Tapping into rhythm generation circuitry in humans during simulated weightlessness conditions

Abstract

An ability to produce rhythmic activity is ubiquitous for locomotor pattern generation and modulation. The role that the rhythmogenesis capacity of the spinal cord plays in injured populations has become an area of interest and systematic investigation among researchers in recent years, despite its importance being long recognized by neurophysiologists and clinicians. Given that each individual interneuron, as a rule, receives a broad convergence of various supraspinal and sensory inputs and may contribute to a vast repertoire of motor actions, the importance of assessing the functional state of the spinal locomotor circuits becomes increasingly evident. Air-stepping can be used as a unique and important model for investigating human rhythmogenesis since its manifestation is largely facilitated by a reduction of external resistance. This article aims to provide a review on current issues related to the "locomotor" state and interactions between spinal and supraspinal influences on the central pattern generator (CPG) circuitry in humans, which may be important for developing gait rehabilitation strategies in individuals with spinal cord and brain injuries.

Keywords: central pattern generator; humans; locomotion; rhythmogenesis; sensory input.

Figure 1

Eliciting non-voluntary limb stepping movements in simulated weightlessness (gravity neutral) conditions. (A) examples of non-voluntary rhythmic movements of the suspended legs induced by quadriceps (Q) muscle vibration and electrical stimulation (ES) of sural and peroneal nerves in one representative subject from the study of Selionov et al. (2009). An upward deflection of traces denotes flexion in the hip and knee joint angles and dorsiflexion in the ankle joint. Note the absence of ankle joint rotations during evoked air-stepping. (B) An example of evoked rhythmic leg movements during hand walking in one subject from the study of Sylos-Labini et al. (2014a). RF, rectus femoris, BF, biceps femoris, TA, tibialis anterior, LG, lateral gastrocnemius, FCU, flexor carpi ulnaris, BIC, biceps brachii, DELTa, anterior deltoid, ST, and semitendinosus. Hand and foot denote anterior-posterior displacements of the left hand and foot.

Figure 2

Kinematic features of non-voluntary air-stepping movements. (A) one-legged vs. two-legged air-stepping evoked by quadriceps muscle vibration. Upper panels—histogram of the phase shift between hip and knee joints across subjects and probes. Note similar occurrence of forward and backward one-legged air-stepping and predominantly forward 2-legged stepping. Low panels—examples of transitions (in the middle of the record) from FW to BW stepping and vice versa in 2 subjects. (B) examples of rhythmic leg movements evoked by continuous electrical stimulation (ES) of the sural nerve in the absence (left) and presence (right) of small (25 N) force applied to the forefoot part of the foot. The force was applied approximately in the direction of the longitudinal axis of the body using a long elastic thread cord. The length of the thread cord was about 5 m so that fluctuations in its force due to the length changes were minimal (<10%) during air-stepping. Eight consecutive cycles are shown for each condition. Note the appearance of noticeable oscillations in the ankle joint angle and activity in the distal muscles in the presence of small load force (adapted from Selionov et al., 2009).

Figure 3

Motor responses during voluntary and non-voluntary air-stepping in healthy subjects. (A) background EMG activity (upper panel) and motor evoked potentials (lower panel) in response to transcranial magnetic stimulation of the motor cortex (MEPs, mean ± SE, n = 8 subjects) in the BF muscle during different phases of the step cycle. (B) background soleus EMG activity (upper panel) and H-reflex (lower panel) modulation. Asterisks denote significant differences. Note facilitation of motor responses during voluntary stepping. Adapted from Solopova et al. (2014).

Figure 4

EMG activity and rhythmic leg movements induced by epidural spinal cord electrical stimulation (SCES) in SCI patients in a supine position. (A) epidural SCES (upper panel) and an example of EMG recordings (bottom panel) obtained from quadriceps (Q), hamstrings (H), tibialis anterior (TA), and triceps surae (TS) during SCES at 31 Hz. The goniometer traces of the knee joint angle illustrate the corresponding induced rhythmical movements of the lower limbs. Adapted from Minassian et al. (2004). (B) SCES-induced rhythmic leg movements in SCI patients. During SCES, the patient was lying supine and the legs were suspended on elastic straps in a position such that the hip and knee joints were in semi-flexion (top panel). Middle panels: an example of stepping-like movements at ~1 Hz evoked with 2 Hz SCES in one SCI patient. On the right—duration of stepping cycle in relationship to the frequency of SCES in this patient. The frequency gradually increased from 3 to 100 Hz and then decreased from 100 to 0.5 Hz. Bottom panel: location of the effective zone for initiating alternating stepping-like movements with SCES in a group of paraplegic patients (n = 29). Adapted from Shapkova (2004).