Conditioning-test Intervals Research Articles

Evaluation of mechanomyogram efficacy as a tool for assessing paired-pulse inhibition of blink reflex early R1 component.

Paired-pulse stimulation provides clinically useful information regarding sensory inhibition. When supraorbital nerve stimulation is repeated within a short interval, the response to the second stimulation is reduced to varying degrees. This magnitude of change in stimulation response can be monitored by electromyogram (EMG) or by mechanomyogram (MMG) as in this report. MMG has some advantages such as being less time consuming and lacking stimulus artifact. We compared the use of MMG and EMG to validate MMG as an effective method of assessing blink reflex paired-pulse inhibition. Eight volunteers participated. Participants received electrical stimulation to the supraorbital nerve of each side. A paired-pulse paradigm was employed, varying the conditioning-test interval between 5 and 800 ms. The R1 component of the induced blink reflex was simultaneously recorded by EMG using a pair of electrodes placed on the lower eyelid and by MMG using an accelerometer placed between the electrodes. The correlation coefficient of the R1 amplitude between MMG and EMG of the grand-averaged waveforms was 0.99. The average participant r value was .91 (range .76-.99). Similar analyses were performed for the amplitude variation of the second response relative to the first response. Results correlated well, yielding r values of .97 and .86 for the grand-averaged waveform and the average for each subject. The present results demonstrate that MMG could be an alternative to EMG in assessing paired-pulse inhibition of the electrical blink reflex R1 component.

Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration.

Transcutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation. In this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS. Analysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle specific-motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode's position. Improvements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.&#xD.

Neuronal Actions of Transspinal Stimulation on Locomotor Networks and Reflex Excitability During Walking in Humans With and Without Spinal Cord Injury.

This study investigated the neuromodulatory effects of transspinal stimulation on soleus H-reflex excitability and electromyographic (EMG) activity during stepping in humans with and without spinal cord injury (SCI). Thirteen able-bodied adults and 5 individuals with SCI participated in the study. EMG activity from both legs was determined for steps without, during, and after a single-pulse or pulse train transspinal stimulation delivered during stepping randomly at different phases of the step cycle. The soleus H-reflex was recorded in both subject groups under control conditions and following single-pulse transspinal stimulation at an individualized exactly similar positive and negative conditioning-test interval. The EMG activity was decreased in both subject groups at the steps during transspinal stimulation, while intralimb and interlimb coordination were altered only in SCI subjects. At the steps immediately after transspinal stimulation, the physiological phase-dependent EMG modulation pattern remained unaffected in able-bodied subjects. The conditioned soleus H-reflex was depressed throughout the step cycle in both subject groups. Transspinal stimulation modulated depolarization of motoneurons over multiple segments, limb coordination, and soleus H-reflex excitability during assisted stepping. The soleus H-reflex depression may be the result of complex spinal inhibitory interneuronal circuits activated by transspinal stimulation and collision between orthodromic and antidromic volleys in the peripheral mixed nerve. The soleus H-reflex depression by transspinal stimulation suggests a potential application for normalization of spinal reflex excitability after SCI.

Reliability of the TMS-conditioned monosynaptic reflex in the flexor carpi radialis muscle

A subthreshold pulse of transcranial magnetic stimulation (TMS) on the motor cortex can modulate the amplitude of the monosynaptic reflex (H-reflex) elicited in the flexor carpi radialis (FCR) muscle, a method known as TMS-conditioning of the H-reflex. The purpose of this study was to establish the intersession reliability of this method over the course of three sessions. Eleven healthy participants received either peripheral nerve stimulation (PNS), TMS or a combination of the two. The intensity of the PNS stimuli was set to evoke a monosynaptic response (H-reflex) corresponding to 10 % of the maximum motor response (Mmax), HM10 %. The conditioning effect of TMS on the monosynaptic reflex was assessed by delivering subthreshold cortical pulses at different conditioning-test intervals (from -7 ms to 7 ms) from peripheral nerve stimulation. The first interval at which facilitation could be observed was deemed early facilitation (EF). Using intraclass correlation coefficients (ICCs), we found excellent reliability for Mmax amplitudes (ICC = 0.98), HM10 % amplitudes (ICC = 0.85) and TMS-conditioned H-reflexes recorded at the interval following EF (EF + 2 ms) (ICC = 0.87). Good reliability (ICCs ranging from 0.67 to 0.77) was found for the other conditioning-test intervals. We conclude that TMS-conditioned H-reflexes are reliable parameters to assess the excitability of corticospinal circuits.

