Modulation of short- and long-interval intracortical inhibition with increasing motor evoked potential amplitude in a human hand muscle

ObjectiveThe aim of the current study was to investigate the effect of increasing test motor evoked potential (MEP) amplitude on short- (SICI) and long-interval intracortical inhibition (LICI) at rest and during activation of the first dorsal interosseous (FDI) muscle.MethodsIn 22 young subjects, a conditioning-test transcranial magnetic stimulation (TMS) paradigm was used to assess SICI and LICI at 5 different test TMS intensities (110–150% motor threshold) in resting and active FDI. In 9 additional subjects, SICI and LICI data were quantified when the test MEP amplitude represented specific proportions of the maximal compound muscle action potential (M_max) in each subject.ResultsTest TMS intensity influenced SICI and LICI in rest and active FDI muscle. The normalised test MEP amplitude (%M_max) did not influence SICI at rest, whereas there was a decrease in LICI at rest and an increase in SICI in active FDI with an increased normalised test MEP amplitude (%M_max).ConclusionsOur results demonstrate differential effects of normalised test MEP amplitude (%M_max) on SICI and LICI in resting and active FDI muscle.SignificanceEstimation of SICI and LICI under some circumstances may be influenced by the normalised test MEP amplitude in subject populations with different M_max characteristics.     

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.     

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.     

Enhanced intracortical inhibition in cerebellar patients

OBJECTIVE: The aim of the study was to examine intracortical excitability in cerebellar patients. METHODS: Short-latency intracortical inhibition (SICI), long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to paired transcranial magnetic stimulation (TMS) were investigated in 8 patients with 'pure' cerebellar syndromes and in 14 age-matched normal controls. The conditioning stimulus for short-latency intracortical inhibition and intracortical facilitation was set at 70% of the resting motor threshold (RMT) and preceded the test stimulus (110-120% of the resting motor threshold) by interstimulus intervals (ISIs) of 1-30 ms. For the long-latency intracortical inhibition determinations, the conditioning stimulus was set at 120% of the resting motor threshold and preceded the test stimulus (also 120% of the resting motor threshold) by interstimulus intervals of 30-500 ms. RESULTS: No statistically significant differences were found between patients and controls as regards either short-latency intracortical inhibition or intracortical facilitation. A significant prevalence of long-latency intracortical inhibition was present in cerebellar patients at interstimulus intervals of 200-500 ms (conditioned MEP amplitude=29-41% of test MEP) as compared to controls (71-96% of test MEP). The amplitude of conditioned MEPs was persistently less than 45% of the test MEP in six patients, who were studied at interstimulus intervals up to 1000 ms. CONCLUSIONS: Long-latency intracortical inhibition was prevalent and abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation of GABAergic interneurons in the motor cortex of patients may be the mechanism responsible for this abnormality. Our findings seem to be specific to cerebellar diseases and are the opposite of those found in movement disorders such as dystonia and Parkinson's disease. These data suggest that the cerebellum and the basal ganglia may have opposite influences in tuning the excitability of the motor cortex.     

Effects of subthalamic nucleus stimulation on motor cortex excitability in Parkinson's disease

BACKGROUND: Transcranial magnetic stimulation (TMS) studies have found abnormalities in several excitatory and inhibitory circuits in the motor cortex in PD. These include motor evoked potential (MEP) recruitment curve, silent period duration (SP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI). METHODS: The authors studied the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on these circuits in 12 patients with PD treated with STN DBS. Data from nine patients who completed the study were analyzed. Patients remained on their usual medications. The stimulators were set at the optimal parameters (ON), half the optimal amplitude (HALF), and switched off (OFF) in random order. RESULTS: The Unified PD Rating Scale motor scores were significantly lower in the ON compared to the HALF and OFF conditions. Resting SICI, studied with paired-pulse TMS at interstimulus interval of 2 ms, was reduced in the OFF and HALF conditions compared to normal subjects. STN stimulation restored SICI to normal levels. STN stimulation had no effect on motor threshold, MEP recruitment curve, SP, active SICI, ICF, and LICI. CONCLUSIONS: Although restoration of short-interval intracortical inhibition by STN stimulation is similar to the effects of dopaminergic drugs, it has no effect on silent period duration and long-interval intracortical inhibition, which are also influenced by dopaminergic drugs. A previous study found that internal globus pallidus (GPi) stimulation reduced SP but did not change SICI. Thus, GPi and STN stimulation may affect different circuits in the motor cortex.     

