Neuromechanical Strategies for Obstacle Negotiation during Overground Locomotion following Incomplete Spinal Cord Injury in Adult Cats.

Following incomplete spinal cord injury in animals, including humans, substantial locomotor recovery can occur. However, functional aspects of locomotion, such as negotiating obstacles, remains challenging. We collected kinematic and electromyography data in 10 adult cats (5 males, 5 females) before and at weeks 1-2 and 7-8 after a lateral mid-thoracic hemisection on the right side of the cord while they negotiated obstacles of three different heights. Intact cats always cleared obstacles without contact. At weeks 1-2 after hemisection, the ipsilesional right hindlimb contacted obstacles in ∼50% of trials, triggering a stumbling corrective reaction or absent responses, which we termed Other. When complete clearance occurred, we observed exaggerated ipsilesional hindlimb flexion when crossing the obstacle with contralesional Left limbs leading. At weeks 7-8 after hemisection, the proportion of complete clearance increased, Other responses decreased, and stumbling corrective reactions remained relatively unchanged. We found redistribution of weight support after hemisection, with reduced diagonal supports and increased homolateral supports, particularly on the left contralesional side. The main neural strategy for complete clearance in intact cats consisted of increased knee flexor activation. After hemisection, ipsilesional knee flexor activation remained, but it was insufficient or more variable as the limb approached the obstacle. Intact cats also increased their speed when stepping over an obstacle, an increase that disappeared after hemisection. The increase in complete clearance over time after hemisection paralleled the recovery of muscle activation patterns or new strategies. Our results suggest partial recovery of anticipatory control through neuroplastic changes in the locomotor control system.SIGNIFICANCE STATEMENT Most spinal cord injuries (SCIs) are incomplete and people can recover some walking functions. However, the main challenge for people with SCIs that do recover a high level of function is to produce a gait that can adjust to everyday occurrences, such as turning, stepping over an obstacle, etc. Here, we use the cat model to answer two basic questions: How does an animal negotiate an obstacle after an incomplete SCI and why does it fail to safely clear it? We show that the inability to clear an obstacle is because of improper activation of muscles that flex the knee. Animals recover a certain amount of function thanks to new strategies and changes within the nervous system.

Spinal Sensorimotor Circuits Play a Prominent Role in Hindlimb Locomotor Recovery after Staggered Thoracic Lateral Hemisections but Cannot Restore Posture and Interlimb Coordination during Quadrupedal Locomotion in Adult Cats.

Spinal sensorimotor circuits interact with supraspinal and peripheral inputs to generate quadrupedal locomotion. Ascending and descending spinal pathways ensure coordination between the forelimbs and hindlimbs. Spinal cord injury (SCI) disrupts these pathways. To investigate the control of interlimb coordination and hindlimb locomotor recovery, we performed two lateral thoracic hemisections on opposite sides of the cord (right T5-T6 and left T10-T11) at an interval of approximately two months in eight adult cats. In three cats, the spinal cord was transected at T12-T13. We collected electromyography (EMG) and kinematic data during quadrupedal and hindlimb-only locomotion before and after spinal lesions. We show that (1) cats spontaneously recover quadrupedal locomotion following staggered hemisections but require balance assistance after the second one, (2) coordination between the forelimbs and hindlimbs displays 2:1 patterns (two cycles of one forelimb within one hindlimb cycle) and becomes weaker and more variable after both hemisections, (3) left-right asymmetries in hindlimb stance and swing durations appear after the first hemisection and reverse after the second, and (4) support periods reorganize after staggered hemisections to favor support involving both forelimbs and diagonal limbs. Cats expressed hindlimb locomotion the day following spinal transection, indicating that lumbar sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered hemisections. These results reflect a series of changes in spinal sensorimotor circuits that allow cats to maintain and recover some level of quadrupedal locomotor functionality with diminished motor commands from the brain and cervical cord, although the control of posture and interlimb coordination remains impaired.

