Contralateral Motoneurons Research Articles

A RARE CASE OF CONCOMITANT ABDUCENS AND CONTRALATERAL LOWER MOTOR NEURON FACIAL NERVE PALSIES FOLLOWING BLUNT HEAD TRAUMA ASSOCIATED WITH TEMPORAL BONE FRACTURE

This case report describes a case of concomitant abducens and contralateral lower motor neuron facial nerve palsies following blunt head trauma associated with left temporal bone fracture. A 11year old boy was brought to the emergency department with alleged history of fall from swing set. Detailed ocular examination and assessment of function of all the twelve cranial nerves of the patient revealed left oculomotor nerve paresis, left abducens nerve palsy and right sided lower motor neuron (LMN) facial nerve palsy. The patient was run through various neuroimaging investigations which showed longitudinal fracture of the left temporal bone. The patient was treated aggressively with systemic and oral steroids. On discharge, the left oculomotor nerve paresis had healed completely with no improvement in the other two affected cranial nerves. During one month follow up, the abducens and facial nerve palsies still persisted.

A multiple timescale network model of intracellular calcium concentrations in coupled neurons: Insights from ROM simulations

In Fernández-García and Vidal [Physica D 401 (2020) 132129], the authors have analyzed the synchronization features between two identical 3D slow-fast oscillators, symmetrically coupled, and built as an extension of the FitzHugh—Nagumo dynamics generating Mixed-Mode Oscillations. The third variable in each oscillator aims at representing the time-varying intracellular calcium concentration in neurons. The global model is therefore six-dimensional with two fast variables and four slow variables with strong symmetry properties. In the present article, we consider an extension of this model in two different directions. First, we consider heterogeneity among cells and analyze the coupling of two oscillators with different values for one parameter which tunes the intrinsic frequency of the output. We therefore identify new patterns of antiphasic synchronization, with non trivial signatures and that exhibit a Devil’s Staircase phenomenon in signature transitions when varying the coupling gain parameter value. Second, we introduce a network of N cells divided into two clusters: the coupling between neurons in each cluster is excitatory, while the coupling between the two clusters is inhibitory. Such system aims at modelling the interactions between neurons tending to synchronization in each of two subpopulations that inhibit each other, like ipsi- and contra-lateral motoneurons assemblies. To perform the numerical simulations in this case when N is large, as an initial step towards the network analysis, we consider Reduced Order Models in order to save computational costs. We present the numerical reduction results in a network of 100 cells. For the sake of validation of the numerical reduction method, we both compare the outputs and CPU times obtained with the original and the reduced models in different cases of network coupling structures.

Computing Temporal Sequences Associated With Dynamic Patterns on the C. elegans Connectome.

Understanding how the structural connectivity and spatial geometry of a network constrains the dynamics it is able to support is an active and open area of research. We simulated the plausible dynamics resulting from the known C. elegans connectome using a recent model and theoretical analysis that computes the dynamics of neurobiological networks by focusing on how local interactions among connected neurons give rise to the global dynamics in an emergent way. We studied the dynamics which resulted from stimulating a chemosensory neuron (ASEL) in a known feeding circuit, both in isolation and embedded in the full connectome. We show that contralateral motorneuron activations in ventral (VB) and dorsal (DB) classes of motorneurons emerged from the simulations, which are qualitatively similar to rhythmic motorneuron firing pattern associated with locomotion of the worm. One interpretation of these results is that there is an inherent—and we propose—purposeful structural wiring to the C. elegans connectome that has evolved to serve specific behavioral functions. To study network signaling pathways responsible for the dynamics we developed an analytic framework that constructs Temporal Sequences (TSeq), time-ordered walks of signals on graphs. We found that only 5% of TSeq are preserved between the isolated feeding network relative to its embedded counterpart. The remaining 95% of signaling pathways computed in the isolated network are not present in the embedded network. This suggests a cautionary note for computational studies of isolated neurobiological circuits and networks.

