Abstract

Introduction Transcranial magnetic stimulation (TMS) is a useful, non-invasive tool that can explore the functional integrity of the primary motor cortex and corticomotor pathways. Although the application of TMS has rapidly increased in the last decade using upper limb muscle targets, there remains a relative paucity of lower limb studies. Additionally, the paired-pulse TMS paradigms that have been applied to explore lower limb cortical parameters have shown significant variability in motor evoked potential (MEP) amplitudes, questioning the reliability and clinical utility of this technique. Threshold tracking TMS (TT-TMS) was recently developed to overcome such methodological problems, but this protocol has been limited to upper limb studies. Importantly, the inherent differences in upper and lower limb normal cortical function and the differing pattern of disease in lower limb predominant neurological disorders highlights the need for a more robust understanding of lower limb corticomotoneuronal function. Thus, the aim of the present study was to employ TT-TMS to establish lower limb cortical parameters and to investigate side-to-side differences to determine laterality of normal cortical function. Methods Studies were performed in 40 healthy participants recording from the tibialis anterior muscle bilaterally. Three common coil choices (90 mm circular coil, 70 mm figure-8 coil, 110 mm double cone coil) were explored. Single-pulse TMS, paired-pulse TT-TMS and nerve conduction studies were performed. Results The double cone coil had the greatest efficacy, generating a significantly lower resting motor threshold than the circular (p = 0.04) or figure-8 (p = 0.01) coils. Paired-pulse TT-TMS generated an averaged short interval intracortical inhibition of 11.3 ± 1.2%, with an averaged intracortical facilitation of −8.5 ± 1.1%. Central motor conduction time (CMCT) was 8.9 ± 0. 6 ms.There were no differences between dominant and non-dominant sides for all single (RMT, MEP latency, MEP amplitude, MEP/CMAP ratio, CSP and CMCT) and paired-pulse TT-TMS parameters (peak SICI 1 ms, peak SICI 3 ms, averaged SICI and ICF). Similarly, peripheral measures of nerve function were not significantly different between the dominant and non-dominant hemispheres for all measures tested. Conclusion This study successfully assessed cortical excitability and corticospinal pathways from the lower limbs using TT-TMS, establishing normative data, symmetry of normal cortical function, and validating the double cone coil for future studies. These findings can now be applied to explore further aspects of lower limb physiology and used for the clinical interpretation of motor cortical dysfunction across a range of neurological diseases. Together with previously established upper limb TT-TMS, this study will now inevitably allow for a more comprehensive evaluation of normal neuronal processes and patterns of disease across a larger area of cortical representation.

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