Characterizing the effect of low intensity transcranial magnetic stimulation on the soleus H-reflex at rest.

Modulation of a Hoffmann (H)-reflex following transcranial magnetic stimulation (TMS) has been used to assess the nature of signals transmitted from cortical centers to lower motor neurons. Further characterizing the recruitment and time-course of the TMS-induced effect onto the soleus H-reflex adds to the discussion of these pathways and may improve its utility in clinical studies. In 10 healthy controls, TMS was used to condition the soleus H-reflex using TMS intensities from 65 to 110% of the resting motor threshold (RMT). Early facilitation [- 5 to - 3ms condition-test (C-T) interval] was evident when TMS was 110% of RMT (P < 0.05). By comparison, late facilitation (+ 10 to + 20ms C-T interval) was several times larger and observed over a wider range of TMS intensities, including 65-110% of RMT. The early inhibition (- 3 to - 1ms C-T interval) had a low TMS threshold and was elicited over a wide range of intensity from 65% to 95% of RMT (all P < 0.05). A second inhibitory phase was seen ~ 4ms later (+ 1 to + 4ms C-T intervals) and was only observed for a TMS intensity of 95% of RMT (P < 0.05). The present findings reaffirm that subthreshold TMS strongly modulates soleus motor neurons and demonstrates that distinct pathways can be selectively probed at discrete C-T intervals when using specific TMS intensities.

Repeated and patterned stimulation of cutaneous reflex pathways amplifies spinal cord excitability.

Priming with patterned stimulation of antagonist muscle afferents induces modulation of spinal cord excitability as evidenced by changes in group Ia reciprocal inhibition. When assessed transiently with a condition-test pulse paradigm, stimulating cutaneous afferents innervating the foot reduces Ia presynaptic inhibition and facilitates soleus Hoffmann (H)-reflex amplitudes. Modulatory effects (i.e., priming) of longer lasting sensory stimulation of cutaneous afferents innervating the foot have yet to be examined. As a first step, we examined how priming with 20 min of patterned and alternating stimulation between the left and right foot affects spinal cord excitability. During priming, stimulus trains (550 ms; consisting of twenty-eight 1-ms pulses at 51 Hz, 1.2 times the radiating threshold) were applied simultaneously to the sural and plantar nerves of the ankle. Stimulation to the left and right ankle was out of phase by 500 ms. We evoked soleus H-reflexes and muscle compound action potentials (M waves) before and following priming stimulation to provide a proxy measure of spinal cord excitability. H-reflex and M-wave recruitment curves were recorded at rest, during brief (<2 min) arm cycling, and with sural conditioning [train of five 1-ms pulses at 2 times the radiating threshold (RT) with a condition-test interval (C-T) = 80 ms]. Data indicate an increase in H-reflex excitability following priming via patterned sensory stimulation. Transient sural conditioning was less effective following priming, indicating that the increased excitability of the H-reflex is partially attributable to reductions in group Ia presynaptic inhibition. Sensory stimulation to cutaneous afferents, which enhances spinal cord excitability, may prove useful in both rehabilitation and performance settings.NEW & NOTEWORTHY Priming via patterned stimulation of the nervous system induces neuroplasticity. Yet, accessing previously known cutaneous reflex pathways to alter muscle reflex excitability has not yet been examined. Here, we show that sensory stimulation of the cutaneous afferents that innervate the foot sole can amplify spinal cord excitability, which, in this case, is attributed to reductions in presynaptic inhibition.