Histochemical Characterization of the Vestibular Y-Group in Monkey

The Y-group plays an important role in the generation of upward smooth pursuit eye movements and contributes to the adaptive properties of the vertical vestibulo-ocular reflex. Malfunction of this circuitry may cause eye movement disorders, such as downbeat nystagmus. To characterize the neuron populations in the Y-group, we performed immunostainings for cellular proteins related to firing characteristics and transmitters (calretinin, GABA-related proteins and ion channels) in brainstem sections of macaque monkeys that had received tracer injections into the oculomotor nucleus. Two histochemically different populations of premotor neurons were identified: The calretinin-positive population represents the excitatory projection to contralateral upgaze motoneurons, whereas the GABAergic population represents the inhibitory projection to ipsilateral downgaze motoneurons. Both populations receive a strong supply by GABAergic nerve endings most likely originating from floccular Purkinje cells. All premotor neurons express nonphosphorylated neurofilaments and are ensheathed by strong perineuronal nets. In addition, they contain the voltage-gated potassium channels Kv1.1 and Kv3.1b which suggests biophysical similarities to high-activity premotor neurons of vestibular and oculomotor systems. The premotor neurons of Y-group form a homogenous population with histochemical characteristics compatible with fast-firing projection neurons that can also undergo plasticity and contribute to motor learning as found for the adaptation of the vestibulo-ocular reflex in response to visual-vestibular mismatch stimulation. The histochemical characterization of premotor neurons in the Y-group allows the identification of the homologue cell groups in human, including their transmitter inputs and will serve as basis for correlated anatomical-neuropathological studies of clinical cases with downbeat nystagmus.

Crossed activation of thoracic trunk motoneurons by medullary reticulospinal neurons.

Activation of contralateral muscles by supraspinal neurons, or crossed activation, is critical for bilateral coordination. Studies in mammals have focused on the neural circuits that mediate cross activation of limb muscles, but the neural circuits involved in crossed activation of trunk muscles are still poorly understood. In this study, we characterized functional connections between reticulospinal (RS) neurons in the medial and lateral regions of the medullary reticular formation (medMRF and latMRF) and contralateral trunk motoneurons (MNs) in the thoracic cord (T7 and T10 segments). To do this, we combined electrical microstimulation of the medMRF and latMRF and calcium imaging from single cells in an ex vivo brain stem-spinal cord preparation of neonatal mice. Our findings substantiate two spatially distinct RS pathways to contralateral trunk MNs. Both pathways originate in the latMRF and are midline crossing, one at the level of the spinal cord via excitatory descending commissural interneurons (reticulo-commissural pathway) and the other at the level of the brain stem (crossed RS pathway). Activation of these RS pathways may enable different patterns of bilateral trunk coordination. Possible implications for recovery of trunk function after stroke or spinal cord injury are discussed.NEW & NOTEWORTHY We identify two spatially distinct reticulospinal pathways for crossed activation of trunk motoneurons. Both pathways cross the midline, one at the level of the brain stem and the other at the level of the spinal cord via excitatory commissural interneurons. Jointly, these pathways provide new opportunities for repair interventions aimed at recovering trunk functions after stroke or spinal cord injury.

Intra- and intersegmental neural network architectures determining rhythmic motor activity in insect locomotion

Abstract The coordinated movement of the extremities of an animal during locomotion is achieved by the interaction between groups of neurons called central pattern generators (CPGs). In the absence of any sensory input this network creates a stable rhythmic motor activity that is essential for a successful coordination between limbs. Studying the structure and the interaction between different parts of the CPG network is therefore of particular interest. This work is motivated by recent experimental results reported by Mantziaris et al. (2017) [12] . By chemically activating both isolated and interconnected deafferented thoracic segments (ganglia) of the stick insect Mantziaris et al. (2017) [12] analyzed the interactions between contralateral networks that drive the levator-depressor muscle pairs, which are responsible for the upward-downward movement of the legs. The results of the experimental analysis showed that intrasegmental phase relations differ between isolated segments. In particular, in isolated segments where the control networks of the middle and hind legs reside, i.e. in the meso- and metathoracic ganglia, the phase relations between activities of the contralateral depressor motoneurons were in-phase and anti-phase, respectively. Moreover, the phase relations switched to in-phase and stabilized when the ganglia were interconnected. Using the phase reduction of an intersegmental network model of stick insect locomotion presented in our previous work (Yeldesbay et al. (2017) [22]), we built a reduced model of the intra- and intersegmental network controlling levator-depressor activity in the meso- and metathoracic ganglia. By examining the intra- and intersegmental phase differences in the model we identified the properties of the network couplings that replicate the results observed in the experiments. We applied the theoretical analysis to escape type CPGs and revealed a set of possible contra- and ipsilateral synaptic connections. Finally, we defined general features of the couplings between CPGs of any type that maintain the phase relations observed in the experiments.

