Effects of Cathodal Trans-Spinal Direct Current Stimulation on Mouse Spinal Network and Complex Multijoint Movements

Abstract

Cathodal trans-spinal direct current (c-tsDC) stimulation is a powerful technique to modulate spinal excitability. However, the manner in which c-tsDC stimulation modulates cortically evoked simple single-joint and complex multijoint movements is unknown. To address this issue, anesthetized mice were suspended with the hindlimb allowed to move freely in space. Simple and complex multijoint movements were elicited with short and prolonged trains of electrical stimulation, respectively, delivered to the area of primary motor cortex representing the hindlimb. In addition, spinal cord burst generators are known to be involved in a variety of motor activities, including locomotion, postural control, and voluntary movements. Therefore, to shed light into the mechanisms underlying movements modulated by c-tsDC stimulation, spinal circuit activity was induced using GABA and glycine receptor blockers, which produced three rates of spinal bursting activity: fast, intermediate, and slow. Characteristics of bursting activity were assessed during c-tsDC stimulation. During c-tsDC stimulation, significant increases were observed in (1) ankle dorsiflexion amplitude and speed; (2) ankle plantarflexion amplitude, speed, and duration; and (3) complex multijoint movement amplitude, speed, and duration. However, complex multijoint movement tracing showed that c-tsDC did not change the form of movements. In addition, spinal bursting activity was significantly modulated during c-tsDC stimulation: (1) fast bursting activity showed increased rate, amplitude, and duration; (2) intermediate bursting activity showed increased rate and duration, but decreased amplitude; and (3) slow bursting activity showed increased rate, but decreased duration and amplitude. These results suggest that c-tsDC stimulation amplifies cortically evoked movements through spinal mechanisms.

Trans-Spinal Direct Current Stimulation Alters Muscle Tone in Mice with and without Spinal Cord Injury with Spasticity

“…This agrees with previous studies, despite differences in location of the return electrode (Fuortes, 1954;Eccles et al, 1962). Recently, we showed that trans-spinal direct current stimulation (DCS) modulates spinal interneuron excitability (Ahmed, 2013b). In addition, trans-spinal DCS had previously been shown to modulate the excitability of primary afferent fibers via their presynaptic terminals (Eccles et al, 1962).…”

“…The two lengthening velocities used were within the range that can be produced by cortically evoked dorsiflexion in mice (Ahmed, 2013b 1). In addition, stretch-induced nerve discharges were higher in animals with spinal cord injury.…”

“…This was also confirmed by cutting the TS tendon, which had a stretch capacity of 3.5 mm. The velocity of the stretches was based on the velocity of the cortically evoked dorsiflexion movement (Ahmed, 2013b), which was between 200 mm/s (low velocity) and 500 mm/s (high velocity). Therefore, the stretch system was adjusted to produce lengthening movements at the low (209 mm/s) and high velocities (475 mm/s).…”

“…4). This suggests that DCS affects spinal motoneurons by increasing or decreasing excitability drive from spinal interneurons that are not involved in the stretch reflex (Ahmed, 2013b), akin to the effect of brainstem on spinal motoneuron pools (Takakusaki, 2008). However, H-reflex was attenuated by spinal-to-sciatic DCS and increased by sciatic-to-spinal DCS, suggesting that modulation of transmission from group Ia afferents to motoneurons by DCS may be involved in reducing stretch responses.…”

Does Trans-Spinal Direct Current Stimulation Alter Phrenic Motoneurons and Respiratory Neuromechanical Outputs in Humans? A Double-Blind, Sham-Controlled, Randomized, Crossover Study

“…In the light of our results and based on our current understanding of tsDCS mechanisms , it is conceivable that the mechanisms underlying enhanced DiMEPs after tsDCS could also involve changes in neurotransmission, which would be in line with the fact that (1) glutamate drives the pathway to PMNs during inspiration (McCrimmon et al, 1989;Chitravanshi and Sapru, 1996) and modulates synaptic strength in the short and long term via NMDA receptors (Rekling et al, 2000;McGuire et al, 2008); (2) GABA is intimately involved in respiratory motor control, as PMNs are inhibited by GABA A receptors during the expiratory phase of respiration (Fedorko et al, 1983;Merrill and Fedorko, 1984); and, (3) PMN NMDA receptors also contribute to excitatory neurotransmission (Chitravanshi and Sapru, 1996) and are implicated in many models of plasticity including phrenic LTF (Golder, 2009). This idea is also supported by recent arguments from animal studies: (1) both anodal and cathodal tsDCS increased glutamate analog D-2,3-3 H-aspartic acid release in vitro (Ahmed and Wieraszko, 2012), and (2) it has been proposed that cathodal tsDCS may act by directly inhibiting the spinal GABAergic system or by exerting overexcitation of postsynaptic neurons (Ahmed, 2013) likely through increased glutamate release (Ahmed and Wieraszko, 2012). The fact that The INTERVENTION factor consists of three levels: anodal, cathodal, and sham tsDCS.…”