in postural m. soleus of the mammal after cessation of its contractile activity. Changes in the complex of signaling pathways in the transitional period are triggered by a group of molecular messengers which are directly dependent on the contractile activity. Established was the function of increasing ATP concentration and ensuing reduction in phosphorylation of АМP-activated protein kinase (АМPК), as well as expression of slow myosin, regulators of mitochondria and ribosomes biogenesis and resting membrane potential at the initial stage of muscle inactivity. ATP-dependent processes contribute to NO reduction and Ca2+ions accumulation in muscle fibers. Changes in these messengers precisely underlie the subsequent atrophic developments, transformation of myosin phenotype, muscle fiber atony and mitochondrial dysfunction. At the same time, due to still not clearly understood changes in excitability of spinal motoneurons, within three day of inactivity the postural muscle demonstrates spontaneous activity with a gradually growing amplitude of electromyographic signals. Results of the investigations of signal processes in the postural muscle during the transition from activity to inactivity and back to autonomic activity suggest difference and nonuniformity and nonlinearity of these processes and change of mechanisms driving the destructive events.

Age Characteristics of Fatigue During Cyclic Work of Maximum Power

The purpose of the article is a study the age-related features of changes in the functional state of the neuromuscular apparatus during cyclic work before failure in laboratory conditions. Methods:14 adult ski racers (25-28 years old) candidates for masters of sports and 12 teenagers (14-15 years old) I and II sports categories took part in the study. As the maximum physical load (before failure), an imitation of alternating two-step walking in place was used.For each subject, the walking pace was 75% of the maximum.Ski racers performed imitation under an electronic metronome. The length of the step remained unchanged throughout the study; the duration of the simulation reached 30-40 minutes.The following physiological indicators were used to assess the state of the neuromuscular apparatus: reflex excitability of spinal motoneurons (according to the amplitude of the maximum H-response); latent period of H- and M-responses; the speed of propagation of excitation along the sensory and motor fibers of the tibial nerve in the area of the popliteal fossa and the medial condyle (bone) of the tibia using the "Micro-Neuro-Soft" electroneuromyography.Results. It was established that the relative share of motoneurons participating in the reflex response is the same in resting adults and young skiers. The duration of physical exercise in teenagers reached approximately the same values ​​as adult athletes and is 30-40 minutes. However, the dynamics of the studied functional indicators had their own specific features: in young ski racers, the amplitude of the H-response when refusing to continue working decreased by only 24.0% compared to the initial level. Conclusion. Reflex excitability of spinal motoneurons after performing cyclic work of maximum power in adult athletes is more pronounced than in adolescent athletes, which indicates faster fatigue after testing, but high physical performance during testing.

Lumbar trans-spinal direct current stimulation: A modeling-experimental approach to dorsal root ganglia stimulation.

The excitability of spinal motor neurons (MN) can be altered through subthreshold currents, such as transcutaneous spinal direct-current stimulation (tsDCS). Current evidence shows that tsDCS can interfere with ascending somatosensory pathways and lower motor neurons' (LMN) excitability, which points to its therapeutic potential for repairing altered spinal responses. We aim to define the best tsDCS montage for maximizing the electric field (E-field) in the lumbar spinal cord (L-SC) by computer modeling; and to apply this montage to measure the effect on LMN excitability and somatosensory evoked potentials (SSEP). A human volume conductor model was obtained from an available database. The E-field distribution was calculated considering three different electrode settings aiming at maximizing the field at L-SC and right dorsal root ganglia (DRG). The best electrode setting was then selected and applied in a blind crossover pseudo-randomized study including 14 subjects. tsDCS was delivered for 15 min (cathodal vs. sham) over L2 vertebra level (4 mA, 144 mC/cm2), and its effect on F-waves, H-reflex (including homosynaptic depression, HD) and SSEPs was investigated in the lower limbs. All simulated montages showed higher current density and E-field magnitudes between the electrodes (>0.15 V/m), with a major longitudinal component and with rostral-caudal direction. The induced E-field involved the sensory ganglia and was maximum in the right T8-left L2 montage, which was the one selected for the experimental protocol. We disclosed a statistically significant increase of the H-reflex amplitude at 0.1 Hz, after cathodal tsDCS (c-tsDCS) on both sides. No other significant change was observed. Our results can suggest the c-tsDCS applied to the L-SC and DRG can modulate synaptic efficiency increasing lower motor neurons response to Ia fibers excitation. The possible implications of our findings for treating clinical conditions will be addressed in future studies.

