Pyramidal Tract Neurons Research Articles

The activity of primary motor cortex corticospinal neurons during tool use by macaque monkeys.

It has been suggested that the distinctive capacity of some nonhuman primates to use tools may reflect a well-developed corticospinal system and, in particular, direct cortico-motoneuronal (CM) connections to hand muscles. We investigated the activity of corticospinal neurons in the primary motor cortex hand area during the use of a tool by two adult macaque monkeys. They used a light rake to retrieve food rewards placed in their extrapersonal space. An analysis of EMG activity showed that the rake task involved a complex interaction of muscles acting on the digits, hand, and arm. Sixty-nine corticospinal neurons were identified antidromically as pyramidal tract neurons (PTNs). When tested on the rake task, most (64 of 69; 93%) showed a significant modulation of their discharge during at least one of three task periods: grasping the rake, projecting it beyond the food reward, and then pulling it back to retrieve the reward. Discharge patterns were heterogeneous, and many PTNs showed significant suppression of discharge during raking. Seventeen of the 69 PTNs recorded during the rake task were further identified as CM cells, exerting clear postspike facilitation on digit muscles, demonstrating that the CM system contributes to the skilled use of tools. We compared the activity of each PTN on the rake task with that during precision grip. Most PTNs (90%) modulated their activity significantly for both tasks, demonstrating that PTNs activated by a task involving fractionated movements of the digits are also recruited during rake use, although there were often contrasting patterns of PTN recruitment and muscle activity for the two tasks.

Angiogenesis induced by CNS inflammation promotes neuronal remodeling through vessel-derived prostacyclin

Angiogenesis is a prominent feature of central nervous system (CNS) disease and has roles in both the continued promotion of inflammation and the subsequent repair processes. Here we report that prostacyclin (or prostaglandin I(2) (PGI(2))) derived from new vessels promotes axonal remodeling of injured neuronal networks after CNS inflammation. In a localized model of experimental autoimmune encephalomyelitis (EAE), new vessels formed around the inflammatory lesion, followed by sprouting of adjacent corticospinal tract (CST) fibers. These sprouting fibers formed a compensatory motor circuit, leading to recovery of motor function. Capillary endothelial cell-derived prostacyclin bound to its receptor, the type I prostaglandin receptor (IP receptor), on CST neurons, promoting sprouting of CST fibers and contributing to the repair process. Inhibition of prostacyclin receptor signaling impaired motor recovery, whereas the IP receptor agonist iloprost promoted axonal remodeling and motor recovery after the induction of EAE. These findings reveal an important function of angiogenesis in neuronal rewiring and suggest that prostacyclin is a promising molecule for enhancing functional recovery from CNS disease.

Transcranial Direct Current Stimulation Effects on the Excitability of Corticospinal Axons of the Human Cerebral Cortex

BackgroundTranscranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability non-invasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation of motor cortex excitability. ObjectiveTo further elucidate the underlying physiological mechanisms of tDCS. MethodsWe recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 20 min period of anodal tDCS in a conscious patient who had electrode implanted in the cervical epidural space for the control of pain. We performed magnetic stimulation of the motor cortex using a direction of the induced current in the brain capable of activating both corticospinal axons, evoking D-wave activity, and cortico-cortical axons projecting upon corticospinal cells, evoking I-wave activity. ResultsAnodal tDCS increased the excitability of cortical circuits generating both D and I-wave activity, with a more prolonged effect on D-wave activity. The changes in motor evoked potential recorded from hand muscles produced by tDCS were in agreement with the effects produced on intracortical circuitry. ConclusionsEpidural recordings of corticospinal activity in our patient indicate that anodal tDCS develops its facilitatory effects by an increase in the excitability of corticospinal axons and by an increase of activity in cortico-cortical projections onto pyramidal tract neurones, modulating motor cortex excitability with both synaptic (I waves) and non-synaptic (D waves) mechanisms.