Modulation of soleus H-reflex excitability following cervical transspinal conditioning stimulation in humans

The aim of this study was to establish the effects of transcutaneous spinal cord (transspinal) stimulation over the cervical region on soleus H-reflex excitability in healthy subjects while at rest. Reflex effects were established at subthreshold and suprathreshold cervical transspinal conditioning stimulation intensities of the extensor carpi radialis transspinal evoked potential. Twenty soleus H-reflexes at 0.125 Hz were recorded randomly under control conditions and following transspinal conditioning stimulation at conditioning-test intervals that ranged from 0 to 55 ms and tested in increment of 5 ms steps and at 100 ms. Cervical transspinal stimulation at suprathreshold and not at subthreshold intensities produced short, medium, and long-latency soleus H-reflex facilitation. The observed facilitatory reflex effects are consistent with activation of excitatory components of long propriospinal neurons. We propose the use of cervical transspinal stimulation to potentiate excitatory neuronal interactions between arms and legs in neurological disorders.

Short-term effect of a close-fitting type of walking assistive device on spinal cord reciprocal inhibition

One of the major problems with walking encountered by patients with spastic hemiplegia is diminished toe clearance due to spasticity of their leg muscles. To improve their walking, a specialized robot assist for ankle movements (RE-Gait) has been utilized. The present study examined the neurophysiological effects whether spinal cord reciprocal Ia inhibition (RI) in the leg was altered by using RE-Gait. Sixteen patients with a clinical diagnosis of stroke were divided into the two groups, RE-Gait walking group (Group R) and normal (controlled) walking group (Group C). In each group, they walked on a flat floor for 15 min with or without RE-Gait. The depression of soleus (Sol) H-reflexes conditioned by common peroneal nerve stimuli with the conditioning-test (C-T) intervals of 1, 2, 3, and 4 ms were assessed before and immediately after each walking session. After the intervention, the LSM (SE) of Sol H-reflex amplitude with 1, 2 and 3 ms C-T interval conditions were significantly decreased in group R (1 ms: 88.15 (4.60), 2 ms: 86.37 (4.60), 3 ms: 89.68 (4.62)) compared to group C (1 ms: 105.57 (4.56), 2 ms: 100.89 (4.58), 3 ms: 107.72 (4.58)) [1 ms: p = 0.012, 2 ms: p = 0.035, 3 ms: p = 0.011]. Walking assistive robot that targets ankle movements might be a new rehabilitation tool for regulating spinal cord excitability.

Transspinal stimulation downregulates activity of flexor locomotor networks during walking in humans

The objective of this study was to establish the effects of transspinal stimulation on short-latency tibialis anterior (TA) flexion reflex during walking in healthy humans. Single pulse transspinal stimulation was delivered at a conditioning-test (C-T) interval either after (~20 ms) or simultaneously with the last pulse of the pulse train (0 ms) delivered to the medial arch of the right foot. Transspinal stimulation was delivered at sub- and supra-threshold intensities of the spinally-mediated TA transspinal evoked potential. Stimulation was delivered randomly at different phases of the step cycle, based on the foot switch threshold signal, which was divided into 16 equal bins. The TA flexion reflex facilitation under control conditions occurred at heel contact and then progressively from late stance phase reaching its peak at early and late swing phases. Transspinal stimulation at a negative and suprathreshold 0 ms C-T interval depressed flexion reflex excitability at all phases of the step cycle. The short-latency TA flexion reflex depression was possibly mediated through spinal inhibitory interneurons acting at both pre- and post- motoneuronal sites or by transspinal stimulation affecting directly the activity of the flexor half spinal center. These results reveal direct actions of transspinal stimulation on human spinal locomotor networks.

