Selective modulation of intracortical inhibition by low-intensity Theta Burst Stimulation

ObjectiveTheta Burst Stimulation (TBS) is a repetitive transcranial magnetic stimulation paradigm which has effects on both excitatory and inhibitory intracortical pathways when applied at an intensity of 80% of active motor threshold. As intracortical inhibitory pathways have a lower threshold for activation than excitatory pathways, we sought to determine whether it was possible to selectively target cortical inhibitory circuitry by reducing the intensity of TBS to 70% of active motor threshold.MethodsMotor evoked potentials (MEPs), short latency intracortical facilitation (SICF), intracortical facilitation (ICF) and short interval intracortical inhibition (SICI) were measured at baseline, 5–20 and 20–35 min following continuous (cTBS) and intermittent (iTBS) low-intensity TBS in nine healthy subjects.ResultsLow-intensity cTBS significantly reduced SICI 5–20 min following stimulation, whilst having no effect on MEPs, SICF or ICF. Low-intensity iTBS had no effect on SICI, MEPs, SICF or ICF.ConclusionsIt is possible to selectively target intracortical inhibitory networks for modulation by low-intensity TBS, however, responses may critically depend upon the particular paradigm chosen.SignificanceThese findings have important implications for the treatment of neurological disorders where abnormal levels of intracortical inhibition are present, such as Parkinson’s disease and focal hand dystonia and requires further investigation.     

TMS for staging and predicting functional decline in frontotemporal dementia

ObjectiveTo evaluate if transcranial magnetic stimulation (TMS) measures correlate with disease severity and predict functional decline in frontotemporal dementia (FTD) phenotypes.MethodsPaired-pulse TMS was used to investigate the activity of different intracortical circuits in 171 FTD patients (122 bvFTD, 31 avPPA, 18 svPPA) and 74 healthy controls. Pearson’s correlations were used to analyze the association between TMS measures and disease severity, while multiple regression analysis was used to identify the best clinical or neurophysiological measure to predict functional decline at 12 months.ResultsWe observed significant strong correlations between TMS measures [short interval intracortical inhibition-facilitation (SICI-ICF) and long interval intracortical inhibition (LICI)], and disease severity (evaluated with the FTLD-CDR) (all r > 0.5, p < 0.005).SICI-ICF, short interval intracortical facilitation (SICF) and LICI were also significant predictors of functional decline, evaluated as the change in FTLD-CDR scores at 12 months (all p < 0.005), while at the stepwise multiple regression analysis, SICI was the best predictor of disease progression, accounting for 72.5% of the variation in FTLD-CDR scores at 12 months (adjusted R² = 0.72, p < 0.001).ConclusionsThe present study has shown that the dysfunction of inhibitory and facilitatory intracortical circuits, evaluated with TMS, correlates with disease severity and progression, accurately predicting functional decline at 12 months, better than any other investigated marker.     

Transcranial magnetic stimulation modulation of corticospinal excitability by targeting cortical I-waves with biphasic paired-pulses

Background

Transcranial magnetic stimulation (TMS) induced I-wave behavior can be demonstrated at neuronal population level using paired-pulses and by observing short-interval cortical facilitation (SICF). Advancements in stimulator technology have made it possible to apply biphasic paired-pulses to induce SICF.

An acute bout of exercise modulates both intracortical and interhemispheric excitability