Determining the Neuromuscular Adaptations to Strength Training in Older Adults: A Systematic Review and Meta-analysis

Introduction: There are observable decreases in muscle strength as a result of ageing that occur from the age 50. The age-related loss of maximal force production is thought to occur as a result of changes within the neuromuscular system. Changes in both maximal force production and rate of force development (RFD) are due to age-related changes within supraspinal (i.e., reduced motor cortex excitability, increased cortical inhibition), spinal (reduced spinal motoneurone excitability which influences motor unit recruitment and discharge rates) and muscular changes (mainly reduced muscle mass).

Spastic muscle stiffness evaluated using ultrasound elastography and evoked electromyogram in patients following severe traumatic brain injury: an observational study

ABSTRACT Objective To determine the relationship between muscle stiffness assessed using ultrasound shear wave elastography, spinal motor neuron excitability assessed using the F wave, and clinical findings of spasticity in patients with spastic muscle overactivity following severe traumatic brain injury. Methods This study enrolled 17 inpatients with severe traumatic brain injury and 20 healthy volunteers. Biceps brachii muscle stiffness was then evaluated using ultrasound shear wave speed. Spinal motor neuron excitability was evaluated using the F/M ratio recorded from abductor pollicis brevis muscle. Clinical parameters, such as the modified Ashworth scale and modified Tardieu scale, were assessed in the patient with traumatic brain injury. Results The patients with traumatic brain injury group had a significantly higher shear wave speed and F/M ratio compared with the healthy group. A higher shear wave speed was correlated with higher clinical spastic severity in patients with traumatic brain injury. The F/M ratio was not significantly correlated with clinical spastic severity. Conclusion Ultrasound shear wave elastography might be helpful for assessing muscle stiffness in patients with spastic muscle overactivity following severe traumatic brain injury. Further studies comprising larger cohorts are warranted.

Differences in motor imagery strategy change behavioral outcome

Kinesthetic motor imagery (KMI) involves imagining the feeling and experience of movements. We examined the effects of KMI, number visualizing, and KMI with number visualizing on the excitability of spinal motor neurons and a behavioral outcome measure in a pinch force task. Healthy participants (13 men and 8 women; mean age: 24.8 ± 5.5 years) were recruited. We compared the F-waves of the left thenar muscles after stimulating the left median nerve at the wrist during each motor imagery condition after a practice session. The KMI condition consisted of imagining muscle contraction, the number visualizing condition consisted of imagining the pinch force increasing numerically, and the KMI with number visualizing consisted of alternating between the KMI and imagining the pinch force increasing numerically. Before and after motor imagery, the time required to adjust to the target pinch force was compared. The time required to adjust the pinch force was shorter in the KMI with number visualizing condition than in the KMI and number visualizing conditions. There was no difference in the F/M amplitude ratio between each MI strategy condition, indicating the excitability of spinal motor neurons. Numerical information helped to improve the ability of participants to perform KMI.

Role of the Dopamine Subtype 1 Receptor (D1R) Modulation of the Ih Current in Rhythmic Spinal Mammalian Motor Networks