Prolonged time course of population excitatory postsynaptic potentials in motoneurons of chronic stroke survivors.

Hyperexcitability of spinal motoneurons may contribute to muscular hypertonia after hemispheric stroke. The origins of this hyperexcitability are not clear, but we hypothesized that prolongation of the Ia excitatory postsynaptic potential (EPSP) in spastic motoneurons may be one potential mechanism, by enabling more effective temporal summation of Ia EPSPs, making action potential initiation easier. Thus, the purpose of this study is to quantify the time course of putative EPSPs in spinal motoneurons of chronic stroke survivors. To estimate the EPSP time course, a pair of low-intensity electrical stimuli was delivered sequentially to the median nerve in seven hemispheric stroke survivors and in six intact individuals, to induce an H-reflex response from the flexor carpi radialis muscle. H-reflex response probability was then used to quantify the time course of the underlying EPSPs in the motoneuron pool. A population EPSP estimate was then derived, based on the probability of evoking an H-reflex from the second test stimulus in the absence of a reflex response to the first conditioning stimulus. Our experimental results showed that in six of seven hemispheric stroke survivors, the apparent rate of decay of the population EPSP was markedly slower in spastic compared with contralateral (stroke) and intact motoneuron pools. There was no significant difference in EPSP time course between the contralateral side of stroke survivors and control subject muscles. We propose that one potential mechanism for hyperexcitability of spastic motoneurons in chronic stroke survivors may be associated with this prolongation of the Ia EPSP time course. Our subthreshold double-stimulation approach could provide a noninvasive tool for quantifying the time course of EPSPs in both healthy and pathological conditions. NEW & NOTEWORTHY Spastic motoneurons in stroke survivors showed a prolonged Ia excitatory postsynaptic potential (EPSP) time course compared with contralateral and intact motoneurons, suggesting that one potential mechanism for hyperexcitability of spastic motoneurons in chronic stroke survivors may be associated with this prolongation of the Ia EPSP time course.

Dye-coupling between neonatal spinal motoneurons and interneurons revealed by prolonged back-filling of a ventral root with a low molecular weight tracer in the mouse

We investigated dye-coupling between motoneurons in the L6 segment of the neonatal mouse spinal cord that contains limb-innervating motoneurons and sexually dimorphic motor nuclei. Using an isolated spinal cord preparation, we back-filled the cut, L6 ventral root with the small molecule Neurobiotin, or the much larger dextran-conjugated fluorophores for 16–24 hours. Motoneurons and parasympathetic preganglionic neurons were filled with both markers, but dye-coupling was only seen with Neurobiotin fills. Following a neurobiotin fill, fluorescence was observed in contralateral motoneurons, in motoneurons innervating adjacent ventral roots, and in ChAT-negative, putative interneurons outside of the motoneuron pools in addition to the directly back-labeled L6 motoneurons. It is known that the gap junction protein connexin-36 is widely expressed in the sexually dimorphic motoneurons of the L6 segment, suggesting that the dye-coupling is mediated by gap junctions. The technique has revealed previously unknown connections of motoneurons in the neonatal mouse cord that are likely to play important roles in the development and function of spinal circuits.