Primary motor cortex (M1) excitability is modulated following a single session of cycling exercise. Specifically, short‐interval intracortical inhibition and intracortical facilitation are altered following a session of cycling, suggesting that exercise affects the excitability of varied cortical circuits. Yet we do not know whether a session of exercise also impacts the excitability of interhemispheric circuits between, and other intracortical circuits within, M1. Here we present two experiments designed to address this gap in knowledge. In experiment 1, single and paired pulse transcranial magnetic stimulation (TMS) were used to measure intracortical circuits including, short‐interval intracortical facilitation (SICF) tested at 1.1, 1.5, 2.7, 3.1 and 4.5 ms interstimulus intervals (ISIs), contralateral silent period (CSP) and interhemispheric interactions by measuring transcallosal inhibition (TCI) recorded from the abductor pollicus brevis muscles. All circuits were assessed bilaterally pre and two time points post (immediately, 30 min) moderate intensity lower limb cycling. SICF was enhanced in the left hemisphere after exercise at the 1.5 ms ISI. Also, CSP was shortened and TCI decreased bilaterally after exercise. In Experiment 2, corticospinal and spinal excitability were tested before and after exercise to investigate the locus of the effects found in Experiment 1. Exercise did not impact motor‐evoked potential recruitment curves, Hoffman reflex or V‐wave amplitudes. These results suggest that a session of exercise decreases intracortical and interhemispheric inhibition and increases facilitation in multiple circuits within M1, without concurrently altering spinal excitability. These findings have implications for developing exercise strategies designed to potentiate M1 plasticity and skill learning in healthy and clinical populations.     

Threshold tracking primary motor cortex inhibition: the influence of current direction

Paired‐pulse transcranial magnetic stimulation (TMS) can be used to probe inhibitory activity in primary motor cortex (M1). Recruitment of descending volleys with TMS depends on the induced current direction in M1. Anterior‐posterior (AP) stimulation preferentially activates late indirect‐ (I‐) waves that are most susceptible to paired‐pulse TMS. Threshold tracking TMS can assess intracortical inhibition; however, previous studies have only used a current direction that preferentially recruits early I‐waves [posterior‐anterior (PA)]. Our objective was to examine intracortical inhibition with threshold tracking TMS designed to preferentially recruit early vs. late I‐waves with PA and AP stimulation respectively. Electromyographic recordings were obtained from the right first dorsal interosseous muscle of 15 participants (21–50 years). Motor evoked potentials elicited by TMS over left M1 were recorded for PA, AP and lateromedial (LM) induced currents, with I‐wave recruitment calculated as the onset latency difference between PA‐LM and AP‐LM. Short‐ and long‐interval intracortical inhibition (SICI and LICI) were examined across a range of conditioning stimulus intensities and interstimulus intervals (3 and 100–260 ms) with threshold tracking TMS for PA and AP stimulation. SICI and LICI were greater for AP compared with PA current direction using threshold tracking. In addition, the efficacy of late I‐wave recruitment was associated with the extent of SICI for AP but not PA stimulation, and was not associated with LICI. These findings indicate that threshold tracking with an AP‐induced current provides a more robust and sensitive measure of M1 intracortical inhibition than PA.     

Influence of Waveform and Current Direction on Short-Interval Intracortical Facilitation: A Paired-Pulse TMS Study

BackgroundTranscranial magnetic stimulation (TMS) of the human primary motor hand area (M1-HAND) can produce multiple descending volleys in fast-conducting corticospinal neurons, especially so-called indirect waves (I-waves) resulting from trans-synaptic excitation. Facilitatory interaction between these I-waves can be studied non-invasively using a paired-pulse paradigm referred to as short-interval intracortical facilitation (SICF).Objective/hypothesisWe examined whether SICF depends on waveform and current direction of the TMS pulses.MethodsIn young healthy volunteers, we applied single- and paired-pulse TMS to M1-HAND. We probed SICF by pairs of monophasic or half-sine pulses at suprathreshold stimulation intensity and inter-stimulus intervals (ISIs) between 1.0 and 5.0 ms. For monophasic paired-pulse stimulation, both pulses had either a posterior–anterior (PA) or anterior–posterior (AP) current direction (AP–AP or PA–PA), whereas current direction was reversed between first and second pulse for half-sine paired-pulse stimulation (PA–AP and AP–PA).ResultsMonophasic AP–AP stimulation resulted in stronger early SICF at 1.4 ms relative to late SICF at 2.8 and 4.4 ms, whereas monophasic PA–PA stimulation produced SICF of comparable size at all three peaks. With half-sine stimulation the third SICF peak was reduced for PA–AP current orientation compared with AP–PA.ConclusionSICF elicited using monophasic as well as half-sine pulses is affected by current direction at clearly suprathreshold intensities. The impact of current orientation is stronger for monophasic compared with half-sine pulses. The direction-specific effect of paired-pulse TMS on the strength of early versus late SICF shows that different cortical circuits mediate early and late SICF.     

