Neuroprosthetic rehabilitation and translational mechanism after severe spinal cord injury

Traumatic SCIs have long-term health, economic and social consequences, stressing the urgency to develop interventions to improve recovery after such injuries. Today, the only proven effective interventions to enhance recovery after SCI are activity-based rehabilitation therapies, such as locomotor training. However, locomotor training shows no or very limited efficacy to improve function after a severe SCI that induces paralysis of the limbs. To mimic the outcome of severe but incomplete SCI in rodents, we developed a model of double opposite-side lateral hemisections termed staggered hemisection in adult rats. This model induced permanent paralysis below the level of injury but leaves an intervening gap of intact neural tissue that provides a substrate for recovery. We showed that this SCI leads to degradation of motor functions, which correlates with the formation of aberrant neuronal connections below the lesion. Robotic devices with a rehabilitative purpose should act as propulsive or postural neuroprosthesis allowing training under natural conditions. Our versatile robotic interface provides multidirectional bodyweight support during overground locomotion in rats. We next evaluated the effects of robot-assisted gait training enabled by electrochemical stimulation of spinal circuits to restore locomotion after staggered hemisection SCI. We found that after two months of daily training, paralyzed rats recovered the ability to initiate, sustain and adjust bipedal locomotion while supported in the robot under electrochemical stimulation. This recovery correlated with ubiquitous reorganization of corticospinal, brainstem, and intraspinal fibers. We next evaluated whether this treatment was capable of restoring supraspinal control of locomotion after a clinically relevant SCI. Rats received a severe contusion of the spinal cord that spared less than 10% of intact tissue. Robot-assisted rehabilitation restored weight-bearing locomotion in all the trained rats when stimulated electrochemicallay and in a subset of rats in the absence of any enabling factors which paralelled with the reorganization of axonal projections of reticulospinal fibers below the contusion. Virus-mediated silencing of reticulospinal neurons projecting to lumbar segments demonstrated that these inputs were necessary to initiate and sustain walking after training. When delaying the onset of training by two months, in the chronic stage, all the rats regained voluntary locomotor movements but the extent of the recovery was reduced compared to rats trained early after SCI. The results provide a strong rationale to evaluate the impact of neuroprosthetic training to improve motor functions in human patients with incomplete SCI. Translation of treatment paradigms developed in rodent models into effective clinical applications remains a major challenge in biomedical research. Here, we studied recovery of motor functions in more than 400 quadriplegic patients who presented various degree of spinal cord damage laterality. We found that recovery increases with the asymmetry of early motor deficits. We conclude that emergence of spinal cord decussating corticospinal fibers and bilateral motor cortex projections during mammalian evolution supports greater recovery after lateralized SCI primates compared to rodents. Novel experimental models and dedicated therapeutic strategies are necessary to take advantage of this powerful neuronal substrate for recovery after SCI

Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury

Severe spinal cord injury in humans leads to a progressive neuronal dysfunction in the chronic stage of the injury. This dysfunction is characterized by premature exhaustion of muscle activity during assisted locomotion, which is associated with the emergence of abnormal reflex responses. Here, we hypothesize that undirected compensatory plasticity within neural systems caudal to a severe spinal cord injury contributes to the development of neuronal dysfunction in the chronic stage of the injury. We evaluated alterations in functional, electrophysiological and neuromorphological properties of lumbosacral circuitries in adult rats with a staggered thoracic hemisection injury. In the chronic stage of the injury, rats exhibited significant neuronal dysfunction, which was characterized by co-activation of antagonistic muscles, exhaustion of locomotor muscle activity, and deterioration of electrochemically-enabled gait patterns. As observed in humans, neuronal dysfunction was associated with the emergence of abnormal, long-latency reflex responses in leg muscles. Analyses of circuit, fibre and synapse density in segments caudal to the spinal cord injury revealed an extensive, lamina-specific remodelling of neuronal networks in response to the interruption of supraspinal input. These plastic changes restored a near-normal level of synaptic input within denervated spinal segments in the chronic stage of injury. Syndromic analysis uncovered significant correlations between the development of neuronal dysfunction, emergence of abnormal reflexes, and anatomical remodelling of lumbosacral circuitries. Together, these results suggest that spinal neurons deprived of supraspinal input strive to re-establish their synaptic environment. However, this undirected compensatory plasticity forms aberrant neuronal circuits, which may engage inappropriate combinations of sensorimotor networks during gait executio

