Central Pattern Generator Activity Research Articles

STEERING FROM THE REAR: COORDINATION OF CENTRAL PATTERN GENERATORS UNDERLYING NAVIGATION BY ASCENDING INTERNEURONS.

Understanding how animals coordinate movements to achieve goals is a fundamental pursuit in neuroscience. Here we explore how neurons that reside in posterior lower-order regions of a locomotor system project to anterior higher-order regions to influence steering and navigation. We characterized the anatomy and functional role of a population of ascending interneurons in the ventral nerve cord of Drosophila larvae. Through electron microscopy reconstructions and light microscopy, we determined that the cholinergic 19f cells receive input primarily from premotor interneurons and synapse upon a diverse array of postsynaptic targets within the anterior segments including other 19f cells. Calcium imaging of 19f activity in isolated central nervous system (CNS) preparations in relation to motor neurons revealed that 19f neurons are recruited into most larval motor programmes. 19f activity lags behind motor neuron activity and as a population, the cells encode spatio-temporal patterns of locomotor activity in the larval CNS. Optogenetic manipulations of 19f cell activity in isolated CNS preparations revealed that they coordinate the activity of central pattern generators underlying exploratory headsweeps and forward locomotion in a context and location specific manner. In behaving animals, activating 19f cells suppressed exploratory headsweeps and slowed forward locomotion, while inhibition of 19f activity potentiated headsweeps, slowing forward movement. Inhibiting activity in 19f cells ultimately affected the ability of larvae to remain in the vicinity of an odor source during an olfactory navigation task. Overall, our findings provide insights into how ascending interneurons monitor motor activity and shape interactions amongst rhythm generators underlying complex navigational tasks.

Caterpillars (Manduca sexta) parasitized by the wasp Cotesia congregata stop chewing despite an intact motor system.

The parasitic wasp Cotesia congregata suppresses feeding in its host, the caterpillar Manduca sexta, during specific periods of wasp development. We examined both feeding behaviour and the neurophysiology of the mandibular closer muscle in parasitized and unparasitized control M. sexta to determine how the wasp may accomplish this. To test whether the wasps activated a pre-existing host mechanism for feeding cessation, we examined the microstructure of feeding behaviour in caterpillars that stopped feeding due to illness-induced anorexia or an impending molt. These microstructures were compared to that shown by parasitized caterpillars. While there were overall differences between parasitized and unparasitized caterpillars, the groups showed similar progression in feeding microstructure as feeding ended, suggesting a common pattern for terminating a meal. Parasitized caterpillars also consumed less leaf area in 100 bites than control caterpillars at around the same time their feeding microstructure changed. The decline in food consumption was accompanied by fewer spikes/burst and shorter burst durations in chewing muscle electromyograms. Similar extracellular results were obtained from the motorneuron of the mandibular closer muscle. However, chewing was dramatically re-activated in non-feeding parasitized caterpillars if the connectives posterior to the subesophageal ganglion were severed. The same result was observed in unparasitized caterpillars given the same treatment. Our results suggest that the reduced feeding in parasitized caterpillars was not due to damage to the central pattern generator (CPG) for chewing, motor nerves or chewing muscles, but was more likely due to a suppression of chewing CPG activity by ascending or descending inputs.

Modulation of reflex responses of the anterior and posterior bellies of the digastric muscle in freely moving rats.

Chewing and licking are primarily activated by central pattern generator (CPG) neuronal circuits in the brainstem and when activated trigger repetitive rhythmic orofacial movements such as chewing, licking and swallowing. These CPGs are reported to modulate orofacial reflex responses in functions such as chewing. This study explored the modulation of reflex responses in the anterior and posterior bellies (ant-Dig and post-Dig, respectively) of the digastric muscle evoked by low-intensity trigeminal stimulation in conscious rats. The ant-Dig and post-Dig reflexes were evoked by using low-intensity electrical stimulation applied to either the right or left inferior alveolar nerve. Peak-to-peak amplitudes and onset latencies were measured. No difference was observed between threshold and onset latency for evoking ant-Dig and post-Dig reflexes, suggesting that the latter was also evoked disynaptically. The peak-to-peak amplitude of both reflexes was significantly reduced during chewing, licking and swallowing as compared to resting period and was lowest during the jaw-closing phase of chewing and licking. Onset latency was significantly largest during the jaw-closing phase. Inhibitory level was similar between the ant-Dig and post-Dig reflex responses and between the ipsilateral and contralateral sides. These results suggest that both the ant-Dig and post-Dig reflex responses were significantly inhibited, probably due to CPG activation during feeding behaviours to maintain coordination of jaw and hyoid movements and hence ensure smooth feeding mechanics.