Parietal transcranial direct current stimulation modulates primary motor cortex excitability

The posterior parietal cortex is part of the cortical network involved in motor learning and is structurally and functionally connected with the primary motor cortex (M1). Neuroplastic alterations of neuronal connectivity might be an important basis for learning processes. These have however not been explored for parieto‐motor connections in humans by transcranial direct current stimulation (tDCS). Exploring tDCS effects on parieto‐motor cortical connectivity might be functionally relevant, because tDCS has been shown to improve motor learning. We aimed to explore plastic alterations of parieto‐motor cortical connections by tDCS in healthy humans. We measured neuroplastic changes of corticospinal excitability via motor evoked potentials (MEP) elicited by single‐pulse transcranial magnetic stimulation (TMS) before and after tDCS over the left posterior parietal cortex (P3), and 3 cm posterior or lateral to P3, to explore the spatial specificity of the effects. Furthermore, short‐interval intracortical inhibition/intracortical facilitation (SICI/ICF) over M1, and parieto‐motor cortical connectivity were obtained before and after P3 tDCS. The results show polarity‐dependent M1 excitability alterations primarily after P3 tDCS. Single‐pulse TMS‐elicited MEPs, M1 SICI/ICF at 5 and 7 ms and 10 and 15 ms interstimulus intervals (ISIs), and parieto‐motor connectivity at 10 and 15 ms ISIs were all enhanced by anodal stimulation. Single pulse‐TMS‐elicited MEPs, and parieto‐motor connectivity at 10 and 15 ms ISIs were reduced by cathodal tDCS. The respective corticospinal excitability alterations lasted for at least 120 min after stimulation. These results show an effect of remote stimulation of parietal areas on M1 excitability. The spatial specificity of the effects and the impact on parietal cortex–motor cortex connections suggest a relevant connectivity‐driven effect.     

GABA-ergic tone hypothesis in hepatic encephalopathy – Revisited

ObjectiveThe GABA hypothesis of hepatic encephalopathy (HE) proposes an increased cerebral GABA-ergic tone in HE but has not been investigated in vivo in HE-patients yet. Cortical GABA-ergic and glutamatergic neurotransmission in HE-patients were evaluated using transcranial magnetic stimulation.MethodsTwenty-one patients with HE grade 1 and 2 and age matched controls participated in the study. GABA-ergic (short- and long-interval intracortical inhibition (SICI and LICI)) and glutamatergic (intracortical and short-interval intracortical facilitation (ICF and SICF)) excitability of the primary motor cortex (M1) and global corticospinal excitability (motor threshold, motor evoked potential recruitment curve (MEP-RC) were compared between the groups. SICI and ICF were correlated to the critical flicker frequency (CFF) as measure for disease severity.ResultsIn HE-patients, the slope of MEP-RC was significantly shallower compared to healthy controls. SICI was significantly reduced in patients with HE grade 2 compared to healthy controls. In HE-patients, SICI and ICF was significantly correlated to CFF.ConclusionAlthough global corticospinal excitability was reduced in HE-patients, GABA-ergic inhibition was reduced in M1 depending on HE severity. Moreover CFF related alteration of GABAergic and glutamatergic neurotransmission in patients with HE could support the notion of a severity dependent alteration of cortical excitability.SignificanceThe decrease of cortical GABA-ergic tone challenges the classical GABA hypothesis in HE.     