Mills\u2019 syndrome revisited

Mills’ syndrome is an idiopathic, slowly progressive, spastic hemiparesis. We describe three cases that have been under review for a minimum of 11 years (range 11–19). In all patients, symptoms started in a leg, with a mean age of onset of 59 years (range 53–63). The only abnormality on laboratory investigations was a mildly elevated CSF protein in one case. MRI demonstrated focal T2 hyper-intensity located eccentrically in the cervical cord ipsilateral to the symptomatic side. No cerebral abnormality was demonstrated. Whilst visual and somatosensory evoked potentials were unremarkable, motor evoked potentials were abnormal in all patients: central motor conduction times were significantly prolonged unilaterally in two patients and bilaterally but asymmetrically in the third. Beta-band (15–30 Hz) intermuscular coherence, a potentially more sensitive method of assessing upper motor neuron integrity, was absent unilaterally in one patient and bilaterally in the other two. One patient developed amyotrophy and thus a picture of amyotrophic lateral sclerosis after 16 years, suggesting that Mills’ syndrome is part of the motor neuron disease spectrum. Both amyotrophy and subclinical contralateral upper motor neuron disease can therefore be features of Mills’ syndrome. However, even with the most sensitive electrodiagnostic techniques, unilateral upper motor neuron disease can remain the only abnormality for as long as 10 years. We conclude that whilst Mills’ syndrome should be classified as a motor neuron disorder, it is a distinct nosological entity which can be distinguished from amyotrophic lateral sclerosis, upper motor neuron-dominant amyotrophic lateral sclerosis and primary lateral sclerosis. We propose diagnostic criteria for Mills’ syndrome, and estimate a point prevalence of at least 1.2:1,000,000 based on our well-defined referral population in the North of England.

Functional hemispheric asymmetries during the planning and manual control of virtual avatar movements.

Both hemispheres contribute to motor control beyond the innervation of the contralateral alpha motoneurons. The left hemisphere has been associated with higher-order aspects of motor control like sequencing and temporal processing, the right hemisphere with the transformation of visual information to guide movements in space. In the visuomotor context, empirical evidence regarding the latter has been limited though the right hemisphere’s specialization for visuospatial processing is well-documented in perceptual tasks. This study operationalized temporal and spatial processing demands during visuomotor processing and investigated hemispheric asymmetries in neural activation during the unimanual control of a visual cursor by grip force. Functional asymmetries were investigated separately for visuomotor planning and online control during functional magnetic resonance imaging in 19 young, healthy, right-handed participants. The expected cursor movement was coded with different visual trajectories. During planning when spatial processing demands predominated, activity was right-lateralized in a hand-independent manner in the inferior temporal lobe, occipito-parietal border, and ventral premotor cortex. When temporal processing demands overweighed spatial demands, BOLD responses during planning were left-lateralized in the temporo-parietal junction. During online control of the cursor, right lateralization was not observed. Instead, left lateralization occurred in the intraparietal sulcus. Our results identify movement phase and spatiotemporal demands as important determinants of dynamic hemispheric asymmetries during visuomotor processing. We suggest that, within a bilateral visuomotor network, the right hemisphere exhibits a processing preference for planning global spatial movement features whereas the left hemisphere preferentially times local features of visual movement trajectories and adjusts movement online.

Intra- and intersegmental influences among central pattern generating networks in the walking system of the stick insect.

To efficiently move around, animals need to coordinate their limbs. Proper, context-dependent coupling among the neural networks underlying leg movement is necessary for generating intersegmental coordination. In the slow-walking stick insect, local sensory information is very important for shaping coordination. However, central coupling mechanisms among segmental central pattern generators (CPGs) may also contribute to this. Here, we analyzed the interactions between contralateral networks that drive the depressor trochanteris muscle of the legs in both isolated and interconnected deafferented thoracic ganglia of the stick insect on application of pilocarpine, a muscarinic acetylcholine receptor agonist. Our results show that depressor CPG activity is only weakly coupled between all segments. Intrasegmental phase relationships differ between the three isolated ganglia, and they are modified and stabilized when ganglia are interconnected. However, the coordination patterns that emerge do not resemble those observed during walking. Our findings are in line with recent studies and highlight the influence of sensory input on coordination in slowly walking insects. Finally, as a direct interaction between depressor CPG networks and contralateral motoneurons could not be observed, we hypothesize that coupling is based on interactions at the level of CPG interneurons.NEW & NOTEWORTHY Maintaining functional interleg coordination is vitally important as animals locomote through changing environments. The relative importance of central mechanisms vs. sensory feedback in this process is not well understood. We analyzed coordination among the neural networks generating leg movements in stick insect preparations lacking phasic sensory feedback. Under these conditions, the networks governing different legs were only weakly coupled. In stick insect, central connections alone are thus insufficient to produce the leg coordination observed behaviorally.

