Probing the orientation specificity of excitatory and inhibitory circuitries in the primary motor cortex with multi-channel TMS

Background: The electric field orientation is a crucial parameter for optimizing the excitation of neuronal tissue in transcranial magnetic stimulation (TMS). Yet, the effects of stimulus orientation on the short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) paradigms are poorly known, mainly due to significant technical challenges in manipulating the TMS-induced stimulus orientation within milliseconds. Objective: Our aim is to assess the effect of the TMS-induced stimulus orientation on the SICI and ICF paradigms and search for the optimal orientations to maximize the facilitation and suppression of the motor evoked potentials (MEP). Methods: We applied paired-pulse multi-channel TMS in healthy subjects to generate SICI and ICF with conditioning and test pulses in the same, opposite, and perpendicular orientations to each other. The conditioning- and test-stimulus intensities were 80% and 110% of the resting motor threshold, respectively. Results: Both SICI and ICF were significantly affected by the conditioning- and test-stimulus orientation. MEP suppression and facilitation were strongest with both pulses delivered in the same direction. SICI with a 2.5-ms and ICF with a 6.0-ms interstimulus interval (ISI) were more sensitive to changes in stimulus orientation compared with SICI at 0.5- and ICF at 8.0-ms ISIs, respectively. Conclusion: Our findings provide evidence that SICI and ICF at specific ISIs are mediated by distinct mechanisms. Such mechanisms exhibit a preferential orientation depending on the anatomical and morphological arrangement of inhibitory and excitatory neuronal populations. We also demonstrate that the SICI and ICF can be maximized by adjusting the TMS-induced electric field orientation.

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Effect of stimulus orientation and intensity on short-interval intracortical inhibition (SICI) and facilitation (SICF): A multi-channel transcranial magnetic stimulation study

PLoS ONE ◽

10.1371/journal.pone.0257554 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0257554

Author(s):

Sergei Tugin ◽

Victor H. Souza ◽

Maria A. Nazarova ◽

Pavel A. Novikov ◽

Aino E. Tervo ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Short Interval ◽

Intracortical Inhibition ◽

Stimulus Orientation ◽

Electronic Control ◽

Field Orientation ◽

Neuronal Populations ◽

Resting Motor Threshold ◽

Strongly Connected

Besides stimulus intensities and interstimulus intervals (ISI), the electric field (E-field) orientation is known to affect both short-interval intracortical inhibition (SICI) and facilitation (SICF) in paired-pulse transcranial magnetic stimulation (TMS). However, it has yet to be established how distinct orientations of the conditioning (CS) and test stimuli (TS) affect the SICI and SICF generation. With the use of a multi-channel TMS transducer that provides electronic control of the stimulus orientation and intensity, we aimed to investigate how changes in the CS and TS orientation affect the strength of SICI and SICF. We hypothesized that the CS orientation would play a major role for SICF than for SICI, whereas the CS intensity would be more critical for SICI than for SICF. In eight healthy subjects, we tested two ISIs (1.5 and 2.7 ms), two CS and TS orientations (anteromedial (AM) and posteromedial (PM)), and four CS intensities (50, 70, 90, and 110% of the resting motor threshold (RMT)). The TS intensity was fixed at 110% RMT. The intensities were adjusted to the corresponding RMT in the AM and PM orientations. SICI and SICF were observed in all tested CS and TS orientations. SICI depended on the CS intensity in a U-shaped manner in any combination of the CS and TS orientations. With 70% and 90% RMT CS intensities, stronger PM-oriented CS induced stronger inhibition than weaker AM-oriented CS. Similar SICF was observed for any CS orientation. Neither SICI nor SICF depended on the TS orientation. We demonstrated that SICI and SICF could be elicited by the CS perpendicular to the TS, which indicates that these stimuli affected either overlapping or strongly connected neuronal populations. We concluded that SICI is primarily sensitive to the CS intensity and that CS intensity adjustment resulted in similar SICF for different CS orientations.