Differential modulations of ipsilateral and contralateral beta (de)synchronization during unimanual force production

Unilateral movement is usually accompanied by ipsilateral activity in the primary motor cortex (M1). It is still largely unclear whether this activity reflects interhemispheric 'cross-talk' of contralateral M1 that facilitates movement, or results from processes that inhibit motor output. We investigated the role of beta power in ipsilateral M1 during unimanual force production. Significant ipsilateral beta desynchronization occurred during continuous dynamic but not during static force production. Moreover, event-related time-frequency analysis revealed bilateral desynchronization patterns, whereas post-movement synchronization was confined to the contralateral hemisphere. Our findings indicate that ipsilateral activation is not merely the result of interhemispheric cross-talk but involves additional processes. Given observations of differential blood oxygen level-dependent responses in ipsilateral and contralateral M1, and the correlation between beta desynchronization and the firing rate of pyramidal tract neurons in contralateral M1 during movement, we speculate that beta desynchronization in contra- and ipsilateral M1 arises from distinct neural activation patterns.

Microglia activation along the corticospinal tract following traumatic brain injury in the rat: A neuroanatomical study

Traumatic injury to the brain often manifests itself symptomatically and structurally long after the traumatic event. The cellular basis of this complex response is not completely understood. However, we hypothesized that microglia might contribute to the brain-wide process. To test this hypothesis, we employed optical and electron microscopy to study the microglia in rat brains up to 2months after digitally controlled cortical impact (CCI) to produce traumatic brain injury (TBI). We also used antibodies against ED-1 and Iba-1, respectively, as markers for activated and resting microglia. ED-1 positive microglial cells are observed accompanying the entire corticospinal tract (CST) on the injured side, but not the control, contralateral side of the brain at 2months. In this case, ED-1 and Iba-1 were observed to co-localize uniquely on the injured side of the brain. At earlier times following CCI, ultrastructural studies reveal that microglial cells have very irregular shapes and have many processes that intermingle with degenerating nerve axons of the CST in the hindbrain pyramids. These cells appear to be engulfing degenerating myelinated axons. The debris within the cells is converted to lipofuscin, the antigen for the ED-1 antibody, and remains in the cell cytoplasm throughout the life of the cell. We conclude, as hypothesized, that microglia are critical cellular components. Based on observed close association with myelin degeneration, interdigitating activated microglia may be contributing to damage control. Finally, based on the close neuroanatomical relationship between the lesioned corticospinal tract and the wide distribution of activated microglia, primary signals from CST neurons per se, may be directing microglial responses along the entire damaged rat neuroaxis. The role of persistent activation of microglia has not been determined.

Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract

Axon regeneration in the central nervous system normally fails, in part because of a developmental decline in the intrinsic ability of CNS projection neurons to extend axons. Members of the KLF family of transcription factors regulate regenerative potential in developing CNS neurons. Expression of one family member, KLF7, is down-regulated developmentally, and overexpression of KLF7 in cortical neurons in vitro promotes axonal growth. To circumvent difficulties in achieving high neuronal expression of exogenous KLF7, we created a chimera with the VP16 transactivation domain, which displayed enhanced neuronal expression compared with the native protein while maintaining transcriptional activation and growth promotion in vitro. Overexpression of VP16-KLF7 overcame the developmental loss of regenerative ability in cortical slice cultures. Adult corticospinal tract (CST) neurons failed to up-regulate KLF7 in response to axon injury, and overexpression of VP16-KLF7 in vivo promoted both sprouting and regenerative axon growth in the CST of adult mice. These findings identify a unique means of promoting CST axon regeneration in vivo by reengineering a developmentally down-regulated, growth-promoting transcription factor.