Coordinated control of the tongue during suckling-like activity and respiration.

The tongue can move freely and is important in oral motor functions. Tongue movement must be coordinated with movement of the hyoid, mandible, and pharyngeal wall, to which it is attached. Our previous study using isolated brainstem-spinal cord preparations showed that application of N-methyl-D-aspartate induces rhythmic activity in the hypoglossal nerve that is coincident with rhythmic activity in the ipsilateral trigeminal motor nerve. Partial or complete midline transection of the preparation only abolishes activity in the trigeminal motor nerve; therefore, the neuronal network contributing to coordinated activity of the jaw/tongue muscles is located on both sides of the preparation and sends motor commands to contralateral trigeminal motoneurons. Arterially perfused decerebrate rat preparations exhibit stable inspiratory activity in the phrenic nerve, with efferent nerves innervating the upper airway muscles (the hypoglossal nerve, a branch of the cervical spinal nerve, the external branch of the superior laryngeal nerve, and the recurrent laryngeal nerve) under normocapnic conditions (5% CO2). During hypercapnia (8% CO2), pre-inspiratory discharges appear in all nerves innervating upper airway muscles. Such coordinated activity in the pre-inspiratory phase contributes to dilation of the upper airway and improves hypercapnia.

Goji fruit (Lycium barbarum) protects sciatic nerve function against crush injury in a model of diabetic stress

Excess fructose consumption causes changes in functioning of the central and peripheral nervous systems, which increase the vulnerability of peripheral nerves to traumatic injury. The aim of this study was to evaluate the electrophysiological parameters of responses of motoneurons of the spinal cord at high-frequency stimulation of the distal part of the injured sciatic nerve in a model of diabetic stress under action of Lycium barbarum (LB). Male albino rats were given with drinking water with 50% concentration of dietary fructose for 6 weeks. Starting on the 7th week a crush injury of the left sciatic nerve was carried out. Some of the animals received fructose post-injury for 3 weeks and some of the animals received fructose+dry LB fruits for 3 weeks. In the fructose+crush+LВ group a relatively proportional division of tetanic and posttetanic potentiation and depression in responses of ipsilateral and contralateral motoneurons was observed, which would suggest the modulatory role of LB in short-term synaptic plasticity formation. Generally, LB fruit is able to modulate central nervous system reorganization, amplifying positive adaptive changes that improve functional recovery and promote selective target reinnervation in high fructose-diet rats with sciatic nerve crush-injury.

Discharge of Mid‐Cervical Neurons Following Cervical Spinal Cord Injury

Prior anatomical and neurophysiologic data suggest that mid‐cervical interneurons may contribute to the control of phrenic motor output after cervical spinal cord injury (cSCI). To explore this possibility, we recorded spinal interneuron bursting patterns and phrenic motor output in rats with chronic cSCI. Twelve weeks following lateral C2 hemi‐section (C2Hx), bilateral phrenic nerve activity was recorded in urethane anesthetized and mechanically ventilated rats (N=5). A multi‐electrode recording array was bilaterally inserted at C4 to enable simultaneous recording of mid‐cervical neuron discharge ipsilateral and contralateral to C2Hx. In this initial evaluation, neuronal discharge patterns were classified as tonic (i.e., active across the entire respiratory cycle) or phasic (i.e., active during only the inspiratory or expiratory phases). Spike triggered averaging of phrenic nerve activity based on discharge of recorded cells was used to identify phrenic motoneurons, all other cells were classified as interneurons for this analysis. Only interneurons (versus motoneurons) were identified in recordings ipsilateral to C2Hx, and these cells primarily burst in a tonic firing pattern (tonic: 91% and phasic: 9% of ipsilateral cells). In contrast, on the contralateral side phrenic motoneurons were readily recorded (26% of contralateral cells) and a greater proportion of phasic interneurons were detected (phasic: 26% and tonic: 48% of contralateral cells). Spike triggered averaging produced no evidence of direct (monosynaptic) coupling between interneurons and either the contra‐ or ipsilateral phrenic motoneuron pool. These preliminary findings confirm altered propriospinal neuron discharge in the ipsilateral vs. contralateral cord immediately caudal to chronic C2Hx injury. The precise role of mid‐cervical propriospinal neurons in respiratory recovery after cSCI remains unclear. Since we did not detect cells that were directly antecedent to the phrenic pool, our data suggest that following cSCI, “connectivity” between respiratory‐modulated spinal interneurons and the phrenic nucleus may involve polysynaptic pathways.Support or Funding InformationFunding: APS Undergraduate Summer Research Fellowship (SP), 1R01NS080180‐01A1 (DF), 1F32NS095620‐01 (KS), and Department of Defense W81XWH‐14‐1‐0625 (PR).