Spinal sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered thoracic lateral hemisections but cannot restore posture and interlimb coordination during quadrupedal locomotion in adult cats.

Spinal sensorimotor circuits interact with supraspinal and peripheral inputs to generate quadrupedal locomotion. Ascending and descending spinal pathways ensure coordination between the fore-and hindlimbs. Spinal cord injury disrupts these pathways. To investigate the control of interlimb coordination and hindlimb locomotor recovery, we performed two lateral thoracic hemisections placed on opposite sides of the cord (right T5-T6 and left T10-T11) at an interval of approximately two months in eight adult cats. In three cats, we then made a complete spinal transection caudal to the second hemisection at T12-T13. We collected electromyography and kinematic data during quadrupedal and hindlimb-only locomotion before and after spinal lesions. We show that 1) cats spontaneously recover quadrupedal locomotion following staggered hemisections but require balance assistance after the second one, 2) coordination between the fore-and hindlimbs displays 2:1 patterns and becomes weaker and more variable after both hemisections, 3) left-right asymmetries in hindlimb stance and swing durations appear after the first hemisection and reverse after the second, and 4) support periods reorganize after staggered hemisections to favor support involving both forelimbs and diagonal limbs. Cats expressed hindlimb locomotion the day following spinal transection, indicating that lumbar sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered hemisections. These results reflect a series of changes in spinal sensorimotor circuits that allow cats to maintain and recover some level of quadrupedal locomotor functionality with diminished motor commands from the brain and cervical cord, although the control of posture and interlimb coordination remains impaired. Significance Statement: Coordinating the limbs during locomotion depends on pathways in the spinal cord. We used a spinal cord injury model that disrupts communication between the brain and spinal cord by sectioning half of the spinal cord on one side and then about two months later, half the spinal cord on the other side at different levels of the thoracic cord in cats. We show that despite a strong contribution from neural circuits located below the second spinal cord injury in the recovery of hindlimb locomotion, the coordination between the forelimbs and hindlimbs weakens and postural control is impaired. We can use our model to test approaches to restore the control of interlimb coordination and posture during locomotion after spinal cord injury.

Modulation of the gait pattern during split-belt locomotion after lateral spinal cord hemisection in adult cats.

Most previous studies investigated the recovery of locomotion in animals and people with incomplete spinal cord injury (SCI) during relatively simple tasks (e.g., walking in a straight line on a horizontal surface or a treadmill). We know less about the recovery of locomotion after incomplete SCI in left-right asymmetric conditions, such as turning or stepping along circular trajectories. To investigate this, we collected kinematic and electromyography data during split-belt locomotion at different left-right speed differences before and after a right thoracic lateral spinal cord hemisection in nine adult cats. After hemisection, although cats still performed split-belt locomotion, we observed several changes in the gait pattern compared with the intact state at early (1-2 wk) and late (7-8 wk) time points. Cats with larger lesions showed new coordination patterns between the fore- and hindlimbs, with the forelimbs taking more steps. Despite this change in fore-hind coordination, cats maintained consistent phasing between the fore- and hindlimbs. Adjustments in cycle and phase (stance and swing) durations between the slow and fast sides allowed animals to maintain 1:1 left-right coordination. Periods of triple support involving the right (ipsilesional) hindlimb decreased in favor of quad support and triple support involving the other limbs. Step and stride lengths decreased with concurrent changes in the right fore- and hindlimbs, possibly to avoid interference. The above adjustments in the gait pattern allowed cats to retain the ability to locomote in asymmetric conditions after incomplete SCI. We discuss potential plastic neuromechanical mechanisms involved in locomotor recovery in these conditions.NEW & NOTEWORTHY Everyday locomotion often involves left-right asymmetries, when turning, walking along circular paths, stepping on uneven terrains, etc. To show how incomplete spinal cord injury affects locomotor control in asymmetric conditions, we collected data before and after a thoracic lateral spinal hemisection on a split-belt treadmill with one side stepping faster than the other. We show that adjustments in kinematics and muscle activity allowed cats to retain the ability to perform asymmetric locomotion after hemisection.