Rare phenomena of central rhythm and pattern generation in a case of complete spinal cord injury

Lumbar central pattern generators (CPGs) control the basic rhythm and coordinate muscle activation underlying hindlimb locomotion in quadrupedal mammals. The existence and function of CPGs in humans have remained controversial. Here, we investigated a case of a male individual with complete thoracic spinal cord injury who presented with a rare form of self-sustained rhythmic spinal myoclonus in the legs and rhythmic activities induced by epidural electrical stimulation (EES). Analysis of muscle activation patterns suggested that the myoclonus tapped into spinal circuits that generate muscle spasms, rather than reflecting locomotor CPG activity as previously thought. The EES-induced patterns were fundamentally different in that they included flexor-extensor and left-right alternations, hallmarks of locomotor CPGs, and showed spontaneous errors in rhythmicity. These motor deletions, with preserved cycle frequency and period when rhythmic activity resumed, were previously reported only in animal studies and suggest a separation between rhythm generation and pattern formation. Spinal myoclonus and the EES-induced activity demonstrate that the human lumbar spinal cord contains distinct mechanisms for generating rhythmic multi-muscle patterns.

Automated Evaluation of Respiratory Signals to Provide Insight Into Respiratory Drive

The diaphragm muscle is the primary inspiratory muscle in mammals and is highly active throughout life. The repetitive activation of the diaphragm muscle (and of other muscles driven by central pattern generator activity) presents an opportunity to analyze these physiological data on a per‐event basis. Here we highlight the development and implementation of the Automated Evaluation of Respiratory Signals (AERS) algorithm to detect individual respiratory events across a range of motor behaviors. Because different respiratory‐related signals provide different types of information, the AERS algorithm is designed to be robust regardless of the signal type—e.g., diaphragm electromyography (EMG) and transdiaphragmatic pressure (Pdi). Individual respiratory event data obtained from adult rats were assessed using the AERS algorithm. This analysis revealed diaphragm root‐mean‐square (RMS) EMG and Pdi were lowest during eupnea, increased slightly in response to hypoxia‐hypercapnia (10% O2 ‐ 5% CO2), and increased approximately 3‐fold in response to airway occlusion compared to the eupneic baseline. The coefficient of variation (CV) within subjects was less than 10% across all behaviors for both RMS EMG and Pdi. By contrast, the CV was approximately 30% across subjects. Respiratory rate was increased by ~20 breaths/min during hypoxia‐hypercapnia compared to eupnea, as expected based on previous work from our lab and others. The respiratory rate CV within subjects was less than 10% during eupnea and hypoxia‐hypercapnia; during airway occlusion, the CV was ~17%, likely owing to the small number of respiratory events (2‐5) analyzed for this behavior per animal. For eupnea and hypoxia‐hypercapnia, the CV across subjects was ~20%, whereas during airway occlusion it was ~25%. Overall, our findings validate the mean values across various measures of respiratory motor output compared to standard subject means approach. However, per‐event analyses greatly enhance statistical power, allowing detection of physiologically relevant measures by taking within‐subject variability into account. Additionally, the AERS analyses show that various measures of respiratory variability as well as time‐frequency analyses can provide deeper insights into respiratory drive when accounting for individual respiratory events. These analyses can be effectively applied to a variety of models of respiratory motor unit loss or dysfunction (e.g., spinal cord injury and aging), allowing the extraction of large amounts of data from respiratory signals for more comprehensive assessments. Our findings suggest that the AERS approach may be particularly beneficial in reducing animal numbers in certain types of studies, for the detection of physiological changes reflected in respiratory signals with interventions causing gain or loss of function, and for analyses of respiratory variability, where breath‐to‐breath dynamics are important.

