Cortical Inhibition in Symptomatic and Remitted Mania Compared to Healthy Subjects: A Paired-pulse TMS Study

2017 ◽  
Vol 41 (S1) ◽  
pp. S76-S76
Author(s):  
N. Sanjay ◽  
R. Basavaraju ◽  
S. Biradar ◽  
U. Mehta ◽  
M. Kesavan ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Intracortical Inhibition ◽  
Cortical Inhibition ◽  
First Episode ◽  
Future Research ◽  
Motor Threshold ◽  
Gaba A ◽  
Paired Pulse ◽  
Resting Motor Threshold ◽  
First Dorsal Interosseous Muscle

IntroductionCortical inhibition (CI) is a neurophysiological outcome of the interaction between GABA inhibitory interneurons and other excitatory neurons. Transcranial magnetic stimulation (TMS) measures of CI deficits have been documented in both symptomatic and remitted bipolar disorder (BD) suggesting it could be a trait marker. The effects of medications and duration of illness may contribute to these findings.ObjectiveTo study CI in BD.AimsTo compare CI across early-course medication-naive BD-mania, remitted first episode mania (FEM) and healthy subjects (HS).MethodsSymptomatic BD subjects having < 3 episodes, currently in mania and medication-naive (n = 27), remitted FEM (n = 27; YMRS < 12 and HDRS < 8) and 45 HS, matched for age and gender, were investigated. Resting motor threshold (RMT) and 1-millivolt motor threshold (MT1) were estimated from the right first dorsal interosseous muscle. Paired-pulse TMS measures of short (SICI; 3ms) and long interval intracortical inhibition (LICI; 100ms) were acquired. Group differences in measures of CI were examined using ANOVA.ResultsTable 1.ConclusionsSymptomatic mania patients had the highest motor thresholds and the maximum LICI indicating a state of an excessive GABA-B neurotransmitter tone. Remitted mania patients had deficits in SICI indicating reduced GABA-A neurotransmitter tone. Putative changes in GABA-A neurotransmitter system activity with treatment may be investigated in future studies. CI has received less attention in BD as compared to schizophrenia and is a potential avenue for future research in this area.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Large-scale analysis of interindividual variability in single and paired-pulse TMS data: results from the ‘Big TMS Data Collaboration’

2021 ◽  
Author(s):  
Daniel T. Corp ◽  
Hannah G. K. Bereznicki ◽  
Gillian M. Clark ◽  
George J. Youssef ◽  
Peter J. Fried ◽  
...  
Keyword(s):  
Large Scale ◽  
Interindividual Variability ◽  
Single Pulse ◽  
List Type ◽  
Scale Analysis ◽  
Motor Threshold ◽  
Paired Pulse ◽  
Significant Relationships ◽  
Large Scale Analysis ◽  
Resting Motor Threshold

AbstractObjectiveInterindividual variability of single and paired-pulse TMS data has limited the clinical and experimental applicability of these methods. This study brought together over 60 TMS researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability.Methods118 corresponding authors provided deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and pp TMS data.Results687 healthy participant’s TMS data was pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual’s single pulse TMS amplitude. Baseline MEP amplitude, M1 hemisphere, and biphasic AMT significantly predicted SICI response. Baseline MEP amplitude, test stimulus intensity, interstimulus interval, monophasic RMT, monophasic AMT, and biphasic RMT significantly predicted ICF response. Age, M1 hemisphere, and TMS machine significantly predicted motor threshold.ConclusionsThis large-scale analysis has identified a number of factors influencing participants’ responses to single and paired pulse TMS. We provide specific recommendations to increase the standardisation of TMS methods within and across laboratories, thereby minimising interindividual variability in single and pp TMS data.Highlights687 healthy participant’s TMS data was pooled across 35 studiesSignificant relationships between age and resting motor thresholdSignificant relationships between baseline MEP amplitude and SICI/ICF

scholarly journals Measures of Cortical Inhibition by Paired-Pulse Transcranial Magnetic Stimulation in Anesthetized Rats

