Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fiber tracts are often incapable of maintaining and modulating the activity of lower spinal motor centers. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibers by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control center for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated vs. n = 7 unstimulated vs. n = 7 untrained rats) and chronic (n = 14 stimulated vs. n = 9 unstimulated vs. n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability.

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This paper explores a variety of potential issues one has to address when estimating intergenerational mobility with historical data. Many studies are potentially affected by bias originating from individuals emigrating and thus dropping out of the sample, missing information on the life-cycle, and imperfectly linking data sets. Unique panel data on Zurich's citizenry between 1799 and 1926 entail information on true intergenerational links, and allow to follow individuals across the globe and time. This information enables me to explore how father-son mobility estimates are affected by excluding emigrating individuals, occupational patterns over the life-cycle, and linking procedures. The results suggest that focusing on geographically immobile individuals might decrease the estimated level of social mobility. The estimated level of mobility depends on both the father's and the son's age at classification but does not exhibit a monotone trend in the direction of the bias. Most recent linking procedures do not generate significant bias in the sample of Zurich citizens due to the high level of detail of the data combined with a small population size.

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