Segmental organization of vestibulospinal inputs to spinal interneurons mediating crossed activation of thoracolumbar motoneurons in the neonatal mouse.

Vestibulospinal pathways activate contralateral motoneurons (MNs) in the thoracolumbar spinal cord of the neonatal mouse exclusively via axons descending ipsilaterally from the vestibular nuclei via the lateral vestibulospinal tract (LVST; Kasumacic et al., 2010). Here we investigate how transmission from the LVST to contralateral MNs is mediated by descending commissural interneurons (dCINs) in different spinal segments. We test the polysynaptic nature of this crossed projection by assessing LVST-mediated ventral root (VR) response latencies, manipulating synaptic responses pharmacologically, and tracing the pathway transynaptically from hindlimb extensor muscles using rabies virus (RV). Longer response latencies in contralateral than ipsilateral VRs, near-complete abolition of LVST-mediated calcium responses in contralateral MNs by mephenesin, and the absence of transsynaptic RV labeling of contralateral LVST neurons within a monosynaptic time window all indicate an overwhelmingly polysynaptic pathway from the LVST to contralateral MNs. Optical recording of synaptically mediated calcium responses identifies LVST-responsive ipsilateral dCINs that exhibit segmental differences in proportion and dorsoventral distribution. In contrast to thoracic and lower lumbar segments, in which most dCINs are LVST responsive, upper lumbar segments stand out because they contain a much smaller and more ventrally restricted subpopulation of LVST-responsive dCINs. A large proportion of these upper lumbar LVST-responsive dCINs project to contralateral L5, which contains many of the hindlimb extensor MNs activated by the LVST. A selective channeling of LVST inputs through segmentally and dorsoventrally restricted subsets of dCINs provides a mechanism for targeting vestibulospinal signals differentially to contralateral trunk and hindlimb MNs in the mammalian spinal cord.

Probing diversity within subpopulations of locomotor-related V0 interneurons.

The V0 interneuronal population is derived from Dbx1 expressing progenitors. Initial studies on these interneurons in the mouse spinal cord demonstrated that they project commissural axons and are involved in coordinating left-right alternation during locomotion. Subsequent work has indicated that the V0 population can be divided into genetically distinct ventral (V0V) and dorsal (V0D) subpopulations, and experimental evidence suggests that each is responsible for left-right alternation at different locomotor speeds. In this study, we perform a series of experiments to probe the location and connectivity of these subpopulations in neonatal mice and demonstrate that they are more diverse than previously predicted. While the distribution of either subpopulation remains consistent along the extent of the lumbar spinal cord, a cluster of V0D cells lateral to the central canal receive substantial input from primary afferents. Retrograde tracing and activity dependent labeling experiments demonstrate that a group of V0 interneurons located in this same region preferentially project axons towards contralateral motoneurons via an oligosynaptic pathway, and are active during fictive locomotion. Our results suggest that this subset of V0 interneurons may be primarily responsible for coordination of left-right alternation during locomotion. Furthermore these experiments indicate that while genetic identity is one determinant of the function of a neuron during locomotion, the specific position in which the cell is located may also play a key role.

Excitability of the change in contralateral spinal motor neurons caused by voluntary arm motor learning: a study of different practices

Excitability of the change in contralateral spinal motor neurons caused by voluntary arm motor learning: a study of different practices

Estimating the time course of population excitatory postsynaptic potentials in motoneurons of spastic stroke survivors.