Les paraplégies spastiques autosomiques récessives au Maroc (PS)

Hereditary spastic paraplegia (SPG) is a clinically and genetically heterogeneous group of neurodegenerative disorders that are clinically characterised by progressive spasticity and weakness of the lower-limbs (pure SPG) and, majoritorian, additional more extensive neurological or non-neurological manifestations (complex or complicated SPG). Pure SPG is characterised by progressive spasticity and weakness of the lower-limbs, and occasionally sensory disturbances or bladder dysfunction. Complex SPGs additionally include cognitive impairment, dementia, epilepsy, extrapyramidal disturbances, cerebellar involvement, retinopathy, optic atrophy, deafness, polyneuropathy, or skin lesions in the absence of coexisting disorders. Nineteen SPGs follow an autosomal-dominant (AD-SPG), 27 an autosomal-recessive (AR-SPG), 5 X-linked (XL-SPG), and one a maternal trait of inheritance. SPGs are due to mutations in genes encoding for proteins involved in the maintenance of corticospinal tract neurons. Among the AD-SPGs, 40–45% of patients carry mutations in the SPAST-gene (SPG4) and 10% in the ATL1-gene (SPG3), while the other 9 genes are more rarely involved (NIPA1 (SPG6), KIAA0196 (SPG8), KIF5A (SPG10), RNT2 (SPG12), SPGD1 (SPG13), BSCL2 (SPG17), REEP1 (SPG31), ZFYVE27 (SPG33, debated), and SLC33A1 (SPG42, debated)). Among the AR-SPGs, ~ 20% of the patients carry mutations in the KIAA1840 (SPG11) gene whereas the 15 other genes are rarely mutated and account for SPGs in single families yet (CYP7B1 (SPG5), SPG7 (SPG7), ZFYVE26 (SPG15), ERLIN2 (SPG18), SPG20 (SPG20), ACP33 (SPG21), KIF1A (SPG30), FA2H (SPG35), NTE (SPG39), GJA12/GJC2 (SPG44), KIAA0415 (SPG48) and 4 genes encoding for the AP4-complex (SPG47)). Among the XL-SPGs, 3 causative genes have been identified (L1CAM (SPG1), PLP1 (SPG2), and SLC16A2 (SPG22)). The diagnosis of SPGs is based on clinical, instrumental and genetic investigations. Treatment is exclusively symptomatic.

Pyramidal tract neurons receptive to different forelimb joints act differently during locomotion

During locomotion, motor cortical neurons projecting to the pyramidal tract (PTNs) discharge in close relation to strides. How their discharges vary based on the part of the body they influence is not well understood. We addressed this question with regard to joints of the forelimb in the cat. During simple and ladder locomotion, we compared the activity of four groups of PTNs with somatosensory receptive fields involving different forelimb joints: 1) 45 PTNs receptive to movements of shoulder, 2) 30 PTNs receptive to movements of elbow, 3) 40 PTNs receptive to movements of wrist, and 4) 30 nonresponsive PTNs. In the motor cortex, a relationship exists between the location of the source of afferent input and the target for motor output. On the basis of this relationship, we inferred the forelimb joint that a PTN influences from its somatosensory receptive field. We found that different PTNs tended to discharge differently during locomotion. During simple locomotion shoulder-related PTNs were most active during late stance/early swing, and upon transition from simple to ladder locomotion they often increased activity and stride-related modulation while reducing discharge duration. Elbow-related PTNs were most active during late swing/early stance and typically did not change activity, modulation, or discharge duration on the ladder. Wrist-related PTNs were most active during swing and upon transition to the ladder often decreased activity and increased modulation while reducing discharge duration. These data suggest that during locomotion the motor cortex uses distinct mechanisms to control the shoulder, elbow, and wrist.

Do spinocerebellar neurones forward information on spinal actions of neurones in the feline red nucleus?