Automated evaluation of respiratory signals to provide insight into respiratory drive

The diaphragm muscle (DIAm) is the primary inspiratory muscle in mammals and is highly active throughout life displaying rhythmic activity. The repetitive activation of the DIAm (and of other muscles driven by central pattern generator activity) presents an opportunity to analyze these physiological data on a per-event basis rather than pooled on a per-subject basis. The present study highlights the development and implementation of a graphical user interface-based algorithm using an analysis of critical points to detect the onsets and offsets of individual respiratory events across a range of motor behaviors, thus facilitating analyses of within-subject variability. The algorithm is designed to be robust regardless of the signal type (e.g., EMG or transdiaphragmatic pressure). Our findings suggest that this approach may be particularly beneficial in reducing animal numbers in certain types of studies, for assessments of perturbation studies where the effects are relatively small but potentially physiologically meaningful, and for analyses of respiratory variability.

Synergistic interaction between sensory inputs and propriospinal signalling underlying quadrupedal locomotion.

Stimulation of hindlimb afferent fibres can both stabilize and increase the activity of fore- and hindlimb motoneurons during fictive locomotion. The increase in motoneuron activity is at least partially due to the production of doublets of action potentials in a subpopulation of motoneurons. These results were obtained using an in vitro brainstem/spinal cord preparation of neonatal rat. Quadrupedal locomotion relies on a dynamic coordination between central pattern generators (CPGs) located in the cervical and lumbar spinal cord, and controlling the fore- and hindlimbs, respectively. It is assumed that this CPG interaction is achieved through separate closed-loop processes involving propriospinal and sensory pathways. However, the functional consequences of a concomitant involvement of these different influences on the degree of coordination between the fore- and hindlimb CPGs is still largely unknown. Using an in vitro brainstem/spinal cord preparation of neonatal rat, we found that rhythmic, bilaterally alternating stimulation of hindlimb sensory input pathways elicited coordinated hindlimb and forelimb CPG activity. During pharmacologically induced fictive locomotion, lumbar dorsal root (DR) stimulation entrained and stabilized an ongoing cervico-lumbar locomotor-like rhythm and increased the amplitude of both lumbar and cervical ventral root bursting. The increase in cervical burst amplitudes was correlated with the occurrence of doublet action potential firing in a subpopulation of motoneurons, enabling the latter to transition between low and high frequency discharge according to the intensity of DR stimulation. Moreover, our data revealed that propriospinal and sensory pathways act synergistically to strengthen cervico-lumbar interactions. Indeed, split-bath experiments showed that fully coordinated cervico-lumbar fictive locomotion was induced by combining pharmacological stimulation of either the lumbar or cervical CPGs with lumbar DR stimulation. This study thus highlights the powerful interactions between sensory and propriospinal pathways which serve to ensure the coupling of the fore- and hindlimb CPGs for effective quadrupedal locomotion.

Neuropeptide Modulation Increases Dendritic Electrical Spread to Restore Neuronal Activity Disrupted by Temperature.

Peptide neuromodulation has been implicated to shield neuronal activity from acute temperature changes that can otherwise lead to loss of motor control or failure of vital behaviors. However, the cellular actions neuropeptides elicit to support temperature-robust activity remain unknown. Here, we find that peptide neuromodulation restores rhythmic bursting in temperature-compromised central pattern generator (CPG) neurons by counteracting membrane shunt and increasing dendritic electrical spread. We show that acutely rising temperatures reduced spike generation and interrupted ongoing rhythmic motor activity in the crustacean gastric mill CPG. Neuronal release and extrinsic application of Cancer borealis tachykinin-related peptide Ia (CabTRP Ia), a substance-P-related peptide, restored rhythmic activity. Warming led to a significant decrease in membrane resistance and a shunting of the dendritic signals in the main gastric mill CPG neuron. Using a combination of fluorescent calcium imaging and electrophysiology, we observed that postsynaptic potentials and antidromic action potentials propagated less far within the dendritic neuropil as the system warmed. In the presence of CabTRP Ia, membrane shunt decreased and both postsynaptic potentials and antidromic action potentials propagated farther. At elevated temperatures, CabTRP Ia restored dendritic electrical spread or extended it beyond that at cold temperatures. Selective introduction of the CabTRP Ia conductance using a dynamic clamp demonstrated that the CabTRP Ia voltage-dependent conductance was sufficient to restore rhythmic bursting. Our findings demonstrate that a substance-P-related neuropeptide can boost dendritic electrical spread to maintain neuronal activity when perturbed and reveals key neurophysiological components of neuropeptide actions that support pattern generation in temperature-compromised conditions.SIGNIFICANCE STATEMENT Changes in body temperature can have detrimental consequences for the well-being of an organism. Temperature-dependent changes in neuronal activity can be especially dangerous if they affect vital behaviors. Understanding how temperature changes disrupt neuronal activity and identifying how to ameliorate such effects is critically important. Our study of a crustacean circuit shows that warming disrupts rhythmic neuronal activity by increasing membrane shunt and reducing dendritic electrical spread in a key circuit neuron. Through the ionic conductance activated by it, substance-P-related peptide modulation restored electrical spread and counteracted the detrimental temperature effects on rhythmic activity. Because neuropeptides are commonly implicated in sustaining neuronal activity during perturbation, our results provide a promising mechanism to support temperature-robust activity.

