Competition with primary sensory afferents drives remodeling of corticospinal axons in mature spinal motor circuits

Injury to the mature motor system drives significant spontaneous axonal sprouting instead of axon regeneration. Knowing the circuitlevel determinants of axonal sprouting is important for repairing motor circuits after injury to achieve functional rehabilitation. Competitive interactions are known to shape corticospinal tract axon outgrowth and withdrawal during development. Whether and how competition contributes to reorganization of mature spinal motor circuits is unclear. To study this question, we examined plastic changes in corticospinal axons in response to two complementary proprioceptive afferent manipulations: (1) enhancing proprioceptive afferents activity by electrical stimulation; or (2) diminishing their input by dorsal rootlet rhizotomy. Experiments were conducted in adult rats. Electrical stimulation produced proprioceptive afferent sprouting that was accompanied by significant corticospinal axon withdrawal and a decrease in corticospinal connections on cholinergic interneurons in the medial intermediate zone and C boutons on motoneurons. In contrast, dorsal rootlet rhizotomy led to a significant increase in corticospinal connections, including those on cholinergic interneurons; C bouton density increased correspondingly. Motor cortex-evoked muscle potentials showed parallel changes to those of corticospinal axons, suggesting that reciprocal corticospinal axon changes are functional. Using the two complementary models, we showed that competitive interactions between proprioceptive and corticospinal axons are an important determinant in the organization of mature corticospinal axons and spinal motor circuits. The activity- and synaptic space-dependent properties of the competition enables prediction of the remodeling of spared corticospinal connection and spinal motor circuits after injury and informs the target-specific control of corticospinal connections to promote functional recovery

Changes in descending motor pathway connectivity after corticospinal tract lesion in macaque monkey.

Damage to the corticospinal tract is a leading cause of motor disability, for example in stroke or spinal cord injury. Some function usually recovers, but whether plasticity of undamaged ipsilaterally descending corticospinal axons and/or brainstem pathways such as the reticulospinal tract contributes to recovery is unknown. Here, we examined the connectivity in these pathways to motor neurons after recovery from corticospinal lesions. Extensive unilateral lesions of the medullary corticospinal fibres in the pyramidal tract were made in three adult macaque monkeys. After an initial contralateral flaccid paralysis, motor function rapidly recovered, after which all animals were capable of climbing and supporting their weight by gripping the cage bars with the contralesional hand. In one animal where experimental testing was carried out, there was (as expected) no recovery of fine independent finger movements. Around 6 months post-lesion, intracellular recordings were made from 167 motor neurons innervating hand and forearm muscles. Synaptic responses evoked by stimulating the unlesioned ipsilateral pyramidal tract and the medial longitudinal fasciculus were recorded and compared with control responses in 207 motor neurons from six unlesioned animals. Input from the ipsilateral pyramidal tract was rare and weak in both lesioned and control animals, suggesting a limited role for this pathway in functional recovery. In contrast, mono- and disynaptic excitatory post-synaptic potentials elicited from the medial longitudinal fasciculus significantly increased in average size after recovery, but only in motor neurons innervating forearm flexor and intrinsic hand muscles, not in forearm extensor motor neurons. We conclude that reticulospinal systems sub-serve some of the functional recovery after corticospinal lesions. The imbalanced strengthening of connections to flexor, but not extensor, motor neurons mirrors the extensor weakness and flexor spasm which in neurological experience is a common limitation to recovery in stroke survivors

Extensive Cortical Convergence to Primate Reticulospinal Pathways.

Early evolution of the motor cortex included development of connections to brainstem reticulospinal neurons; these projections persist in primates. In this study, we examined the organization of corticoreticular connections in five macaque monkeys (one male) using both intracellular and extracellular recordings from reticular formation neurons, including identified reticulospinal cells. Synaptic responses to stimulation of different parts of primary motor cortex (M1) and supplementary motor area (SMA) bilaterally were assessed. Widespread short latency excitation, compatible with monosynaptic transmission over fast-conducting pathways, was observed, as well as longer latency responses likely reflecting a mixture of slower monosynaptic and oligosynaptic pathways. There was a high degree of convergence: 56% of reticulospinal cells with input from M1 received projections from M1 in both hemispheres; for SMA, the equivalent figure was even higher (70%). Of reticulospinal neurons with input from the cortex, 78% received projections from both M1 and SMA (regardless of hemisphere); 83% of reticulospinal cells with input from M1 received projections from more than one of the tested M1 sites. This convergence at the single cell level allows reticulospinal neurons to integrate information from across the motor areas of the cortex, taking account of the bilateral motor context. Reticulospinal connections are known to strengthen following damage to the corticospinal tract, such as after stroke, partially contributing to functional recovery. Extensive corticoreticular convergence provides redundancy of control, which may allow the cortex to continue to exploit this descending pathway even after damage to one area.SIGNIFICANCE STATEMENT The reticulospinal tract (RST) provides a parallel pathway for motor control in primates, alongside the more sophisticated corticospinal system. We found extensive convergent inputs to primate reticulospinal cells from primary and supplementary motor cortex bilaterally. These redundant connections could maintain transmission of voluntary commands to the spinal cord after damage (e.g., after stroke or spinal cord injury), possibly assisting recovery of function