We recently demonstrated that feline ventral spinocerebellar tract (VSCT) neurones monitor descending commands for voluntary movements initiated by pyramidal tract (PT) neurones as well as locomotor movements relayed by reticulospinal (RS) neurones. The aim of the present study was to examine whether VSCT neurones likewise monitor descending commands from the red nucleus (RN). Extracellular records from the spinal border (SB) subpopulation of VSCT neurons revealed that a third (31%) of SB neurones may be discharged by trains of stimuli applied in the RN. Moreover, when RN stimuli failed to discharge SB neurones they facilitated activation of some of these neurones by RS and/or PT neurones, while activation of other SB neurones was depressed. We propose that the facilitation and depression of actions of RS neurones by RN neurones might serve to reflect a higher or lower excitability of motoneurones and therefore a likely higher or lower efficacy of the RS descending commands, prompting the cerebellum to adjust the activation of reticulospinal neurones. Activation of SB neurones by RN stimuli alone would also allow monitoring and adjusting the RN descending commands. Intracellular records from SB neurones revealed both monosynaptic and disynaptic EPSPs and disynaptic IPSPs evoked by RN stimuli. The disynaptic actions remained following transection of axons of reticulospinal neurones within the medullary longitudinal fascicle (MLF) and were therefore taken to be relayed primarily by spinal neurones, in contrast to EPSPs and IPSPs evoked by PT stimuli found to be relayed by reticulospinal rather than spinal neurones.

Processing information related to centrally initiated locomotor and voluntary movements by feline spinocerebellar neurones

Feed-back information on centrally initiated movements is processed at both supraspinal and spinal levels and is forwarded by a variety of neurones. The aim of the present study was to examine how descending commands relayed by reticulospinal neurones are monitored by a population of spinocerebellar tract neurones. Our main question was whether a spinal border (SB) subpopulation of ventral spinocerebellar tract (VSCT) neurones monitor actions of reticulospinal neurones with input from the mesencephalic locomotor region (MLR) as well as from pyramidal tract (PT) neurones. In the majority of intracellularly recorded SB neurons, stimuli applied in the MLR and in the medullary pyramids evoked EPSPs in parallel with EPSPs evoked by stimulation of axons of reticulospinal neurones in the medial longitudinal fascicle (MLF). In extracellularly recorded neurones short trains of stimuli applied in the ipsilateral and contralateral pyramids potently facilitated discharges evoked from the MLF, as well as EPSPs recorded intracellularly. In both cases the facilitation involved the disynaptic but not the monosynaptic actions. These results indicate that reticulospinal neurones activating SB neurones (or more generally VSCT neurones) are co-excited by axon-collaterals of other reticulospinal neurones and by fibres stimulated within the MLR and PTs. The study leads to the conclusion that these spinocerebellar neurones monitor descending commands for centrally initiated voluntary as well as locomotor movements relayed by reticulospinal neurones. Thereby they may provide the cerebellum with feed-back information on the likely outcome of these commands and any corrections needed to avoid errors in the issuing movements.

Feedback Modulation: A Window into Cortical Function

A recent study demonstrates involvement of primary motor cortex in task-dependent modulation of rapid feedback responses; cortical neurons resolve locally ambiguous sensory information, producing sophisticated responses to disturbances.

Large Identified Pyramidal Cells in Macaque Motor and Premotor Cortex Exhibit “Thin Spikes”: Implications for Cell Type Classification

