Altered cutaneous reflexes to non-noxious stimuli in the triceps surae of people with chronic incomplete spinal cord injury.

Following spinal cord injury (SCI) task-dependent modulation of spinal reflexes are often impaired. To gain insight into the state of the spinal interneuronal pathways following injury, we studied the amplitude modulation of triceps surae cutaneous reflexes to non-noxious stimuli during standing and early-to-mid stance phase of walking in participants with and without chronic incomplete SCI. Reflex eliciting nerve stimulation was delivered to the superficial peroneal, sural, and distal tibial nerves about the ankle. Reflexes were analyzed in the short (SLR, 50-80 ms post stimulation onset) and the medium (MLR, 80-120 ms) latency response windows. Further, the relation between cutaneous and H-reflexes was also examined during standing. In participants without injuries the soleus SLR was modulated task-dependently with nerve specificity, and the soleus and medial gastrocnemius MLRs were modulated task-dependently. In contrast, participants with SCI, no task-dependent or nerve-specific modulation of triceps cutaneous reflexes was observed. The triceps surae cutaneous and H-reflexes were not correlated in either group (r = 0.01-0.37). The presence of cutaneous reflexes but the absence of significant amplitude modulation may suggest impaired function of spinal interneuronal pathways in this population. The lack of correlation between the cutaneous and H-reflexes may suggest that interneurons that are involved in H-reflex modulation and cutaneous reflex modulation do not receive common input, or the impact of the common input is outweighed by other input. Present findings highlight the importance of examining multiple spinal reflexes to better understanding spinal interneuronal pathways that affect motor control in people after SCI.

Effects of active and sham tDCS on the soleus H-reflex during standing.

Weak transcranial direct current stimulation (tDCS) is known to affect corticospinal excitability and enhance motor skill acquisition, whereas its effects on spinal reflexes in actively contracting muscles are yet to be established. Thus, in this study, we examined the acute effects of Active and Sham tDCS on the soleus H-reflex during standing. In fourteen adults without known neurological conditions, the soleus H-reflex was repeatedly elicited at just above M-wave threshold throughout 30 min of Active (N = 7) or Sham (N = 7) 2-mA tDCS over the primary motor cortex in standing. The maximum H-reflex (Hmax) and M-wave (Mmax) were also measured before and immediately after 30 min of tDCS. The soleus H-reflex amplitudes became significantly larger (by 6%) ≈1 min into Active or Sham tDCS and gradually returned toward the pre-tDCS values, on average, within 15 min. With Active tDCS, the amplitude reduction from the initial increase appeared to occur more swiftly than with Sham tDCS. An acute temporary increase in the soleus H-reflex amplitude within the first minute of Active and Sham tDCS found in this study indicates a previously unreported effect of tDCS on the H-reflex excitability. The present study suggests that neurophysiological characterization of Sham tDCS effects is just as important as investigating Active tDCS effects in understanding and defining acute effects of tDCS on the excitability of spinal reflex pathways.

Cutaneous inputs from perineal region facilitate spinal locomotor activity and modulate cutaneous reflexes from the foot in spinal cats.

It is well known that mechanically stimulating the perineal region potently facilitates hindlimb locomotion and weight support in mammals with a spinal transection (spinal mammals). However, how perineal stimulation mediates this excitatory effect is poorly understood. We evaluated the effect of mechanically stimulating (vibration or pinch) the perineal region on ipsilateral (9-14 ms onset) and contralateral (14-18 ms onset) short-latency cutaneous reflex responses evoked by electrically stimulating the superficial peroneal or distal tibial nerve in seven adult spinal cats where hindlimb movement was restrained. Cutaneous reflexes were evoked before, during, and after mechanical stimulation of the perineal region. We found that vibration or pinch of the perineal region effectively triggered rhythmic activity, ipsilateral and contralateral to nerve stimulation. When electrically stimulating nerves, adding perineal stimulation modulated rhythmic activity by decreasing cycle and burst durations and by increasing the amplitude of flexors and extensors. Perineal stimulation also disrupted the timing of the ipsilateral rhythm, which had been entrained by nerve stimulation. Mechanically stimulating the perineal region decreased ipsilateral and contralateral short-latency reflex responses evoked by cutaneous inputs, a phenomenon we observed in muscles crossing different joints and located in different limbs. The results suggest that the excitatory effect of perineal stimulation on locomotion and weight support is mediated by increasing the excitability of central pattern-generating circuitry and not by increasing excitatory inputs from cutaneous afferents of the foot. Our results are consistent with a state-dependent modulation of reflexes by spinal interneuronal circuits.

