Plasticity of motor threshold and motor-evoked potential amplitude – A model of intrinsic and synaptic plasticity in human motor cortex?

2012 ◽  
Vol 5 (4) ◽  
pp. 586-593 ◽  
Author(s):  
Igor Delvendahl ◽  
Nikolai H. Jung ◽  
Nicola G. Kuhnke ◽  
Ulf Ziemann ◽  
Volker Mall
2021 ◽  
pp. 154596832199233
Author(s):  
Brenton Hordacre ◽  
Duncan Austin ◽  
Katlyn E. Brown ◽  
Lynton Graetz ◽  
Isabel Pareés ◽  
...  

Background In preclinical models, behavioral training early after stroke produces larger gains compared with delayed training. The effects are thought to be mediated by increased and widespread reorganization of synaptic connections in the brain. It is viewed as a period of spontaneous biological recovery during which synaptic plasticity is increased. Objective To look for evidence of a similar change in synaptic plasticity in the human brain in the weeks and months after ischemic stroke. Methods We used continuous theta burst stimulation (cTBS) to activate synapses repeatedly in the motor cortex. This initiates early stages of synaptic plasticity that temporarily reduces cortical excitability and motor-evoked potential amplitude. Thus, the greater the effect of cTBS on the motor-evoked potential, the greater the inferred level of synaptic plasticity. Data were collected from separate cohorts (Australia and UK). In each cohort, serial measurements were made in the weeks to months following stroke. Data were obtained for the ipsilesional motor cortex in 31 stroke survivors (Australia, 66.6 ± 17.8 years) over 12 months and the contralesional motor cortex in 29 stroke survivors (UK, 68.2 ± 9.8 years) over 6 months. Results Depression of cortical excitability by cTBS was most prominent shortly after stroke in the contralesional hemisphere and diminished over subsequent sessions ( P = .030). cTBS response did not differ across the 12-month follow-up period in the ipsilesional hemisphere ( P = .903). Conclusions Our results provide the first neurophysiological evidence consistent with a period of enhanced synaptic plasticity in the human brain after stroke. Behavioral training given during this period may be especially effective in supporting poststroke recovery.


2010 ◽  
Vol 103 (1) ◽  
pp. 511-518 ◽  
Author(s):  
R. F. H. Cash ◽  
U. Ziemann ◽  
K. Murray ◽  
G. W. Thickbroom

In human motor cortex transcranial magnetic stimulation (TMS) has been used to identify short-interval intracortical inhibition (SICI) corresponding to γ-aminobutyric acid type A (GABAA) effects and long-interval intracortical inhibition (LICI) and the cortical silent period (SP) corresponding to postsynaptic GABAB effects. Presynaptic GABAB effects, corresponding to disinhibition, can also be identified with TMS and have been shown to be acting during LICI by measuring SICI after a suprathreshold priming stimulus (PS). The duration of disinhibition is not certain and, guided by studies in experimental preparations, we hypothesized that it may be longer-lasting than postsynaptic inhibition, leading to a period of late cortical disinhibition and consequently a net increase in corticospinal excitability. We tested this first by measuring the motor-evoked potential (MEP) to a test stimulus (TS), delivered after a PS at interpulse intervals (IPIs) ≤300 ms that encompassed the period of PS-induced LICI and its aftermath. MEP amplitude was initially decreased, but then increased at IPIs of 190–210 ms, reaching 160 ± 17% of baseline 200 ms after PS ( P < 0.05). SP duration was 181 ± 5 ms. A second experiment established that the onset of the later period of increased excitability correlated with PS intensity ( r2 = 0.99) and with the duration of the SP ( r2 = 0.99). The third and main experiment demonstrated that SICI was significantly reduced in strength at all IPIs ≤220 ms after PS. We conclude that TMS-induced LICI is associated with a period of disinhibition that is at first masked by LICI, but that outlasts LICI and gives rise to a period during which disinhibition predominates and net excitability is raised. Identification of this late period of disinhibition in human motor cortex may provide an opportunity to explore or modulate the behavior of excitatory networks at a time when inhibitory effects are restrained.


