Response to Comment on “Restoring Voluntary Control of Locomotion After Paralyzing Spinal Cord Injury”

Abstract

Sławińska et al. questioned the involvement of supraspinal centers in restoring locomotion after multisystem neuroprosthetic training in rats with paralyzing spinal cord injury. Here, we clarify misconceptions and present additional results illustrating the robust influence of brain input on electrochemically enabled spinal circuitries. We reassert that our intervention reestablished supraspinal control over hindlimb locomotion in paralyzed rats.A century ago, Sherrington reported the unexpected ability of isolated spinal circuits to generate rhythmic leg movements in response to sensory input (1). Since this seminal observation, spinal locomotion has been described in various species and conditions (2). We exploited this concept to design an electrochemical neuroprosthesis (3) and training procedures (4, 5) that restored full weight-bearing locomotion in rats with a complete spinal cord injury (SCI). Sławińska et al., as well as many others (6, 7), reported comparable observations in mice (8), rats (9), and cats (10) over the past three decades.These hindlimb movements, however, remain involuntary. In spinal animals, quadrupedal hindlimb locomotion occurs in the complete absence of supraspinal input and is controlled via sensory ensembles (5,11,12). For example, the intact forelimbs initiate locomotion and sustain propulsion during quadrupedal gait, which generates sensory feedback in the hindlimbs due to biomechanical coupling. Like the rear person in a pantomime horse, lumbosacral circuitries can recognize these task-specific sensory states and use this information to coordinate complex movements. In a recent study (11), we demonstrated that, as early as 10 days after a paralyzing SCI, quadrupedally positioned rats produced weightbearing locomotion, climbed a staircase, and steered in a curve during electrochemically enabled motor states. We did not report these results in our Science paper (13) because lumbosacral circuits control these seemingly complex quadrupedal movements without contribution from supraspinal centers. Therefore, they presented no novelty in the framework of this study. Indeed, rats with the same SCI were incapable of initiating bipedal walking [ figure 1C and movie S1 in (13)]. They also failed to sustain robotically initiated locomotion [figure S6 in (13)]. Moreover, when the robot moved nontrained rats toward a staircase, the isolated spinal circuits failed to adjust gait movements, which led to a dramatic collapse against the staircase. Together, these results demonstrate that the absence of supraspinal input led to the inability to initiate, sustain, and modulate bipedal hindlimb locomotion overground. They also reveal that quadrupedal locomotor testing yields inconclusive results and that bipedal walking is a more appropriate paradigm to uncover the ability of supraspinal centers to functionally access lumbosacral circuits.In (13), we described a type of motor control that is radically different from automated spinal stepping: that is, the recovery of supraspinal control over a rang...

Decoding bipedal locomotion from the rat sensorimotor cortex

“…Non-stable units were excluded from the following analyses. The FRs were computed from spike trains (figure 3(C)) by applying a Gamma kernel (alpha=1.5, beta=10; Townsend et al 2011). With this setting, the FRs at any time were only influenced by the spikes that had occurred up to 50 ms before, but not afterwards.…”

“…The design and effectiveness of lower-limb neurprostheses to restore walking in paralyzed patients critically depends on the ability to predict locomotor-related information from cortical activity. Decoding limb kinematics has previously been demonstrated for arm-reaching movements with signals from the motor cortex in monkeys (Schwartz et al 2006, Vargas-Irwin et al 2010, and an approach based on high-level motor information has also been shown, but with signals from parietal, intraparietal, and premotor cortices (Sherberger et al 2005, Mulliken et al 2008, Fluet et al 2010, Carpaneto et al 2011, Townsend et al 2011. Our decoding study demonstrated that signals from the rat sensorimotor cortex contain information about both hindlimb continuous kinematic variables, as demonstrated by Fitzsimmons (2009) for macaques, and more robustly, high-level locomotor states, such as gait phases and walking pattern types.…”

Preclinical upper limb neurorobotic platform to assess, rehabilitate, and develop therapies

“…For example, our previously developed multidirectional body weight support interface enabled both quadrupedal and bipedal locomotion ( 22 ). Albeit artificial, the bipedal posture abolished the contribution of upper limbs, thus restricting movement components to the studied lower limbs ( 24 ). Similarly, we reasoned that the difficulty to maintain quadrupedal posture after neurological disorders may affect the ability of rats to execute upper limb movements or may even favor compensatory contribution of the hindlimbs.…”

Cerebral Theta-Burst Stimulation Combined with Physiotherapy in Patients with Incomplete Spinal Cord Injury: A Pilot Randomized Controlled Trial

“…Considering evidence from previous research (47), the possible reasons are related to the long-term potentiation effect of iTBS by altering the effectiveness of synaptic interactions (46). iTBS not only improved the WS and SL of patients with SCI, but also effectively increased the stability of lower limb movement control and improved walking quality and ADL People with SCI have a high rate of disability because effective nerve regeneration and neural circuit reconstruction have not resolved after the injury (48,49). Clinically, a large number of patients with SCI have incomplete injuries.…”

“…People with SCI have a high rate of disability because effective nerve regeneration and neural circuit reconstruction have not resolved after the injury ( 48 , 49 ). Clinically, a large number of patients with SCI have incomplete injuries.…”