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Intracortical Inhibition During Volitional Inhibition of Prepared Action

Journal of Neurophysiology ◽

10.1152/jn.01334.2005 ◽

2006 ◽

Vol 95 (6) ◽

pp. 3371-3383 ◽

Cited By ~ 192

Author(s):

James P. Coxon ◽

Cathy M. Stinear ◽

Winston D. Byblow

Keyword(s):

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Short Interval ◽

Intracortical Inhibition ◽

Corticomotor Excitability ◽

Hand Muscles ◽

Cortical Level ◽

A Site ◽

Intrinsic Hand Muscles ◽

Inhibitory Networks

Volitional inhibition is the voluntary prevention of a prepared movement. Here we ask whether primary motor cortex (M1) is a site of convergence of cortical activity associated with movement preparation and volitional inhibition. Volitional inhibition was studied by presenting a stop signal before execution of an anticipated response that requires a key lift to intercept a revolving dial. Motor evoked potentials (MEPs) were elicited in intrinsic hand muscles by transcranial magnetic stimulation (TMS) to assess corticomotor excitability and short interval intracortical inhibition (sICI) during task performance. The closer the stop cue was presented to the anticipated response, the harder it was for subjects to inhibit their response. Corticomotor pathway excitability was temporally modulated during volitional inhibition. Using subthreshold TMS, corticomotor excitability was reduced for Stop trials relative to Go trials from 140 ms after the cue. sICI was significantly greater for Stop trials compared with Go trials at a time that preceded the onset of muscle activity associated with the anticipated response. These results provide evidence that volitional inhibition is exerted at a cortical level and that inhibitory networks within M1 contribute to volitional inhibition of prepared action.

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Event-related desynchronization reflects downregulation of intracortical inhibition in human primary motor cortex

Journal of Neurophysiology ◽

10.1152/jn.01092.2012 ◽

2013 ◽

Vol 110 (5) ◽

pp. 1158-1166 ◽

Cited By ~ 108

Author(s):

Mitsuaki Takemi ◽

Yoshihisa Masakado ◽

Meigen Liu ◽

Junichi Ushiba

Keyword(s):

Motor Cortex ◽

Motor Imagery ◽

Sensorimotor Cortex ◽

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Short Interval ◽

Hand Movement ◽

Intracortical Inhibition ◽

Imagery Task ◽

Event Related Desynchronization

There is increasing interest in electroencephalogram (EEG)-based brain-computer interface (BCI) as a tool for rehabilitation of upper limb motor functions in hemiplegic stroke patients. This type of BCI often exploits mu and beta oscillations in EEG recorded over the sensorimotor areas, and their event-related desynchronization (ERD) following motor imagery is believed to represent increased sensorimotor cortex excitability. However, it remains unclear whether the sensorimotor cortex excitability is actually correlated with ERD. Thus we assessed the association of ERD with primary motor cortex (M1) excitability during motor imagery of right wrist movement. M1 excitability was tested by motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) with transcranial magnetic stimulation (TMS). Twenty healthy participants were recruited. The participants performed 7 s of rest followed by 5 s of motor imagery and received online visual feedback of the ERD magnitude of the contralateral hand M1 while performing the motor imagery task. TMS was applied to the right hand M1 when ERD exceeded predetermined thresholds during motor imagery. MEP amplitudes, SICI, and ICF were recorded from the agonist muscle of the imagined hand movement. Results showed that the large ERD during wrist motor imagery was associated with significantly increased MEP amplitudes and reduced SICI but no significant changes in ICF. Thus ERD magnitude during wrist motor imagery represents M1 excitability. This study provides electrophysiological evidence that a motor imagery task involving ERD may induce changes in corticospinal excitability similar to changes accompanying actual movements.

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Writing's Shadow: Corticospinal Activation during Letter Observation

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00205 ◽

2012 ◽

Vol 24 (5) ◽

pp. 1138-1148 ◽

Cited By ~ 6

Author(s):

Masahiro Nakatsuka ◽

Mohamed Nasreldin Thabit ◽

Satoko Koganemaru ◽

Ippei Nojima ◽

Hidenao Fukuyama ◽

...

