O2-037 Reliability of resting motor threshold, short interval intracortical inhibition and intracortical facilitation determined by adaptive threshold hunting method

Abstract In Parkinson’s disease, striatal dopamine depletion produces profound alterations in the neural activity of the cortico-basal ganglia motor loop, leading to dysfunctional motor output and parkinsonism. A key regulator of motor output is the balance between excitation and inhibition in the primary motor cortex, which can be assessed in humans with transcranial magnetic stimulation techniques. Despite decades of research, the functional state of cortical inhibition in Parkinson’s disease remains uncertain. Towards resolving this issue, we applied paired-pulse transcranial magnetic stimulation protocols in 166 patients with Parkinson’s disease (57 levodopa-naïve, 50 non-dyskinetic, 59 dyskinetic) and 40 healthy controls (age-matched with the levodopa-naïve group). All patients were studied OFF medication. All analyses were performed with fully automatic procedures to avoid confirmation bias, and we systematically considered and excluded several potential confounding factors such as age, gender, resting motor threshold, EMG background activity and amplitude of the motor evoked potential elicited by the single-pulse test stimuli. Our results show that short-interval intracortical inhibition is decreased in Parkinson’s disease compared to controls. This reduction of intracortical inhibition was obtained with relatively low-intensity conditioning stimuli (80% of the resting motor threshold) and was not associated with any significant increase in short-interval intracortical facilitation or intracortical facilitation with the same low-intensity conditioning stimuli, supporting the involvement of cortical inhibitory circuits. Short-interval intracortical inhibition was similarly reduced in levodopa-naïve, non-dyskinetic and dyskinetic patients. Importantly, intracortical inhibition was reduced compared to control subjects also on the less affected side (n = 145), even in de novo drug-naïve patients in whom the less affected side was minimally symptomatic (lateralized Unified Parkinson’s Disease Rating Scale part III = 0 or 1, n = 23). These results suggest that cortical disinhibition is a very early, possibly prodromal feature of Parkinson’s disease.

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Abstract TMP43: Differential Cortical Effect Modulated by Anodal, Cathodal and Bihemispheric Transcranial Direct Current Stimulation (tDCS) in Patients With Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tmp43 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Pratik Y Chhatbar ◽

William DeVries ◽

Emily Grattan ◽

Steven A Kautz ◽

Wuwei Feng

Keyword(s):

Ischemic Stroke ◽

Cortical Excitability ◽

Motor Evoked Potentials ◽

Single Pulse ◽

Intracortical Inhibition ◽

Motor Threshold ◽

Stroke Patients ◽

Intracortical Facilitation ◽

Abductor Pollicis Brevis ◽

Resting Motor Threshold

Introduction: The differential brain modulatory effects across hemispheres from different montages in stroke patients is not well established. We aimed to investigate the cortical excitability on lesional and contra-lesional hemisphere modulated by anodal, cathodal and bihemispheric montage at 4 mA tDCS strengths. Hypothesis: Bihemispheric tDCS montage induces more cortical excitability on the lesional hemisphere. Methods: Eighteen aging stroke patients with unilateral ischemic stroke of 6 or more months and inducible motor evoked potentials (MEP) underwent 3 sessions of 30 minutes 4 mA tDCS combined with occupational therapy. Each session was at least 2 days apart and consisted of one of the 3 different montages: anodal (Anode: lesional C3/C4, Cathode: non-lesional FP1/FP2), cathodal (Anode: lesional FP1/FP2, Cathode: non-lesional C3/C4), or bihemispheric (Anode: lesional C3/C4, Cathode: non-lesional C3/C4). We collected MEP size, short intracortical inhibition (SICI, 3 ms) and intracortical facilitation (ICF, 15 ms) on bilateral abductor pollicis brevis (APB) muscles using single or paired pulse TMS at 5 timepoints (baseline and four post-tDCS 12 minutes apart sessions). Results: All 18 subjects had comparable resting motor threshold (rMT) across 3 montages (see A). Bihemispheric tDCS montage offered significantly larger peak-to-peak MEP responses on the lesioned cortex (ANOVA, F=8.97, P<0.01) but not on the non-lesioned cortex (ANOVA, F=0.86, P=0.42). These differences were apparent in single pulse, SICI and ICF (see B). Conclusion: Our findings support that bihemispheric montage is better suited in post-stroke motor recovery tDCS applications.