Phase-Dependent Crossed Inhibition Mediating Coordination of Anti-phase Bilateral Rhythmic Movement: A Mini Review.

The activity of the left and right central pattern generators (CPGs) is efficiently coordinated during locomotion. To achieve this coordination, the interplay between the CPG controlling one leg and that controlling another must be present. Previous findings in aquatic vertebrates and mammalians suggest that the alternate activation of the left and right CPGs is mediated by the commissural interneurons crossing the midline of the spinal cord. Especially, V0 commissural interneurons mediate crossed inhibition during the alternative activity of the left and right CPGs. Even in humans, phase-dependent modulation of the crossed afferent inhibition during gait has been reported. Based on those previous findings, crossed inhibition of the CPG in one leg side caused by the activation of the contralateral CPG is a possible mechanism underlying the coordination of the anti-phase rhythmic movement of the legs. It has been hypothesized that the activity of the flexor half center in the CPG inhibits the contralateral flexor half center, but crossed inhibition of the extensor half center is not present because of the existence of the double limb support during gait. Nevertheless, previous findings on the phase-dependent crossed inhibition during anti-phase bilateral movement of the legs are not in line with this hypothesis. For example, extensor activity caused crossed inhibition of the flexor half center during bilateral cycling of the legs. In another study, the ankle extensor was inhibited at the period switching from extension to flexion during anti-phase rhythmic movement of the ankles. In this review article, I provide a critical discussion about crossed inhibition mediating the coordination of the anti-phase bilateral rhythmic movement of the legs.

Effect of Aging, Gender and Sensory Stimulation of TRPV1 Receptors with Capsaicin on Spontaneous Swallowing Frequency in Patients with Oropharyngeal Dysphagia: A Proof-of-Concept Study.

Spontaneous swallowing contributes to airway protection and depends on the activation of brainstem reflex circuits in the central pattern generator (CPG). We studied the effect of age and gender on spontaneous swallowing frequency (SSF) in healthy volunteers and assessed basal SSF and TRPV1 stimulation effect on SSF in patients with post-stroke oropharyngeal dysphagia (OD). The effect of age and gender on SSF was examined on 141 healthy adult volunteers (HV) divided into three groups: GI—18–39 yr, GII—40–59 yr, and GIII—>60 yr. OD was assessed by the Volume–Viscosity Swallowing Test (VVST). The effect of sensory stimulation with capsaicin 10−5 M (TRPV1 agonist) was evaluated in 17 patients with post-stroke OD, using the SSF. SSF was recorded in all participants during 10 min using surface electromyography (sEMG) of the suprahyoid muscles and an omnidirectional accelerometer placed over the cricothyroid cartilage. SSF was significantly reduced in GII (0.73 ± 0.50 swallows/min; p = 0.0385) and GIII (0.50 ± 0.31 swallows/min; p < 0.0001) compared to GI (1.03 ± 0.62 swallows/min), and there was a moderate significant correlation between age and SFF (r = −0.3810; p < 0.0001). No effect of gender on SSF was observed. Capsaicin caused a strong and significant increase in SSF after the TRPV1 stimulation when comparing to basal condition (pre-capsaicin: 0.41 ± 0.32 swallows/min vs post-capsaicin: 0.81 ± 0.51 swallow/min; p = 0.0003). OD in patients with post-stroke OD and acute stimulation with TRPV1 agonists caused a significant increase in SSF, further suggesting the potential role of pharmacological stimulation of sensory pathways as a therapeutic strategy for CPG activation in patients with OD.

