Electrical Spinal Stimulation, and Imagining of Lower Limb Movements to Modulate Brain-Spinal Connectomes That Control Locomotor-Like Behavior

Yury Gerasimenko, Dimitry Sayenko, Parag Gad, Justin Kozesnik, Tatiana Moshonkina, Aleksandr Grishin, Aleksandr Pukhov, Sergey Moiseev, Ruslan Gorodnichev, Victor Selionov, Inessa Kozlovskaya, V Reggie Edgerton, Yury Gerasimenko, Dimitry Sayenko, Parag Gad, Justin Kozesnik, Tatiana Moshonkina, Aleksandr Grishin, Aleksandr Pukhov, Sergey Moiseev, Ruslan Gorodnichev, Victor Selionov, Inessa Kozlovskaya, V Reggie Edgerton

Abstract

Neuronal control of stepping movement in healthy human is based on integration between brain, spinal neuronal networks, and sensory signals. It is generally recognized that there are continuously occurring adjustments in the physiological states of supraspinal centers during all routines movements. For example, visual as well as all other sources of information regarding the subject's environment. These multimodal inputs to the brain normally play an important role in providing a feedforward source of control. We propose that the brain routinely uses these continuously updated assessments of the environment to provide additional feedforward messages to the spinal networks, which provides a synergistic feedforwardness for the brain and spinal cord. We tested this hypothesis in 8 non-injured individuals placed in gravity neutral position with the lower limbs extended beyond the edge of the table, but supported vertically, to facilitate rhythmic stepping. The experiment was performed while visualizing on the monitor a stick figure mimicking bilateral stepping or being motionless. Non-invasive electrical stimulation was used to neuromodulate a wide range of excitabilities of the lumbosacral spinal segments that would trigger rhythmic stepping movements. We observed that at the same intensity level of transcutaneous electrical spinal cord stimulation (tSCS), the presence or absence of visualizing a stepping-like movement of a stick figure immediately initiated or terminated the tSCS-induced rhythmic stepping motion, respectively. We also demonstrated that during both voluntary and imagined stepping, the motor potentials in leg muscles were facilitated when evoked cortically, using transcranial magnetic stimulation (TMS), and inhibited when evoked spinally, using tSCS. These data suggest that the ongoing assessment of the environment within the supraspinal centers that play a role in planning a movement can routinely modulate the physiological state of spinal networks that further facilitates a synergistic neuromodulation of the brain and spinal cord in preparing for movements.

Keywords: TMS; brain-spinal connectome; imaging; locomotor circuitry; transcutaenous spinal cord stimulation.

Figures

Figure 1
Figure 1
Localization of the surface EEG electrodes (A). Position of the subject placed in gravity-neutral device. Visual imagery non-stepping (VI-NS) (B). Visual imagery stepping (VIS) (C).
Figure 2
Figure 2
Angular excursions of the right knee joint and EMG activity in the medial hamstring (MH) in right and left legs, right medial gastrocnemius (RMG), and right tibialis anterior (RTA) during gradual (by 5 mA) increasing intensity of spinal stimulation alone (A) and in the presence of visual imagery of stepping (VIS) (B) in Subject D.G. Knee excursion and EMG bursts marked by a gray background (A,B) are displayed with an extended time scale in (C,D), correspondingly. Plots of amplitude displacements (E) and cycle period (F) of knee joint during tSCS alone and VIS+tSCS. Kinematics coordination based on knee (left) and knee (right) movements during tSCS (G) and VIS+tSCS (H). Pattern of reciprocity for EMG activity of the HM (left) and HM (right) during tSCS (I) and VIS+tSCS (J). EMG calibration: mV.
Figure 3
Figure 3
Angular excursions of the right knee joint and corresponding rectified EMG activity in the left and in the right hamstrings when stimulating at T11,30 Hz (A,C) and when combining with imagining stepping (B,D) in subjects TM(A,B) and VS(D,E). (C) Mean peak-to-peak excursion amplitudes (% of tSCS alone) at the knee joint and the corresponding cycle period durations (F) are shown for the 8–10 step-like movements in a gravity-neutral apparatus in response to stimulation at T11 only and at VIS+tSCS for three subjects: vs, sh, and tm (subject vs and sh were tested twice). *Significantly different at p < 0.05.
Figure 4
Figure 4
Angular excursions of the knee joint and corresponding EMG activity in the vastus lateralis (VL), medial hamstring (MH), medial gastrocnemius (MG), and tibialis anterior (TA) muscles during tSCS alone at T11 and VIS+tSCS in two subjects (A,B) are shown. tSCS was initiated and VIS was subsequently added (indicated by vertical line). In subject (B) the VIS+tSCS generated a robust, but highly erratic motor output, with each motor pool generating qualitatively different EMG patterns. EMG calibration: mV.
Figure 5
Figure 5
An example of the on-off effects of visual imagery of stepping (VIS) and visual imagery of non-stepping (VI-NS) and/or spinal stimulation on the excursion at the right knee joint and the EMG activity in the hamstring. Effects of VIS, VI-NS, and stop imagining stepping (No-VIS), i.e., not looking at any image are shown. Data from same subject, same session (A–C).
Figure 6
Figure 6
Scalp topographic mapping of the frequency components of EEG activity during the rest, voluntary, and passive stepping performance, as well as during visual imagery stepping (VIS) in the presence and the absence of tSCS.
Figure 7
Figure 7
Averaged sEMP during tSCS delivered at L1 and MEPs during TMS, recorded in mm. vastus lateralis (VL), rectus femoris (RF), medial hamsting (MH), medial gastrocnemius (MG) and tibialis anterior (TA) in one participant at rest (orange) and during voluntary stepping (blue) (A) as well as during visual imagery stepping (blue) (B).
Figure 8
Figure 8
(A) Mean ± SEM (N = 7 for SCS, and 5 for TMS), (B) mean 4–6 evoked responses per subject) percent changes of peak-to peak amplitude relative to the rested state, of the motor evoked responses in MG and TA muscles in response to TMS and tSCS at a stimulation (L1) during: voluntary stepping movements, and visual imagery stepping (VIS). *Significantly different at p < 0.05.
Figure 9
Figure 9
(A) Recruitmentcurves of sEMP to L1 stimulation and (B) recruitment curves of MEPs to TMS (mean ± SEM) in right leg muscles at rest (blue) and during VIS (red) (N = 6 subjects). Percentage of changes of peak-to peak amplitude of the motor evoked responses (relative to rest) induced during knee flexion or knee extension during voluntary stepping and during VIS. RVL, right vastus lateralis; RMH, right medial hamstrings; RTA, right tibialis anterior; RMG, right medial gastrocnemius muscles. *Significantly different at p < 0.05.

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