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Increase in Short-Interval Intracortical Facilitation of the Motor Cortex after Low-Frequency Repetitive Magnetic Stimulation of the Unaffected Hemisphere in the Subacute Phase after Stroke

Neural Plasticity ◽

10.1155/2015/407320 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 14

Author(s):

Eduardo Arruda Mello ◽

Leonardo G. Cohen ◽

Sarah Monteiro dos Anjos ◽

Juliana Conti ◽

Karina Nocelo F. Andrade ◽

...

Keyword(s):

Motor Cortex ◽

Magnetic Stimulation ◽

Repetitive Transcranial Magnetic Stimulation ◽

Short Interval ◽

Low Frequency ◽

Intracortical Inhibition ◽

Active Group ◽

Intracortical Facilitation ◽

Resting Motor Threshold ◽

Stimulation Of

Low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere (UH-LF-rTMS) in patients with stroke can decrease interhemispheric inhibition from the unaffected to the affected hemisphere and improve hand dexterity and strength of the paretic hand. The objective of this proof-of-principle study was to explore, for the first time, effects of UH-LF-rTMS as add-on therapy to motor rehabilitation on short-term intracortical inhibition (SICI) and intracortical facilitation (ICF) of the motor cortex of the unaffected hemisphere (M1UH) in patients with ischemic stroke. Eighteen patients were randomized to receive, immediately before rehabilitation treatment, either active or sham UH-LF-rTMS, during two weeks. Resting motor threshold (rMT), SICI, and ICF were measured inM1UHbefore the first session and after the last session of treatment. There was a significant increase in ICF in the active group compared to the sham group after treatment, and there was no significant differences in changes in rMT or SICI. ICF is a measure of intracortical synaptic excitability, with a relative contribution of spinal mechanisms. ICF is typically upregulated by glutamatergic agonists and downregulated by gabaergic antagonists. The observed increase in ICF in the active group, in this hypothesis-generating study, may be related toM1UHreorganization induced by UH-LF-rTMS.

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Hyperexcitability and impaired intracortical inhibition in patients with fragile-X syndrome

Translational Psychiatry ◽

10.1038/s41398-019-0650-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Florence Morin-Parent ◽

Camille Champigny ◽

Angelina Lacroix ◽

François Corbin ◽

Jean-François Lepage

Keyword(s):

Fragile X Syndrome ◽

Fragile X ◽

Short Interval ◽

Silent Period ◽

Intracortical Inhibition ◽

Primary Objective ◽

Healthy Controls ◽

Intracortical Facilitation ◽

Cortical Hyperexcitability ◽

Resting Motor Threshold

AbstractFragile-X syndrome (FXS) is characterized by neurological and psychiatric problems symptomatic of cortical hyperexcitability. Recent animal studies identified deficient γ-aminobutyricacid (GABA) inhibition as a key mechanism for hyperexcitability in FXS, but the GABA system remains largely unexplored in humans with the disorder. The primary objective of this study was to assess GABA-mediated inhibition and its relationship with hyperexcitability in patients with FXS. Transcranial magnetic stimulation (TMS) was used to assess cortical and corticospinal inhibitory and excitatory mechanisms in 18 patients with a molecular diagnosis of FXS and 18 healthy controls. GABA-mediated inhibition was measured with short-interval intracortical inhibition (GABAA), long-interval intracortical inhibition (GABAB), and the corticospinal silent period (GABAA+B). Net intracortical facilitation involving glutamate was assessed with intracortical facilitation, and corticospinal excitability was measured with the resting motor threshold. Results showed that FXS patients had significantly reduced short-interval intracortical inhibition, increased long-interval intracortical inhibition, and increased intracortical facilitation compared to healthy controls. In the FXS group, reduced short-interval intracortical inhibition was associated with heightened intracortical facilitation. Taken together, these results suggest that reduced GABAA inhibition is a plausible mechanism underlying cortical hyperexcitability in patients with FXS. These findings closely match those observed in animal models, supporting the translational validity of these markers for clinical research.