Associative plasticity in intracortical inhibitory circuits in human motor cortex

ObjectivePaired associative stimulation (PAS) is a transcranial magnetic stimulation technique inducing Hebbian-like synaptic plasticity in the human motor cortex (M1). PAS is produced by repetitive pairing of a peripheral nerve shock and a transcranial magnetic stimulus (TMS). Its effect is assessed by a change in size of a motor evoked response (MEP). MEP size results from excitatory and inhibitory influences exerted on cortical pyramidal cells, but no robust effects on inhibitory networks have been demonstrated so far.MethodIn 38 healthy volunteers, we assessed whether a PAS intervention influences three intracortical inhibitory circuits: short (SICI) and long (LICI) intracortical inhibitions reflecting activity of GABA_A and GABA_B interneurons, respectively, and long afferent inhibition (LAI) reflecting activity of somatosensory inputs.ResultsAfter PAS, MEP sizes, LICI and LAI levels were significantly changed while changes of SICI were inconsistent. The changes in LICI and LAI lasted 45 min after PAS. Their direction depended on the delay between the arrival time of the afferent volley at the cortex and the TMS-induced cortical activation during the PAS.ConclusionsPAS influences inhibitory circuits in M1.SignificancePAS paradigms can demonstrate Hebbian-like plasticity at selected inhibitory networks as well as excitatory networks.     

Threshold Tracked Short-Interval Intracortical Inhibition More Closely Predicts the Cortical Response to Transcranial Magnetic Stimulation

ObjectivesShort-interval intracortical inhibition (SICI) is a paired-pulse transcranial magnetic stimulation (TMS) technique that is commonly used to quantify intracortical inhibitory tone in the primary motor cortex. Whereas conventional measures of SICI (C-SICI) quantify inhibition by the amplitude of the motor evoked potential (MEP), alternative measures involving threshold tracked SICI (TT-SICI) instead record the TMS intensity required to maintain a consistent MEP amplitude. Although both C-SICI and TT-SICI are thought to reflect inhibition mediated by γ-aminobutyric acid type A (GABA_A) receptors, recent evidence suggests that the mechanisms involved with each measure may not be equivalent. This study aimed to use combined TMS-electroencephalography (TMS-EEG) to investigate the cortical mechanisms contributing to C-SICI and TT-SICI.Materials and MethodsIn 20 young adults (30.6 ± 8.1 years), C-SICI and TT-SICI were recorded with multiple conditioning intensities, using both posterior-to-anterior (PA) and anterior-to-posterior (AP) induced currents, and this was compared with the TMS-evoked EEG potential (TEP).ResultsWe found no relationship between the magnitude of C-SICI and TT-SICI within each current direction. However, there was a positive relationship between the slope (derived from multiple conditioning intensities) of inhibition recorded with C-SICI and TT-SICI, but only with a PA current. Furthermore, irrespective of conditioning intensity or current direction, measures of C-SICI were unrelated to TEP amplitude. In contrast, TT-SICI was predicted by the P30 generated with AP stimulation.ConclusionsOur findings further demonstrate that C-SICI and TT-SICI likely reflect different facets of GABA_A-mediated processes, with inhibition produced by TT-SICI appearing to align more closely with TMS-EEG measures of cortical excitability.     

Corticomotor excitability and plasticity following complex visuomotor training in young and old adults

Previous studies with transcranial magnetic stimulation (TMS) have shown that advancing age may influence plasticity induction in human motor cortex (M1), but these changes have been assessed with TMS-induced paradigms or simple motor tasks. The aim of this study was to examine changes in corticospinal excitability and intracortical inhibition as markers of corticomotor plasticity following complex motor training in young and old adults. Electromyographic recordings were obtained from the right first dorsal interosseous (FDI) muscle of 16 young (20-35 years) and 16 older (aged 60-75 years) adults before and after motor skill training. Motor training consisted of three 6-minute blocks of a complex visuomotor task that required matching the metacarpophalangeal (MCP) joint angle of the index finger using abduction-adduction movements. Single- and paired-pulse TMS over the left M1 was used to assess changes in right FDI motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before and after each training block. Visuomotor tracking performance was diminished in old compared with young adults throughout training. However, improvement in tracking error was similar for young and old adults (7-24% increase in each training block). For young and old adults, motor training increased FDI MEP amplitude (≥ 20%) and reduced the magnitude of SICI (≥ 19%) after each visuomotor training block, reflecting use-dependent plasticity. However, no difference in corticomotor plasticity (change in MEP or SICI) was observed between young and old adults. Further studies are needed to identify the experimental or behavioral factors that might contribute to the maintenance of corticomotor plasticity in older adults.     

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.     

