Possible differences between the time courses of presynaptic and postsynaptic GABA<Subscript>B</Subscript> mediated inhibition in the human motor cortex

Paired-pulse transcranial magnetic stimulation (TMS) can be used to non-invasively evaluate human motor cortical inhibitory circuits such as short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). Pharmacological studies suggested that SICI is mediated by GABA_A receptors while LICI is probably mediated by GABA_B receptors. A previous study also showed that SICI and LICI are mediated by separate neuronal populations and that LICI inhibits SICI, possibly through presynaptic GABA_B receptors. The aim of this study was to examine whether the time course of motor-evoked potentials (MEP) inhibition by LICI, likely mediated through postsynaptic GABA_B receptors, is different from SICI inhibition by LICI, likely mediated through presynaptic GABA_B receptors. Nine healthy volunteers were studied and MEP were recorded from the first dorsal interosseous muscle. A triple-stimulus TMS paradigm was used to evaluate the effect of LICI at ISIs of 100 and 150 ms on SICI. LICI at 100 and 150 ms caused a similar degree of MEP inhibition. LICI at 100 ms led to a significant reduction of SICI but LICI at 150 ms had no effect on SICI. Repeated measures ANOVA revealed a significant interaction between the LICI mediated inhibition of SICI and ISI (P = 0.0072). These findings suggest that the time courses of presynaptic and postsynaptic GABA_B receptors mediated inhibition are different in the human motor cortex.     

Differing effects of intracortical circuits on plasticity

Practice of a motor task leads to an increase in amplitude of motor-evoked potentials (MEP) in the exercised muscle. This is termed practice-dependent plasticity, and is abolished by the NMDA antagonist dextromethorphan and the GABA_A agonist lorazepam. Here, we sought to determine whether specific subtypes of GABA_A circuits are responsible for this effect by comparing the action of the non-selective agonist, lorazepam with that of the selective GABA_A-alpha₁ receptor agonist, zolpidem. In seven healthy subjects, transcranial magnetic stimulation (TMS) was used to quantify changes in amplitude of MEP after practice of a ballistic motor task. In addition we measured how the same drugs affected MEP amplitudes and the excitability of a number of cortical inhibitory circuits [short-interval intracortical inhibition (SICI), short-interval afferent inhibition (SAI) and long-interval intracortical inhibition]. This allowed us to explore correlations between drugs effects in measures of cortical excitability and practice-dependent plasticity of MEP amplitudes. As previously reported, lorazepam increased SICI and decreased SAI, while zolpidem only decreased SAI. The new findings were that practice-dependent plasticity of MEPs was impaired by lorazepam but not zolpidem, and that this was negatively correlated with lorazepam-induced changes in SICI but not SAI. This suggests that the intracortical circuits involved in SICI (and not neurons expressing GABA_A-alpha₁ receptor subunits that are implicated in SAI) may be involved in controlling the amount of practice-dependent MEP plasticity. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The role of GABAB receptors in intracortical inhibition in the human motor cortex

While GABA_B receptors are thought to have an important role in mediating long interval intracortical inhibition (LICI) in the human motor cortex, the effect of a selective GABA_B receptor agonist on this measure has not been directly tested. Nine healthy volunteers ingested either 50 mg baclofen (BAC) or placebo (PBO) in a randomized, double blind crossover design, with the second session one week later. We used transcranial magnetic stimulation to assess motor threshold, motor evoked potential (MEP) amplitude, cortical silent period (CSP) duration, short interval intracortical inhibition (SICI) and LICI before and 90 min following drug intake. There was no specific effect of drug on motor threshold, MEP amplitude or CSP duration. BAC resulted in a significant increase in LICI (P=0.002) and a significant decrease in SICI (P=0.046) while PBO had no effect. Our findings demonstrate that the enhanced GABA_B receptor activation results in differential effects on these two measures of intracortical inhibition in the human motor cortex. The increase in LICI is likely to be a result of increased GABA_B receptor mediated inhibitory post-synaptic potentials, while the reduction in SICI may relate to the activation of pre-synaptic GABA_B receptors reducing GABA release.     