Recovery cycles of posterior root-muscle reflexes evoked by transcutaneous spinal cord stimulation and of the H reflex in individuals with intact and injured spinal cord.

Posterior root-muscle (PRM) reflexes are short-latency spinal reflexes evoked by epidural or transcutaneous spinal cord stimulation (SCS) in clinical and physiological studies. PRM reflexes share key physiological characteristics with the H reflex elicited by electrical stimulation of large-diameter muscle spindle afferents in the tibial nerve. Here, we compared the H reflex and the PRM reflex of soleus in response to transcutaneous stimulation by studying their recovery cycles in ten neurologically intact volunteers and ten individuals with traumatic, chronic spinal cord injury (SCI). The recovery cycles of the reflexes, i.e., the time course of their excitability changes, were assessed by paired pulses with conditioning-test intervals of 20–5000 ms. Between the subject groups, no statistical difference was found for the recovery cycles of the H reflexes, yet those of the PRM reflexes differed significantly, with a striking suppression in the intact group. When comparing the reflex types, they did not differ in the SCI group, while the PRM reflexes were more strongly depressed in the intact group for durations characteristic for presynaptic inhibition. These differences may arise from the concomitant stimulation of several posterior roots containing afferent fibers of various lower extremity nerves by transcutaneous SCS, producing multi-source heteronymous presynaptic inhibition, and the collective dysfunction of inhibitory mechanisms after SCI contributing to spasticity. PRM-reflex recovery cycles additionally obtained for bilateral rectus femoris, biceps femoris, tibialis anterior, and soleus all demonstrated a stronger suppression in the intact group. Within both subject groups, the thigh muscles showed a stronger recovery than the lower leg muscles, which may reflect a characteristic difference in motor control of diverse muscles. Based on the substantial difference between intact and SCI individuals, PRM-reflex depression tested with paired pulses could become a sensitive measure for spasticity and motor recovery.

Altered modulation of motor cortical excitability by electrical stimulation over the cerebellum in chronic migraine

Previous structural neuroimaging studies suggest that patients with chronic migraine (CM) with and without medication overuse have abnormal structural changes within the cerebellum. In humans, cerebellum exerts a suppressive effect on the contralateral motor cortical response through a cerebello-thalamo-cortical pathway. We recruited 10 patients affected from CM without medication overuse and 10 heathy volunteers (HVs). After a conditioning single pulse high-voltage electrical stimulation delivered over the posterior surface of the mastoid processes, a TMS pulse was delivered over the contralateral motor cortex with 5, 7, 10, and 15 ms interstimulus interval (ISI) in random order. Motor cortical excitability changes were evaluated by amplitude changes of EMG responses from the FDI muscle to motor cortical stimulation. In HVs, suppression occurred at ISI of 5 ms and lasted few milliseconds. In CM patients, conditioning electric stimulation over the cerebellum did not reduce the size of MEPs to test TMS of the motor cortex at conditioning-test intervals of 5 ms. Here, we found neurophysiological evidence for dysfunctional cerebello-thalamo-cortical inhibitory pathway in CM. Whether these functional abnormalities are due to primary abnormal cerebellar inhibitory dysfunction or are secondary to a disrupted cerebellar-thalamic-cortical connectivity, remains to be determined.

Vestibulospinal and Corticospinal Modulation of Lumbosacral Network Excitability in Human Subjects.