Assessment of cortical excitability using threshold tracking techniques

Conventional paired-pulse transcranial magnetic stimulation (TMS) techniques of assessing cortical excitability are limited by fluctuations in the motor evoked potential (MEP) amplitude. The aim of the present study was to determine the feasibility of threshold tracking TMS for assessing cortical excitability in a clinical setting and to establish normative data. Studies were undertaken in 26 healthy controls, tracking the MEP response from abductor pollicis brevis. Short-interval intracortical inhibition (SICI) occurred up to an interstimulus interval (ISI) of 7-10 ms, with two distinct peaks evident, at ISIs of < or =1 and 3 ms, followed by intracortical facilitation to an ISI of 30 ms. Long-interval intracortical inhibition (LICI) occurred at ISIs of 50-300 ms, peaking at 150 ms. The present study has confirmed the effectiveness of the threshold tracking TMS technique in reliably and reproducibly measuring cortical excitability. Simultaneous assessment of upper and lower motor neuronal function with threshold tracking techniques may help to determine the site of disease onset and patterns of progression in neurodegenerative diseases.     

Selective and nonselective benzodiazepine agonists have different effects on motor cortex excitability

Transcranial magnetic stimulation (TMS) is a useful method to study pharmacological effects on motor cortex excitability. Zolpidem is a selective agonist of the benzodiazepine receptor subtype BZ1 and has a distinct pharmacological profile compared to diazepam. To study the different effects of these two drugs on the cortical inhibitory system, TMS was performed before and after administration of a single oral dose of zolpidem (10 mg) and diazepam (5 mg) in six healthy volunteers. TMS tests included the determination of resting and active motor threshold (MT) and measurements of the amplitudes of motor evoked potentials, intracortical facilitation (ICF), short-latency intracortical inhibition (SICI), and long-latency intracortical inhibition (LICI), and determination of the cortical silent period (CSP). Both drugs were without effect on the active or resting MT and decreased the ICF. Prolongation of the CSP and enhancement of LICI only in the presence of zolpidem point to a specific BZ1-related mechanism underlying the long-lasting component of cortical inhibition. This selective modulation of the CSP and the LICI points to a specific role of BZ1 receptors in the control of inhibitory neuronal loops within the primary motor cortex.     

Comparison of transcranial magnetic stimulation measures obtained at rest and under active conditions and their reliability

Transcranial magnetic stimulation (TMS) studies investigating motor cortex reorganization in clinical populations use a variety of measurements, with some performed at rest and others with the muscle slightly contracted. Surprisingly there are still a limited number of studies focusing on relationship between TMS-measures obtained at rest and during active muscle contraction in healthy individuals. The purpose of this study was to: (1) compare resting and active TMS-measures and assess their association; (2) determine their respective short- and long-term reliability. Motor threshold (MT), motor evoked potentials (MEP) amplitude, map area, normalized map volume, map center of gravity (CoG) and short-interval intracortical inhibition (SICI) of the first dorsal interosseous (FDI) muscle were assessed in 12 healthy subjects. Subjects were tested three times (with a short (four days) and a long (>1 month) inter-session interval). No significant difference was found between resting and active measures, except for MT. Active MT was on average at 82% of resting MT. Good short- and long-term reliability were found for MT and CoG (in resting and active conditions), for the SICI and MEP amplitude at rest and for the normalized map volume under active condition. In conclusion, maps of FDI muscle obtained at rest and during active contraction are very similar to each other in healthy individuals when differences in MT are taken into account. Most TMS measures present good reliability when obtained under the appropriate condition, with comparable short-term and long-term reliability.     

Effects of remote muscle contraction on transcranial magnetic stimulation-induced motor evoked potentials and silent periods in humans.

OBJECTIVE: To determine to what extent tonic contraction of the testing muscle modulates the effect of remote muscle contraction on motor evoked potentials (MEPs) and cortical silent periods (CSPs) in resting and active proximal and distal muscles following transcranial magnetic stimulation (TMS). In addition, we tested whether the remote effect on MEP was observable when the test MEP was small. METHODS: While performing tonic abductions of the first dorsal interosseous (FDI), flexor carpi radialis, or anterior deltoid muscles, subjects made phasic dorsiflexions of the right ankle at various forces. MEPs and CSPs were induced by separately optimized TMS intensities and locations in the left motor cortex and recorded electromyographically. RESULTS: Phasic dorsiflexion increased MEP amplitude and shortened CSP duration in a dorsiflexion intensity-dependent manner in all muscles tested. At test MEPs <10% of Mmax, remote effects on MEP amplitude and CSP duration were significantly attenuated while the testing muscle was active. CONCLUSIONS: Phasic contraction of remote muscles potentiates excitatory- and suppresses inhibitory intracortical neuronal pathways converging on corticospinal tract cells innervating the upper limb muscles even when they are active. However, the magnitude of the remote effect on MEP amplitude strongly depends on the test MEP amplitude. SIGNIFICANCE: Although remote effects on MEP amplitude and CSP duration are observed even when the test muscle is active, the magnitude of the remote effect strongly depends on TMS intensity.     