Galaxy Zoo and ALFALFA: Atomic Gas and the Regulation of Star Formation in Barred Disc Galaxies

We study the observed correlation between atomic gas content and the likelihood of hosting a large scale bar in a sample of 2090 disc galaxies. Such a test has never been done before on this scale. We use data on morphologies from the Galaxy Zoo project and information on the galaxies' HI content from the ALFALFA blind HI survey. Our main result is that the bar fraction is significantly lower among gas rich disc galaxies than gas poor ones. This is not explained by known trends for more massive (stellar) and redder disc galaxies to host more bars and have lower gas fractions: we still see at fixed stellar mass a residual correlation between gas content and bar fraction. We discuss three possible causal explanations: (1) bars in disc galaxies cause atomic gas to be used up more quickly, (2) increasing the atomic gas content in a disc galaxy inhibits bar formation, and (3) bar fraction and gas content are both driven by correlation with environmental effects (e.g. tidal triggering of bars, combined with strangulation removing gas). All three explanations are consistent with the observed correlations. In addition our observations suggest bars may reduce or halt star formation in the outer parts of discs by holding back the infall of external gas beyond bar co-rotation, reddening the global colours of barred disc galaxies. This suggests that secular evolution driven by the exchange of angular momentum between stars in the bar, and gas in the disc, acts as a feedback mechanism to regulate star formation in intermediate mass disc galaxies.Comment: 16 pages, 10 figures. In press at MNRAS. v2 contains corrections found in proof

Frequency and properties of bars in cluster and field galaxies at intermediate redshifts

We present a study of large-scale bars in field and cluster environments out to redshifts of ~0.8 using a final sample of 945 moderately inclined disk galaxies drawn from the EDisCS project. We characterize bars and their host galaxies and look for relations between the presence of a bar and the properties of the underlying disk. We investigate whether the fraction and properties of bars in clusters are different from their counterparts in the field. The total optical bar fraction in the redshift range z=0.4-0.8 (median z=0.60), averaged over the entire sample, is 25% (20% for strong bars). For the cluster and field subsamples, we measure bar fractions of 24% and 29%, respectively. We find that bars in clusters are on average longer than in the field and preferentially found close to the cluster center, where the bar fraction is somewhat higher (~31%) than at larger distances (~18%). These findings however rely on a relatively small subsample and might be affected by small number statistics. In agreement with local studies, we find that disk-dominated galaxies have a higher optical bar fraction (~45%) than bulge-dominated galaxies (~15%). This result is based on Hubble types and effective radii and does not change with redshift. The latter finding implies that bar formation or dissolution is strongly connected to the emergence of the morphological structure of a disk and is typically accompanied by a transition in the Hubble type. (abridged)Comment: 17 pages, accepted for publication in A&

Galaxy Zoo: The Environmental Dependence of Bars and Bulges in Disc Galaxies

We present an analysis of the environmental dependence of bars and bulges in disc galaxies, using a volume-limited catalogue of 15810 galaxies at z<0.06 from the Sloan Digital Sky Survey with visual morphologies from the Galaxy Zoo 2 project. We find that the likelihood of having a bar, or bulge, in disc galaxies increases when the galaxies have redder (optical) colours and larger stellar masses, and observe a transition in the bar and bulge likelihoods, such that massive disc galaxies are more likely to host bars and bulges. We use galaxy clustering methods to demonstrate statistically significant environmental correlations of barred, and bulge-dominated, galaxies, from projected separations of 150 kpc/h to 3 Mpc/h. These environmental correlations appear to be independent of each other: i.e., bulge-dominated disc galaxies exhibit a significant bar-environment correlation, and barred disc galaxies show a bulge-environment correlation. We demonstrate that approximately half (50 +/- 10%) of the bar-environment correlation can be explained by the fact that more massive dark matter haloes host redder disc galaxies, which are then more likely to have bars. Likewise, we show that the environmental dependence of stellar mass can only explain a small fraction (25 +/- 10%) of the bar-environment correlation. Therefore, a significant fraction of our observed environmental dependence of barred galaxies is not due to colour or stellar mass dependences, and hence could be due to another galaxy property. Finally, by analyzing the projected clustering of barred and unbarred disc galaxies with halo occupation models, we argue that barred galaxies are in slightly higher-mass haloes than unbarred ones, and some of them (approximately 25%) are satellite galaxies in groups. We also discuss implications about the effects of minor mergers and interactions on bar formation.Comment: 20 pages, 18 figures; references updated; published in MNRA