Restless Legs Syndrome (RLS) is a chronic sensorimotor disorder that has been recently associated with decreased expression of inhibitory Gi‐coupled adenosine A1 receptors (A1Rs), leading to increased dopamine release (hyperdopaminergic signaling) within the central nervous system. Previous studies have shown that A1Rs specifically inhibit the Gs‐coupled dopamine D1 receptor (D1R) subtype through a functional A1R‐D1R heteromer receptor complex. Furthermore, D1Rs control spinal motor neuron (MN) excitability by increasing cyclic adenosine monophosphate (cAMP) concentration and opening hyperpolarization‐activated cyclic nucleotide‐gated non‐selective cation channel (HCN). This finding raises the possibility of increased HCN activity underlying some of the motor dysfunctions associated with periodic leg movements (PLMS) during sleep in RLS. Thus, this study aims to elucidate the importance of the D1 receptor subtype on modulating the hyperpolarization‐activated cation current (Ih) in spinal mammalian motor networks. I hypothesized that blocking Ih in the presence of a D1R agonist (enhanced dopaminergic modulation) would slow locomotor activity and disrupt MN bursting stability. Neonatal (P0‐P5; n = 7) mouse spinal cord preparations were used to measure MN bursting activity patterns including amplitude, duration, and cycle period of extracellular ventral root (L2 and L5) recordings via suction electrodes. Treatment conditions include serotonin (9‐15 μM 5‐HT) and N‐methyl‐D‐aspartate (6 μM NMDA) with and without a D1R agonist (10 μM SKF38393) to assess the effect of D1R on rhythmic bursting. Subsequently, an Ih blocker (1 μM ZD7288) was added to observe the importance of Ih in modulating MN burst activity. For both L2 and L5 roots, blocking the Ih current led to increases in burst amplitude, duration, and cycle period in respect to the control 5‐HT/NMDA condition. Our results propose that D1Rs play a significant role in modulating Ih by increasing cAMP levels and opening HCN1 channels at a more depolarized membrane potential. Future experiments involve: 1) using TM5 transmembrane disrupting peptide to disrupt A1R‐D1R heteromers in spinal MNs (and use TM7 as a negative control) to confirm if dopamine modulation of Ih activity is linked to the A1R‐D1R heteromer complexes and 2) applying adenyl cyclase activators and blockers to verify that the modulation of the Ih current is through the D1R‐mediated Gs second messenger pathway.

Effects of action observation and motor imagery of walking on the corticospinal and spinal motoneuron excitability and motor imagery ability in healthy participants.

Action observation (AO) and motor imagery (MI) are used for the rehabilitation of patients who face difficulty walking. Rehabilitation involving AO, MI, and AO combined with MI (AO+MI) facilitates gait recovery after neurological disorders. However, the mechanism by which it positively affects gait function is unclear. We previously examined the neural mechanisms underlying AO and MI of walking, focusing on AO+MI and corticospinal and spinal motor neuron excitability, which play important roles in gait function. Herein, we investigated the effects of a short intervention using AO+MI of walking on the corticospinal and spinal motor neuron excitability and MI ability of participants. Twelve healthy individuals participated in this study, which consisted of a 20 min intervention. Before the experiment, we measured MI ability using the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2). We used motor evoked potential and F-wave measurements to evaluate the corticospinal and spinal motor neuron excitability at rest, pre-intervention, 0 min, and 15 min post-intervention. We also measured corticospinal excitability during MI of walking and the participant’s ability to perform MI using a visual analog scale (VAS). There were no significant changes in corticospinal and spinal motor neuron excitability during and after the intervention using AO+MI (p>0.05). The intervention temporarily increased VAS scores, thus indicating clearer MI (p<0.05); however, it did not influence corticospinal excitability during MI of walking (p>0.05). Furthermore, there was no significant correlation between the VMIQ-2 and VAS scores and changes in corticospinal and spinal motor neuron excitability. Therefore, one short intervention using AO+MI increased MI ability in healthy individuals; however, it was insufficient to induce plastic changes at the cortical and spinal levels. Moreover, the effects of intervention using AO+MI were not associated with MI ability. Our findings provide information about intervention using AO+MI in healthy individuals and might be helpful in planning neurorehabilitation strategies.

Causal relationships between brain and spinal motor neuron excitability during motor imagery: Using NIRS and evoked electromyogram study

In this study, we elucidated the neural basis of motor imagery by using a powerful statistical method in addition to simultaneous brain and spinal measurements using NIRS and evoked electromyogram. We instructed the healthy participants to kinesthetic imagine for contracting the left thenar muscle at 50% maximal voluntary contraction. We examined F-waves and oxygenated-hemoglobin (oxy-Hb) levels simultaneously during motor imagery and the resting condition. During motor imagery was increased the oxy-Hb levels of the supplementary motor area, orbitofrontal cortex, frontopolar cortex, and dorsolateral prefrontal cortex, F-wave/M-wave amplitude ratio, and persistence than in the resting condition. However, other regions of interest, except supplementary motor area, did not correlate with spinal motor neuron excitability. We estimated the causal relationship using structural equation modeling for the brain regions and spinal motor neuron excitability that changed during motor imagery. As a clear series of causal factors, the supplementary motor area involved in the adjustment of gain control of spinal motor neuron excitability, and the dorsolateral prefrontal cortex was connected to the supplementary motor area by an indirect pathway through the parietal lobe region. Therefore, supplementary motor area, dorsolateral prefrontal cortex and spinal motor neuron excitability may play an important role in the execution of motor imagery.