Functional Connectivity of Human Premotor and Motor Cortex Explored with Repetitive Transcranial Magnetic Stimulation
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Connections between the premotor cortex and the primary motor cortex are dense and are important in the visual guidance of arm movements. We have shown previously that it is possible to engage these connections in humans and to measure the net amount of inhibition/facilitation from premotor to motor cortex using single-pulse transcranial magnetic stimulation (TMS). The aim of this study was to test whether premotor activation can affect the excitability of circuits within the primary motor cortex (M1) itself. Repetitive TMS (rTMS), which is known to produce effects that outlast the train at the site of stimulation, was given for 20 min at 1 Hz over premotor, primary motor, and sensory areas of cortex at an intensity of 80% of the active motor threshold for the motor hand area. The excitability of some corticocortical connections in M1 was probed by using paired-pulse testing of intracortical inhibition (ICI) and intracortical facilitation (ICF) with a coil placed over the motor cortex hand area. rTMS over the premotor cortex, but not other areas, changed the time course of the ICI/ICF for up to 1 hr afterward without affecting motor thresholds or motor-evoked potential recruitment. The cortical silent period was also shortened. The implication is that rTMS at a site distant from the motor cortex can change the excitability of circuits intrinsic to the motor cortex.Keywords:
Premotor cortex
Facilitation
Connections between the premotor cortex and the primary motor cortex are dense and are important in the visual guidance of arm movements. We have shown previously that it is possible to engage these connections in humans and to measure the net amount of inhibition/facilitation from premotor to motor cortex using single-pulse transcranial magnetic stimulation (TMS). The aim of this study was to test whether premotor activation can affect the excitability of circuits within the primary motor cortex (M1) itself. Repetitive TMS (rTMS), which is known to produce effects that outlast the train at the site of stimulation, was given for 20 min at 1 Hz over premotor, primary motor, and sensory areas of cortex at an intensity of 80% of the active motor threshold for the motor hand area. The excitability of some corticocortical connections in M1 was probed by using paired-pulse testing of intracortical inhibition (ICI) and intracortical facilitation (ICF) with a coil placed over the motor cortex hand area. rTMS over the premotor cortex, but not other areas, changed the time course of the ICI/ICF for up to 1 hr afterward without affecting motor thresholds or motor-evoked potential recruitment. The cortical silent period was also shortened. The implication is that rTMS at a site distant from the motor cortex can change the excitability of circuits intrinsic to the motor cortex.
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During exercise, changes occur at many sites in the motor pathway, including the muscle fiber, motoneuron, motor cortex, and “upstream” of the motor cortex. Some of the changes result in fatigue, which can be defined as a decrease in ability to produce maximal muscle force voluntarily. Transcranial magnetic stimulation (TMS) over the human motor cortex reveals changes in both motor evoked potentials (MEPs) and the silent period during and after fatiguing voluntary contractions in normal subjects. The relationship of these changes to loss of force or fatigue is unclear. However, during a sustained maximal contraction TMS evokes extra force from the muscle and thus demonstrates the development of suboptimal output from the motor cortex, that is, fatigue at a supraspinal level. In some patients with symptoms of fatigue, the response to TMS after exercise is altered, but the changed MEP behavior is not yet linked to particular symptoms or pathology. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 18–29, 2001
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Temporal interference (TI) could stimulate deep motor cortex and induce movement without affecting the overlying cortex in previous mouse studies. However, there is still lack of evidence on potential TI effects in human studies. To fill this gap, we collected resting-state functional magnetic resonance imaging data on 40 healthy young participants both before and during TI stimulation on the left primary motor cortex (M1). We also chose a widely used simulation approach (tDCS) as a baseline condition. In the stimulation session, participants were randomly allocated to 2 mA TI or tDCS for 20 minutes. We used a seed-based whole brain correlation analysis method to quantify the strength of functional connectivity among different brain regions. Our results showed that both TI and tDCS significantly boosted functional connection strength between M1 and secondary motor cortex (premotor cortex and supplementary motor cortex). This is the first time to demonstrate substantial stimulation effect of TI in the human brain.
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Paired transcranial magnetic stimulation (TMS) has been applied as a probe to test functional connectivity within distinct cortical areas of the motor system. Depending on the intensity of a conditioning stimulus applied to different areas of the cortical motor network both facilitation and inhibition may be detected in the primary motor cortex (M1), ipsilaterally or contralaterally to the site of conditioning stimulation. Civardi (2001) and our group (Koch; unpublished data) reported that conditioning stimuli applied to the dorsal premotor cortex (PMd) may induce distinct effects on ipsilateral M1 depending on the intensity of stimulation. Low conditioning intensities provoked inhibition with a maximum at 90% active motor threshold (AMT) which turned into facilitation when higher intensities (120% AMT and 110% RMT, respectively) were applied.
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The effectiveness of transcranial direct current stimulation (tDCS) placed over the motor hotspot (thought to represent the primary motor cortex (M1)) to modulate motor network excitability is highly variable. The premotor cortex-particularly the dorsal premotor cortex (PMd)-may be a promising alternative target to reliably modulate motor excitability, as it influences motor control across multiple pathways, one independent of M1 and one with direct connections to M1. This double-blind, placebo-controlled preliminary study aimed to differentially excite motor and premotor regions using high-definition tDCS (HD-tDCS) with concurrent functional magnetic resonance imaging (fMRI). HD-tDCS applied over either the motor hotspot or the premotor cortex demonstrated high inter-individual variability in changes on cortical motor excitability. However, HD-tDCS over the premotor cortex led to a higher number of responders and greater changes in local fMRI-based complexity than HD-tDCS over the motor hotspot. Furthermore, an analysis of individual motor hotspot anatomical locations revealed that, in more than half of the participants, the motor hotspot is not located over anatomical M1 boundaries, despite using a canonical definition of the motor hotspot. This heterogeneity in stimulation site may contribute to the variability of tDCS results. Altogether, these preliminary findings provide new considerations to enhance tDCS reliability.
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