Human brain cortical correlates of short-latency afferent inhibition: a combined EEG-TMS study

When linking in time electrical stimulation of the peripheral nerve with transcranial magnetic stimulation (TMS), the excitability of the motor cortex can be modulated to evoke clear inhibition, as reflected by the amplitude decrement in the motor-evoked potentials (MEPs). This specific property, designated short-latency afferent inhibition (SAI), occurs when the nerve-TMS interstimulus interval (ISI) is approximately 25 ms and is considered to be a corticothalamic phenomenon. The aim of the present study was to use the electroencephalographic (EEG) responses to navigated-TMS coregistration to better characterize the neuronal circuits underlying SAI. The present experimental set included magnetic resonance imaging (MRI)-navigated TMS and 60-channel TMS-compatible EEG devices. TMS-evoked EEG responses and MEPs were analyzed in eight healthy volunteers; ISIs between median nerve and cortical stimulation were determined relative to the latency of the individual N20 component of the somatosensory-evoked potential (SEP) obtained after stimulation of the median nerve. ISIs from the latency of the N20 plus 3 ms and N20 plus 10 ms were investigated. In all experimental conditions, TMS-evoked EEG responses were characterized by a sequence of negative deflections peaking at approximately 7, 44, and 100 ms alternating with positive peaks at approximately 30, 60, and 180 ms post-TMS. Moreover, ISI N20+3 ms modulated both EEG-evoked activity and MEPs. In particular, it inhibited MEP amplitudes, attenuated cortical P60 and N100 responses, and induced motor cortex beta rhythm selective decrement of phase locking. The findings of the present experiment suggest the cortical origin of SAI that could result from the cortico-cortical activation of GABAergic-mediated inhibition onto the corticospinal neurons modulated by cholinergic activation able to reducing intralaminar inhibition and promoting intracolumnar inhibition.     

Active eye fixation performance in 940 young men: effects of IQ,schizotypy, anxiety and depression

Cortical activity depends on the balance between excitatory and inhibitory influences. Several different excitatory and inhibitory systems in the human motor cortex can be tested by transcranial magnetic stimulation (TMS). While considerable information is known about these different inhibitory and excitatory phenomena individually, how they are related to each other and how they interact is not well understood. Several recent studies have investigated the interactions between some of these circuits by applying them together. It has been found that short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI) are mediated by different circuits. LICI appears to inhibit SICI, which may occur through presynaptic GABA_B receptors. Interhemispheric inhibition elicited by stimulation of the contralateral motor cortex also inhibits SICI and may share inhibitory mechanisms with LICI. Long-interval afferent inhibition induced by median nerve stimulation inhibits LICI but does not interact with SICI. Based on these results, a model of interactions between different inhibitory systems that can be tested and refined in the future is proposed. Further studies of the interaction between different cortical inhibitory and excitatory circuits should improve our understanding of the functional organization of the motor cortex and allow better interpretation of abnormal findings in disease states. It may also be developed into a new way of studying the pathophysiology of diseases and the effects of intervention.     

Interactions between long latency afferent inhibition and interhemispheric inhibitions in the human motor cortex

Various inhibitory pathways exist in the human brain which are crucial in modulating motor cortex output and they can be investigated non-invasively using transcranial magnetic stimulation. Interhemispheric inhibition (IHI) is one form of cortical inhibition. It can be elicited by stimulation of the opposite motor cortex at interstimulus intervals (ISIs) of 10 ms (IHI10) or 40 ms (IHI40) and inhibitions at these intervals are probably mediated by different mechanisms. Peripheral sensory stimulation can also inhibit the motor cortex. Median nerve stimulation produces long latency afferent inhibition (LAI) at ISI 200 ms. LAI inhibits another form of cortical inhibition known as long interval intracortical inhibition (LICI) and a study that examined the interaction between IHI10 and LICI hypothesized that they are mediated by an overlapping population of inhibitory neurones. We tested this hypothesis by examining the interaction between IHI10, IHI40 and LAI. With increasing test MEP amplitude LAI, IHI10 and IHI40 all decreased. There was no correlation between the strength of LAI, IHI10 and IHI40. In the presence of LAI, IHI10 was slightly but significantly reduced compared to IHI10 alone. There was no correlation between the reduction in IHI10 in the presence of LAI and the strength of LAI or IHI10. In the presence of LAI, IHI40 was significantly reduced compared to IHI40 alone. LAI produced a greater decrease in IHI40 than in IHI10. The decrease in IHI40 in the presence of LAI strongly correlated with the strength of LAI but not with the strength of IHI40. Reducing the strength of LAI, IHI10 and IHI40 still resulted in similar interaction between IHI10 and LAI but markedly decreased the effect of LAI on IHI40. We conclude that LAI and IHI10 do not directly inhibit each other but LAI probably inhibits IHI40. LICI is more likely to be related to IHI40 than to IHI10.     