Recent studies have suggested that extracellular recordings of putative cortical interneurons have briefer spikes than those of pyramidal neurons, providing a means of identifying cortical cell types in recordings from awake monkeys. To test this, we investigated the spike duration of antidromically identified pyramidal tract neurons (PTNs) recorded from primary motor (M1) or ventral premotor cortex (area F5) in 4 awake macaque monkeys. M1 antidromic latencies (ADLs) were skewed toward short ADLs (151 PTNs; 0.5-5.5 ms, median 1.1 ms) and significantly different from that of F5 ADLs (54 PTNs; 1.0-6.9 ms, median 2.6 ms). The duration of PTN spikes, recorded with a high-pass filter of 300 Hz and measured from the negative trough to the positive peak of the spike waveform, ranged from 0.15 to 0.71 ms. Importantly, we found a positive linear correlation between ADL and spike duration in both M1 (R(2) = 0.40, p < 0.001) and F5 (R(2) = 0.57, p < 0.001). Thus PTNs with the shortest ADL (fastest axons) had the briefest spikes, and since PTN soma size is correlated with axon size and conduction velocity, it is likely that the largest pyramidal neurons (Betz cells in M1) have spikes with short durations (0.15-0.45 ms), which overlap heavily with those reported for putative interneurons in previous studies in non-primates. In summary, one class of physiologically identified cortical pyramidal neuron exhibits a wide variety of spike durations and the results suggest that spike duration alone may not be a reliable indicator of cell type.

A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18)

Hereditary Spastic Paraplegia (HSP) is a clinically and genetically heterogeneous group of neurological disorders that are characterized by progressive spasticity of the lower extremities. We describe an extended consanguineous Saudi family in which HSP is linked to SPG18, a previously reported autosomal recessive locus, and show that it is associated with a nullimorphic deletion of ERLIN2, a component of endoplasmic reticulum associated degradation. This finding adds to the growing diversity of cellular functions that are now known to be involved in the maintenance of the corticospinal tract neurons.

A reassessment of whether cortical motor neurons die following spinal cord injury.

Over the past century, the question of whether the cells of origin of the corticospinal tract (CST) die following spinal cord injury (SCI) has been debated. A recent study reported an approximately 20% loss of retrogradely labeled cortical motoneurons following damage to their axons resulting from SCI at T9 (Hains et al. [2003] J. Comp. Neurol. 462:328-341). In follow-up studies, however, we failed to find any evidence of loss of CST axons in the medullary pyramid, which must occur if CST neurons die. Here, we seek to resolve the discrepancy by re-evaluating possible loss of CST neurons using the same techniques as Hains et al. (quantitative analysis of retrograde labeling and staining for cell death markers including TUNEL and Hoechst labeling of the nuclei). Following either dorsal funiculus lesions at thoracic level 9 (T9) or lateral hemisection at cervical level 5 (C5), our results reveal no evidence for a loss of retrogradely labeled neurons and no evidence for TUNEL staining of axotomized cortical motoneurons. These results indicate that CST cell bodies do not undergo retrograde cell death following SCI, and therefore targeting such cell death is not a valid therapeutic target.

Harnessing activity-dependent plasticity in the developing corticospinal system to restore motor function after perinatal brain injury

The corticospinal tract (CST) is the principal motor contr ol pathway for skilled movements. The CST, as well as the motor behaviors that it is important for controlling, has a p rotracted postnatal development in humans and many animals. We first discuss our experiments in the cat, showing that CST neu ronal activity is important for normal development of the tract; especially for development of the proper pattern of connections between CST axons and neurons in spinal cord motor circuits. We compare our results in the cat using neural pathway tracing techniques with research on development of the CST in humans using transcranial magnetic stimulation, showing that the cat model captures key features of normal human CST development. In the human, damage to the CST during development produces cerebral palsy, a debilitating motor control disorder. Cerebr al palsy research suggests that the motor signs of this condition refl ect both the loss of development of a strong contralateral CST, together with development of aberrant dense ipsilateral connections between the CST and spinal motor circuits. We have developed a cat model of unilateral (i.e., hemiplegic) cerebral palsy that both captures these key defects in CST connections and exhibits motor control impairments. We discuss our work, showing that harnessing activity-dependent processes later in development is capable of both restoring the proper connections of the CST in this model and restoring normal motor function.