Author(s):  
Aysun Soysal ◽  
Ismail Sobe ◽  
Turan Atay ◽  
Aysu Sen ◽  
Baki Arpaci

Objective:To assess the impact of the disease stage and therapy on motor cortical excitability in Parkinson’s disease (PD).Methods:Twenty newly diagnosed and medication-free, early stage patients, 20 late stage patients under antiparkinsonian therapy and 20 normal healthy controls were included. Motor threshold (MT), amplitudes of motor evoked potential (MEP), motor evoked potential amplitude/compound muscle action potential amplitude (MEP/CMAP) ratio, central motor conduction time (CMCT) and cortical silent period (CSP) were measured by stimulation of the motor cortex using a 13.5 cm circular coil and recordings from abductor digiti minimi muscle. Following the first study protocol, early stage patients were given therapy and the same protocol was repeated three months later.Results:Motor threshold was lower; and the MEP/CMAP ratio was higher in early and late stage patients than normals. In early stage patients after proper therapy, the MTs became higher than before therapy, but still remained lower than normals. In late stage patients, the CMCTs were shorter than the early stage patients before therapy and normals, but there was no difference between the early stage patients and normals. In early stage patients after therapy, the CMCT became longer than before therapy and this difference was significant in both late stage patients and normals. Although more prominent in late stage patients, the CSP duration in both PD groups was found shorter than normals. In early stage patients, after therapy, the CSP durations became significantly longer compared with before therapy.Conclusion:These findings suggest that the motor cortical excitability increases in PD because of the impairment of the corticomotoneuronal inhibitory system.


1998 ◽  
Vol 80 (6) ◽  
pp. 2870-2881 ◽  
Author(s):  
Robert Chen ◽  
Alda Tam ◽  
Cathrin Bütefisch ◽  
Brian Corwell ◽  
Ulf Ziemann ◽  
...  

Chen, Robert, Alda Tam, Cathrin Bütefisch, Brian Corwell, Ulf Ziemann, John C. Rothwell, and Leonardo G. Cohen. Intracortical inhibition and facilitation in different representations of the human motor cortex. J. Neurophysiol. 80: 2870–2881, 1998. Intracortical inhibition (ICI) and intracortical facilitation (ICF) of the human motor cortex can be studied with paired transcranial magnetic stimulation (TMS). Plastic changes and some neurological disorders in humans are associated with changes in ICI and ICF. Although well characterized in the hand representation, it is not known if ICI and ICF vary across different body part representations. Therefore we studied ICI and ICF in different motor representations of the human motor cortex. The target muscles were rectus abdominus (RA), biceps brachii (BB), abductor pollicis brevis (APB), quadriceps femoris (QF), and abductor hallucis (AH). For each muscle, we measured the rest and active motor thresholds (MTs), the motor-evoked potential (MEP) stimulus-response curve (MEP recruitment), ICI, and ICF. The effects of different interstimulus intervals (ISIs) were studied with a conditioning stimulus (CS) intensity of 80% active MT. The effects of different CS intensities were studied at ISI of 2 ms for ICI and ISI of 15 ms for ICF. MT was lowest for APB, followed by BB, AH, and QF, and was highest for RA. Except for BB, MEP recruitment was generally steeper for muscles with lower MT. ICI and ICF were present in all the motor representations tested. The stimulus intensity necessary to elicit ICI was consistently lower than that required to elicit ICF, suggesting that they are mediated by separate mechanisms. Despite wide differences in MT and MEP recruitment, the absolute CS intensities (expressed as percentage of the stimulator's output) required to elicit ICI and ICF appear unrelated to MT and MEP recruitment in the different muscles tested. These findings suggest that the intracortical mechanisms for inhibition and facilitation in different motor representations are not related to the strength of corticospinal projections.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Prachaya Srivanitchapoom ◽  
Jung E. Park ◽  
Nivethida Thirugnanasambandam ◽  
Pattamon Panyakaew ◽  
Vesper Fe Marie Ramos ◽  
...  

Introduction.Paired associative stimulation (PAS) is an established technique to investigate synaptic plasticity in the human motor cortex (M1). Classically, to induce long-term depression- (LTD-) or long-term potentiation-like effects in the human M1, studies have used low frequency and long duration trains of PAS. In the present study, we explored an LTD-like effect using very short duration and low frequency ofPAS10 msprotocols in human M1.Methods.Six protocols of low frequencyPAS10 ms(ranging from 0.2 Hz to 1 Hz) were investigated with very short durations of 1 and 2 minutes stimulation. Six healthy volunteers were included in each protocol. We obtained motor-evoked potentials from right abductor pollicis brevis muscle before and after applyingPAS10 msup to 30 minutes. After we foundPAS10 msprotocol which induced an LTD-like effect, we tested that protocol on additional 5 subjects.Results.One-way repeated-measures ANOVA showed that only the group of 1-minute stimulation of 0.25 Hz induced an LTD-like effect. When adding the additional subjects, the effect remained and lasted for 30 minutes.Conclusion.Low frequency and very short duration ofPAS10 mspotentially induced an LTD-like effect in human M1. With further verification, this method might be useful for research relating to synaptic plasticity by reducing the duration of study and minimizing subject discomfort.