As part of a project aimed to develop a novel, non-invasive techniques for comprehensive assessment of supraspinal-spinal connectivity in humans, the present study sought to explore the convergence of descending vestibulospinal and corticospinal pathways onto lumbosacral motor pools. Transcutaneous electrical spinal stimulation-evoked motor potentials were recorded from knee and ankle flexors and extensors in resting neurologically intact participants. Descending influences on lumbosacral motor neurons were studied using galvanic vestibular (GVS) or transcranial magnetic stimulation (TMS) to elicit descending vestibulospinal or corticospinal volleys, respectively. Facilitatory conditioning effects of descending corticospinal volleys were manifested by a significant increase of spinally evoked motor potentials in recorded knee and ankle muscles bilaterally, and were observed at the 10–30 ms conditioning-test intervals (CTIs); whereas, facilitatory conditioning effects of vestibulospinal volleys manifested at longer latencies (CTIs of 90 and 110 ms), and lasted up to 250 ms. TMS mediated volleys revealed the conditioning effects at both short and long latencies, suggestive of both direct and indirect influence. In contrast, vestibulospinally mediated conditioning effects occurred at longer latencies, consistent with this pathway’s known anatomical and functional interfaces with other descending systems including the reticulospinal pathway and, suggestively, propriospinal interneurons. Our work demonstrates the utility and sensitivity of transcutaneous spinal stimulation in human neurophysiological studies as a technique for quantitative characterization of excitatory conditioning effects in multiple lumbosacral motor pools, obtained through descending pathways. This characterization becomes critical in understanding the neuroplasticity in the central nervous system during motor learning and neurological recovery.

Neural interactions between transspinal evoked potentials and muscle spindle afferents in humans

The objective of this study was to establish neural interactions between transspinal evoked potentials (TEPs) and muscle spindle group Ia afferents in healthy humans. Soleus H-reflexes were assessed following transspinal stimulation at conditioning-test (C-T) intervals that ranged from negative to positive 100 ms. TEPs were recorded from the right and left ankle/knee flexor and extensor muscles, and their amplitude was assessed following stimulation of soleus muscle spindle group Ia afferents at similar C-T intervals. Transspinal conditioning stimulation produced a short-latency, long-lasting soleus H-reflex depression. Excitation of muscle spindle group Ia afferents produced depression of ipsilateral ankle TEPs and medium-latency facilitation of the ipsilateral knee TEPs. At specific C-T intervals, the soleus H-reflex and ipsilateral ankle TEPs were summated based on their relative onset and duration. No changes were observed in the contralateral TEPs. These effects were exerted at both peripheral and spinal levels. Both transspinal and muscle spindle group Ia afferent stimulation produce long-lasting depression of the soleus H-reflex and TEPs, respectively. Transspinal stimulation may promote targeted neuromodulation and can be utilized in upper motoneuron lesions to normalize spinal reflex hyper-excitability and alter excitation thresholds of peripheral nerve axons.

New paradigm for auditory paired pulse suppression.

Sensory gating is a mechanism of sensory processing used to prevent an overflow of irrelevant information, with some indexes, such as prepulse inhibition (PPI) and P50 suppression, often utilized for its evaluation. In addition, those are clinically important for diseases such as schizophrenia. In the present study, we investigated long-latency paired-pulse suppression of change-related cortical responses using magnetoencephalography. The test change-related response was evoked by an abrupt increase in sound pressure by 15 dB in a continuous sound composed of a train of 25-ms pure tones at 65 dB. By inserting a leading change stimulus (prepulse), we observed suppression of the test response. In Experiment 1, we examined the effects of conditioning-test intervals (CTI) using a 25-ms pure tone at 80 dB as both the test and prepulse. Our results showed clear suppression of the test response peaking at a CTI of 600 ms, while maximum inhibition was approximately 30%. In Experiment 2, the effects of sound pressure on prepulse were examined by inserting prepulses 600 ms prior to the test stimulus. We found that a paired-pulse suppression greater than 25% was obtained by prepulses larger than 77 dB, i.e., 12 dB louder than the background, suggesting that long latency suppression requires a relatively strong prepulse to obtain adequate suppression, different than short-latency paired-pulse suppression reported in previous studies. In Experiment 3, we confirmed similar levels of suppression using electroencephalography. These results suggested that two identical change stimuli spaced by 600 ms were appropriate for observing the long-latency inhibition. The present method requires only a short inspection time and is non-invasive.

A dissociation between renewal and contextual fear conditioning in juvenile rats.