Paired-pulse afferent modulation of TMS responses reveals a selective decrease in short latency afferent inhibition with age

Changes in motor cortical excitability were examined in 2 groups of participants, young (18-30 years of age, n = 25) and senior (65-82 years of age, n = 31), using paired-pulse afferent stimulation with transcranial magnetic stimulation (TMS). Motor evoked potentials (MEPs) elicited by TMS at suprathreshold intensity (120% motor threshold) were first recorded in unconditioned trials (TMS alone) and then in conditioned trials, in which TMS pulses were preceded by median nerve stimulation at 3 different interstimulus intervals (ISI; 20, 50, and 200 ms). Conditioning of MEP responses revealed a similar pattern of modulation in the 2 age groups, with 2 periods of inhibition at 20- and 200-ms ISIs, separated by a period in which MEPs tended to return to baseline at a 50-ms ISI. Afferent-induced inhibition at the short interval (i.e., SAI 20-ms ISI), was selectively reduced in seniors, with half of them showing either low or no MEP suppression. Age-associated changes in SAI level were also good predictors of performance on tests of processing speed and dexterity. The selective decrease in SAI exhibited by many seniors is consistent with reported alterations in intracortical inhibition with age. Our observations also highlight the potential value of SAI, as a putative marker of central cholinergic activity, in predicting declines in motor and cognitive function with age.     

Effects of attention on inhibitory and facilitatory phenomena elicited by paired-pulse transcranial magnetic stimulation in healthy subjects

We investigated whether human attentional processes influence the activity of intracortical inhibitory and excitatory circuits—short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and the intracortical facilitation (ICF)—elicited by paired-pulse transcranial magnetic stimulation (TMS) in healthy subjects. In eight healthy subjects we tested SICI, LICI and ICF under different attention-demanding conditions: “relaxed”, “target hand” and “non-target hand”. To compare the effects of attentional levels on SICI, LICI and ICF with those produced on the MEPs elicited by repetitive TMS (rTMS), in the same subjects we also delivered supra-threshold 5-Hz rTMS under the same three experimental conditions. To disclose whether attentional processes act selectively on circuits engaged by TMS delivered at 5 Hz frequency and at an interstimulus interval (ISI) of 200 ms, we also investigated the effects of different attention levels on paired-pulse TMS delivered at the 200 ms ISI and on the MEP size during 1-Hz rTMS. Attentional levels had no influence on SICI, ICF and LICI activated by paired-pulse TMS, but increased the MEP facilitation elicited by 5-Hz rTMS. Varying the attention level left the findings from 1-Hz rTMS unchanged. The finding that attention leaves the activity of intracortical inhibitory and excitatory circuits elicited by paired-pulse TMS unchanged but influences the MEP facilitation elicited by 5-Hz rTMS suggests that attention operates only when the stimulation entrains neural circuits made up of a large number of cortical cells with plasticity properties.     

Long-interval intracortical inhibition in a human hand muscle

When two motor cortical stimuli are delivered with an interstimulus interval of 50–200 ms, the response (motor evoked potential; MEP) to the second stimulus is typically suppressed. This phenomenon is termed long-interval intracortical inhibition (LICI), although data from one subject suggest that facilitation is possible. Moreover, we recently showed that suppression can be mediated at a spinal level. We characterized LICI more fully by exploring a broad range of contraction strengths and test stimulus intensities. MEPs were evoked in first dorsal interosseous by transcranial magnetic stimulation over the motor cortex. Single test and paired (conditioning-test interval of 100 ms) stimuli at intensities of 100–160% resting motor threshold were delivered at rest or during brief contractions of 10, 25, or 100% maximal voluntary force. Inhibition or facilitation was quantified with the standard ratio in which conditioned MEPs were expressed as a percentage of unconditioned MEPs. Inhibition was greatest at weak–moderate contraction strengths and least at rest and during maximal efforts. Both at rest and during maximal efforts, MEPs evoked by strong stimuli were facilitated. In a subset of subjects, cervicomedullary stimulation was used to activate the corticospinal tract to identify possible spinal influences on changes to MEPs. Contraction strength and test stimulus intensity each had different effects on unconditioned and conditioned MEP size, and hence, LICI is highly dependent on both factors. Further, because motoneurons are facilitated during contraction but disfacilitated after a strong conditioning stimulus, the standard ratio of LICI is of questionable validity during voluntary contractions.     