Distribution of delta and mu opioid receptor mRNA in rodent dorsal root ganglia neurons.

Primary afferents are responsible for transmitting signals produced by noxious stimuli from the periphery to the spinal cord. Mu and delta opioid receptors (MOP and DOP) have analgesic properties and are highly expressed in dorsal root ganglia (DRG) neurons. In humans, spinal DOP is almost exclusively located on central terminals of DRG neurons, whereas in rodents, it is expressed both on presynaptic terminals and spinal neurons. In this study, we aimed to assess the distribution of MOP and DOP in the DRGs of mice and rats. Using in situ hybridization and immunofluorescence, we visualized MOP and DOP mRNA together with various neuronal markers. In rats and mice, we show that both receptors are expressed, albeit to different extents, in all types of neurons, namely, large and medium myelinated neurons (NF200-positive), small nonpeptidergic (IB4- or P2X3R-positive) and peptidergic C fibres (Tac1-positive). Overall, DOP mRNA was found to be mainly expressed in large and medium myelinated neurons, whereas MOP mRNA was mainly found in C fibres. The distribution of MOP and DOP, however, slightly differs between rats and mice, with a higher proportion of small nonpeptidergic C fibres expressing DOP mRNA in mice than in rats. We further found that neither morphine nor inflammation affected the distribution of the receptor mRNA. Because of their location, our results confirm that MOP and DOP have the potential to alleviate similar types of pain and that this effect could slightly differ between species.

Regional surface chlorophyll trends and uncertainties in the global ocean.

Changes in marine primary productivity are key to determine how climate change might impact marine ecosystems and fisheries. Satellite ocean color sensors provide coverage of global ocean chlorophyll with a combined record length of ~ 20 years. Coupled physical-biogeochemical models can inform on expected changes and are used here to constrain observational trend estimates and their uncertainty. We produce estimates of ocean surface chlorophyll trends, by using Coupled Model Intercomparison Project (CMIP5) models to form priors as a "first guess", which are then updated using satellite observations in a Bayesian spatio-temporal model. Regional chlorophyll trends are found to be significantly different from zero in 18/23 regions, in the range ± 1.8% year-1. A global average of these regional trends shows a net positive trend of 0.08 ± 0.35% year-1, highlighting the importance of considering chlorophyll changes at a regional level. We compare these results with estimates obtained with the commonly used "vague" prior, representing no independent knowledge; coupled model priors are shown to slightly reduce trend magnitude and uncertainties in most regions. The statistical model used here provides a robust framework for making best use of all available information and can be applied to improve understanding of global change.

Ocean colour signature of climate change.

Monitoring changes in marine phytoplankton is important as they form the foundation of the marine food web and are crucial in the carbon cycle. Often Chlorophyll-a (Chl-a) is used to track changes in phytoplankton, since there are global, regular satellite-derived estimates. However, satellite sensors do not measure Chl-a directly. Instead, Chl-a is estimated from remote sensing reflectance (RRS): the ratio of upwelling radiance to the downwelling irradiance at the ocean's surface. Using a model, we show that RRS in the blue-green spectrum is likely to have a stronger and earlier climate-change-driven signal than Chl-a. This is because RRS has lower natural variability and integrates not only changes to in-water Chl-a, but also alterations in other optically important constituents. Phytoplankton community structure, which strongly affects ocean optics, is likely to show one of the clearest and most rapid signatures of changes to the base of the marine ecosystem.

Emerging negative Atlantic Multidecadal Oscillation index in spite of warm subtropics.

