H-reflex conditioning with TMS: An important electrophysiological tool in motor neuroscience?!
Final Report Abstract
A current main research topic in the behavioural neurosciences concerns the understanding neural circuits functions. Apart from basic research interests, a better mechanistic understanding would be valuable for society, in order to develop better treatment options for neurologically diseased patients. A crucial factor that limits progress in behavioural neurosciences research in humans relates to methodological constraints of non-invasive techniques. Although new developments have been made in the recent years that allow investigations beyond the level of brain areas, currently availble methods do not offer both, spatial and temporal resolution, in sufficient quality. In the current project, we harnessed an already existing non-invasive electrophysiological technique offering sufficient temporal resultion in the millsecond range. This technique consists of a combination of transcranial magnetic stimulation and peripheral nerve stimulation. We asked about the depths of spatial resolution possible with this technique, and questioned whether and which anatomical elements at the circuit level can be studied. Therefore, we systematically varied stimulus parameters, compared the outcome of the non-invasive measurements with outcomes from invasive techniques applied in humans (for which the physiological and anatomical understanding of mechanisms is better). Further, we combined measurements in humans with in-vivo as well as in-vitro measurements in non-human primates, namely in old-world monkeys with a similar anatomy and physiology of the motor system to that of humans. As the main result, we demonstrated that if distinct adjustments of stimulus parameters are made and a strict experimental protocol is followed, neural activity changes of neural circuits located at different motor cortex layers (supragranular/infragranular) can be estimated with the noninvasive H-reflex conditioning technique. This laminar-sensitivity of the technique is complemented by the ability to assess neural activity changes of more complex and anatomically less well defined circuits, comprising cortical and subcortical (spinal) structures. Further, on the basis of our experiments we could demonstrate that assumed mechanisms derived from certain specialized non-invasive transcranial magnetic stimulation approaches involving double magnetic pulses may be wrong. Specifically, mechanisms assumed in previous publications using this double-pulse paradigms were little supported by the outcome of our experiments. Consequently, we recommend that interpretation of mechanisms derived from these measures should be made carefully. In conclusion, the ability of testing anatomically describable cortical circuits with sufficient temporal resolution with a non-invasive technique has consequences for future experiments. The method will help to improve our understanding of functions of anatomical elements of the human brain for the control of behaviour, and it may be helpful in deciphering pathophysiological mechanisms with the aim of developing adequat treatment strategies.
Publications
- (2018). Assessing the contribution of D- and I-waves to changes in motoneurone excitability with spinal H-reflexes. J Neurophysiol 119:933-943
Niemann N, Wiegel P, Kurz A, Rothwell JC, Leukel C
(See online at https://doi.org/10.1152/jn.00671.2017) - (2018). Evidence for a subcortical contribution to intracortical facilitation. Eur J Neurosci 47:1311-1319
Wiegel P, Niemann N, Rothwell JC, Leukel C
(See online at https://doi.org/10.1111/ejn.13934) - (2019). Non-invasive assessment of superficial and deep layer circuits in human motor cortex. J Phys 597, 2975 – 2991
Kurz A, Wei X, Wiegel P, Leukel C, Baker SN
(See online at https://doi.org/10.1113/JP277849)