2013 ◽  
Vol 109 (1) ◽  
pp. 106-112 ◽  
Author(s):  
R. F. H. Cash ◽  
F. L. Mastaglia ◽  
G. W. Thickbroom

A single transcranial magnetic stimulation (TMS) pulse typically evokes a short series of spikes in corticospinal neurons [known as indirect (I)-waves] which are thought to arise from transynaptic input. Delivering a second pulse at inter-pulse intervals (IPIs) corresponding to the timing of these I-waves leads to a facilitation of the response, and if stimulus pairs are delivered repeatedly, a persistent LTP-like increase in excitability can occur. This has been demonstrated at an IPI of 1.5 ms, which corresponds to the first I-wave interval, in an intervention referred to as ITMS (I-wave TMS), and it has been argued that this may have similarities with timing-dependent plasticity models. Consequently, we hypothesized that if the second stimulus is delivered so as not to coincide with I-wave timing, it should lead to LTD. We performed a crossover study in 10 subjects in which TMS doublets were timed to coincide (1.5-ms IPI, ITMS1.5) or not coincide (2-ms IPI, ITMS2) with I-wave firing. Single pulse motor-evoked potential (MEP) amplitude, resting motor threshold (RMT), and short-interval cortical inhibition (SICI) were measured from the first dorsal interosseous (FDI) muscle. After ITMS1.5 corticomotor excitability was increased by ∼60% for 15 min ( P < 0.05) and returned to baseline by 20 min. Increasing the IPI by just 500 μs to 2 ms reversed the aftereffect, and MEP amplitude was significantly reduced (∼35%, P < 0.05) for 15 min before returning to baseline. This reduction was not associated with an increase in SICI, suggesting a reduction in excitatory transmission rather than an increase in inhibitory efficacy. RMT also remained unchanged, suggesting that these changes were not due to changes in membrane excitability. Amplitude-matching ITMS2 did not modulate excitability. The results are consistent with timing-dependent synaptic LTP/D-like effects and suggest that there are plasticity mechanisms operating in the human motor cortex with a temporal resolution of the order of a few hundreds of microseconds.


2011 ◽  
pp. S107-S112 ◽  
Author(s):  
N. V. ILIĆ ◽  
S. MILANOVIĆ ◽  
J. KRSTIĆ ◽  
Đ. D. BAJEC ◽  
M. GRAJIĆ ◽  
...  

Since recently, it is possible, using noninvasive cortical stimulation, such as the protocol of paired associative stimulation (PAS), to induce the plastic changes in the motor cortex, in humans that mimic Hebb's model of learning. Application of TMS conjugated with peripheral electrical stimulation at strictly coherent temporal manner lead to convergence of inputs in the sensory-motor cortex, with the consequent synaptic potentiation or weakening, if applied repetitively. However, when optimal interstimulus interval (ISI) for induction of LTP-like effects is applied as a single pair, Motor evoked potential (MEP) amplitude inhibition is observed, the paradigm known as short-latency afferent inhibition (SLAI). Aiming to resolve this paradox, PAS protocols were applied, with 200 repetitions of TMS pulses paired with median nerve electrical stimulation, at ISI equal to individual latencies of evoked response of somatosensory cortex (N20) (PASLTP), and at ISI of N20 shortened for 5 msec (PASLTD) – protocols that mimic LTP-like changes in the human motor cortex. MEP amplitudes before, during and after interventions were measured as an indicator based on output signals originating from the motor system. Post-intervention MEP amplitudes following the TMS protocols of PASLTP and PASLTD were facilitated and depressed, respectively, contrary to MEP amplitudes during intervention. During PASLTP MEP amplitudes were significantly decreased in case of PASLTP, while in the case of PASLTD an upward trend was observed. In conclusions, a possible explanation for the seemingly paradoxical effect of PAS can be found in the mechanism of homeostatic modulation of plasticity. Those findings indicate the existence of complex relationships in the development of plasticity induced by stimulation, depending on the level of the previous motor cortex excitability.


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