Multi-electrode stimulation in somatosensory cortex increases probability of detection

Objective. Brain machine interfaces (BMIs) that decode control signals from motor cortex have developed tremendously in the past decade, but virtually all rely exclusively on vision to provide feedback. There is now increasing interest in developing an afferent interface to replace natural somatosensation, much as the cochlear implant has done for the sense of hearing. Preliminary experiments toward a somatosensory neuroprosthesis have mostly addressed the sense of touch, but proprioception, the sense of limb position and movement, is also critical for the control of movement. However, proprioceptive areas of cortex lack the precise somatotopy of tactile areas. We showed previously that there is only a weak tendency for neighboring neurons in area 2 to signal similar directions of hand movement. Consequently, stimulation with the relatively large currents used in many studies is likely to activate a rather heterogeneous set of neurons. Approach. Here, we have compared the effect of single-electrode stimulation at subthreshold levels to the effect of stimulating as many as seven electrodes in combination. Main results. We found a mean enhancement in the sensitivity to the stimulus (d′) of 0.17 for pairs compared to individual electrodes (an increase of roughly 30%), and an increase of 2.5 for groups of seven electrodes (260%). Significance. We propose that a proprioceptive interface made up of several hundred electrodes may yield safer, more effective sensation than a BMI using fewer electrodes and larger currents

¿Se han modificado las preferencias de los ciudadanos sobre las políticas de bienestar en España (1985-2005)?

Este trabajo es uno de los frutos empíricos del proyecto de investigación Reformas en el Estado de Bienestar: Actores y Apoyos Ciudadanos (REBAAC), http://www.iesam.csic.es/proyecto/rebaac.htm, dirigido por Luis Moreno, que se completará en los próximos meses con otros escritos sobre el tema.[EN] In recent years pressures for the reform of the Welfare State have been voiced despite that public opinion has kept opposed to the retrenchment of social policies. Some studies have pointed out that governments have learned how to avoid popular resistance to the reforms due to a change in citizens’ attitudes. This Working Paper explores the attitudes of the Spaniards with respect to the process and outcomes of the welfare policies implemented in Spain in the last 20 years. Whenever possible this paper takes a comparative. Time series have been worked out covering the period under analysis. Likewise, preferences towards the various welfare policies and these and other public policies are also compared. The two main conclusions are that the support for the welfare policies is solid (despite some qualifications) and that the public preference for the meso or intermediate level of government as provider of social policies has increased.[ES] En los últimos años parece que las presiones para la reforma del Estado de Bienestar están siendo más insistentes que una opinión pública hasta ahora opuesta a cualquier tipo de recorte de los programas sociales. Algunos estudios sugieren que los gobiernos parecen haber aprendido como esquivar la resistencia de los ciudadanos a las reformas aprovechando un supuesto cambio en sus actitudes durante los últimos años. Con esta hipótesis de cambio en las actitudes ciudadanas se exploran en este trabajo las preferencias de los españoles hacia el proceso y los resultados de las políticas del bienestar en los últimos veinte años. Siempre que es posible se sigue una estrategia comparativa. Por un lado, se han construido series temporales que cubren todo el periodo estudiado y, por otro, se comparan las preferencias entre las políticas de bienestar y entre éstas y el resto de las políticas públicas. Las dos conclusiones más significativas son que, si bien con algunos matices, el apoyo a la provisión pública del bienestar continúa siendo muy sólido y crece también la preferencia por el nivel intermedio de gobierno como proveedor de tales programas de bienestar

Classification of neurons in the primate reticular formation and changes after recovery from pyramidal tract lesion

The reticular formation is important in primate motor control, both in health and during recovery after brain damage. Little is known about the different neurons present in the reticular nuclei. Here we recorded extracellular spikes from the reticular formation in five healthy female awake behaving monkeys (193 cells), and in two female monkeys 1 year after recovery from a unilateral pyramidal tract lesion (125 cells). Analysis of spike shape and four measures derived from the interspike interval distribution identified four clusters of neurons in control animals. Cluster 1 cellshadaslowfiringrate. Cluster 2 cell shad narrow spikes and irregular firing, which of ten included high-frequencybursts. Cluster3cellswere highly rhythmic and fast firing. Cluster 4 cells showed negative spikes. A separate population of 42 cells was antidromically identified as reticulospinal neurons in five anesthetized female monkeys. The distribution of spike width in these cells closely overlaid the distribution for cluster 2, leading us tentatively to suggest that cluster 2 included neurons with reticulospinal projections. In animals after corticospinal lesion, cells could be identified in all four clusters. The firing rate of cells in clusters 1 and 2 was increased in lesioned animals relative to control animals (by 52% and 60%, respectively); cells in cluster 2 were also more regular and more bursting in the lesioned animals. We suggest that changes in both membrane properties and local circuits within the reticular formation occur following lesioning, potentially increasing reticulospinal output to help compensate for lost corticospinal descending drive