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Effect of fatigue-related group III/IV afferent firing on intracortical inhibition and facilitation in hand muscles

Journal of Applied Physiology ◽

10.1152/japplphysiol.00595.2019 ◽

2020 ◽

Vol 128 (1) ◽

pp. 149-158 ◽

Cited By ~ 2

Author(s):

Christopher Latella ◽

Onno van der Groen ◽

Cassio V. Ruas ◽

Janet L. Taylor

Keyword(s):

Short Interval ◽

Intracortical Inhibition ◽

Voluntary Activation ◽

Intracortical Facilitation ◽

Group Iii ◽

Hand Muscles ◽

Resting Motor Threshold ◽

Before And After ◽

Muscle Afferent ◽

Related Group

Fatiguing exercise causes a reduction in motor drive to the muscle. Group III/IV muscle afferent firing is thought to contribute to this process; however, the effect on corticospinal and intracortical networks is poorly understood. In two experiments, participants performed sustained maximal isometric finger abductions of the first dorsal interosseous (FDI) muscle, with postexercise blood flow occlusion (OCC) to maintain the firing of group III/IV afferents or without occlusion (control; CON). Before and after exercise, single- and paired-pulse transcranial magnetic stimulation (TMS) tested motor evoked potentials (MEPs), intracortical facilitation [ICF (12 ms)], and short-interval intracortical inhibition [SICI2 (2 ms), SICI3 (3 ms)]. Ulnar nerve stimulation elicited maximal M waves (MMAX). For experiment 1 ( n = 16 participants), TMS intensities were 70% and 120% of resting motor threshold (RMT) for the conditioning and MEP stimuli, respectively. For experiment 2 ( n = 16 participants), the MEP was maintained at 1 mV before and after exercise and the conditioning stimulus individualized. In experiment 1, MEP/MMAX was reduced after exercise (~48%, P = 0.007) but was not different between conditions. No changes occurred in ICF or SICI. In experiment 2, MEP/MMAX increased (~27%, P = 0.027) and less inhibition (SICI2: ~21%, P = 0.021) occurred after exercise for both conditions, whereas ICF decreased for CON only (~28%, P = 0.006). MEPs and SICI2 were modulated by fatiguing contractions but not by group III/IV afferent firing, whereas sustained afferent firing appeared to counteract postexercise reductions in ICF in FDI. The findings do not support the idea that actions of group III/IV afferents on motor cortical networks contribute to the reduction in voluntary activation observed in other studies. NEW & NOTEWORTHY This is the first study to investigate, in human hand muscles, the action of fatigue-related group III/IV muscle afferent firing on intracortical facilitation and inhibition. In fatigued and nonexercised hand muscles, intracortical inhibition is reduced after exercise but is not modulated differently by the firing of group III/IV afferents. However, facilitation is maintained for the fatigued muscle when group III/IV afferents fire, but these results are unlikely to explain the reduction in voluntary activation observed in other studies.

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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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Effects of water immersion on short- and long-latency afferent inhibition, short-interval intracortical inhibition, and intracortical facilitation

Clinical Neurophysiology ◽

10.1016/j.clinph.2013.04.008 ◽

2013 ◽

Vol 124 (9) ◽

pp. 1846-1852 ◽

Cited By ~ 11

Author(s):

Daisuke Sato ◽

Koya Yamashiro ◽

Takuya Yoshida ◽

Hideaki Onishi ◽

Yoshimitsu Shimoyama ◽

...