The M-current works in tandem with the persistent sodium current to set the speed of locomotion.

The central pattern generator (CPG) for locomotion is a set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current (INaP). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current (IM): a subthreshold noninactivating outward current blocked by 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) and enhanced by N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide (ICA73). Immunostaining and mutant mice highlight an important role of Kv7.2-containing channels in mediating IM. Pharmacological modulation of IM regulates the emergence and the frequency regime of both pacemaker and CPG activities and controls the speed of locomotion. Computational models captured these results and showed how an interplay between IM and INaP endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how IM and INaP work in tandem to set the speed of locomotion.

Phase-Dependent Response to Afferent Stimulation During Fictive Locomotion: A Computational Modeling Study.

Central pattern generators (CPGs) in the spinal cord generate rhythmic neural activity and control locomotion in vertebrates. These CPGs operate under the control of sensory feedback that affects the generated locomotor pattern and adapt it to the animal's biomechanics and environment. Studies of the effects of afferent stimulation on fictive locomotion in immobilized cats have shown that brief stimulation of peripheral nerves can reset the ongoing locomotor rhythm. Depending on the phase of stimulation and the stimulated nerve, the applied stimulation can either shorten or prolong the current locomotor phase and the locomotor cycle. Here, we used a mathematical model of a half-center CPG to investigate the phase-dependent effects of brief stimulation applied to CPG on the CPG-generated locomotor oscillations. The CPG in the model consisted of two half-centers mutually inhibiting each other. The rhythmic activity in each half-center was based on a slowly inactivating, persistent sodium current. Brief stimulation was applied to CPG half-centers in different phases of the locomotor cycle to produce phase-dependent changes in CPG activity. The model reproduced several results from experiments on the effect of afferent stimulation of fictive locomotion in cats. The mechanisms of locomotor rhythm resetting under different conditions were analyzed using dynamic systems theory methods.

Neuromodulation of central pattern generators and its role in the functional recovery of central pattern generator activity.

Neuromodulators play an important role in how the nervous system organizes activity that results in behavior. Disruption of the normal patterns of neuromodulatory release or production is known to be related to the onset of severe pathologies such as Parkinson's disease, Rett syndrome, Alzheimer's disease, and affective disorders. Some of these pathologies involve neuronal structures that are called central pattern generators (CPGs), which are involved in the production of rhythmic activities throughout the nervous system. Here I discuss the interplay between CPGs and neuromodulatory activity, with particular emphasis on the potential role of neuromodulators in the recovery of disrupted neuronal activity. I refer to invertebrate and vertebrate model systems and some of the lessons we have learned from research on these systems and propose a few avenues for future research. I make one suggestion that may guide future research in the field: neuromodulators restrict the parameter landscape in which CPG components operate, and the removal of neuromodulators may enable a perturbed CPG in finding a new set of parameter values that can allow it to regain normal function.

Chapter 26 - Clinical neurophysiology of NREM parasomnias

The nonrapid eye movement (NREM) parasomnias range from age-related developmental phenomena in children to aggressive and injurious motor behaviors in all age groups. These parasomnias are commonly referred to as disorders of arousal and are an important cause of sleep-related injury. Genetic predisposition plays a role in the disorders of arousal, most evident in sleepwalking. Important concepts guiding our current understanding of the pathophysiology of the NREM parasomnias include sleep state instability (a propensity for arousal during NREM sleep), sleep inertia (incomplete awakening from NREM sleep), state dissociation (an ability to simultaneously straddle both NREM sleep and wakefulness), and activation of central pattern generators (permitting expression of subcortically determined motor behaviors without conscious higher cortical input). Management is multifaceted with an emphasis on education and nonpharmacologic measures. The purpose of this chapter is to review wake and NREM neurobiology and update our current understanding of NREM parasomnia pathophysiology, epidemiology, genetics, clinical features, precipitating factors, neurophysiologic evaluation, diagnosis, and clinical management.

Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation.