Vestibulo-perceptual influences upon the vestibulo-spinal reflex.

The vestibular system facilitates gaze and postural stability via the vestibulo-ocular (VOR) and vestibulo-spinal reflexes, respectively. Cortical and perceptual mechanisms can modulate long-duration VOR responses, but little is known about whether high-order neural phenomena can modulate short-latency vestibulo-spinal responses. Here, we investigate this by assessing click-evoked cervical vestibular myogenic-evoked potentials (VEMPS) during visual roll motion that elicited an illusionary sensation of self-motion (i.e. vection). We observed that during vection, the amplitude of the VEMPs was enhanced when compared to baseline measures. This modulation in VEMP amplitude was positively correlated with the subjective reports of vection strength. That is, those subjects reporting greater subjective vection scores exhibited a greater increase in VEMP amplitude. Control experiments showed that simple arousal (cold-induced discomfort) also increased VEMP amplitude but that, unlike vection, it did not modulate VEMP amplitude linearly. In agreement, small-field visual roll motion that did not induce vection failed to increase VEMP amplitude. Taken together, our results demonstrate that vection can modify the response of vestibulo-collic reflexes. Even short-latency brainstem vestibulo-spinal reflexes are influenced by high-order mechanisms, illustrating the functional importance of perceptual mechanisms in human postural control. As VEMPs are inhibitory responses, we argue that the findings may represent a mechanism whereby high-order CNS mechanisms reduce activity levels in vestibulo-collic reflexes, necessary for instance when voluntary head movements need to be performed.

Presynaptic inhibition in restless legs syndrome.

Introduction: Restless legs syndrome (RLS) is a condition that particularly urges at night in resting and causes the need to move the legs. Although the pathophysiology has not yet been clarified, dopamine and iron metabolism and spinal cord pathologies are blamed for causing the condition. There are few studies on spinal reflex mechanisms on RLS. In the present study, we aimed to investigate the role of presynaptic inhibition (PreI) in the spinal cord in RLS.Methods: Fourteen patients with RLS and 14 controls with similar demographic characteristics were included in the study. Soleus muscle H-reflex (Ht) investigation was performed for subjects whose electrophysiologic investigation was normal. The Ht response was conditioned to the stimulation of the common peroneal nerve (CPN) (Hc). The test and conditioned stimulation intervals were kept between 10 ms, 20 ms, 30 ms, 40 ms, 50 ms, 75 ms, 100 ms, 150 ms and 200 ms. In each inter-stimulus interval, nonparametric repeat measurement evaluations were conducted with the percentage value of Hc/Ht. The Hc/Ht values of the study and control groups in the same intervals were compared separately.Results: A significant decrease was detected in Hc values in the control group in the repeat measurement values at 20 ms and 100 ms inter-stimulus intervals; however, there was not decrease in any intervals in the patient's group.Conclusion: The absence of any decrease in Hc reflexes for 20-100 ms intervals revealed that discernible PreI was vanished in RLS patients.

Mechanically stimulating the lumbar region inhibits locomotor-like activity and increases the gain of cutaneous reflexes from the paws in spinal cats.

Mechanically stimulating the dorsal lumbar region inhibits locomotion and reduces weight support during standing in rabbits and cats. However, how this inhibitory effect from the lumbar skin is mediated is poorly understood. Here we evaluated the effect of mechanically stimulating (vibration or pinch) the dorsal lumbar region on short-latency (8- to 13-ms onset) cutaneous reflex responses, evoked by electrically stimulating the superficial peroneal or distal tibial nerves, in seven adult cats with a low thoracic spinal transection (spinal cats). Cutaneous reflexes were evoked before, during, and after mechanical stimulation of the dorsal lumbar region. We found that mechanically stimulating the lumbar region by vibration or manual pinch abolished alternating bursts of activity between flexors and extensors initiated by nerve stimulation. The activity of extensor muscles was abolished bilaterally, whereas the activity of some ipsilateral flexor muscles was sustained during vibration/pinch. Mechanically stimulating the lumbar region increased ipsilateral and contralateral short-latency excitatory responses evoked by cutaneous inputs, a phenomenon that was generalized to muscles crossing different joints and located in different limbs. Our results indicate that the inhibitory effect on locomotion and weight support is not mediated by reducing cutaneous reflex gain and instead points to an inhibition of central pattern-generating circuitry, particularly the extensor component. The results provide greater insight into interactions between different types of somatosensory inputs within spinal motor circuits.NEW & NOTEWORTHY Vibration or pinch of the lumbar region in spinal-transected cats abolished alternating bursts of activity between flexors and extensors initiated by nerve stimulation. Mechanically stimulating the lumbar region increased ipsilateral and contralateral short-latency excitatory responses evoked by cutaneous inputs in hindlimb muscles. Sensory inputs from mechanoreceptors of the lumbar region do not mediate their inhibitory effect on locomotion and weight support by reducing the gain of short-latency excitatory cutaneous reflexes from the foot.

