Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restored walking in people with spinal cord injury (SCI). However, EES was delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed a software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis, as part of an ongoing clinical trial (clinicaltrials.gov, NCT02936453). Within a single day, activity-specific stimulation programs enabled the three individuals to stand, walk, cycle, swim, and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

Quantitative spinal cord (SC) magnetic resonance imaging (MRI) is fraught with challenges, among which is the lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for the three main 3T MRI vendors: GE, Philips and Siemens. The protocol provides valuable metrics for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area (CSA) computation, multi-echo gradient echo for gray matter CSA, as well as magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. The spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects, as detailed in the companion paper [REF-DATA]. The spine generic protocol is open-access and its latest version can be found at: https://spinalcordmri.org/protocols. The protocol will serve as a valuable starting point for researchers and clinicians implementing new SC imaging initiatives. Note to the reviewer/editor/publisher: the companion paper is referred to as [REF-DATA]6/52 121 122dealing with cervical myelopathy and MS populations. Applications of the MethodThe proposed protocol is not geared towards a specific disease and it is suitable for imaging WM pathology (demyelination and Wallerian degeneration via axon/myelin-sensitive 122 https://mssociety.ca/about-ms-research/about-our-research-program/research-we-fund/canadian-prospect ive-cohort-study-to-understand-progression-in-ms-canproco 121 https://www.wingsforlife.com/us/research/imaging-spinal-cord-injury-and-assessing-its-predictive-value-th e-inspired-study-2675/ 9/52

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The spinal cord is the main interface between the brain and the periphery. It notably plays a central role in motor control, as spinal motoneurons activate skeletal muscles involved in voluntary movements. Yet, the spinal mechanisms underlying human movement generation have not been completely elucidated. In this regard, functional magnetic resonance imaging (fMRI) represents a potential tool to probe spinal cord function non-invasively and with high spatial resolution. Nonetheless, a thorough characterization of this approach is still lacking, currently limiting its impact. Here, we aimed at systematically quantifying to which extent fMRI can reveal spinal cord activity along the rostrocaudal direction. We investigated changes in the blood oxygenation level dependent signal of the human cervical spinal cord during bimanual upper limb movements (wrist extension, wrist adduction and finger abduction) in nineteen healthy volunteers. Prior to scanning, we recorded the muscle activity associated with these movements in order to reconstruct the theoretical motor-pool output pattern using an anatomybased mapping of the electromyographic (EMG) waveforms. EMG-derived spinal maps were characterized by distinct rostrocaudal patterns of activation, thus confirming the task-specific features of the different movements. Analogous activation patterns were captured using spinal cord fMRI. Finally, an additional fMRI dataset was acquired from a subset of the participants (n = 6) to deploy a multivoxel pattern analysis, which allowed successful decoding of movements. These combined results suggest that spinal cord fMRI can be used to image rostrocaudal activation patterns reflecting the underlying activity of the motoneuron pools innervating the task-related muscles. Spinal cord fMRI offers the prospect of a novel tool to study motor processes and potentially their modification following neurological motor disorders.

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/. The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.

same b-vector), this artifact is not visible (mountSinai03, right panel). Such an artifact could be problematic for image registration with regularization along the S-I axis, or for performing diffusion tractography. (e) b = 0 image from a DWI scan (perform02) acquired with poor shimming and resulting signal dropout. (f) Another example of poor shimming resulting in sub-efficient fat saturation, with the fat being aliased on top of the SC. Here we show the mean DWI scan of a participant from the single subject database (perform). (g) Effect of pulsatile movement on a non-cardiac gated acquisition (single subject, juntendoAchieva). Diffusion-weighted scans (sagittal view) acquired at three b-vecs fairly orthogonal to the SC (i.e., diffusion-specific signal attenuation should be minimum in the SC), showing abrupt signal drop at a few slices (red arrows), likely due to cardiac-related pulsatile effects.

In the original version of this Data Descriptor, the legend to Figure 16 incorrectly stated that the figure depicts the results of the multi-subject study for the MT protocol and that the mean MTR was computed. The legend has now been corrected to indicate that the figure depicts the results of the multi-subject study for the DWI scan and that the FA was computed. This has now been corrected in the PDF and HTML versions of the Data Descriptor.

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