Reduced intracortical inhibition during the foreperiod of a warned reaction time task

Reaction time (RT) is shortened when the response signal is preceded by a warning signal, a finding that has been attributed to response preparation during the foreperiod between the warning and response signals. Research suggests an increased excitability of cortical movement representations associated with response preparation during the foreperiod of a warned RT task (Davranche et al. in Eur J Neurosci 25:3766–3774, 2007). However when the foreperiod duration is short and constant, the motor evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation (TMS) during the foreperiod is suppressed (Touge et al. in Clin Neurophysiol 111:1216–1226, 1998), suggesting a competing inhibitory process. Three experiments measured MEP amplitude and intracortical inhibition during the foreperiod of a warned RT task in which the response was a flexion of the right index finger. Experiments 1 and 2 measured short-interval intracortical inhibition (SICI) with paired TMS pulses separated by inter-stimulus intervals (ISIs) of 3 (SICI₃) and 1.5 ms (SICI_1.5), respectively. Experiment 3 measured long-interval intracortical inhibition (LICI) with paired TMS pulses with an ISI of 100 ms (LICI₁₀₀). In all experiments MEP amplitude was smaller in the warned condition than in the unwarned condition. There was less SICI₃ in the warned condition than in the unwarned condition (Experiment 1) whereas SICI_1.5 was similar in both conditions (Experiment 2). There was less LICI₁₀₀ in the warned condition than in the unwarned condition (Experiment 3). The intracortical inhibitory processes measured here cannot explain the suppression of MEP amplitude in the warned condition. We propose that the suppression of MEP amplitude is the result of an inhibitory mechanism, which acts on primary motor cortex to prevent premature response during the foreperiod.     

Sensorimotor integration to cutaneous afferents in humans: the effect of the size of the receptive field

Transcranial magnetic stimulation (TMS) can be used to study sensorimotor integration in humans non-invasively. Motor excitability has been found to be inhibited when afferent stimuli are given to a peripheral nerve and precede TMS at interstimulus intervals (ISIs) of 20–50 ms. This phenomenon has been referred to as short-latency afferent inhibition (SAI). To better understand the functional meaning of these phenomena, we examined the effect of the size of the receptive field on SAI to cutaneous afferents in upper-limb sensorimotor areas in humans. We examined the effect of the stimulation of the isolated right first (D₁), second (D₂) and third finger (D₃), the right second and third finger together (D₂₃) and the right first three fingers together (D₁₂₃) on the amplitude of motor evoked potentials (MEPs) to TMS in hand and forearm muscles. We examined the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles. Digital stimulation preceded TMS at ISIs of 20–50 ms. The effect of D₂ stimulation was MEP inhibition (SAI), which was more marked and consistent in APB and FDI muscles than in ECR and FCR muscles. Similarly, D₁ and D₃ stimulation caused MEP reduction, while no MEP enhancement could be found to single finger stimulation. In contrast, D₁₂₃ stimulation induced less effective SAI in upper-limb muscles. MEP potentiation was recorded in some muscles to D₁₂₃ stimulation. A significant difference between D₂ and D₁₂₃ stimulation was found in APB (ISIs = 30–50 ms) and FDI (ISIs = 40–50 ms) muscles, but not in forearm muscles. The effect to D₂₃stimulation on MEP amplitude was intermediate between those to D₂ and D₁₂₃ stimulation. Our data suggest that motor excitability to cutaneous afferents may be influenced by the size of the receptive fields, this effect being the result of increasing convergence between hand afferents in the somatosensory system. These phenomena appear to be topographically arranged across the representation of upper-limb muscles. These findings may help to understand the functional significance of SAI in normal physiology and pathophysiology.     

Exploring the connectivity between the cerebellum and motor cortex in humans

Animal studies have shown that cerebellar projections influence both excitatory and inhibitory neurones in the motor cortex but this connectivity has yet to be demonstrated in human subjects. In human subjects, magnetic or electrical stimulation of the cerebellum 5–7 ms before transcranial magnetic stimulation (TMS) of the motor cortex decreases the TMS-induced motor-evoked potential (MEP), indicating a cerebellar inhibition of the motor cortex (CBI). TMS also reveals inhibitory and excitatory circuits of the motor cortex, including a short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). This study used magnetic cerebellar stimulation to investigate connections between the cerebellum and these cortical circuits. Three experiments were performed on 11 subjects. The first experiment showed that with increasing test stimulus intensities, LICI, CBI and ICF decreased, while SICI increased. The second experiment showed that the presence of CBI reduced SICI and increased ICF. The third experiment showed that the interaction between CBI and LICI reduced CBI. Collectively, these findings suggest that cerebellar stimulation results in changes to both inhibitory and excitatory neurones in the human motor cortex.     