Keyword(s):

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Short Interval ◽

Single Pulse ◽

Random Order ◽

Intracortical Inhibition ◽

Corticospinal Excitability ◽

Motor Memory ◽

F Wave ◽

The Right

We can recognize handwritten letters despite the variability among writers. One possible strategy is exploiting the motor memory of orthography. By using TMS, we clarified the excitatory and inhibitory neural circuits of the motor corticospinal pathway that might be activated during the observation of handwritten letters. During experiments, participants looked at the handwritten or printed single letter that appeared in a random order. The excitability of the left and right primary motor cortex (M1) was evaluated by motor-evoked potentials elicited by single-pulse TMS. Short interval intracortical inhibition (SICI) of the left M1 was evaluated using paired-pulse TMS. F waves were measured for the right ulnar nerve. We found significant reduction of corticospinal excitability only for the right hand at 300–400 msec after each letter presentation without significant changes in SICI. This suppression is likely to be of supraspinal origin, because of no significant alteration in F-wave amplitudes. These findings suggest that the recognition of handwritten letters may include the implicit knowledge of “writing” in M1. The M1 activation associated with that process, which has been shown in previous neuroimaging studies, is likely to reflect the active suppression of the corticospinal excitability.

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Corticomotor plasticity and learning of a ballistic thumb training task are diminished in older adults

Journal of Applied Physiology ◽

10.1152/japplphysiol.00443.2009 ◽

2009 ◽

Vol 107 (6) ◽

pp. 1874-1883 ◽

Cited By ~ 101

Author(s):

Nigel C. Rogasch ◽

Tamara J. Dartnall ◽

John Cirillo ◽

Michael A. Nordstrom ◽

John G. Semmler

Keyword(s):

Older Adults ◽

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Short Interval ◽

Intracortical Inhibition ◽

Training Task ◽

Abductor Pollicis Brevis ◽

Corticomotor Excitability ◽

Old Adults ◽

Young Subjects

This study examined changes in corticomotor excitability and plasticity after a thumb abduction training task in young and old adults. Electromyographic (EMG) recordings were obtained from right abductor pollicis brevis (APB, target muscle) and abductor digiti minimi (ADM, control muscle) in 14 young (18–24 yr) and 14 old (61–82 yr) adults. The training task consisted of 300 ballistic abductions of the right thumb to maximize peak thumb abduction acceleration (TAAcc). Transcranial magnetic stimulation (TMS) of the left primary motor cortex was used to assess changes in APB and ADM motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before, immediately after, and 30 min after training. No differences in corticomotor excitability (resting and active TMS thresholds, MEP input-output curves) or SICI were observed in young and old adults before training. Motor training resulted in improvements in peak TAAcc in young (177% improvement, P < 0.001) and old (124%, P = 0.005) subjects, with greater improvements in young subjects ( P = 0.002). Different thumb kinematics were observed during task performance, with increases in APB EMG related to improvements in peak TAAcc in young ( r2 = 0.46, P = 0.008) but not old ( r2 = 0.09, P = 0.3) adults. After training, APB MEPs were 50% larger ( P < 0.001 compared with before) in young subjects, with no change after training in old subjects ( P = 0.49), suggesting reduced use-dependent corticomotor plasticity with advancing age. These changes were specific to APB, because no training-related change in MEP amplitude was observed in ADM. No significant association was observed between change in APB MEP and improvement in TAAcc with training in individual young and old subjects. SICI remained unchanged after training in both groups, suggesting that it was not responsible for the diminished use-dependent corticomotor plasticity for this task in older adults.

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Distributed cortical structural properties contribute to motor cortical excitability and inhibition

10.1101/178301 ◽

2017 ◽

Author(s):

Eran Dayan ◽

Virginia López-Alonso ◽

Sook-Lei Liew ◽

Leonardo G. Cohen

Keyword(s):

Motor Cortex ◽

Structural Properties ◽

Motor Function ◽

Primary Motor Cortex ◽

Cortical Excitability ◽

Motor Evoked Potentials ◽

Short Interval ◽

Intracortical Inhibition ◽

Corticospinal Excitability ◽

Support Vector

AbstractThe link between the local structure of the primary motor cortex and motor function has been well documented. However, motor function relies on a network of interconnected brain regions and the link between the structural properties characterizing these distributed brain networks and motor function remains poorly understood. Here, we examined whether distributed patterns of brain structure, extending beyond the primary motor cortex can help classify two forms of motor function: corticospinal excitability and intracortical inhibition. To this effect, we recorded high-resolution structural magnetic resonance imaging scans in 25 healthy volunteers. To measure corticospinal excitability and inhibition in the same volunteers we recorded motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) and short-interval intracortical inhibition (SICI) in a separate session. Support vector machine (SVM) pattern classification was used to identify distributed multivoxel gray matter areas, which distinguished subjects who had lower and higher MEPs and SICIs. We found that MEP and SICI classification could be predicted based on a widely distributed, largely non-overlapping pattern of voxels in the frontal, parietal, temporal, occipital and cerebellar regions. Thus, structural properties distributed over the brain beyond the primary motor cortex relate to motor function.