We investigated whether juvenile rats do not express renewal following extinction of conditioned fear due to their inability to form a long-term contextual fear memory. In experiment 1, postnatal day (P) 18 and 25 rats received 3 white-noise and footshock pairings, followed by 60 white-noise alone presentations the next day. When tested in a different context to extinction, P25 rats displayed renewal whereas P18 rats did not. Experiments 2A and 2B surprisingly showed that P18 and P25 rats do not show differences in contextual and cued fear, regardless of the conditioning-test intervals and the number of white-noise-footshock pairings received. Finally, we observed age differences in contextual fear when P25 rats were weaned at P21 in experiment 3. These results indicate that the developmental dissociation observed in renewal of extinguished fear is not related to the widely believed late emergence of contextual fear learning.

P209 The priming-effects of theta burst stimulation on lower extremity spinal reciprocal inhibition induced by peripheral patterned electrical stimulation

Introduction Peripheral patterned electrical stimulation (PES) to the common peroneal nerve modulates the spinal reciprocal inhibition from the tibialis anterior muscle (TA) to the soleus muscle (SOL) through spinal plasticity mechanisms, which have essential roles in functional recovery of the lower limb after spinal cord injury or stroke. Furthermore, modulation of cortex excitability is thought to modify spinal plasticity. Objectives This study aimed to investigate the priming-effects of intermittent theta burst stimulation (iTBS) over the primary motor cortex on PES-induced spinal plasticity in healthy subjects. Materials & methods Ten healthy volunteers have participated in the single-masked, sham-controlled, crossover study. All participants received iTBS to the TA motor hot-spot in three separated sessions: (1) iTBS before PES; (2) iTBS after PES; and (3) sham iTBS before PES. iTBS consisted of 10 bursts, in each of which composed of three stimuli at 50 Hz, at 5 Hz repeated every 10 s for a total of 600 stimuli (200 s). For the sham stimulation, iTBS was delivered with a coil held flipped over on the TA hotspot at a reduced intensity following the same procedure of real iTBS. PES involved stimulating the right common peroneal nerve with a train of ten 100-Hz pulses every 2 s for 20 min. To counterbalance the intervention time of iTBS before and after PES, rest period (200 s) was set for each task. Reciprocal inhibition from TA to SOL was assessed using a soleus H-reflex conditioning-test paradigm. The conditioning-test inter-stimulus intervals were 2 (RI2ms), 20 (RI20ms) and 100 ms (RI100ms).Reciprocal inhibition was assessed at baseline, before PES, and at 0, 15, 30, and 45 min after PES. Results iTBS before PES significantly enhanced RI2ms at 0 and 15 min after PES as compared with the baseline values. In contrast, iTBS after PES and sham iTBS before PES only enhanced RI2ms at the time point immediately after PES. RI100ms was significantly increased only under the iTBS before PES protocol, immediately after PES. Conclusion These findings confirm the hypothesis that spinal plasticity can be modified by altering the motor cortical excitability, and provide a greater understanding of the mechanisms underlying spinal plasticity to help for developing newer rehabilitation strategies.

Soleus Hoffmann reflex amplitudes are specifically modulated by cutaneous inputs from the arms and opposite leg during walking but not standing.