Impaired motor cortical facilitatory-inhibitory circuit interaction in Parkinson’s disease

ObjectiveMotor cortical (M1) inhibition and facilitation can be studied with short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF). These circuits are altered in Parkinson’s disease (PD). The sensorimotor measure short latency afferent inhibition (SAI) is possibly altered in PD. The aim was to determine if the manner in which these circuits interact with each other is abnormal in PD.MethodsFifteen PD patients were studied at rest in ON and OFF medication states, and were compared to 16 age-matched controls. A triple-stimulus transcranial magnetic stimulation paradigm was used to elicit a circuit of interest in the presence of another circuit.ResultsSICF was increased in PD OFF and PD ON conditions compared to controls. SICI facilitated SICF in controls and PD ON, but not in PD OFF. SICF in the presence of SICI negatively correlated with UPDRS-III scores in OFF and ON medication conditions. SAI showed similar inhibition of SICI in controls, PD OFF and PD ON conditions.ConclusionsThe facilitatory effect of SICI on SICF is absent in PD OFF, but is restored with dopaminergic medication.SignificanceImpaired interaction between M1 circuits is a pathophysiological feature of PD.     

Modulation of I-Wave Generating Pathways With Repetitive Paired-Pulse Transcranial Magnetic Stimulation: A Transcranial Magnetic Stimulation–Electroencephalography Study

ObjectivesRepetitive paired-pulse transcranial magnetic stimulation (iTMS) at indirect (I) wave intervals increases motor-evoked potentials (MEPs) produced by transcranial magnetic stimulation (TMS) to primary motor cortex (M1). However, the effects of iTMS at early and late intervals on the plasticity of specific I-wave circuits remain unclear. This study therefore aimed to assess how the timing of iTMS influences intracortical excitability within early and late I-wave circuits. To investigate the cortical effects of iTMS more directly, changes due to the intervention were also assessed using combined TMS-electroencephalography (EEG).Material and MethodsEighteen young adults (aged 24.6 ± 4.2 years) participated in four sessions in which iTMS targeting early (1.5-millisecond interval; iTMS_1.5) or late (4.0-millisecond interval; iTMS_4.0) I-waves was applied over M1. Neuroplasticity was assessed using both posterior-to-anterior (PA) and anterior-to-posterior (AP) stimulus directions to record MEPs and TMS-evoked EEG potentials (TEPs) before and after iTMS. Short-interval intracortical facilitation (SICF) at interstimulus intervals of 1.5 and 4.0 milliseconds was also used to index I-wave activity.ResultsMEP amplitude was increased after iTMS (p < 0.01), and this was greater for PA responses (p < 0.01) but not different between iTMS intervals (p = 0.9). Irrespective of iTMS interval and coil current, SICF was facilitated after the intervention (p < 0.01). Although the N45 produced by AP stimulation was decreased by iTMS_1.5 (p = 0.04), no other changes in TEP amplitude were observed.ConclusionsThe timing of iTMS failed to influence which I-wave circuits were potentiated by the intervention. In contrast, decreases in the N45 suggest that the neuroplastic effects of iTMS may include disinhibition of intracortical inhibitory processes.     

The effect of acute and chronic nicotine consumption on intra-cortical inhibition and facilitation: A transcranial magnetic stimulation study

ObjectiveThe aim of the present study was to explore the impact of acute and chronic nicotine consumption on measures of intracortical inhibition and facilitation.MethodsThis study involved 50 chronic heavy cigarette smokers and 40 healthy subjects matched for age, sex and educational level, with no history of chronic nicotine intake. Intracortical inhibition and facilitation were assessed using transcranial magnetic stimulation (TMS) measures of motor threshold (MT), short- and long-interval intra-cortical inhibition (SICI, LICI), cortical silent period (CSP) and intra-cortical facilitation (ICF). Basal serum levels of cotinine were measured in the healthy group and at ½ and 2 h after smoking a single cigarette in the chronic smokers.ResultsThere was enhanced SICI and reduced ICF in smokers (independent of time after smoking) compared with non-smokers. The former suggests a chronic effect of increased nicotine levels on GABA-A neurotransmission whereas the latter suggests an additional effect on glutamatergic transmission. There were no significant differences between smokers and non-smokers in other TMS parameters. There was a significant negative correlation between cotinine levels at ½ h after smoking and SICI at 3 ms ISI (P < 0.001). There were no significant differences in any of the neurophysiological measures between smokers at ½ h versus 2 h after smoking a single cigarette.ConclusionChronic nicotine consumption enhances SICI, and reduces ICF, supporting the hypothesis that nicotine acts as a neuromodulator of GABA-A and glutamate neurotransmission.     