The intrinsic oscillatory activity of central pattern generators underlies motor rhythm. We review and discuss recent findings that address the origin of Caenorhabditis elegans motor rhythm. These studies propose that the A- and mid-body B-class excitatory motor neurons at the ventral cord function as non-bursting intrinsic oscillators to underlie body undulation during reversal and forward movements, respectively. Proprioception entrains their intrinsic activities, allows phase-coupling between members of the same class motor neurons, and thereby facilitates directional propagation of undulations. Distinct pools of premotor interneurons project along the ventral nerve cord to innervate all members of the A- and B-class motor neurons, modulating their oscillations, as well as promoting their bi-directional coupling. The two motor sub-circuits, which consist of oscillators and descending inputs with distinct properties, form the structural base of dynamic rhythmicity and flexible partition of the forward and backward motor states. These results contribute to a continuous effort to establish a mechanistic and dynamic model of the C. elegans sensorimotor system. C. elegans exhibits rich sensorimotor functions despite a small neuron number. These findings implicate a circuit-level functional compression. By integrating the role of rhythm generation and proprioception into motor neurons, and the role of descending regulation of oscillators into premotor interneurons, this numerically simple nervous system can achieve a circuit infrastructure analogous to that of anatomically complex systems. C. elegans has manifested itself as a compact model to search for general principles of sensorimotor behaviours.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.

Functional Recovery of a Locomotor Network after Injury: Plasticity beyond the Central Nervous System.

Many animals depend on descending information from the brain for the initiation and proper execution of locomotion. Interestingly, after injury and the loss of such inputs, locomotor function can sometimes be regained without the regrowth of central connections. In the medicinal leech, Hirudo verbana, we have shown that crawling reemerges after removal of descending inputs. Here, we studied the mechanisms underlying this return of locomotion by asking if central pattern generators (CPGs) in crawl-recovered leeches are sufficient to produce crawl-specific intersegmental coordination. From recovered animals, we treated isolated chains of ganglia with dopamine to activate the crawl CPGs (one crawl CPG per ganglion) and observed fictive crawl-like bursting in the dorsal-longitudinal-excitor motoneuron (DE-3), an established crawl-monitor neuron. However, these preparations did not exhibit crawl-specific coordination across the CPGs. Although the crawl CPGs always generated bidirectional activation of adjacent CPGs, we never observed crawl-appropriate intersegmental phase delays. Because central circuits alone were unable to organize crawl-specific coordination, we tested the coordinating role of the peripheral nervous system. In transected leeches normally destined for recovery, we removed afferent information to the anterior-most (lead) ganglion located below the nerve-cord transection site. In these dually treated animals, overt crawling was greatly delayed or prevented. After filling the peripheral nerves with Neurobiotin tracer distal to the nerve-root lesion, we found a perfect correlation between regrowth of peripheral neuronal fibers and crawl recovery. Our study establishes that during recovery after injury, crawl-specific intersegmental coordination switches to a new dependence on afferent information.

Effectiveness of Activity-Based Therapy in Comparison with Surface Spinal Stimulation in People with Traumatic Incomplete Spinal Cord Injury for Activation of Central Pattern Generator for Locomotion: Study Protocol for a 24-Week Randomized Controlled Trial.

Study DesignA multi-centric randomized controlled trial to be conducted at two sites, department of phyhysiotherapypy, Punjabi University, Patiala and rehabilitation department, Indian Spinal Injury Centre, New Delhi, India.PurposeTo determine the effectiveness of activity-based therapy in comparison with surface spinal stimulation (SSS) in traumatic incomplete spinal cord injury (SCI) with special reference to locomotion—a central pattern generator controlled function.Overview of LiteratureA major goal for many patients after SCI is to regain the function of locomotion. It is crucial that rehabilitation strives to maximize locomotor ability and functional recovery after SCI. Experimental evidence of improvement in stepping and motor control after activity-based training in animal models and human SCI has been translated into clinical neuro-rehabilitation.MethodsControl group participants will undertake an intensive 24-week duration thrice weekly program of activity-based therapy. In addition to this the participants in experimental group will also receive a session of 45 minutes of SSS on thrice weekly basis. The primary analysis for our study will be at 24 weeks. Linear regression will be used to determine the mean between-group differences and 95% confidence interval for all continuous outcomes using baseline scores and group allocation as covariates.Results The primary outcome measure is improvement in the level of walking index for SCI-II. The secondary outcome measures are modified Ashworth scale, Penn spasm frequency score, spinal cord independence measure-III, SCI functional ambulation inventory, Hoffman’s reflex, somatosensory evoked potential, and American Spinal Injury Association Impairment Scale scores.ConclusionsAn insight into training-induced mechanisms will be of great importance to fine tune such combined treatments and vindicate their efficacy in restoration of locomotion and functional activities in individuals with SCI.