Sequential Activation of Motor Cortical Neurons Contributes to Intralimb Coordination During Reaching in the Cat by Modulating Muscle Synergies

We examined the contribution of the motor cortex to the control of intralimb coordination during reaching in the standing cat. We recorded the activity of 151 pyramidal tract neurons (PTNs) in the forelimb representation of three cats during a task in which the cat reached forward from a standing position to press a lever. We simultaneously recorded the activity of muscles in the contralateral forelimb acting around each of the major joints. Cell activity was recorded with and without the presence of an obstacle requiring a modification of limb trajectory. The majority of the PTNs (134/151, 89%) modulated their discharge activity at some period of the reach while 84/151 (56%) exhibited a significant peak or trough of activity as the limb was transported from its initial position to the lever. These phasic changes of activity were distributed sequentially throughout the transport phase. A cluster analysis of muscle activity in two of the cats showed the presence of five muscle synergies during this transport period. One of the synergies was related to the lift of the paw from the support surface, two to flexion of the limb and dorsiflexion of the paw, one to preparation for contact with the lever, and one to the transport of the entire limb forward; a sixth synergy was activated during the lever press. An analysis of the phase of cell activity with respect to the phase of activity of muscles selected to represent each of these synergies showed that different populations of PTNs were activated sequentially and coincidentally with each synergy. We suggest that this sequential activation of populations of PTNs is compatible with a contribution to the initiation and modulation of functionally distinct groups of synergistic muscles and ultimately serves to ensure the appropriate multiarticular, intralimb coordination of the limb during reaching.

Determining which mechanisms lead to activation in the motor cortex: A modeling study of transcranial magnetic stimulation using realistic stimulus waveforms and sulcal geometry

Objective To determine which mechanisms lead to activation of neurons in the motor cortex during transcranial magnetic stimulation (TMS) with different current directions and pulse waveforms. Methods The total electric field induced in a simplified model of a cortical sulcus by a figure-eight coil was calculated using the finite element method (FEM). This electric field was then used as the input to determine the response of compartmental models of several types of neurons. Results The modeled neurons were stimulated at different sites: fiber bends for pyramidal tract neurons, axonal terminations for cortical interneurons and axon collaterals, and a combination of both for pyramidal association fibers. All neurons were more easily stimulated by a PA - directed electric field, except association fibers. Additionally, the second phase of a biphasic pulse was found to be more efficient than the first phase of either monophasic or biphasic pulses. Conclusions The stimulation threshold for different types of neurons depends on the pulse waveform and relative current direction. The reported results might account for the range of responses obtained in TMS of the motor cortex when using different stimulation parameters. Significance Modeling studies combining electric field calculations and neuronal models may lead to a deeper understanding of the effect of the TMS-induced electric field on cortical tissue, and may be used to improve TMS coil and waveform design.

P7-10 Asymmetry of motor unit number estimation (MUNE) in patients with amyotrophic lateral sclerosis

Objective: Development of an electrophysiological biomarker of corticospinal tract (CST) degeneration for application as an electrodiagnostic test in Amyotrophic Lateral Sclerosis (ALS). ALS is a sporadic, progressive and fatal neurodegenerative disorder, which is characterised by loss of motoneurones within the brainstem and spinal cord, and degeneration of corticospinal tract (CST) neurons. While electrodiagnostic techniques for identifying motoneurone degeneration in ALS are well established, those for CST disease are not. We now have evidence from experiments in macaque monkeys that 15 30Hz intermuscular coherence (IMC), which is a measure of coupling between two EMG signals in the 15 30Hz frequency range, can be used to assess the integrity of the CST. We have therefore begun investigating the utility of IMC as an electrodiagnostic test in ALS patients. Methods: IMC was measured in 23 patients with ALS, including 10 patients with primary lateral sclerosis (PLS), the pure upper motor neurone variant of ALS in which there is only CST degeneration, and 6 patients with progressive muscular atrophy (PMA) the pure lower motor neurone variant of ALS. We also performed similar measures on healthy age-matched controls. Results: Significant 15 30Hz IMC was found in all patients with PMA, all age-matched controls (n = 15) and all non age-matched controls (n = 20) tested to date. However, none of the patients with PLS had significant 15 30Hz IMC. Conclusions: 15 30Hz IMC is dependent upon an intact CST and appears to be an inexpensive, simple and robust measure of CST degeneration in ALS. We are now investigating the diagnostic sensitivity and specificity of 15 30Hz IMC prospectively in a group of patients with clinically suspected/possible ALS, in which a significant proportion are likely to have an ALS mimic syndrome.