Long-lasting effects of transcranial static magnetic field stimulation on motor cortex excitability

Background

Transcranial static magnetic field stimulation (tSMS) was recently added to the family of inhibitory non-invasive brain stimulation techniques. However, the application of tSMS for 10–20?min over the motor cortex (M1) induces only short-lasting effects that revert within few minutes.

Short-interval intracortical inhibition as a function of inter-stimulus interval: Three methods compared

BackgroundShort-interval intracortical inhibition (SICI), as measured by threshold-tracking as a function of inter-stimulus interval (ISI), has been proposed as a useful biomarker for amyotrophic lateral sclerosis (ALS), but its relationship to conventional amplitude measurements has not been established.MethodsSerial tracking of SICI at increasing ISIs from 1 to 7 ms (T-SICIs) was compared in 50 healthy control subjects with the same ISIs tracked in parallel (T-SICIp), and with conventional amplitude measurements (A-SICI). For T-SICIp and A-SICI, pairs of conditioning and test stimuli with different ISIs were pseudo-randomised and interspersed with test-alone stimuli given at regular intervals. Thresholds were estimated by regression of log peak-to-peak amplitude on stimulus.ResultsT-SICIp and A-SICI were closely related: a ten-fold reduction in amplitude corresponding to an approximately 18% increase in threshold. Threshold increases were greater for T-SICIs than for T-SICIp at 3.5–5 ms (P < 0.001). This divergence depended on the initial settings and whether ISIs were progressively increased or decreased, and was attributed to the limitations of the serial tracking protocol. SICI variability between subjects was greatest for T-SICIs estimates and least for A-SICI, and only A-SICI estimates revealed a significant decline in inhibition with age.ConclusionsThe serial tracking protocol did not accurately show the dependence of inhibition on ISI. Randomising ISIs gives corresponding SICI measures, whether tracking thresholds or measuring amplitude measurements. SICI variability suggested that A-SICI measurements may be the most sensitive to loss of inhibition.     

Conditioning the Cortical Silent Period with Paired Transcranial Magnetic Stimulation

BackgroundA single supra-threshold pulse of transcranial magnetic stimulation (TMS) over human motor cortex elicits multiple descending volleys (I-waves) that generate a motor evoked potential (MEP) followed by a period of electromyographic silence in the tonically contracted target muscle (silent period; SP). A sub-threshold conditioning stimulus (CS) delivered at inter-pulse intervals (IPIs) of 1-5 ms after a supra-threshold test stimulus (TS) conditions I-waves elicited by TS and can increase MEP amplitude (short-interval intracortical facilitation; SICF), however its effect on the SP remains unknown.ObjectiveWe investigated whether it is possible to modulate the SP resulting from a TS by delivering a sub-threshold CS 1–5 ms later.MethodsPaired-pulse TMS was delivered while subjects performed slight contraction of the first dorsal interosseous muscle. SICF and SP duration were measured at each IPI and compared to amplitude-matched MEPs evoked by single-pulse TMS.ResultsPaired stimulation at IPI 2–5 ms prolonged the SP by 21 ± 3% (P < 0.001) but had no effect on MEP amplitude. At shorter IPIs the CS increased MEP amplitude (by 170 ± 31%), but the SP was not prolonged when compared to an amplitude-matched single-pulse stimulus.ConclusionThe SP can be modified by a CS applied during the early phase of its genesis. We suggest that this is in keeping with an early GABA_A contribution to the SP, and it is possible that this new conditioning paradigm may offer another means for probing the excitability of cortical inhibitory networks in human motor cortex.     