Electrical stimulation of cutaneous nerves innervating heteronymous limbs (the arms or contralateral leg) modifies the excitability of soleus Hoffmann (H-) reflexes. The differences in the sensitivities of the H-reflex pathway to cutaneous afferents from different limbs and their modulation during the performance of motor tasks (i.e., standing and walking) are not fully understood. In the present study, we investigated changes in soleus H-reflex amplitudes induced by electrical stimulation of peripheral nerves. Selected targets for conditioning stimulation included the superficial peroneal nerve, which innervates the foot dorsum in the contralateral ankle (cSP), and the superficial radial nerve, which innervates the dorsum of the hand in the ipsilateral (iSR) or contralateral wrist (cSR). Stimulation and subsequent reflex assessment took place during the standing and early-stance phase of treadmill walking in ten healthy subjects. Cutaneous stimulation produced long-latency inhibition (conditioning-test interval of ~100ms) of the H-reflex during the early-stance phase of walking, and the inhibition was stronger following cSP stimulation compared with iSR or cSR stimulation. In contrast, although similar conditioning stimulation significantly facilitated the H-reflex during standing, this effect remained constant irrespective of the different conditioning sites. These findings suggest that cutaneous inputs from the arms and contralateral leg had reversible effects on the H-reflex amplitudes, including inhibitions with different sensitivities during the early-stance phase of walking and facilitation during standing. Furthermore, the differential sensitivities of the H-reflex modulations were expressed only during walking when the locations of the afferent inputs were functionally relevant.

Effects of paired transcutaneous electrical stimulation delivered at single and dual sites over lumbosacral spinal cord

It was demonstrated previously that transcutaneous electrical stimulation of multiple sites over the spinal cord is more effective in inducing robust locomotor behavior as compared to the stimulation of single sites alone in both animal and human models. To explore the effects and mechanisms of interactions during multi-site spinal cord stimulation we delivered transcutaneous electrical stimulation to the single or dual locations over the spinal cord corresponding to approximately L2 and S1 segments. Spinally evoked motor potentials in the leg muscles were investigated using single and paired pulses of 1ms duration with conditioning-test intervals (CTIs) of 5 and 50ms. We observed considerable post-stimulation modulatory effects which depended on CTIs, as well as on whether the paired stimuli were delivered at a single or dual locations, the rostro-caudal relation between the conditioning and test stimuli, and on the muscle studied. At CTI-5, the paired stimulation delivered at single locations (L2 or S1) provided strong inhibitory effects, evidenced by the attenuation of the compound responses as compared with responses from either single site. In contrast, during L2–S1 paradigm, the compound responses were potentiated. At CTI-50, the magnitude of inhibition did not differ among paired stimulation paradigms. Our results suggest that electrical stimuli delivered to dual sites over the lumbosacral enlargement in rostral-to-caudal order, may recruit different populations of motor neurons initially through projecting sensory and intraspinal connections and then directly, resulting in potentiation of the compound spinally evoked motor potentials. The interactive and synergistic effects indicate multi-segmental convergence of descending and ascending influences on the neuronal circuitries during electrical spinal cord stimulation.

Characteristics of preceding Ia activity on postactivation depression in health and disease.

Previous activation of the soleus Ia afferents causes a depression in the amplitude of the H-reflex. This mechanism is referred to as postactivation depression (PAD) and is suggested to be presynaptically mediated. With the use of a paired reflex depression paradigm (eliciting two H-reflexes with conditioning-test intervals from 80 ms to 300 ms), PAD was examined in a group of healthy individuals and a group of hemiplegic patients. Healthy individuals showed substantial depression of the test H-reflex at all intervals. Although the patient group showed substantially less depression at all intervals, increasing the interval between the two reflexes sharply reduced the depression. In a separate experiment, we varied the size of the conditioning H-reflex against a constant test H-reflex. In healthy individuals, by increasing the size of the conditioning H-reflex, the amplitude of the test H-reflex exponentially decreased. In the patient group, however, this pattern was dependent on the conditioning-test interval; increasing the size of the conditioning H-reflex caused an exponential decrease in the size of the test reflex at intervals shorter than 150 ms. This pattern was similar to that of healthy individuals. However, conducting the same protocol at a longer interval (300 ms) in these patients resulted in an abnormal pattern (instead of an exponential decrease in the size of the test reflex, exaggerated responses were observed). Fisher discriminant analysis suggested that these two patterns (which differed only in the timing between the two stimuli) were substantially different from each other. Therefore, it is suggested that the abnormal pattern of PAD in hemiplegic stroke patients could be a contributing factor for the pathophysiology of spasticity.

Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury.

Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs.