The research team, led by M. C. Hall of Monash University together with colleagues including S. Jaberzadeh, recruited nineteen healthy adults, ten men and nine women, with a mean age of 41.8 years. None had neurological, psychological or physical impairments, and none were taking medications. Each volunteer completed a safety screening questionnaire, gave informed consent under the Declaration of Helsinki, and was tested at roughly the same time of day, around ten in the morning, after abstaining from caffeine and alcohol for twenty-four hours. The entire experiment, in which every participant experienced both stimulus directions, fit into a single session of approximately forty minutes, with the order of conditions randomized to guard against fatigue or order effects.

The target muscle was the tibialis anterior, the shin muscle that lifts the foot, recorded through surface electromyography electrodes placed over its belly with a ground electrode on the patella. Participants sat upright in a chair with legs extended and head supported while a figure-of-eight butterfly coil, driven by a MagPro R30 stimulator, delivered pulses over the left motor cortex. The researchers first identified the hotspot, the scalp location roughly one centimetre lateral and posterior to the vertex that produced the largest and most consistent motor evoked potentials across at least five consecutive stimuli. That hotspot was then marked and monitored throughout the session to guarantee that both stimulus directions probed the same patch of cortex.

The two orientations compared were the classic oblique directions used in most motor cortex work: posterior-to-anterior, in which the induced current sweeps from the back of the head toward the front at forty-five degrees to the midline, and anterior-to-posterior, the reverse sweep at one hundred thirty-five degrees. Contemporary biophysical models suggest that stimulus direction does not simply alter the gross flow of current in the brain. Instead, it biases the recruitment of distinct neuronal populations and intracortical networks depending on cortical geometry and the orientation of axons within the motor cortex. Posterior-to-anterior stimulation tends to engage earlier-recruited interneuronal circuits, whereas anterior-to-posterior stimulation more strongly engages later-recruited networks. Because these partially overlapping circuits underpin different excitability measures, the direction of the pulse can, in principle, tilt the balance of what the coil reveals.

Resting motor threshold, the stimulator intensity needed to evoke a reliable response in a resting muscle, was measured with a maximum-likelihood estimation program, the TMS Motor Threshold Assessment Tool, using a criterion of a motor evoked potential above fifty microvolts. The result was strikingly dull: thresholds were almost identical between directions, at 61.16 plus or minus 13.28 percent of maximum stimulator output for anterior-to-posterior and 60.58 plus or minus 11.26 percent for posterior-to-anterior, a difference that was nowhere near statistical significance. The test intensity needed to evoke a standardized baseline response of roughly half a millivolt also did not differ between orientations. In other words, the raw corticospinal output of the leg motor cortex, the direct highway from cortex to spinal cord, appeared indifferent to which way the current was flowing.

The paired-pulse experiments told a more interesting story. In these paradigms, a subthreshold conditioning pulse precedes a suprathreshold test pulse at a defined interval, probing the intracortical circuits that the conditioning pulse activates. Short-interval intracortical inhibition, measured at a three-millisecond interval, is thought to reflect fast-acting inhibition mediated by GABA-A receptors. Intracortical facilitation, measured at ten milliseconds, is believed to involve facilitatory glutamatergic mechanisms, particularly NMDA receptor activity. Long-interval intracortical inhibition, probed here with two suprathreshold pulses separated by one hundred fifty milliseconds, indexes slower inhibition carried by GABA-B receptors. For each measure, thirty paired-pulse trials were recorded per direction, and conditioned responses were expressed as a percentage of the unconditioned test response for the same orientation.

When the team analyzed these trial-level data with a linear mixed-effects model, treating participants as random intercepts to account for the nesting of repeated observations, a weak but statistically significant interaction emerged between stimulus direction and paired-pulse condition. Post hoc analyses traced this interaction to a single measure: intracortical facilitation. Anterior-to-posterior stimulation produced significantly greater facilitation than posterior-to-anterior stimulation, with conditioned responses averaging about 154.85 percent of the test response in the anterior-to-posterior direction against about 144.33 percent in the posterior-to-anterior direction. Short-interval and long-interval inhibition, by contrast, showed no significant differences between directions at all. The GABA-A and GABA-B mediated inhibitory processes of the leg motor cortex appeared essentially blind to pulse direction, while the excitatory facilitatory networks responded differently depending on which way the current swept.

This pattern is the mirror image of several upper-limb findings. In the hand area, studies comparing the same oblique orientations have often reported stronger inhibitory responses, including greater short-interval and long-interval inhibition, with anterior-to-posterior stimulation. The authors suggest that the deeper cortical representation of the leg, its distinct geometry near the interhemispheric fissure, and the greater scalp-to-cortex distance may reduce directional sensitivity in the leg motor cortex, or may bias recruitment toward different intracortical networks than those engaged in the hand area. They are careful to note that paired-pulse TMS cannot isolate specific I-wave components or descending volleys; the findings reflect net intracortical excitability, and interpretations about preferential recruitment of particular interneuronal populations remain indirect, resting on prior literature rather than direct physiological confirmation.

The study has clear limits that the authors acknowledge. Medio-lateral and latero-medial orientations, which some prior lower-limb work has suggested may be optimal for leg stimulation, were not tested, so the conclusions apply only to the two oblique directions compared. Neuronavigation was not used, although consistent hotspot localization procedures were maintained across conditions. Motor evoked potential onset latencies and descending volleys were not directly assessed, and the sample size estimate relied on paired t-test approximations rather than formal mixed-model power calculations, meaning smaller directional effects may have gone undetected. Considerable inter-individual variability in TMS measures, shaped by cortical anatomy, coil-to-cortex distance and corticospinal organization, was not specifically probed.

Even so, the selective directional sensitivity of facilitatory circuits in the leg motor cortex carries practical weight. For researchers using paired-pulse TMS to study the neural control of gait, balance and mobility, or to track plasticity in neurological conditions affecting the lower limbs, the direction of the coil may matter more for excitatory measures than for inhibitory ones, and standardizing orientation across studies could be critical for comparability. The authors point toward future work incorporating MRI-guided neuronavigation, individualized electric field modeling with tools such as SimNIBS, and within-subject comparisons of all four major stimulus directions to clarify how cortical anatomy and field orientation shape recruitment of corticospinal and intracortical networks during lower-limb stimulation. For now, the message is that when it comes to the brain’s control of the legs, which way the current flows may quietly decide what the magnet reveals.

Subject of Research: The effects of transcranial magnetic stimulation coil direction on corticospinal and intracortical excitability of the lower limb motor cortex in healthy adults

Article Title: The effects of TMS stimulus direction on corticospinal and cortico‐cortical excitability of the lower limb in healthy adults

Article References: Hall, M. C., Zoghi, M., Perraton, L., & Jaberzadeh, S. (2026). The effects of TMS stimulus direction on corticospinal and cortico‐cortical excitability of the lower limb in healthy adults. Physiological Reports, 14(20), Article e71144. https://doi.org/10.14814/phy2.71144

Image Credits: AI Generated

DOI: 10.14814/phy2.71144

Keywords: transcranial magnetic stimulation, motor cortex, tibialis anterior, intracortical facilitation, short-interval intracortical inhibition, long-interval intracortical inhibition, resting motor threshold, lower limb, GABA, corticospinal excitability, paired-pulse TMS, Physiological Reports