Time course of functional recovery during the first 3 mo after surgical transection and repair of nerves to the feline soleus and lateral gastrocnemius muscles.

Locomotion outcomes after peripheral nerve injury and repair in cats have been described in the literature for the period immediately following the injury (muscle denervation period) and then again for an ensuing period of long-term recovery (at 3 mo and longer) resulting in muscle self-reinnervation. Little is known about the changes in muscle activity and walking mechanics during midrecovery, i.e., the early reinnervation period that takes place between 5 and 10 wk of recovery. Here, we investigated hindlimb mechanics and electromyogram (EMG) activity of ankle extensors in six cats during level and slope walking before and every 2 wk thereafter in a 14-wk period of recovery after the soleus (SO) and lateral gastrocnemius (LG) muscle nerves in one hindlimb were surgically transected and repaired. We found that the continued increase in SO and LG EMG magnitudes and corresponding changes in hindlimb mechanics coincided with the formation of neuromuscular synapses revealed in muscle biopsies. Throughout the recovery period, EMG magnitude of SO and LG during the stance phase and the duration of the stance-related activity were load dependent, similar to those in the intact synergistic medial gastrocnemius and plantaris. These results and the fact that EMG activity of ankle extensors and locomotor mechanics during level and upslope walking recovered 14 wk after nerve transection and repair suggest that loss of the stretch reflex in self-reinnervated muscles may be compensated by the recovered force-dependent feedback in self-reinnervated muscles, by increased central drive, and by increased gain in intermuscular motion-dependent pathways from intact ankle extensors. NEW & NOTEWORTHY This study provides new evidence that the timeline for functional recovery of gait after peripheral nerve injury and repair is consistent with the time required for neuromuscular junctions to form and muscles to reach preoperative tensions. Our findings suggest that a permanent loss of autogenic stretch reflex in self-reinnervated muscles may be compensated by recovered intermuscular force-dependent and oligosynaptic length-dependent feedback and central drive to regain adequate locomotor output capabilities during level and upslope walking.

Nicotine-mediated neuroprotection of rat spinal networks against excitotoxicity.

Activation of neuronal nicotinic acetylcholine receptors (nAChRs) by nicotine is reported to protect brain neurons from glutamate excitotoxicity. We inquired whether a similar phenomenon can occur in the rat isolated spinal cord (or spinal slice culture) challenged by a transient (1 hr) application of kainate (a powerful glutamate receptor agonist) to induce excitotoxicity mimicking spinal injury in vitro. We recorded spinal reflexes and fictive locomotion generated by the locomotor central pattern generator before and 24 hr after applying kainate. We also monitored network activity with Ca2+ imaging and counted neurons and glia with immunohistochemical methods. In control conditions, nicotine (1 µM; 4 hr) depressed reflexes and fictive locomotion with slow recovery and no apparent neurotoxicity at 24 hr although synchronous Ca2+ transients appeared in slice cultures. Kainate nearly halved neuron numbers (while sparing glia), decreased reflexes and Ca2+ transients, and suppressed fictive locomotion. When nicotine was applied (4 hr) after washout of kainate, fictive locomotor cycles appeared 24 hr later though with low periodicity, and significant protection of neurons, including motoneurons, was observed. Nicotine applied together with kainate and maintained for further 4 hr yielded better neuroprotection, improved fictive locomotion expression and reversed the depression of Ca2+ transients. nAChR antagonists did not intensify kainate neurotoxicity and inhibited the neuroprotective effects of nicotine. These data suggest that nicotine was efficacious to limit histological and functional excitotoxic damage probably because it activated and then desensitized nAChRs on excitatory and inhibitory network neurons to prevent triggering intracellular cell death pathways.