Sea surface temperatures in the northern North Atlantic have shown a marked decrease over the past several years. The sea surface in the subpolar gyre is now as cold as it was during the last cold phase of the Atlantic Multidecadal Oscillation index in the 1990s. This climate index is associated with shifts in hurricane activity, rainfall patterns and intensity, and changes in fish populations. However, unlike the last cold period in the Atlantic, the spatial pattern of sea surface temperature anomalies in the Atlantic is not uniformly cool, but instead has anomalously cold temperatures in the subpolar gyre, warm temperatures in the subtropics and cool anomalies over the tropics. The tripole pattern of anomalies has increased the subpolar to subtropical meridional gradient in SSTs, which are not represented by the AMO index value, but which may lead to increased atmospheric baroclinicity and storminess. Here we show that the recent Atlantic cooling is likely to persist, as predicted by a statistical forecast of subsurface ocean temperatures and consistent with the irreversible nature of watermass changes involved in the recent cooling of the subpolar gyre.

Rapid emergence of climate change in environmental drivers of marine ecosystems.

Climate change is expected to modify ecological responses in the ocean, with the potential for important effects on the ecosystem services provided to humankind. Here we address the question of how rapidly multiple drivers of marine ecosystem change develop in the future ocean. By analysing an ensemble of models we find that, within the next 15 years, the climate change-driven trends in multiple ecosystem drivers emerge from the background of natural variability in 55% of the ocean and propagate rapidly to encompass 86% of the ocean by 2050 under a 'business-as-usual' scenario. However, we also demonstrate that the exposure of marine ecosystems to climate change-induced stress can be drastically reduced via climate mitigation measures; with mitigation, the proportion of ocean susceptible to multiple drivers within the next 15 years is reduced to 34%. Mitigation slows the pace at which multiple drivers emerge, allowing an additional 20 years for adaptation in marine ecological and socio-economic systems alike.

Observing climate change trends in ocean biogeochemistry: when and where.

Understanding the influence of anthropogenic forcing on the marine biosphere is a high priority. Climate change-driven trends need to be accurately assessed and detected in a timely manner. As part of the effort towards detection of long-term trends, a network of ocean observatories and time series stations provide high quality data for a number of key parameters, such as pH, oxygen concentration or primary production (PP). Here, we use an ensemble of global coupled climate models to assess the temporal and spatial scales over which observations of eight biogeochemically relevant variables must be made to robustly detect a long-term trend. We find that, as a global average, continuous time series are required for between 14 (pH) and 32 (PP) years to distinguish a climate change trend from natural variability. Regional differences are extensive, with low latitudes and the Arctic generally needing shorter time series (<~30 years) to detect trends than other areas. In addition, we quantify the 'footprint' of existing and planned time series stations, that is the area over which a station is representative of a broader region. Footprints are generally largest for pH and sea surface temperature, but nevertheless the existing network of observatories only represents 9-15% of the global ocean surface. Our results present a quantitative framework for assessing the adequacy of current and future ocean observing networks for detection and monitoring of climate change-driven responses in the marine ecosystem.

Tropical nighttime warming as a dominant driver of variability in the terrestrial carbon sink.

The terrestrial biosphere is currently a strong carbon (C) sink but may switch to a source in the 21st century as climate-driven losses exceed CO2-driven C gains, thereby accelerating global warming. Although it has long been recognized that tropical climate plays a critical role in regulating interannual climate variability, the causal link between changes in temperature and precipitation and terrestrial processes remains uncertain. Here, we combine atmospheric mass balance, remote sensing-modeled datasets of vegetation C uptake, and climate datasets to characterize the temporal variability of the terrestrial C sink and determine the dominant climate drivers of this variability. We show that the interannual variability of global land C sink has grown by 50-100% over the past 50 y. We further find that interannual land C sink variability is most strongly linked to tropical nighttime warming, likely through respiration. This apparent sensitivity of respiration to nighttime temperatures, which are projected to increase faster than global average temperatures, suggests that C stored in tropical forests may be vulnerable to future warming.

Catalogue of abrupt shifts in Intergovernmental Panel on Climate Change climate models.

