TMS coil orientation and muscle activation influence lower limb intracortical excitability

Highlights

• TMS coil orientation influenced the threshold for activation of a lower limb muscle.

• Intracortical excitability in resting muscle varied depending on TMS coil orientation.

• Intracortical excitability was differentially modulated by TMS coil orientation in resting and active muscle.

Abstract

Introduction

Previous research with transcranial magnetic stimulation (TMS) indicates that coil orientation (TMS current direction) and muscle activation state (rest or active) modify corticospinal and intracortical excitability of upper limb muscles. However, the extent to which these factors influence corticospinal and intracortical excitability of lower limb muscles is unknown. This study aimed to examine how variations in coil orientation and muscle activation affect corticospinal and intracortical excitability of tibialis anterior (TA), a lower leg muscle.

Methods

In 21 young (21.6 ± 3.3 years, 11 female) adults, TMS was administered to the motor cortical representation of TA in posterior-anterior (PA) and mediolateral (ML) orientations at rest and during muscle activation. Single-pulse TMS measures of motor evoked potential amplitude, in addition to resting and active motor thresholds, were used to index corticospinal excitability, whereas paired-pulse TMS measures of short-interval intracortical inhibition (SICI) and facilitation (SICF), and long-interval intracortical inhibition (LICI), were used to assess excitability of intracortical circuits.

Results

For single-pulse TMS, motor thresholds and test TMS intensity were lower for ML stimulation (all P < 0.05). In a resting muscle, ML TMS produced greater SICI (P < 0.001) and less SICF (both P < 0.05) when compared with PA TMS. In contrast, ML TMS in an active muscle resulted in reduced SICI but increased SICF (both P ≤ 0.001) when compared with PA TMS.

Conclusion

TMS coil orientation and muscle activation influence measurements of intracortical excitability recorded in the tibialis anterior, and are therefore important considerations in TMS studies of lower limb muscles.

Introduction

Transcranial magnetic stimulation (TMS) is a method of non-invasive brain stimulation that can be used to assess corticospinal and intracortical excitability, providing robust measures of excitatory and inhibitory activity within primary motor cortex (M1). TMS over M1 generates a complex descending volley in corticospinal neurons that consists of direct (D) waves, representing direct activation close to the intial axonal segment, and indirect (I) waves that result from trans-synaptic input from intracortical circuits. The D and I-waves of a descending volley summate at the spinal cord to produce a motor evoked potential (MEP) in the target muscle (Ziemann and Rothwell, 2000, Ortu et al., 2008, Di Lazzaro et al., 2012). In addition, paired-pulse TMS is used to quantify intracortical excitability, which reflects the activity of complex inhibitory (GABAergic) and facilitatory (glutamatergic) networks in M1 (Kujirai et al., 1993, Di Lazzaro et al., 1998, Petroff, 2002, Cash et al., 2017). Numerous factors related to the TMS approach that influence measures of corticospinal and intracortical excitability within M1 (e.g. coil type, orientation and TMS intensity) have been identified, but these have largely been established in upper limb muscles. In contrast, much less is known about how these methodological factors influence TMS measures of corticospinal and intracortical excitability in lower limb muscles.

Given their importance in posture, maintenance of balance and locomotion (Joseph, 1985, Kleim and Jones, 2008, Mille et al., 2014) there has been growing interest in assessing M1 characteristics for the neural control of lower limb muscles (Yamaguchi et al., 2012, Hirano et al., 2015, Ward et al., 2016, Tatemoto et al., 2019). However, it is more challenging to activate lower limb muscles with TMS (compared with upper limb muscles) due to a smaller cortical representation that lies deep within the interhemispheric fissure (Allison et al., 1996, Terao et al., 2000). Because of this, previous studies investigating lower limb muscles have used different TMS approaches which lack comparability with data obtained in upper limb muscles. For example, TMS studies on the lower limb have typically used double-cone coils, which can have a greater penetrating depth in the cortex (Deng et al., 2008) and are associated with greater discomfort than more commonly used circular or figure-of-eight coils (Deng et al., 2013, Panyakaew et al., 2016, Fernandez et al., 2018). Furthermore, the unique shape of the double-cone coil makes it challenging to use in orientations other than posterior-to-anterior (PA) or anterior-to-posterior direction (AP) (Deng et al., 2013, Fernandez et al., 2018). This provides a methodological limitation, given the recent evidence that mediolaterally directed (ML) induced current may be a more effective approach for targeting lower limb muscles (Terao et al., 2000, Smith et al., 2017, Kesar et al., 2018). However, the specific direction of TMS stimulation can influence the composition of the corticospinal descending volley, which may affect measurements of intracortical activity (Di Lazzaro et al., 2012, Di Lazzaro and Rothwell, 2014, Opie et al., 2020). Accordingly, the effect of coil orientation on intracortical excitability for control of lower limb muscles is unknown, and is a major focus of the current study.

Another factor that influences measures of corticospinal and intracortical excitability is muscle activation. In general, voluntary contraction increases the excitability of corticospinal and spinal motor neurons to generate a facilitation in the motor evoked potential (MEP) of the target muscle. This decreases the threshold for TMS to generate a response in the muscle, which is why studies in the lower limb usually involve an active muscle (Roy, 2009, Brownstein et al., 2018, Krishnan, 2019). However, muscle activation in the upper limb has been shown to influence characteristics of the TMS-evoked descending volley by increasing the size of all I-waves (Di Lazzaro et al. 1998), which can influence measures of intracortical inhibition (Ridding et al., 1995, Abbruzzese et al., 1999, Fisher et al., 2002) and facilitation (Ilić et al., 2002, Ortu et al., 2008). It is currently unknown how muscle activation influences specific features of intracortical excitability in lower limb muscles, or how it interacts with the effects of TMS current direction that are induced by changing coil orientation.

The purpose of this study was therefore to examine the effect of coil orientation and muscle activation on corticospinal and intracortical excitability of a lower limb muscle. A figure-of-eight TMS coil was used in PA (conventional orientation) and ML (alternative) orientations (see Fig. 1), as PA TMS is more comparable to TMS in upper limb muscles, and ML current flow may produce a lower motor threshold for lower limb muscles (Terao et al., 2000, Smith et al., 2017). The cortical representation to the tibialis anterior muscle was used as it is commonly assessed with TMS, and is functionally relevant for processes like balance and locomotion (Perez et al., 2004, Cacchio et al., 2011, Smith et al., 2017). Based on previous studies (Terao et al., 2000, Smith et al., 2017), it is hypothesised that both the coil orientation and muscle activation will influence measurements of intracortical excitability in a lower limb muscle.