Galaxy Formation Theory

We review the current theory of how galaxies form within the cosmological framework provided by the cold dark matter paradigm for structure formation. Beginning with the pre-galactic evolution of baryonic material we describe the analytical and numerical understanding of how baryons condense into galaxies, what determines the structure of those galaxies and how internal and external processes (including star formation, merging, active galactic nuclei etc.) determine their gross properties and evolution. Throughout, we highlight successes and failings of current galaxy formation theory. We include a review of computational implementations of galaxy formation theory and assess their ability to provide reliable modelling of this complex phenomenon. We finish with a discussion of several "hot topics" in contemporary galaxy formation theory and assess future directions for this field.Comment: 58 pages, to appear in Physics Reports. This version includes minor corrections and a handful of additional reference

Quantifying the role of bars in the build-up of central mass concentrations in disk galaxies

We analyze the role of bars in the build-up of central mass concentrations in massive, disk galaxies. Our parent sample consists of 3757 face-on disk galaxies with redshifts between 0.01 and 0.05, selected from the seventh Data Release of the Sloan Digital Sky Survey. 1555 galaxies with bars are identified using position angle and ellipticity profiles of the $i$-band light. We compare the ratio of the specific star formation rate measured in the 1-3 kpc central region of the galaxy to that measured for the whole galaxy. Galaxies with strong bars have centrally enhanced star formation; the degree of enhancement depends primarily on the ellipticity of the bar, and not on the size of the bar or on the mass or structure of the host galaxy. The fraction of galaxies with strong bars is highest at stellar masses greater than $3 \times 10^{10} M_{\odot}$, stellar surface densities less than $3 \times 10^8 M_{\odot}$ and concentration indices less than 2.5. In this region of parameter space, galaxies with strong bars either have enhanced central star formation rates, or star formation that is {\em suppressed} compared to the mean. This suggests that bars may play a role in the eventual quenching of star formation in galaxies. Only 50% of galaxies with strongly concentrated star formation have strong bars, indicating that other processes such as galaxy interactions also induce central star-bursts. We also find that the ratio of the size of the bar to that of the disk depends mainly on the colour of the galaxy, suggesting that the growth and destruction of bars are regulated by gas accretion, as suggested by simulations.Comment: 17 pages, 14 figures. Accepted for publication in MNRA

Versatile robotic interface to evaluate, enable and train locomotion and balance after neuromotor disorders

Central nervous system (CNS) disorders distinctly impair locomotor pattern generation and balance, but technical limitations prevent independent assessment and rehabilitation of these subfunctions. Here we introduce a versatile robotic interface to evaluate, enable and train pattern generation and balance independently during natural walking behaviors in rats. In evaluation mode, the robotic interface affords detailed assessments of pattern generation and dynamic equilibrium after spinal cord injury (SCI) and stroke. In enabling mode,the robot acts as a propulsive or postural neuroprosthesis that instantly promotes unexpected locomotor capacities including overground walking after complete SCI, stair climbing following partial SCI and precise paw placement shortly after stroke. In training mode, robot-enabled rehabilitation, epidural electrical stimulation and monoamine agonists reestablish weight-supported locomotion, coordinated steering and balance in rats with a paralyzing SCI. This new robotic technology and associated concepts have broad implications for both assessing and restoring motor functions after CNS disorders, both in animals and in humans