Age-related changes in late synaptic inputs to corticospinal neurons and their functional significance: A paired-pulse TMS study

BackgroundRecent work suggests that the function of intracortical interneurons activated by transcranial magnetic stimulation (TMS) is modified in older adults, with the circuits generating short-interval intracortical facilitation (SICF) at longer intervals appearing to be particularly affected.ObjectiveTo use SICF to quantify age-related changes in the excitability and recruitment of late synaptic inputs to corticospinal neurons, and investigate if changes within these circuits contribute to altered motor performance in older adults.MethodsSICF was recorded with 3 different conditioning intensities in 23 young (23.0 ± 4.2 years) and 21 older (67.1 ± 1.1 years) adults. These measures were performed with conventional (posterior-anterior, PA) and reverse (anterior-posterior, AP) current directions using interstimulus intervals targeting late synaptic inputs to corticospinal neurons (3.5–5.3 ms).ResultsPeak SICF recorded with a PA current (SICF_PA) was reduced in older adults (P < 0.0001), and occurred at a longer latency (P < 0.05). Furthermore, there was reduced recruitment of SICF_PA in older adults (P < 0.0001), but this did not interact with the age-related shift in SICF_PA (P = 0.2). In addition, reduced performance on the Purdue pegboard was predicted by increased SICF_PA (P < 0.04) occurring at longer latencies (P < 0.04) in old but not young adults. For SICF recorded with an AP current (SICF_AP), facilitation was again reduced at longer latencies in older adults (P < 0.0001), but recruitment was not different between groups (P = 0.7) and was unrelated to motor function.ConclusionThese results suggest that there are age-related changes in late synaptic inputs to corticospinal neurons and that these changes influence fine motor performance.     

Normal cortical excitability in Myoclonus-Dystonia — A TMS study

Objective

The aim of the present study is to investigate cortical excitability in patients with DYT 11 positive Myoclonus-Dystonia (M-D), using transcranial magnetic stimulation (TMS).

Methods

Silent period, motor evoked potential (MEP) recruitment curve, short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short interval intracortical facilitation (SICF), with short interstimulus intervals (ISIs) ranging from 1.2 to 3.2 ms, were studied in 15 DYT 11-positive M–D patients and their matched controls. In four patients and matched controls peripheral double pulse electrical nerve stimulation was performed.

Results

All TMS parameters of cortical excitability were normal compared to healthy controls. In the SICF protocol we observed more variable and polyphasic MEPs in M–D patients. Cross-covariance analysis of MEP area revealed a significant correlation difference at ISI 2.2 and 2.8 ms. This increased variability was not seen in other TMS protocols or with peripheral nerve stimulation.

Conclusions

In contrast with other types of dystonia, no changes in cortical excitability were found in DYT 11 patients. Our findings suggest that M–D is both clinically and pathophysiologically a separate entity from other dystonic disorders. Polyphasic MEPs during the SICF protocol in M–D patients could reflect central neuron membrane instability. Application of the SICF protocol in other patient groups has to prove its value in movement disorders.     

Short interval intracortical facilitation correlates with the degree of disability in multiple sclerosis

BackgroundThe Expanded Disability Status Scale (EDSS) is the most widely used measure of disability in MS, however because of its limitations surrogate markers of clinical disability progression are of high interest. Transcranial magnetic stimulation (TMS) measures of demyelination and cortical excitability correlate with disability levels in MS.ObjectiveAim of this study was testing whether paired pulse (pp) TMS represents a reliable surrogate marker to measure clinical disability in MS.MethodsppTMS measures of intracortical synaptic transmission such as short interval intracortical inhibition (SICI), long interval intracortical inhibition (LICI), short interval intracortical facilitation (SICF) and intracortical facilitation (ICF) were collected from 74 patients affected by MS. Correlation of EDSS scores with ppTMS measures was analyzed.ResultsEDSS scores correlated with patient’s age, disease duration, Motor Evoked Potentials latency and thresholds and SICF measures but not with age of onset, SICI, ICF and LICI.ConclusionsThese findings support a possible use of SICF and MEP latency as surrogate markers of disability in MS. Further research is warranted to determine the role of SICF in the follow up of disease progression and to validate its use as an endpoint in multiple sclerosis clinical trials.     