2011 ◽  
Vol 105 (2) ◽  
pp. 615-624 ◽  
Author(s):  
Andrew M. Vahabzadeh-Hagh ◽  
Paul A. Muller ◽  
Alvaro Pascual-Leone ◽  
Frances E. Jensen ◽  
Alexander Rotenberg
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Motor Evoked Potentials ◽  
Intracortical Inhibition ◽  
Inhibitory Response ◽  
Cortical Inhibition ◽  
Disease Models ◽  
Paired Pulse ◽  
Anesthetized Rats

Paired-pulse transcranial magnetic stimulation (ppTMS) is a noninvasive method to measure cortical inhibition in vivo. Long interpulse interval (50–500 ms) ppTMS (LI-ppTMS) provokes intracortical inhibitory circuits and can reveal pathologically impaired cortical inhibition in disorders such as epilepsy. Adaptation of ppTMS protocols to rodent disease models is highly desirable to facilitate basic and translational research. We previously adapted single-pulse TMS (spTMS) methods to rats, but ppTMS has yet to be applied. Specifically, whether ppTMS elicits an inhibitory response in rodents is unknown. ppTMS in rats also requires anesthesia, a setting under which the preservation of these measures is undetermined. We therefore tested, in anesthetized rats, whether anesthetic choice affects spTMS-motor-evoked potentials (MEPs), LI-ppTMS in rats, as in humans, elicits intracortical inhibition of the MEP, and rat LI-ppTMS inhibition is acutely impaired in a seizure model. Rats were anesthetized with pentobarbital (PB) or ketamine-atropine-xylazine (KAX) and stimulated unilaterally over the motor cortex while recording bilateral brachioradialis MEPs. LI-ppTMS was applied analogous to human long interval intracortical inhibition (LICI) protocols, and acute changes in inhibition were evaluated following injection of the convulsant pentylenetetrazole (PTZ). We find that spTMS-evoked MEPs were reliably present under either anesthetic, and that LI-ppTMS elicits inhibition of the conditioned MEP in rats, similar to human LICI, by as much as 58 ± 12 and 71 ± 11% under PB and KAX anesthesia, respectively. LI-ppTMS inhibition was reduced to as much as 53% of saline controls following PTZ injection, while spTMS-derived measures of corticospinal excitability were unchanged. Our data show that regional inhibition, similar to human LICI, is present in rats, can be elicited under PB or KAX anesthesia, and is reduced following convulsant administration. These results suggest a potential for LI-ppTMS as a biomarker of impaired cortical inhibition in murine disease models.

The Corticospinal Reserve Capacity: Reorganization of Motor Area and Excitability As a Novel Pathophysiological Concept in Cervical Myelopathy

Neurosurgery ◽  
2017 ◽  
Vol 83 (4) ◽  
pp. 810-818 ◽  
Author(s):  
Anna Zdunczyk ◽  
Vera Schwarzer ◽  
Michael Mikhailov ◽  
Brendon Bagley ◽  
Tizian Rosenstock ◽  
...  
Keyword(s):  
Cervical Myelopathy ◽  
Silent Period ◽  
Motor Area ◽  
Cortical Inhibition ◽  
Reserve Capacity ◽  
Motor Threshold ◽  
Recruitment Curve ◽  
Japanese Orthopedic Association ◽  
Canal Stenosis ◽  
Resting Motor Threshold

Abstract BACKGROUND In degenerative cervical myelopathy (DCM), the dynamics of disease progression and the outcome after surgical decompression vary interindividually and do not necessarily correlate with radiological findings. OBJECTIVE To improve diagnostic power in DCM by better characterization of the underlying pathophysiology using navigated transcranial magnetic stimulation (nTMS). METHODS Eighteen patients with DCM due to cervical spinal canal stenosis were examined preoperatively with nTMS. On the basis of the initial Japanese Orthopedic Association (JOA) Score, 2 patient groups were established (JOA ≤12/&gt;12). We determined the resting motor threshold, recruitment curve, cortical silent period, and motor area. Accordingly, 8 healthy subjects were examined. RESULTS Although the resting motor threshold was comparable in both groups (P = .578), the corticospinal excitability estimated by the recruitment curve was reduced in patients (P = .022). In patients with only mild symptoms (JOA &gt; 12), a compensatory higher activation of non-primary motor areas was detected (P &lt; .005). In contrast, patients with severe impairment (JOA ≤ 12) showed a higher cortical inhibition (P &lt; .05) and reduced cortical motor area (P &lt; .05) revealing a functional restriction on the cortical level. CONCLUSION Based on these results, we propose a new concept for functional compensation for DCM on the cortical and spinal level, ie corticospinal reserve capacity. nTMS is a useful tool to noninvasively characterize the pattern of functional impairment and compensatory reorganization in patients suffering from DCM. The change in nTMS parameters might serve as a valuable prognostic factor in these patients in the future.

