Extended Data Fig. 4: Preoperative planning for optimal placement of the new paddle lead.

Step 1, CT, structural MRI and functional MRI acquisitions allow to personalize a computational model of the interactions between EES and the spinal cord for each participant. Step 2, The insertion of the new paddle lead within the spinal canal is visualized in the model to anticipate bony structures or ligaments that could deviate the trajectory. Step 3, The new paddle lead is positioned at 6 locations separated by 2 mm, thus covering the entire region of the spinal cord targeted by the therapy. The same procedure was applied to the Specify 5-6-5 lead, except that 2 additional locations were necessary to cover the entire region since this lead is shorter than the new paddle lead. Step 4, The plot shows the recruitment of each dorsal root when simulating the delivery of EES at increasing intensities through the top left electrode of the paddle lead. The same simulations were performed for the electrodes located at each corner of the paddle lead. Step 5, The recruitment of dorsal roots is translated into the recruitment of motor pools based on a transformation matrix that maps the recruitment of afferents to the recruitment of motor pools. The transformation matrix was either based on the averaged location of motor pools across the human population⁷², or the projectome of proprioceptive neurons from key leg muscles identified from functional MRI. Step 6, Applying the transformation matrix depicted in Step 5 allows to convert the predicted recruitment of dorsal roots shown in Step 4 into a prediction of motor pool recruitment. Step 7, For each position of the lead, the recruitment of the targeted motor pools compared to the non-targeted motor pools is measured to obtain a selectivity index. For example, the recruitment of the dorsal root projecting to the L1 spinal segments intends to recruit the motor neurons innervating the iliopsoas muscle to elicit hip flexion. The relative recruitment of the iliopsoas muscle versus the rectus femoris or vastus lateralis muscles is transformed into a selectivity index. For each position of the paddle lead, the selectivity index for the tested electrode is color coded, and the selectivity between the tested locations interpolated to obtain a continuum. Step 8, The selectivity indices obtained for the electrodes located at each corner of the paddle lead (from left to right, targeting motor neurons eliciting hip flexion or ankle extension) are aggregated into a combined selectivity index that defines the performance of the paddle lead at the tested position. The optimal position for the paddle lead was defined as the position for which the highest combined selectivity index was obtained (most yellow rectangle). Step 9, Optimal position of the new paddle lead predicted based on a personalized computational model but a generic distribution of motor neuron locations. Step 10, Intraoperative quantification of the combined selectivity index, and thus identification of the optimal position of the new paddle lead. The predicted optimal position of the paddle lead based on a personalized model with the identified projectomes of proprioceptive neurons matched the optimal position validated intraoperatively, whereas simulations based on the averaged location of motor pools across the human population failed to predict the optimal position. Step 11-13, The procedures described in Steps 8-10 were repeated for the Specify 5-6-5 paddle lead. Note that the intraoperative validation of the optimal position of the Specify 5-6-5 was restricted to one position to minimize the duration of the surgical intervention.