Hyperexcitable motoneurons are likely to contribute to muscle hypertonia after a stroke injury; however, the origins of this hyperexcitability are not clear. One possibility is that the effective duration of the Ia excitatory postsynaptic potential (EPSP) is prolonged, increasing the potential for temporal summation of EPSPs, making action potential initiation easier. Accordingly, the purpose of this study was to quantify the time course of EPSPs in motoneurons of stroke survivors. The experimental protocol, which was based on parameters derived from simulation, involved sequential subthreshold electrical stimuli delivered to the median nerve of hemispheric stroke survivors. The resulting H-reflex responses were recorded in the flexor carpi radialis muscle. H-reflex response probability was then used to quantify the time course of the underlying EPSPs in the motoneuron pool. A population EPSP was estimated based on the probability of evoking an H reflex from the second electrical stimulus in the absence of a reflex response to the first stimulus. The accuracy of this time-course estimate was quantified using a computer simulation that explored a range of feasible EPSP parameters. Our experimental results showed that in all five hemispheric stroke survivors the rate of decay of the population EPSP was consistently slower in spastic compared with the contralateral motoneuron pools. We propose that one potential mechanism for hyperexcitability of motoneurons in spastic stroke survivors may be linked to this prolongation of the Ia EPSP time course. Our subthreshold double-stimulation approach also provides a noninvasive tool for quantifying the time course of EPSPs in both healthy and pathological conditions.

Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse.

Using optical recording of synaptically mediated calcium transients and selective spinal lesions, we investigated the pattern of activation of spinal motoneurons (MNs) by the pontine reticulospinal projection in isolated brain stem-spinal cord preparations from the neonatal mouse. Stimulation sites throughout the region where the pontine reticulospinal neurons reside reliably activated MNs at cervical, thoracic, and lumbar levels. Activation was similar in MNs ipsi- and contralateral to the stimulation site, similar in medial and lateral motor columns that contain trunk and limb MNs, respectively, and similar in the L2 and L5 segments that predominantly contain flexor and extensor MNs, respectively. In nonlesioned preparations, responses in both ipsi- and contralateral MNs followed individual stimuli in stimulus trains nearly one-to-one (with few failures). After unilateral hemisection at C1 on the same side as the stimulation, responses had substantially smaller magnitudes and longer latencies and no longer followed individual stimuli. After unilateral hemisection at C1 on the side opposite to the stimulation, the responses were also smaller, but their latencies were not affected. Thus we distinguish two pontine reticulospinal pathways to spinal MNs, one uncrossed and the other crossed, of which the uncrossed pathway transmits more faithfully and appears to be more direct.

Asymmetries in vestibular evoked myogenic potentials in chronic stroke survivors with spastic hypertonia: Evidence for a vestibulospinal role

ObjectiveIndirect evidence suggests that lateralized changes in motoneuron behavior post-stroke are potentially due to a depolarizing supraspinal drive to the motoneuron pool, but the pathways responsible are unknown. In this study, we assessed vestibular evoked myogenic potentials (VEMPs) in the neck muscles of hemispheric stroke survivors with contralesional spasticity to quantify the relative levels of vestibular drive to the spastic-paretic and contralateral motoneuron pools. MethodsVEMPs were recorded from each sternocleidomastoid muscle in chronic stroke survivors. Side-to-side differences in cVEMP amplitude were calculated and expressed as an asymmetry ratio, a proxy for the relative amount of vestibular drive to each side. ResultsSpastic-paretic VEMPs were larger than contralateral VEMPs in 13/16 subjects. There was a strong positive relationship between the degree of asymmetry and the severity of spasticity in this subset of subjects. Remaining subjects had larger contralateral responses. ConclusionVestibular drive to cervical motoneurons is asymmetric in spastic stroke survivors, supporting our hypothesis that there is an imbalance in descending vestibular drive to motoneuron pools post-stroke. We speculate this imbalance is a consequence of the unilateral disruption of inhibitory corticobulbar projections to the vestibular nuclei. SignificanceThis study sheds new light on the underlying mechanisms of post-stroke spasticity.