scholarly journals Clinically significant acute pain disturbs motor cortex intracortical inhibition and facilitation in orthopedic trauma patients: A TMS study

2019 ◽  
Author(s):  
Marianne Jodoin ◽  
Dominique M. Rouleau ◽  
Audrey Bellemare ◽  
Catherine Provost ◽  
Camille Larson-Dupuis ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Severe Pain ◽  
Cortical Excitability ◽  
Intracortical Inhibition ◽  
Cortical Inhibition ◽  
Trauma Patients ◽  
Orthopedic Trauma ◽  
Resting Motor Threshold ◽  
Clinically Significant ◽  
Intracortical Inhibition And Facilitation

AbstractObjectivePrimary motor (M1) cortical excitability alterations are involved in the development and maintenance of chronic pain. Less is known about M1-cortical excitability implications in the acute phase of an orthopedic trauma. This study aims to assess acute M1-cortical excitability in patients with an isolated upper limb fracture (IULF) in relation to pain intensity.MethodsEighty-four (56 IULF patients <14 days post-trauma and 28 healthy controls) performed a single transcranial magnetic stimulation (TMS) session over M1 (resting motor threshold (rMT); short-intracortical inhibition (SICI); intracortical facilitation (ICF); long-interval cortical inhibition (LICI)). IULF patients were divided into two subgroups according to pain intensity (mild versus moderate to severe pain).ResultsReduced SICI and ICF were found in IULF patients with moderate to severe pain, whereas mild pain was not associated with M1 alterations. Age, sex, and time since the accident had no influence on TMS measures.DiscussionThese findings show altered M1 in the context of acute moderate to severe pain, suggesting early signs of altered GABAergic inhibitory and glutamatergic facilitatory activities.

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

Stroke ◽  
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.

scholarly journals M11. ALTERED TRANSCRANIAL MAGNETIC STIMULATION ELECTROENCEPHALOGRAPHIC MARKERS IN SCHIZOPHRENIA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
Daphne Voineskos ◽  
Reza Zomorrodi ◽  
Zafiris Daskalakis
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Healthy Subjects ◽  
Magnetic Stimulation ◽  
Mean Field ◽  
Single Pulse ◽  
Cortical Inhibition ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Inhibitory Neurotransmission ◽  
Left Dlpfc