Movement Stabilizing Using Afferent Control of Spinal Locomotor CPG Using Chaotic Takagi-Sugeno Fuzzy Logic Systems: A Simulation Study

Background: External control of the function of the central pattern generators (CPGs), exist in the spinal cord, is possible by electrical or chemical stimulation of some of the spinal Afferents. After restarting the activity of spinal cord CPG, the dynamics of movements such as gait can be changed through the time by controlling the rhythm of the CPG. Methods: The purpose of this study was provision of closed loop control algorithm based on the Takagi-Sugeno fuzzy controller in order to adjust the weight of the spinal cord afferents in a neuro-mechanical model with the aim of controlling the rhythm of the CPGs. Rhythm control of CPGs has been done with the aim of implementing the process of resetting the phase during gait in order to stabilize the movement against external disturbances. In this paper, the efficiency of a continuous Takagi-Sugeno fuzzy controller with the efficiency of 2 fuzzy Takagi-Sugeno chaotic controllers has been compared. Results: It was shown by the results obtained from the simulation that the process of resetting the motion phase of the skeletal angle in face of applying disturbance in method of chaotic Takagi-Sugeno fuzzy controller is done with good features in the presence of delayed feedback in decreasing overshoot and undershoot to the amount of 1.982 and 0.17 radians, respectively so that the best amount of afferent to reset the phase and return to the desired angle is provided at the shortest possible time. Conclusion: In this paper, the efficiency of a continuous Takagi-Sugeno fuzzy controller with the efficiency of 2 fuzzy Takagi-Sugeno chaotic controllers has been compared for movement stabilization using spinal cord afferent control. According to the results, the best performance was observed when the chaotic fuzzy Takagi-Sugenocontroller in the presence of delayed feedback was used.

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.

Variations on a theme: species differences in synaptic connectivity do not predict central pattern generator activity.

A fundamental question in comparative neuroethology is the extent to which synaptic wiring determines behavior vs. the extent to which it is constrained by phylogeny. We investigated this by examining the connectivity and activity of homologous neurons in different species. Melibe leonina and Dendronotus iris (Mollusca, Gastropoda, Nudibranchia) have homologous neurons and exhibit homologous swimming behaviors consisting of alternating left-right (LR) whole body flexions. Yet, a homologous interneuron (Si1) differs between the two species in its participation in the swim motor pattern (SMP) and synaptic connectivity. In this study we examined Si1 homologs in two additional nudibranchs: Flabellina iodinea, which evolved LR swimming independently of Melibe and Dendronotus, and Tritonia diomedea, which swims with dorsal-ventral (DV) body flexions. In Flabellina, the contralateral Si1s exhibit alternating rhythmic bursting activity during the SMP and are members of the swim central pattern generator (CPG), as in Melibe The Si1 homologs in Tritonia do not burst rhythmically during the DV SMP but are inhibited and receive bilaterally synchronous synaptic input. In both Flabellina and Tritonia, the Si1 homologs exhibit reciprocal inhibition, as in Melibe However, in Flabellina the inhibition is polysynaptic, whereas in Tritonia it is monosynaptic, as in Melibe In all species, the contralateral Si1s are electrically coupled. These results suggest that Flabellina and Melibe convergently evolved a swim CPG that contains Si1; however, they differ in monosynaptic connections. Connectivity is more similar between Tritonia and Melibe, which exhibit different swimming behaviors. Thus connectivity between homologous neurons varies independently of both behavior and phylogeny.NEW & NOTEWORTHY This research shows that the synaptic connectivity between homologous neurons exhibits species-specific variations on a basic theme. The neurons vary in the extent of electrical coupling and reciprocal inhibition. They also exhibit different patterns of activity during rhythmic motor behaviors that are not predicted by their circuitry. The circuitry does not map onto the phylogeny in a predictable fashion either. Thus neither neuronal homology nor species behavior is predictive of neural circuit connectivity.