Supraspinal control of spinal reflex responses to body bending during different behaviours in lampreys.

KEY POINTS: Spinal reflexes are substantial components of the motor control system in all vertebrates and centrally driven reflex modifications are essential to many behaviours, but little is known about the neuronal mechanisms underlying these modifications. To study this issue, we took advantage of an in vitro brainstem-spinal cord preparation of the lamprey (a lower vertebrate), in which spinal reflex responses to spinal cord bending (caused by signals from spinal stretch receptor neurons) can be evoked during different types of fictive behaviour. Our results demonstrate that reflexes observed during fast forward swimming are reversed during escape behaviours, with the reflex reversal presumably caused by supraspinal commands transmitted by a population of reticulospinal neurons. NMDA receptors are involved in the formation of these commands, which are addressed primarily to the ipsilateral spinal networks. In the present study the neuronal mechanisms underlying reflex reversal have been characterized for the first time. ABSTRACT: Spinal reflexes can be modified during different motor behaviours. However, our knowledge about the neuronal mechanisms underlying these modifications in vertebrates is scarce. In the lamprey, a lower vertebrate, body bending causes activation of intraspinal stretch receptor neurons (SRNs) resulting in spinal reflexes: activation of motoneurons (MNs) with bending towards either the contralateral or ipsilateral side (a convex or concave response, respectively). The present study had two main aims: (i) to investigate how these spinal reflexes are modified during different motor behaviours, and (ii) to reveal reticulospinal neurons (RSNs) transmitting commands for the reflex modification. For this purpose in in vitro brainstem-spinal cord preparation, RSNs and reflex responses to bending were recorded during different fictive behaviours evoked by supraspinal commands. We found that during fast forward swimming MNs exhibited convex responses. By contrast, during escape behaviours, MNs exhibited concave responses. We found RSNs that were activated during both stimulation causing reflex reversal without initiation of any specific behaviour, and stimulation causing reflex reversal during escape behaviour. We suggest that these RSNs transmit commands for the reflex modification. Application of the NMDA antagonist (AP-5) to the brainstem significantly decreased the reversed reflex, suggesting involvement of NMDA receptors in the formation of these commands. Longitudinal split of the spinal cord did not abolish the reflex reversal caused by supraspinal commands, suggesting an important role for ipsilateral networks in determining this type of motor response. This is the first study to reveal the neuronal mechanisms underlying supraspinal control of reflex reversal.

Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord.

In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22-60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5-26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits.

A computational model for epidural electrical stimulation of spinal sensorimotor circuits.

Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled this model with an anatomically realistic axon-cable model of motoneurons, interneurons, and myelinated afferent fibers for antagonistic ankle muscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruited neural structures revealed the lack of direct influence of EES on motoneurons and interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. The model also predicted the capacity of spatially distinct EES to modulate side-specific limb movements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walking after neurological disorders.

Locomotor training improves premotoneuronal control after chronic spinal cord injury.

Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans. In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level. Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day. The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training. The soleus H reflexes evoked at 1.0, 0.33, 0.20, 0.14, and 0.11 Hz were normalized to the H reflex evoked at 0.09 Hz. Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle. Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI. Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients. In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest. During stepping, presynaptic inhibition was modulated in a phase-dependent manner. Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg. The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking.

Reflex inhibition of cutaneous and muscle vasoconstrictor neurons during stimulation of cutaneous and muscle nociceptors.