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Short-interval intracortical inhibition and facilitation targeting upper and lower limb muscles

Scientific Reports ◽

10.1038/s41598-021-01348-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Natalie Mrachacz-Kersting ◽

Andrew James Thomas Stevenson ◽

Ulf Ziemann

Keyword(s):

Motor Evoked Potentials ◽

Short Interval ◽

Intracortical Inhibition ◽

Human Motor Cortex ◽

Lower Limb Muscles ◽

Resting Motor Threshold ◽

Abductor Digiti Minimi ◽

Human Motor ◽

Interstimulus Intervals ◽

Motor Representations

AbstractTranscranial magnetic stimulation (TMS) can be used to study excitability of corticospinal neurons in human motor cortex. It is currently not fully elucidated if corticospinal neurons in the hand vs. leg representation show the same or different regulation of their excitability by GABAAergic and glutamatergic interneuronal circuitry. Using a paired-pulse TMS protocol we tested short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) in 18 healthy participants. Motor evoked potentials were evoked in one hand (abductor digiti minimi) and one leg muscle (tibialis anterior), with systematic variation of the intensities of the first (S1) and second (S2) pulse between 60 and 140% resting motor threshold (RMT) in 10% steps, at two interstimulus intervals of 1.5 and 2.1 ms. For the hand and leg motor representations and for both interstimulus intervals, SICI occurred if the intensities of S1 < RMT and S2 > RMT, while SICF predominated if S1 = S2 ≤ RMT, or S1 > RMT and S2 < RMT. Findings confirm and extend previous evidence that the regulation of excitability of corticospinal neurons of the hand versus leg representation in human primary cortex through GABAAergic and glutamatergic interneuronal circuits is highly similar, and that corticospinal neurons of both representations are activated by TMS transsynaptically in largely identical ways.

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Are ipsilateral motor evoked potentials subject to intracortical inhibition?

Journal of Neurophysiology ◽

10.1152/jn.01139.2015 ◽

2016 ◽

Vol 115 (3) ◽

pp. 1735-1739

Author(s):

Alana B. McCambridge ◽

James W. Stinear ◽

Winston D. Byblow

Keyword(s):

Evoked Potentials ◽

Primary Motor Cortex ◽

Biceps Brachii ◽

Motor Evoked Potentials ◽

Short Interval ◽

Conditioning Stimulus ◽

Elbow Flexion ◽

Intracortical Inhibition ◽

Motor Tasks ◽

Active Motor

Paired-pulse transcranial magnetic stimulation (TMS) can be used to examine intracortical inhibition in primary motor cortex (M1), termed short-interval intracortical inhibition (SICI). To our knowledge, SICI has only been demonstrated in contralateral motor evoked potentials (MEPs). Ipsilateral MEPs (iMEPs) are assumed to reflect excitability of an uncrossed oligosynaptic pathway, and can sometimes be evoked in proximal upper-limb muscles using high-intensity TMS. We examined whether iMEPs in the biceps brachii (BB) would be suppressed by subthreshold conditioning, therefore demonstrating SICI of iMEPs. TMS was delivered to the dominant M1 to evoke conditioned (C) and nonconditioned (NC) iMEPs in the nondominant BB of healthy participants during weak bilateral elbow flexion. The conditioning stimulus intensities tested were 85%, 100%, and 115% of active motor threshold (AMT), at 2 ms and 4 ms interstimulus intervals (ISI). The iMEP ratio (C/NC) was calculated for each condition to assess the amount of inhibition. Inhibition of iMEPs was present at 2 ms ISI with 100% and 115% AMT (both P < 0.03), mediated by a reduction in persistence and size (all P < 0.05). To our knowledge, this is the first demonstration of SICI of iMEPs. This technique may be useful as a tool to better understand the role of ipsilateral M1 during functional motor tasks.