Short-interval and long-interval intracortical inhibition of TMS-evoked EEG potentials

Background

Inhibition in the human motor cortex can be probed by means of paired-pulse transcranial magnetic stimulation (ppTMS) at interstimulus intervals of 2–3 ms (short-interval intracortical inhibition, SICI) or ～100?ms (long-interval intracortical inhibition, LICI). Conventionally, SICI and LICI are recorded as motor evoked potential (MEP) inhibition in the hand muscle. Pharmacological experiments indicate that they are mediated by GABAA and GABAB receptors, respectively.Objective/Hypothesis: SICI and LICI of TMS-evoked EEG potentials (TEPs) and their pharmacological properties have not been systematically studied. Here, we sought to examine SICI by ppTMS-evoked compared to single-pulse TMS-evoked TEPs, to investigate its pharmacological manipulation and to compare SICI with our previous results on LICI.

Intracortical inhibition in the human trigeminal motor system.

OBJECTIVE: To investigate the presence and features of short-interval intracortical inhibition (SICI) in the human trigeminal motor system. METHODS: Surface electromyogram (EMG) was recorded from left and right digastric muscles in 7 subjects, along with additional experiments with intramuscular EMG in 2 subjects. Focal transcranial magnetic stimulation (TMS) was used to activate the motor cortex of one hemisphere and elicit motor evoked potentials (MEPs) in digastric muscles on each side, at rest and while subjects activated the muscles at 10% maximal EMG. Paired or single TMS pulses were delivered in blocks of trials, while conditioning TMS intensity and interstimulus interval (ISI) were varied. RESULTS: At rest, paired TMS (3-ms ISI) with conditioning intensities 0.8-0.9x active motor threshold (TA) reduced the digastric MEP amplitude to a similar extent bilaterally. Conditioning at 0.5-0.7TA did not significantly reduce the MEP. MEP amplitude was reduced to a similar extent in both digastric muscles by ISIs between 1 and 4 ms (0.8TA). Voluntary bilateral activation of digastric muscles reduced the effectiveness of conditioning TMS compared to the resting state, with no differences between sides. The similarity of the responses in both digastric muscles was not due to EMG cross-talk (estimated to be approximately 10% in surface records and approximately 2% in intramuscular records), as the intramuscular records showed the same pattern as the surface records. CONCLUSIONS: The effects of paired-pulse TMS on digastric are similar to those reported for contralateral hand muscles, and are consistent with activation of SICI circuits in M1 by conditioning TMS. Our evidence further suggests that the corticomotor representations of left and right digastric muscles in M1 of a single hemisphere receive analogous inhibitory modulation from SICI circuits. SIGNIFICANCE: SICI has been demonstrated in the face area of motor cortex controlling the trigeminal motor system in normal subjects. This method can be used to investigate abnormalities of SICI in movement disorders affecting the masticatory muscles in humans.     

Intracortical GABAergic dysfunction in patients with fatigue and dysexecutive syndrome after COVID-19

ObjectiveA high proportion of patients experience fatigue and impairment of cognitive functions after coronavirus disease 2019 (COVID-19). Here we applied transcranial magnetic stimulation (TMS) to explore the activity of the main inhibitory intracortical circuits within the primary motor cortex (M1) in a sample of patients complaining of fatigue and presenting executive dysfunction after resolution of COVID-19 with neurological manifestations.MethodsTwelve patients who recovered from typical COVID-19 pneumonia with neurological complications and complained of profound physical and mental fatigue underwent, 9 to 13 weeks from disease onset, a psychometric evaluation including a self-reported fatigue numeric-rating scale (FRS, Fatigue Rating Scale) and the Frontal Assessment Battery (FAB). Intracortical activity was evaluated by means of well-established TMS protocols including short-interval intracortical inhibition (SICI), reflecting GABA_A-mediated inhibition, long-interval intracortical inhibition (LICI), a marker of GABA_B receptor activity, and short-latency afferent inhibition (SAI) that indexes central cholinergic transmission. TMS data were compared to those obtained in a control group of ten healthy subjects (HS) matched by age, sex and education level.ResultsPost-COVID-19 patients reported marked fatigue according to FRS score (8.1 ± 1.7) and presented pathological scores at the FAB based on Italian normative data (12.2 ± 0.7). TMS revealed marked reduction of SICI, and disruption of LICI as compared to HS. SAI was also slightly diminished.ConclusionsThe present study documents for the first time reduced GABAergic inhibition in the M1 in patients who recovered from COVID-19 with neurological complications and manifested fatigue and dysexecutive syndrome.SignificanceTMS may serve as diagnostic tool in cognitive disturbances and fatigue in post-COVID-19 patients.     