Keyword(s):

Water Immersion ◽

Short Interval ◽

Intracortical Inhibition ◽

Intracortical Facilitation ◽

Afferent Inhibition ◽

Long Latency

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FC46.1 Interactions between short interval intracortical facilitation and short interval intracortical inhibition in the human motor cortex

Clinical Neurophysiology ◽

10.1016/j.clinph.2006.06.152 ◽

2006 ◽

Vol 117 ◽

pp. 110

Author(s):

A. Wagle ◽

C. Gunraj ◽

R. Chen

Keyword(s):

Motor Cortex ◽

Short Interval ◽

Intracortical Inhibition ◽

Intracortical Facilitation ◽

Human Motor Cortex ◽

Human Motor

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Effects of short interval intracortical inhibition and intracortical facilitation on short interval intracortical facilitation in human primary motor cortex

The Journal of Physiology ◽

10.1113/jphysiol.2009.181446 ◽

2009 ◽

Vol 587 (23) ◽

pp. 5665-5678 ◽

Cited By ~ 53

Author(s):

Aparna Wagle-Shukla ◽

Zhen Ni ◽

Carolyn A. Gunraj ◽

Nina Bahl ◽

Robert Chen

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Short Interval ◽

Intracortical Inhibition ◽

Intracortical Facilitation

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Cortical dysfunction underlies disability in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458511424308 ◽

2011 ◽

Vol 18 (4) ◽

pp. 425-432 ◽

Cited By ~ 39

Author(s):

Steve Vucic ◽

Therese Burke ◽

Kerry Lenton ◽

Sudarshini Ramanathan ◽

Lavier Gomes ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cortical Excitability ◽

Short Interval ◽

Motor Evoked Potential ◽

Intracortical Inhibition ◽

Progressive Multiple Sclerosis ◽

Conduction Time ◽

Cortical Function ◽

Resting Motor Threshold ◽

Cortical Dysfunction

Background: Gray matter atrophy has been implicated in the development of secondary progressive multiple sclerosis (SPMS). Cortical function may be assessed by transcranial magnetic stimulation (TMS). Determining whether cortical dysfunction was a feature of SPMS could be of pathophysiological significance. Objectives: Consequently, novel paired-pulse threshold tracking TMS techniques were used to assess whether cortical dysfunction was a feature of SPMS. Methods: Cortical excitability studies were undertaken in 15 SPMS, 25 relapsing–remitting MS patients (RRMS) and 66 controls. Results: Short interval intracortical inhibition (SPMS 3.0 ± 2.1%; RRMS 12.8 ± 1.7%, p < 0.01; controls 10.5 ± 0.7%, p < 0.01) and motor evoked potential (MEP) amplitude (SPMS 11.5 ± 2.2%; RRMS 26.3 ± 3.6%, p <0.05; controls 24.7 ± 1.8%, p < 0.01) were reduced in SPMS, while intracortical facilitation (SPMS -5.2 ± 1.9%; RRMS -2.0 ± 1.4, p < 0.05; controls -0.9 ± 0.7, p < 0.01) and resting motor threshold were increased (SPMS 67.5 ± 4.5%; RRMS 56.0 ± 1.5%, p < 0.01; controls 59.0 ± 1.1%, p < 0.001). Further, central motor conduction time was prolonged in SPMS (9.1 ± 1.2 ms, p < 0.001) and RRMS (7.0 ± 0.9 ms, p < 0.05) patients compared with controls (5.5 ± 0.2 ms). The observed changes in cortical function correlated with the Expanded Disability Status Scale. Conclusion: Together, these findings suggest that cortical dysfunction is associated with disability in MS, and documentation of such cortical dysfunction may serve to quantify disease severity in MS.

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