Cutaneous (CVC) and muscle (MVC) vasoconstrictor neurons exhibit typical reflex patterns to physiological stimulation of somatic and visceral afferent neurons. Here we tested the hypothesis that CVC neurons are inhibited by stimulation of cutaneous nociceptors but not of muscle nociceptors and that MVC neurons are inhibited by stimulation of muscle nociceptors but not of cutaneous nociceptors. Activity in the vasoconstrictor neurons was recorded from postganglionic axons isolated from the sural nerve or the lateral gastrocnemius-soleus nerve in anesthetized rats. The nociceptive afferents were excited by mechanical stimulation of the toes of the ipsilateral hindpaw (skin), by hypertonic saline injected into the ipsi- or contralateral gastrocnemius-soleus muscle, or by heat or noxious cold stimuli applied to the axons in the common peroneal nerve or tibial nerve. The results show that CVC neurons are inhibited by noxious stimulation of skin but not by noxious stimulation of skeletal muscle and that MVC neurons are inhibited by noxious stimulation of skeletal muscle but not by noxious stimulation of skin. These inhibitory reflexes are mostly lateralized and are most likely organized in the spinal cord. Stimulation of nociceptive cold-sensitive afferents does not elicit inhibitory or excitatory reflexes in CVC or MVC neurons. The reflex inhibition of activity in CVC or MVC neurons generated by stimulation of nociceptive cutaneous or muscle afferents during tissue injury leads to local increase of blood flow, resulting in an increase of transport of immunocompetent cells, proteins, and oxygen to the site of injury and enhancing the processes of healing.

Withdrawal reflexes in the upper limb adapt to arm posture and stimulus location.

INTRODUCTION: Withdrawal reflexes in the leg adapt in a context-appropriate manner to remove the limb from noxious stimuli, but the extent to which withdrawal reflexes adapt in the arm remains unknown. METHODS: We examined the adaptability of withdrawal reflexes in response to nociceptive stimuli applied in different arm postures and to different digits. Reflexes were elicited at rest, and kinetic and electromyographic responses were recorded under isometric conditions, thereby allowing motorneuron pool excitability to be controlled. RESULTS: Endpoint force changed from a posterior-lateral direction in a flexed posture to predominantly a posterior direction in a more extended posture [change in force angle (mean ± standard deviation) 35.6 ± 5.0°], and the force direction changed similarly with digit I stimulation compared with digit V (change = 22.9 ± 2.9°). CONCLUSIONS: The withdrawal reflex in the human upper limb adapts in a functionally relevant manner when elicited at rest.

Advancing Intraoperative Neurophysiological Monitoring With Human Reflexes.

Human reflexes are simple motor responses that are automatically elicited by various sensory inputs. These reflexes can provide valuable insights into the functioning of the nervous system, particularly the brainstem and spinal cord. Reflexes involving the brainstem, such as the blink reflex, laryngeal adductor reflex, trigeminal hypoglossal reflex, and masseter H reflex, offer immediate information about the cranial-nerve functionality and the overall state of the brainstem. Similarly, spinal reflexes such as the H reflex of the soleus muscle, posterior root muscle reflexes, and sacral reflexes provide crucial information about the functionality of the spinal cord and peripheral nerves. One of the critical benefits of reflex monitoring is that it can provide continuous feedback without disrupting the surgical process due to no movement being induced in the surgical field. These reflexes can be monitored in real time during surgical procedures to assess the integrity of the nervous system and detect potential neurological damage. It is particularly noteworthy that the reflexes provide motor and sensory information on the functional integrity of nerve fibers and nuclei. This article describes the current techniques used for monitoring various human reflexes and their clinical significance in surgery. We also address important methodological considerations and their impact on surgical safety and patient outcomes. Utilizing these methodologies has the potential to advance or even revolutionize the field of intraoperative continuous monitoring, ultimately leading to improved surgical outcomes and enhanced patient care.

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 and F-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 phantom limb pain. 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-day study. We measured pain using the McGill Pain Questionnaire, visual analog scale (VAS), and pain pressure threshold test. We measured spinal reflex and motoneuron excitability using posterior root-muscle (PRM) reflexes and F-waves, respectively. We delivered tSCS for 30 minutes/day for 5 days. Main Results: After 5 days of tSCS, McGill Pain Questionnaire scores decreased by clinically-meaningful amounts for all participants from 34.0±7.0 to 18.3±6.8; however, there were no clinically-significant decreases in VAS scores. Two participants had increased pain pressure thresholds 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±6.1 µC) and low amplitudes, suggesting that in PLP, the spinal cord is hypoexcitable. After 5 days of tSCS, reflex thresholds decreased significantly (38.6±12.2 µC; 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.

Effects of iron-deficient diet on sleep onset and spinal reflexes in a rodent model of Restless Legs Syndrome.