Increased motor cortical excitability after whole-hand electrical stimulation: A TMS study

ObjectiveTo examine the neuromodulatory effect of whole-hand mesh-glove (MG) stimulation on motor cortical pathways, we explored motor cortical excitability before and after suprathreshold whole-hand MG stimulation using transcranial magnetic stimulation (TMS).MethodsTwenty-eight healthy volunteers (14 controls) were studied at baseline, immediately post and 1 h post-MG stimulation for 30 min. Motor thresholds (MTs), motor evoked potentials (MEPs) recruitment curve, short intracortical inhibition (SICI) and intracortical facilitation (ICF) after paired magnetic stimuli were evaluated.ResultsAfter MG stimulation the MTs were significantly reduced and slope of MEP recruitment curve significantly increased; furthermore, the stimulation led to a sustained decrease of SICI and increase of ICF in the contralateral motor cortex. These effects lasted for at least 60 min and were stronger 1 h post-stimulation compared with testing immediately after stimulation. A sham group did not show any differences before and after MG stimulation.ConclusionsWe provide a first demonstration that MG whole-hand stimulation induces increases in motor cortical excitability lasting at least 1 h. Both the strength of the corticospinal projections and the inhibitory and facilitatory intracortical mechanisms are involved. Synaptic modifications such as long-term potentiation mechanisms may underlie this stimulation-induced cortical plasticity changes.SignificancePresent results prove the MG stimulation to be a promising tool in neurorehabilitation.     

Neuroplastic Modulation of Inhibitory Motor Cortical Networks by Spaced Theta Burst Stimulation Protocols

BackgroundContinuous theta burst stimulation (cTBS) suppresses the excitability of motor networks responsible for generating motor evoked potentials (MEPs), and may also modulates the excitability of inhibitory motor networks. However, its effects on intracortical inhibition are modest in comparison to the effects on MEPs. The repeated, spaced, application of cTBS protocols results in more MEP suppression than seen with a single cTBS protocol, but whether this approach is also effective at modulating intracortical inhibition has not been tested.ObjectiveTo determine whether the paired application of cTBS effectively modulates the excitability of intracortical inhibitory motor networks.MethodsSingle and paired-pulse transcranial magnetic stimulation (TMS) were used to assess resting motor threshold (RMT), MEP amplitude, short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI) before and during two time periods (0–10 and 30–40 min) following application of either a single or paired cTBS protocols.ResultsBoth the single and paired cTBS conditions induced a significant reduction in both MEP amplitudes and the level of SICI. While paired cTBS produced a significantly greater MEP suppression than single cTBS, the effects on SICI were similar. Neither single nor paired cTBS had an effect on RMT or LICI.ConclusionsAlthough the repeated application of cTBS protocols may be effective for enhancing modulation of the MEP-generating excitatory motor networks, these findings suggest that this approach offers little advantage when targeting intracortical inhibitory networks.     

Carbamazepine reduces short-interval interhemispheric inhibition in healthy humans

ObjectiveWe sought to elucidate the influence of centrally active drugs on interhemispheric inhibition (IHI) between primary motor cortices in healthy humans.MethodsWe therefore studied IHI before and 2 h after intake of a single oral dose of carbamazepine, dextrometorphane, lorazepam, or placebo and compared it with the well known results for short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Drugs were tested in separate sessions and in random order.ResultsWhile SICI and ICF were not altered by carbamazepine, IHI was reduced at the interstimulus interval of 8 ms. Dextrometorphane tended to enhance SICI and to reduce ICF and had no effect on IHI. Lorazepam reduced ICF as expected and enhanced IHI at the long intervals of 50 and 80 ms. A moderate trend for interhemispheric facilitation was inconsistently observed at the interval 2 ms and blocked by carbamazepine. In addition, carbamazepine increased the motor threshold.ConclusionsWe conclude that circuits mediating short interstimulus intervals of IHI are susceptible to sodium channel blockade.SignificanceThe results increase our knowledge of interhemispheric transmission.