Different contributions of primary motor cortex, reticular formation, and spinal cord to fractionated muscle activation

Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements. NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements

Reticular formation responses to magnetic brain stimulation of primary motor cortex

Transcranial magnetic stimulation (TMS) of cerebral cortex is a popular technique for the non-invasive investigation of motor function. TMS is often assumed to influence spinal circuits solely via the corticospinal tract. We were interested in possible trans-synaptic effects of cortical TMS on the ponto-medullary reticular formation in the brainstem, which is the source of the reticulospinal tract and could also generate spinal motor output. We recorded from 210 single units in the reticular formation of three anaesthetized macaque monkeys whilst TMS was performed over primary motor cortex. Short latency responses were observed consistent with activation of a cortico-reticular pathway. However, we also demonstrated surprisingly powerful responses at longer latency, which often appeared at lower threshold than the earlier effects. These late responses seemed to be generated partly as a consequence of the sound click made by coil discharge, and changed little with coil location. This novel finding has implications for the design of future studies using TMS, as well as suggesting a means of non-invasively probing an otherwise inaccessible important motor centre

Limb-state information encoded by peripheral and central somatosensory neurons:Implications for an afferent interface

A major issue to be addressed in the development of neural interfaces for prosthetic control is the need for somatosensory feedback. Here, we investigate two possible strategies: electrical stimulation of either dorsal root ganglia (DRG) or primary somatosensory cortex (S1). In each approach, we must determine a model that reflects the representation of limb state in terms of neural discharge. This model can then be used to design stimuli that artificially activate the nervous system to convey information about limb state to the subject. Electrically activating DRG neurons using naturalistic stimulus patterns, modeled on recordings made during passive limb movement, evoked activity in S1 that was similar to that of the original movement. We also found that S1 neural populations could accurately discriminate different patterns of DRG stimulation across a wide range of stimulus pulse-rates. In studying the neural coding in S1, we also decoded the kinematics of active limb movement using multi-electrode recordings in the monkey. Neurons having both proprioceptive and cutaneous receptive fields contributed equally to this decoding. Some neurons were most informative of limb state in the recent past, but many others appeared to signal upcoming movements suggesting that they also were modulated by an efference copy signal. Finally, we show that a monkey was able to detect stimulation through a large percentage of electrodes implanted in area 2. We discuss the design of appropriate stimulus paradigms for conveying time-varying limb state information, and the relative merits and limitations of central and peripheral approaches

Etude des effets cardio-respiratoires de la stimulation vagale dans le traitement des épilepsies pharmacorésistantes chez l'homme et l'animal

Nous avons étudié les effets cardio-respiratoires de la stimulation vagale chez des patients traités par la thérapie VNS. Nous avons analysé les enregistrements polysomnographiques de 10 enfants ayant été implanté avec un stimulateur et qui sont suivis dans le service de neuropédiatrie au CHU d Amiens. Chez tous les patients la stimulation entraîne une augmentation de la fréquence respiratoire et une chute de l amplitude de la distension thoraco-abdominale. Ces effets respiratoires sont transitoires, itératifs, et présentent une dynamique temporelle qui a été divisée en trois phases. Ces altérations de la respiration pendant les stimulations sont associées à des chutes de la saturation du sang en oxygène (SaO2) pouvant être de l ordre de 1à 5% chez certains patients. De plus nous avons démontré des modifications de la fréquence et de la variabilité cardiaque durant la stimulation vagale chez certains patients. Ces variations cardio-respiratoires changent en fonction du stade de sommeil. Nous avons mis en place un model animal dans le but d étudier les relations entre les différents paramètres de stimulations et les effets cardio-respiratoires. Un rat implanté avec un stimulateur est enregistré en plethysmographie 24h après son opération. L analyse des réponses cardio-respiratoires au protocole de 81 combinaisons de stimulation a permis de définir un index reflétant la force de stimulation. Ainsi grâce aux réponses cardio-respiratoires, nous pouvons tester le bon fonctionnement du stimulateur et du système nerf-électrode et avoir un dosage individualisé de la stimulation. De plus, l effet thérapeutique de la stimulation peut être dû aux variations cardio-respiratoires et de la SaO2 qui entraînent des chutes itératives de l oxygène cérébral à l origine d un possible pré-conditionnement, et de la mise en place de processus neuroprotecteurs. Le dosage de la stimulation vagale à partir des effets cardio-respiratoires, permettra ainsi d établir une fourchette de doses pour chaque patient, suffisamment fortes pour recruter des fibres et assurer un effet thérapeutique bénéfique sur les crises épileptiques, sans provoquer d effet mettant en danger la vie du patientAMIENS-BU Santé (800212102) / SudocSudocFranceF