Spinal motor mapping by epidural stimulation of lumbosacral posterior roots in humans

Abstract

Epidural electrical stimulation of the spinal cord is an emergent strategy for the neurological recovery of lower-extremity motor function. Motoneuron pools are thought to be recruited by stimulation of posterior roots. Here, we linked electromyographic data of epidurally evoked lower-extremity responses of 34 individuals with upper motoneuron disorders to a population model of the spinal cord constructed using anatomical parameters of thousands of individuals. We identified a relationship between segmental stimulation sites and activated spinal cord segments, which made spinal motor mapping from epidural space possible despite the complex anatomical interface imposed by the posterior roots. Our statistical approach provided evidence for low-threshold sites of posterior roots and effects of monopolar and bipolar stimulation previously predicted by computer modeling and allowed us to test the impact of different upper motoneuron disorders on the evoked responses. Finally, we revealed a statistical association between intraoperative and postoperative mapping of the spinal cord.

Keywords: Clinical Neuroscience; Nervous System Anatomy; Neuroanatomy; Neuroscience.

Conflict of interest statement

The authors declare no competing interests.

© 2020 The Author(s).

Figures

Graphical abstract

Figure 1

Spinal cord and segmental innervation model (A) Straight-line anatomical model of the spine, defined by vertebral body and intervertebral disc heights. (B) Straight-line model of the lumbosacral spinal cord aligned with the spine model. (C) Segmental innervation probabilities (0%–100%) of Add, RF, TA, SM, ST, BF, Gast, and Sol, reflected by the opacity of the respective colors. Sources and values considered in the spine model are specified in Tables S2 and S3, those of the spinal cord model in Tables S4–S6. (D) Distribution of vertebral cathode positions tested; numbers are counts per bin (intervertebral disc or upper, middle, or lower third of vertebral body). Cathode positions tested in different monopolar or bipolar setups in a given subject were counted only once.

Figure 2

Mapping the segmental lumbosacral spinal cord anatomy by epidurally evoked muscle responses—exemplary results (A) EMG responses of RF and TS evoked by epidural stimulation with threshold amplitude, aligned with the respective rostrocaudal cathode positions (black rectangles) and segmental innervations. Neither muscle was recruited from the most rostral site with maximum stimulation (10 V). EMG response derived from three subjects as indicated. (B) (i) Magnetic resonance microscopy images of the spinal cord and the complex peripheral rim composed of posterior and anterior roots shown in cross-sections at spinal cord segmental levels as indicated (Calabrese et al., 2018). (ii) Estimated positions of the left T12–S2 posterior roots reflecting their complex anatomical arrangement (Wall et al., 1990).

Figure 3

PRM-reflex thresholds of RF and TS reflect the segmental lumbosacral spinal cord anatomy (A) Statistical comparison (Kruskal-Wallis test) of cathode distributions separated according to the elicitation of RF- and TS-PRM reflexes and their thresholds (Th). Categories are as follows: No RF and TS responses; RF bias, ThRF < ThTS; Non-selective, ThRF = ThTS; TS bias, ThRF > ThTS. Segmental innervation probabilities are illustrated by the opacity of blue (RF) and red (TS) boxes aligned with the spinal cord model. Data derived from all 34 subjects. (B) ThRF and ThTS of the different categories; the RF-bias category was sub-divided into RF biasnoTS, RF but not TS recruited, and RF biasRF&TS, RF and TS recruited. Statistical comparisons between categories were performed using Kruskal-Wallis test and within categories, using separate Wilcoxon tests. (C) Response thresholds of Add, RF, TA, Ham, and TS per category. In the RF-biasnoTS category, TA responded in three cases only (x) and was not considered in the statistical comparison (linear mixed model). Numbers in parentheses are available datasets per category and muscle; N is the number of subjects per analysis. Boxplots illustrate median cathode locations (A) and response thresholds (B and C), respectively, as bold horizontal lines within boxes spanning the IQR, and whiskers extending to the smallest and largest values that are not outliers (values 1.5–3 times the IQR; plotted as circles). Brackets indicate statistical significance, dotted lines, p < .05, and solid lines, p < .001.

Figure 4

Impact of mono- and bipolar stimulation on selectivity and threshold of PRM-reflex elicitation (A) Electrode setups contributing more than expected under the null hypothesis to the no-responses, RF-bias, non-selective, and TS-bias categories. Cathode (−) positions represent the medians of distributions within the four different categories, cf. Figure 3A, shown with respect to the major segmental innervations of RF and TS. Anodes (+) shield the distribution of the cathodic field (symbolized by blue areas). (B) Dependence of RF- and TS-response thresholds on the electrode setup. Boxplots illustrate median thresholds as bold horizontal lines within boxes spanning the IQR and whiskers extending to the smallest and largest values that are not outliers (values 1.5–3 times the IQR; plotted as circle). Data derived from, monopolar stimulation, ten subjects; wide field, 30 subjects; intermediate field, 18 subjects; and narrow field, 14 subjects. Brackets indicate statistical significance (Kruskal-Wallis tests), dotted lines, p 

Figure 5

PRM-reflex amplitudes reflect the segmental lumbosacral spinal cord anatomy (A) Spinal cord maps of spatial motoneuron pool activation for three cathode distributions (RF bias, non-selective, TS bias) and three stimulation-amplitude levels (threshold, common threshold, maximum) derived from normalized response amplitudes and segmental innervation probabilities. Only major segmental innervations of RF and TS (innervation probabilities ≥44%; Figure 1C) were considered, illustrated by the opacity of blue and red boxes. Data derived from 25 subjects. (B) Polar plots of muscle activation for the three categories and stimulation levels. Radial axes are muscles and polar coordinates are median normalized peak-to-peak amplitudes. (C) Normalized response amplitudes of all muscles studied per category at common threshold and compared using separate linear mixed models. Numbers in parentheses are available datasets per category and muscle. Boxplots illustrate median cathode locations (A) and response thresholds (C), respectively, as bold horizontal lines within boxes spanning the IQR, and whiskers extending to the smallest and largest values that are not outliers (values 1.5–3 times the IQR; plotted as circles) or extreme values (values >3 times the IQR; asterisks). Brackets indicate statistical significance, dotted lines, p 

Figure 6

Intraoperative monitoring predicts postoperative segmental motoneuron pool activation (A) EMG recordings of PRM reflexes evoked in RF and TS at threshold, intraoperatively in the prone and postoperatively in the supine position; five superimposed responses each. RF- versus TS-selectivity of the stimulation intraoperatively was maintained postoperatively, with decreased thresholds. (B) Transitions between categories from the prone to the supine position. Eighty-seven percent of the intraoperative datasets that were classified into either of the two RF-bias categories and 71% of those of the TS-bias category remained within the respective categories postoperatively. Data derived from 16 subjects. (C) Thresholds of RF and TS responses evoked in the prone and supine positions. Data derived from 12 subjects. Thresholds for voltage- and current-controlled stimulators were pooled for the statistical testing, because pairwise comparisons were based on signed ranks (Wilcoxon test). Boxplots illustrate median thresholds as bold horizontal lines within boxes spanning the IQR and whiskers extending to the smallest and largest values that are not outliers (values 1.5–3 times the IQR; plotted as circles) or extreme values (values >3 times the IQR; asterisks). Brackets (dotted lines) indicate statistical significance, p