Abstract Background Cortical inhibition is a neurophysiological process in which cortical gamma-aminobutyric acid (GABA) inhibitory interneurons modulate the activity of pyramidal neurons in the cerebral cortex. Multiple lines of evidence, including neurophysiological and neuropathological, report that individuals with schizophrenia have deficits in cortical inhibition. Combining transcranial magnetic stimulation (TMS) with electroencephalography is a reliable approach to measure inhibitory processes in the cortex. The overall waveform produced by TMS-EEG may index cortical reactivity as a whole and previous investigations have linked the N45 component peak and the N100 component peak with GABA-A and GABA-B inhibitory neurotransmission, respectively. The aim of this study was to stimulate the DLPFC with TMS and examine resultant differences in the TMS-EEG waveform peaks between patients with schizophrenia and healthy subjects. We hypothesized that individuals with schizophrenia will have smaller TMS-evoked potentials, specifically the amplitudes of the N100 and N45 components, those previously related to GABA-ergic inhibition. Methods We applied TMS over the left DLPFC and recorded EEG activity in 48 healthy subjects (mean age: 33.8±5.3) and 46 patients with schizophrenia (mean age: 43.3±6.4). Monophasic TMS pulses were administered using a 7-cm figure-of-8 coil, and two Magstim 200 stimulators connected via a Bistim module. Single pulse TMS was administered over the left DLPFC with 100 total pulses, which were delivered every 5s. Resultant waveforms were extracted and analyzed through custom MATLAB scripts. The TMS-evoked potential waveform was examined through Global Mean Field Amplitude (GMFA) analysis of waveform peaks in each the two groups. Normality of the distribution of each variable was assessed and a Mann Whitney U test was then performed for each variable of interest to assess differences between groups. Results Individuals in the schizophrenia group demonstrated smaller measures of cortical inhibition in the DLPFC. Specifically, smaller amplitudes of the N45 (U=724.00, p=0.004) and N100 peaks (U=831.00, p=0.039), although the overall AUC of the waveform did not differ between groups (U=969.00, p=0.307). Further analysis is underway to examine medication and symptom cluster effects. Discussion These results demonstrate novel findings of deficits in both GABA-A and GABA-B associated measures of cortical inhibition as indexed by single pulse TMS-EEG. This reinforces previous evidence from different research modalities demonstrating overall GABAergic inhibitory deficits in schizophrenia, and specifically provides new support which confirms recent findings of aberrant GABA-Aergic inhibitory neurotransmission in schizophrenia.

scholarly journals Cortical disinhibition in Parkinson’s disease

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3408-3421 ◽  
Author(s):  
Claudia Ammann ◽  
Michele Dileone ◽  
Cristina Pagge ◽  
Valentina Catanzaro ◽  
David Mata-Marín ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Magnetic Stimulation ◽  
Short Interval ◽  
Intracortical Inhibition ◽  
Motor Threshold ◽  
Intracortical Facilitation ◽  
Low Intensity ◽  
Resting Motor Threshold ◽  
Conditioning Stimuli

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.

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

2014 ◽  
Vol 111 (1) ◽  
pp. 26-35 ◽  
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.

Suppression of Corticospinal Excitability During Negative Motor Imagery

2003 ◽  
Vol 90 (4) ◽  
pp. 2303-2309 ◽  
Author(s):  
Young H. Sohn ◽  
Nguyet Dang ◽  
Mark Hallett
Keyword(s):  
Motor Imagery ◽  
Motor Evoked Potentials ◽  
Intracortical Inhibition ◽  
Corticospinal Excitability ◽  
Intracortical Facilitation ◽  
Abductor Pollicis Brevis ◽  
Paired Pulse ◽  
Left Hand ◽  
Resting Motor Threshold ◽  
Conditioning Stimuli

To investigate the effect of negative motor imagery on corticospinal excitability, we performed transcranial magnetic stimulation (TMS) studies in seven healthy subjects during imagination of suppressing movements. Subjects were asked to imagine suppression of TMS-induced twitching movement of their nondominant left hands by attempting to increase the amount of relaxation after receiving an auditory NoGo cue (negative motor imagery), but to imagine squeezing hands after a Go cue (positive motor imagery). Single- and paired-pulse TMS were triggered at 2 s after Go or NoGo cues. Motor-evoked potentials (MEPs) were recorded in the first dorsal interosseus (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles of the left hand. Paired-pulse TMS with subthreshold conditioning stimuli at interstimulus intervals of 2 (short intracortical inhibition) and 15 ms (intracortical facilitation) and that with suprathreshold conditioning stimuli at interstimulus interval of 80 ms (long intracortical inhibition) were performed in both negative motor imagery and control conditions. Compared with the control state (no imagination), MEP amplitudes of FDI (but not APB and ADM) were significantly suppressed in negative motor imagery, but those from all three muscles were unchanged during positive motor imagery. F-wave responses (amplitudes and persistence) were unchanged during both negative and positive motor imagery. During negative motor imagery, resting motor threshold was significantly increased, but short and long intracortical inhibition and intracortical facilitation were unchanged. The present results demonstrate that excitatory corticospinal drive is suppressed during imagination of suppressing movements.

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