Abrupt transitions of regional climate in response to the gradual rise in atmospheric greenhouse gas concentrations are notoriously difficult to foresee. However, such events could be particularly challenging in view of the capacity required for society and ecosystems to adapt to them. We present, to our knowledge, the first systematic screening of the massive climate model ensemble informing the recent Intergovernmental Panel on Climate Change report, and reveal evidence of 37 forced regional abrupt changes in the ocean, sea ice, snow cover, permafrost, and terrestrial biosphere that arise after a certain global temperature increase. Eighteen out of 37 events occur for global warming levels of less than 2°, a threshold sometimes presented as a safe limit. Although most models predict one or more such events, any specific occurrence typically appears in only a few models. We find no compelling evidence for a general relation between the overall number of abrupt shifts and the level of global warming. However, we do note that abrupt changes in ocean circulation occur more often for moderate warming (less than 2°), whereas over land they occur more often for warming larger than 2°. Using a basic proportion test, however, we find that the number of abrupt shifts identified in Representative Concentration Pathway (RCP) 8.5 scenarios is significantly larger than in other scenarios of lower radiative forcing. This suggests the potential for a gradual trend of destabilization of the climate with respect to such shifts, due to increasing global mean temperature change.

Change-point analysis as a tool to detect abrupt climate variations.

Recently, there have been an increasing number of studies using change-point methods to detect artificial or natural discontinuities and regime shifts in climate. However, a major drawback with most of the currently used change-point methods is the lack of flexibility (able to detect one specific type of shift under the assumption that the residuals are independent). As temporal variations in climate are complex, it may be difficult to identify change points with very simple models. Moreover, climate time series are known to exhibit autocorrelation, which corresponds to a model misspecification if not taken into account and can lead to the detection of non-existent shifts. In this study, we extend a method known as the informational approach for change-point detection to take into account the presence of autocorrelation in the model. The usefulness and flexibility of this approach are demonstrated through applications. Furthermore, it is highly desirable to develop techniques that can detect shifts soon after they occur for climate monitoring. To address this, we also carried out a simulation study in order to investigate the number of years after which an abrupt shift is detectable. We use two decision rules in order to decide whether a shift is detected or not, which represents a trade-off between increasing our chances of detecting a shift and reducing the risk of detecting a shift while in reality there is none. We show that, as of now, we have good chances to detect an abrupt shift with a magnitude that is larger than that of the standard deviation in the series of observations. For shifts with a very large magnitude (three times the standard deviation), our simulation study shows that after only 4 years the probabilities of shift detection reach nearly 100 per cent. This reveals that the approach has potential for climate monitoring.

Effects of climate on West Nile Virus transmission risk used for public health decision-making in Quebec.

BACKGROUND: In 2002, major human epidemics of West Nile Virus (WNV) were reported in five cities in the North East region of North America. The present analysis examines the climatic conditions that were conducive to the WNV epidemic, in order to provide information to public health managers who eventually must decide on the implementation of a preventive larvicide spraying program in Quebec, Canada. Two sets of variables, the first observed in the summer of 2002 and the second in the preceding winter were analysed to study their potential as explanatory variables for the emergence of the virus at epidemic levels. RESULTS: Results show that the climatic conditions observed in the year 2002 have contributed to the emergence of the virus and can be observed once every forty years on average. The analysis has shown that the 2002 events observed in several North East North American cities are characterized by two main variables: the number of degree-days below -5 degrees C in the winter (DD-5) and the number of degree-days greater than 25 degrees C in the summer (DD25). CONCLUSION: In the context of a declining rate of human and aviary infection to WNV, this element contributed to the decision to suspend the use of preventive larvicides in the province of Quebec in 2006 and for the foreseeable future. The second part of this study indicates that it is very important to estimate the risk that extreme values can be observed simultaneously in the summer and in the winter preceding the appearance of the virus. The proposed models provide important information to public health officials, weeks before the appearance of the virus, and can therefore be useful to help prevent human epidemics.