Non-homogeneous effect of levodopa on inhibitory circuits in Parkinson's disease and dyskinesia

IntroductionLevodopa-induced dyskinesia in patients with Parkinson's disease (PD) has been shown to be associated with an abnormal plasticity in the motor cortex. We investigated whether changes in the excitability of inhibitory and excitatory motor circuits could underlie maladaptive mechanisms associated with dyskinesia.MethodsUsing single and paired transcranial magnetic stimulation (TMS), we studied motor threshold, silent period (SP) duration, intracortical facilitation (ICF), short intracortical inhibition (SICI) and low- and high-intensity long intracortical inhibition (LICI) in 10 dyskinetic and 10 non-dyskinetic patients, matched for disease and treatment duration, before (OFF state) and after (ON state) levodopa, and in 10 healthy controls.ResultsIn the OFF state, the two groups of patients showed similar motor cortex excitability with a reduced SICI compared to controls. LICI was weaker and increasing stimulation intensity had a lower effect on SP duration in dyskinetic patients than in controls. In dyskinetic patients, in contrast to non-dyskinetic patients, levodopa failed to increase SICI and SP duration, and potentiated to a lesser extent the effect of increasing the stimulation intensity on LICI. Although levodopa improved motor symptoms to a similar extent in both dyskinetic and non-dyskinetic patients, it failed to activate effectively the excitability of the inhibitory systems in dyskinetic patients.DiscussionThese findings suggest that dyskinesia is associated with an abnormal effect of levodopa on cortical motor inhibitory circuits.     

Reliability of single and paired‐pulse transcranial magnetic stimulation in the vastus lateralis muscle

Introduction: Transcranial magnetic stimulation (TMS) is an important tool to examine neurological pathologies, movement disorders, and central nervous system responses to exercise, fatigue, and training. The reliability has not been examined in a functional locomotor knee extensor muscle. Methods: Within‐ (n = 10) and between‐day (n = 16) reliability of single and paired‐paired pulse TMS was examined from the active vastus lateralis. Results: Motor evoked potential amplitude and cortical silent period duration showed good within‐ and between‐day reliability (intraclass correlation coefficient [ICC] ≥ 0.82). Short‐ and long‐interval intracortical inhibition (SICI and LICI, respectively) demonstrated good within‐day reliability (ICC ≥ 0.84). SICI had moderate to good between‐day reliability (ICC ≥ 0.67), but LICI was not repeatable (ICC = 0.47). Intracortical facilitation showed moderate to good within‐day reliability (ICC ≥ 0.73) but poor to moderate reliability between days (ICC ≥ 0.51). Conclusions: TMS can reliably assess cortical function in a knee extensor muscle. This may be useful to examine neurological disorders that affect locomotion. Muscle Nerve 52: 605–615, 2015     

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.     

Are there differences in cortical excitability between akinetic-rigid and tremor-dominant subtypes of Parkinson's disease?

ObjectiveTo assess by transcranial magnetic stimulation (TMS) the excitability of various cortical circuits in akinetic-rigid and tremor-dominant subtypes of Parkinson's disease (PD).MethodsThe study included 92 patients with PD according to UK Brain Bank criteria, with akinetic-rigid (n = 64) or tremor-dominant (n = 28) subtype. Cortical excitability study, including resting and active motor thresholds (rMT and aMT), input—output curve of motor evoked potentials, contralateral and ipsilateral silent periods (cSP and iSP), short and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were measured. The results obtained were compared to a control group of 30 age- and sex-matched healthy subjects.ResultsThe patients in the tremor group had significantly lower rMT and aMT compared to controls and akinetic-rigid patients and significantly shorter iSP duration compared to akinetic-rigid patients, while iSP latency tended to be longer in akinetic-rigid patients compared to controls. There were no significant differences between the two PD subgroups regarding other cortical excitability parameters, including paired-pulse TMS parameters.ConclusionsOnly subtle differences of cortical excitability were found between patients with akinetic-rigid vs. tremor-dominant subtype of PD.SignificanceThe clinical heterogeneity of PD patients probably has an impact on cortical excitability measures, far beyond the akinetic-rigid versus tremor-dominant profile.