P7-7 The condition of bone marrow-MSCs of ALS patients is strongly associated with their prognosis

Objective: Development of an electrophysiological biomarker of corticospinal tract (CST) degeneration for application as an electrodiagnostic test in Amyotrophic Lateral Sclerosis (ALS). ALS is a sporadic, progressive and fatal neurodegenerative disorder, which is characterised by loss of motoneurones within the brainstem and spinal cord, and degeneration of corticospinal tract (CST) neurons. While electrodiagnostic techniques for identifying motoneurone degeneration in ALS are well established, those for CST disease are not. We now have evidence from experiments in macaque monkeys that 15 30Hz intermuscular coherence (IMC), which is a measure of coupling between two EMG signals in the 15 30Hz frequency range, can be used to assess the integrity of the CST. We have therefore begun investigating the utility of IMC as an electrodiagnostic test in ALS patients. Methods: IMC was measured in 23 patients with ALS, including 10 patients with primary lateral sclerosis (PLS), the pure upper motor neurone variant of ALS in which there is only CST degeneration, and 6 patients with progressive muscular atrophy (PMA) the pure lower motor neurone variant of ALS. We also performed similar measures on healthy age-matched controls. Results: Significant 15 30Hz IMC was found in all patients with PMA, all age-matched controls (n = 15) and all non age-matched controls (n = 20) tested to date. However, none of the patients with PLS had significant 15 30Hz IMC. Conclusions: 15 30Hz IMC is dependent upon an intact CST and appears to be an inexpensive, simple and robust measure of CST degeneration in ALS. We are now investigating the diagnostic sensitivity and specificity of 15 30Hz IMC prospectively in a group of patients with clinically suspected/possible ALS, in which a significant proportion are likely to have an ALS mimic syndrome.

Bilateral Postsynaptic Actions of Pyramidal Tract and Reticulospinal Neurons on Feline Erector Spinae Motoneurons

Trunk muscles are important for postural adjustments associated with voluntary movements but little has been done to analyze mechanisms of supraspinal control of these muscles at a cellular level. The present study therefore aimed to investigate the input from pyramidal tract (PT) neurons to motoneurons of the musculus longissimus lumborum of the erector spinae and to analyze to what extent it is relayed by reticulospinal (RS) neurons. Intracellular records from motoneurons were used to evaluate effects of electrical stimulation of medullary pyramids and of axons of RS neurons descending in the medial longitudinal fasciculus (MLF). The results revealed that similar synaptic actions were evoked from the ipsilateral and contralateral PTs, including disynaptic and trisynaptic EPSPs and trisynaptic IPSPs. Stimulation of the MLF-evoked monosynaptic and disynaptic EPSPs and disynaptic or trisynaptic IPSPs in the same motoneurons. All short-latency PSPs of PT origin were abolished by transection of the MLF, while they remained after transection of PT fibers at a spinal level. Hence, RS neurons might serve as the main relay neurons of the most direct PT actions on musculus (m.) longissimus. However, longer-latency IPSPs remaining after MLF or PT spinal lesions and after ipsilateral or contralateral hemisection of spinal cord indicate that PT actions are also mediated by ipsilaterally and/or contralaterally located spinal interneurons. The bilateral effects of PT stimulation thereby provide an explanation why trunk movements after unilateral injuries of PT neurons (e.g., stroke) are impaired to a lesser degree than movements of the extremities.