Low-Frequency Repetitive Transcranial Magnetic Stimulation Targeted to Premotor Cortex Followed by Primary Motor Cortex Modulates Excitability Differently Than Premotor Cortex or Primary Motor Cortex Stimulation Alone
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Premotor cortex
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.
Premotor cortex
Transcranial Direct Current Stimulation
Human brain
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Premotor cortex
Stimulus (psychology)
Pyramidal tracts
Evoked potential
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Studies of use-dependent changes in neural activation have recently focused on the primary motor cortex. To detect the excitability changes in the primary motor cortex after practice in human subjects, motor-evoked potentials by transcranial magnetic stimulation during motor imagery after just 10 sessions of simple index finger abduction were examined. The present results indicate that width of the output map and amplitudes of motor-evoked potential became progressively larger until practice ended. These flexible short-term modulations of human primary motor cortex seem important and could lead to structural changes in the intracortical networks as the skill becomes more learned and automatic, i.e., ‘adaptation’ as one of the neural mechanisms related to motor learning.
Motor Learning
Evoked potential
Motor System
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Premotor cortex
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While experimental studies in the monkey have shown that motor recovery after partial destruction of the hand motor cortex was based on adjacent motor reorganization, functional MRI (fMRI) studies with isolated primary motor cortical stroke have not yet been reported in humans. Based on experimental data, we designed a study to test if recovery after stroke within primary motor cortex (M1) was associated with reorganization within the surrounding motor cortex, i.e. the motor cortex was able to vicariate. Since motor recovery is time-dependent and might be inflected according to the tested task, the delay after stroke and two motor tasks were included in our design. We examined four patients with one ischaemic stroke limited to M1, and four sex- and age-matched healthy controls in a temporally balanced prospective longitudinal fMRI study over three sessions: <20 days, 4 months and 2 years after stroke. The paradigm included two motor tasks, finger tapping (FT) and finger extension (FE). Distinct patterns of motor activation were observed with time for FT and FE. At the first session, FT-related activation was lateralized in the ipsilateral hemisphere while FE-related activation was contralateral, involving bilateral cerebellar regions for both tasks. From 4 months, skilled motor recovery was associated with contralateral dorsal premotor and sensorimotor cortex and ipsilateral cerebellum motor-related activations, leading to lateralized motor patterns for both tasks. For the left recovered hand, FT and FE-related activations within M1 were more dorsal in patients than in controls. This dorsal shift progressively increased over 2 years, reflecting functional reorganization in the motor cortex adjacent to the lesion. In addition, patients showed a reverse representation of FT and FE within M1, corresponding to a greater dorsal shift for FT than for FE. This functional dissociation might reflect the structural subdivision of M1 with two distinct finger motor representations within M1. Recovery of FT, located within the lesioned depth of the rolandic sulcus in controls, might be related to the re-emergence of a new representation in the intact dorsal M1, while FE, located more dorsally, underwent minor reorganization. This is the first fMRI study of humans presenting with isolated M1 stroke comparable with experimental lesions in animals. Despite the small number of patients, our findings showing the re-emergence of a fingers motor task in the intact dorsal M1 instead of in ventral M1 are consistent with ‘vicariation’ models of stroke recovery.
Premotor cortex
Stroke
Supplementary motor area
Finger tapping
Motor System
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Studies of use-dependent changes in neural activation have recently focused on the primary motor cortex. To detect the excitability changes in the primary motor cortex after practice in human subjects, motor-evoked potentials by transcranial magnetic stimulation during motor imagery after just 10 sessions of simple index finger abduction were examined. The present results indicate that width of the output map and amplitudes of motor-evoked potential became progressively larger until practice ended. These flexible short-term modulations of human primary motor cortex seem important and could lead to structural changes in the intracortical networks as the skill becomes more learned and automatic, i.e., 'adaptation' as one of the neural mechanisms related to motor learning.
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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.
Premotor cortex
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Stimulus (psychology)
Motor area
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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.
Premotor cortex
Transcranial Direct Current Stimulation
Supplementary motor area
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Hand muscles
Evoked potential
Hand strength
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Premotor cortex
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