Spinal Excitability Changes after Transspinal and Transcortical Paired Associative Stimulation in Humans

Maria Knikou, Maria Knikou

Abstract

Paired associative stimulation (PAS) produces enduring neuroplasticity based on Hebbian associative plasticity. This study established the changes in spinal motoneuronal excitability by pairing transcortical and transspinal stimulation. Transcortical stimulation was delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Before and after 40 minutes of each PAS protocol, spinal neural excitability was assessed based on the amplitude of the transspinal-evoked potentials (TEPs) recorded from ankle muscles of both legs at different stimulation intensities (recruitment input-output curve). Changes in TEPs amplitude in response to low-frequency stimulation and paired transspinal stimuli were also established before and after each PAS protocol. TEP recruitment input-output curves revealed a generalized depression of TEPs in most ankle muscles of both legs after both PAS protocols that coincided with an increased gain only after transcortical-transspinal PAS. Transcortical-transspinal PAS increased and transspinal-transcortical PAS decreased the low-frequency-dependent TEP depression, whereas neither PAS protocol affected the TEP depression observed upon paired transspinal stimuli. These findings support the notion that transspinal and transcortical PAS has the ability to alter concomitantly cortical and spinal synaptic activity. Transspinal and transcortical PAS may contribute to the development of rehabilitation strategies in people with bilateral increased motoneuronal excitability due to cortical or spinal lesions.

Figures

Figure 1
Figure 1
Paired associative stimulation (PAS) protocol. (a) Simplified diagram of transcranial magnetic stimulation (TMS volley) and transspinal stimulation-mediated volleys during paired stimulation. TMS motor volleys are descending, whilst transspinal stimulation produces both ascending and descending volleys. The ascending volleys are expected to reach both brain hemispheres since transspinal stimulation delivered alone evokes transspinal-evoked potentials (TEPs) in muscles of both legs. (b) Timing of PAS between transcortical and transspinal stimulation. PAS was delivered at customized interstimulus intervals for each subject during which corticospinal neurons activated via TMS arrived at the corticospinal neuron before spinal motoneurons were activated transsynaptically by the transspinal stimulation (transcortical-transspinal PAS), and during which transspinal-mediated ascending volleys arrived at the motor cortex before TMS was delivered over the left primary motor cortex leg area (transspinal-transcortical PAS).
Figure 2
Figure 2
TEPs recruitment curves before and after transcortical-transspinal PAS. Recruitment input-output curves of transspinal-evoked potentials (TEPs) recorded bilaterally from the TA, MG, SOL, and PL muscles from all subjects along with the sigmoid function fitted to the data. The abscissa shows multiples of stimulation intensities corresponding to 50% TEP max (S50). The ordinate shows TEP sizes as a percentage of the homonymous maximal TEP size obtained before transcortical-transspinal PAS. Red or blue arrows indicate statistically significant differences (decreased and increased amplitudes, resp.) before and after PAS based on 2-way repeated measures ANOVA. TA: tibialis anterior; MG: medial gastrocnemius; SOL: soleus; PL: peroneus longus.
Figure 3
Figure 3
TEPs recruitment curves before and after transspinal-transcortical PAS. Recruitment input-output curves of transspinal-evoked potentials (TEPs) recorded bilaterally from the TA, MG, SOL, and PL muscles from all subjects along with the sigmoid function fitted to the data. The abscissa shows multiples of stimulation intensities corresponding to 50% TEP max (S50). The ordinate shows TEP sizes as a percentage of the homonymous maximal TEP size obtained before transspinal-transcortical PAS. Red arrows indicate statistically significant differences (decreased amplitudes) before and after PAS based on repeated measures ANOVA. TA: tibialis anterior; MG: medial gastrocnemius; SOL: soleus; PL: peroneus longus.
Figure 4
Figure 4
Frequency-dependent depression of TEPs. (a) Nonrectified waveform averages of ankle transspinal-evoked potentials (TEPs) recorded from one representative subject at 0.2 and 1.0 Hz. (b, c) Overall percent change of TEPs recorded at 0.2 Hz from the associated TEP recorded at 1.0 Hz before and after each PAS protocol from all subjects. The abscissa shows the muscles from which TEPs were recorded. Error bars indicate SE.
Figure 5
Figure 5
Depression of TEPs in response to paired transspinal stimuli. Nonrectified waveform averages of ankle transspinal-evoked potentials (TEPs) recorded from one representative subject upon paired pulses at interstimulus intervals of 50 and 100 ms at a constant stimulation frequency of 0.2 Hz.
Figure 6
Figure 6
Depression of TEPs in response to paired transspinal stimuli before and after transspinal and transcortical PAS. Overall amplitude of TEP2 as a percentage of the mean TEP1 evoked at interstimulus intervals of 50 (a, c) and 100 ms (b, d) at a stimulation frequency of 0.2 Hz before and after each PAS protocol from all subjects. The abscissa shows the muscles from which TEPs were recorded. Error bars indicate SE. No changes in TEPs depression upon paired pulses before and after transspinal and transcortical PAS were found.

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