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Effects of the motor cortical quadripulse transcranial magnetic stimulation (QPS) on the contralateral motor cortex and interhemispheric interactions

Journal of Neurophysiology ◽

10.1152/jn.00515.2013 ◽

2014 ◽

Vol 111 (1) ◽

pp. 26-35 ◽

Cited By ~ 17

Author(s):

Ryosuke Tsutsumi ◽

Ritsuko Hanajima ◽

Yasuo Terao ◽

Yuichiro Shirota ◽

Shinya Ohminami ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Corpus Callosum ◽

Magnetic Stimulation ◽

Motor Evoked Potentials ◽

Short Interval ◽

Long Term Potentiation ◽

Intracortical Inhibition ◽

Motor Threshold ◽

Resting Motor Threshold

Corpus callosum connects the bilateral primary motor cortices (M1s) and plays an important role in motor control. Using the paired-pulse transcranial magnetic stimulation (TMS) paradigm, we can measure interhemispheric inhibition (IHI) and interhemispheric facilitation (IHF) as indexes of the interhemispheric interactions in humans. We investigated how quadripulse transcranial magnetic stimulation (QPS), one form of repetitive TMS (rTMS), on M1 affects the contralateral M1 and the interhemispheric interactions. QPS is able to induce bidirectional plastic changes in M1 depending on the interstimulus intervals (ISIs) of TMS pulses: long-term potentiation (LTP)-like effect by QPS-5 protocol, and long-term depression-like effect by QPS-50, whose numbers indicate the ISI (ms). Twelve healthy subjects were enrolled. We applied QPS over the left M1 and recorded several parameters before and 30 min after QPS. QPS-5, which increased motor-evoked potentials (MEPs) induced by left M1 activation, also increased MEPs induced by right M1 activation. Meanwhile, QPS-50, which decreased MEPs elicited by left M1 activation, did not induce any significant changes in MEPs elicited by right M1 activation. None of the resting motor threshold, active motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, intracortical facilitation, and short-interval intracortical inhibition in right M1 were affected by QPS. IHI and IHF from left to right M1 significantly increased after left M1 QPS-5. The degree of left first dorsal interosseous MEP amplitude change by QPS-5 significantly correlated with the degree of IHF change. We suppose that the LTP-like effect on the contralateral M1 may be produced by some interhemispheric interactions through the corpus callosum.

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Modulation of intracortical inhibition during physically performed and mentally simulated balance tasks

European Journal of Applied Physiology ◽

10.1007/s00421-020-04577-1 ◽

2021 ◽

Vol 121 (5) ◽

pp. 1379-1388

Author(s):

A. Mouthon ◽

J. Ruffieux ◽

W. Taube

Keyword(s):

Motor Evoked Potentials ◽

Action Observation ◽

Short Interval ◽

Intracortical Inhibition ◽

Mental Simulation ◽

Task Execution ◽

Postural Tasks ◽

Execution Condition ◽

The One ◽

Postural Task

Abstract Purpose Action observation (AO) during motor imagery (MI), so-called AO + MI, has been proposed as a new form of non-physical training, but the neural mechanisms involved remains largely unknown. Therefore, this study aimed to explore whether there were similarities in the modulation of short-interval intracortical inhibition (SICI) during execution and mental simulation of postural tasks, and if there was a difference in modulation of SICI between AO + MI and AO alone. Method 21 young adults (mean ± SD = 24 ± 6.3 years) were asked to either passively observe (AO) or imagine while observing (AO + MI) or physically perform a stable and an unstable standing task, while motor evoked potentials and SICI were assessed in the soleus muscle. Result SICI results showed a modulation by condition (F2,40 = 6.42, p = 0.009) with less SICI in the execution condition compared to the AO + MI (p = 0.009) and AO (p = 0.002) condition. Moreover, switching from the stable to the unstable stance condition reduced significantly SICI (F1,20 = 8.34, p = 0.009) during both, physically performed (− 38.5%; p = 0.03) and mentally simulated balance (− 10%, p < 0.001, AO + MI and AO taken together). Conclusion The data demonstrate that SICI is reduced when switching from a stable to a more unstable standing task during both real task execution and mental simulation. Therefore, our results strengthen and further support the existence of similarities between executed and mentally simulated actions by showing that not only corticospinal excitability is similarly modulated but also SICI. This proposes that the activity of the inhibitory cortical network during mental simulation of balance tasks resembles the one during physical postural task execution.

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