Restless Legs Syndrome (RLS) is a common sensorimotor and a sleep disorder that affects 2.5-10% of the European and North American populations. RLS is also often associated with periodic leg movements during sleep (PLMS). Despite ample evidence of genetic contributions, the underlying mechanisms that elicit the sensory and motor symptoms remain unidentified. Clinically, RLS has been correlated with an altered central iron metabolism, particularly in the brain. While several animal models have been developed to determine the outcome of an altered iron homeostasis on brain function, the potential role of an altered iron homeostasis on sleep and sensorimotor circuits has not yet been investigated. Here, we utilize a mouse model to assess the effects of an iron-deficient (ID) but non-anemic state on sleep time and episodes, and sensorimotor reflexes in male and female mice. We found that animals on the ID diet displayed an increased expression of the transferrin receptor in the spinal cord, confirming the results of previous studies that focused only on the impact of ID in the brain. We also demonstrate that the ID diet reduced hematocrit levels compared to controls but not into the anemic range, and that animals on the ID diet exhibited RLS-like symptoms with regard to sleep onset and spinal cord reflex excitability. Interestingly, the effects on the spinal cord were stronger in females than in males, and the ID diet-induced behaviors were rescued by the return of the animals to the control diet. Taken together, these results demonstrate that diet-induced ID changes to CNS function are both inducible and reversible, and that they mimic the sleep and sensorimotor RLS symptoms experienced in the clinic. We therefore propose replacing the commonly used phrase "brain iron deficiency" (BID) hypothesis in the RLS research field with the term "iron deficiency in the central nervous system" (ID-CNS), to include possible effects of altered iron levels on spinal cord function.

Evaluation of vestibular functions in patients with obstructive sleep apnea syndrome.

BACKGROUND: To determine the anatomical proximity of the vestibular nuclei to the respiratory nuclei and the effect of susceptibility of the posterior labyrinth to a hypoxic state on the vestibular system. OBJECTIVE: It was aimed to evaluate the possible effects of periodic hypoxia on vestibular reflexes and proprioceptive perception in patients with obstructive sleep apnea syndrome (OSAS). MATERIAL AND METHODS: The study was conducted with 40 patients diagnosed with moderate and severe OSAS and 21 healthy individuals. All individuals were evaluated with Dizziness Handicap Inventory, ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), video head impulse test (vHIT), videonystagmography (VNG) and sportKAT 3000. RESULTS: In the vHIT, a statistically significant difference was found between the groups in terms of anterior and posterior semicircular canal vestibulo-ocular reflex gains (p < .05). A negative correlation was found between the lateral gain asymmetry and RALP gain asymmetry and the awake blood oxygen level in the OSAS groups. There was a statistically significant difference between the groups in terms of wave response rates cVEMP 100 dB nHL and oVEMP 100-110 dB nHL (p < .05). CONCLUSION AND SIGNIFICANCE: It was concluded that vestibular reflexes and proprioceptive perception were affected due to periodic/chronic hypoxia in patients with moderate and severe OSAS.

Neural Plasticity in Spinal and Corticospinal Pathways Induced by Balance Training in Neurologically Intact Adults: A Systematic Review.

Balance training, defined here as training of postural equilibrium, improves postural control and reduces the rate of falls especially in older adults. This systematic review aimed to determine the neuroplasticity induced by such training in younger (18-30 years old) and older adults (≥65 years old). We focused on spinal and corticospinal pathways, as studied with electrophysiology, in people without neurological or other systemic disorders. We were specifically interested in the change in the excitability of these pathways before and after training. Searches were conducted in four databases: MEDLINE, CINAHL, Scopus, and Embase. A total of 1,172 abstracts were screened, and 14 articles were included. Quality of the studies was evaluated with the Downs and Black checklist. Twelve of the studies measured spinal reflexes, with ten measuring the soleus H-reflex. The H-reflex amplitude was consistently reduced in younger adults after balance training, while mixed results were found in older adults, with many showing an increase in the H-reflex after training. The differences in results between studies of younger vs. older adults may be related to the differences in their H-reflexes at baseline, with older adults showing much smaller H-reflexes than younger adults. Five studies measured corticospinal and intracortical excitability using transcranial magnetic stimulation. Younger adults showed reduced corticospinal excitability and enhanced intracortical inhibition after balance training. Two studies on older adults reported mixed results after training. No conclusions could be drawn for corticospinal and intracortical plasticity given the small number of studies. Overall, balance training induced measurable change in spinal excitability, with different changes seen in younger compared to older adults.