Effect of volitional inhibition on cortical inhibitory mechanisms

To investigate the effect of volitional inhibition on cortical inhibitory mechanisms, we performed transcranial magnetic stimulation (TMS) studies with a Go/NoGo reaction task in seven healthy subjects. Subjects were asked to extend their right index finger only after Go, but to remain relaxed after NoGo. Single- and paired-pulse TMS were triggered at the average reaction time for the Go response in each subject after Go or NoGo cues. Motor evoked potentials were recorded in the extensor indicis proprius (EIP) and abductor digiti minimi (ADM) muscles of right hand. Paired-pulse TMS with subthreshold conditioning stimuli at interstimulus intervals (ISIs) of 2 ms [short intracortical inhibition (SICI)] and 15 ms [intracortical facilitation (ICF)] and that with suprathreshold conditioning stimuli at ISI of 80 ms [long intracortical inhibition (LICI)] were performed in both Go/NoGo and control conditions. Inhibition of SICI was enhanced in both EIP and ADM after NoGo and was reduced only in EIP after Go. Inhibition of LICI was reduced in both muscles during both conditions, while ICF was not altered. The present results demonstrate that volitional inhibition enhances SICI but reduces LICI nonselectively. These results suggest that these two inhibitory mechanisms act differently during execution and suppression of voluntary movements.     

Conditioning intensity-dependent interaction between short-latency interhemispheric inhibition and short-latency afferent inhibition

The relationship between sensory and transcallosal inputs into the motor cortex may be important in motor performance, but it has not been well studied, especially in humans. The aim of this study was to reveal this relationship by investigating the interaction between short-latency interhemispheric inhibition (SIHI) and short-latency afferent inhibition (SAI) in humans with transcranial magnetic stimulation. SIHI is the inhibition of the primary motor cortex (M1) elicited by contralateral M1 stimulation given ～10 ms before, and it reflects transcallosal inhibition. SAI is the inhibition of M1 elicited by contralateral median nerve stimulation preceding M1 stimulation by ～20 ms. In this investigation, we studied the intensity dependence of SIHI and SAI and the interaction between SIHI and SAI in various conditioning intensities. Subjects were 11 normal volunteers. The degree of effects was evaluated by comparing motor evoked potential sizes recorded from the first dorsal interosseous muscle between a certain condition and control condition. Both SIHI and SAI were potentiated by increment of the conditioning stimulus intensity and saturated at 1.4 times resting motor threshold for SIHI and 3 times sensory threshold for SAI. No significant interaction was observed when either of their intensities was subthreshold for the inhibition on its own. Only when both intensities were strong enough for their inhibition did the presence of one inhibition lessen the other one. On the basis of these findings, we conclude that interneurons mediating SIHI and SAI have mutual, direct, and inhibitory interaction in a conditioning intensity-dependent manner.     

Interactions between short-interval intracortical inhibition and short-latency afferent inhibition in human motor cortex

Transcranial magnetic stimulation (TMS) allows the testing of various inhibitory processes in human motor cortex. Here we aimed at gaining more insight into the underlying physiology by studying the interactions between short-interval intracortical inhibition (SICI) and short-latency afferent inhibition (SAI). SICI and SAI were examined in a slightly contracting hand muscle of healthy subjects by measuring inhibition of a test motor-evoked potential conditioned by a sub-threshold motor cortical magnetic pulse (S1) or an electrical pulse (P) applied to the ulnar nerve at the wrist, respectively. SICI alone and SAI alone had similar magnitude when S1 intensity was set to 90% active motor threshold and P intensity to three times the perceptual sensory threshold. SICI was reduced or even disinhibited when P was co-applied, and SAI was reduced or disinhibited when S1 was co-applied. These interactions did not depend on the exact timing of arrival of P and S1 in motor cortex. A control experiment with a S1 intensity lowered to 70% active motor threshold excluded a contribution by short-interval intracortical facilitation. Finally, SICI with co-applied P correlated linearly with SICI alone with a slope of the regression line close to 1 whereas SAI did not correlate with SAI when S1 was co-applied with a slope of the regression line close to zero. Data indicate that S1 largely eliminates the effects of P when applied together, suggesting dominance of S1 over P. Findings strongly support the idea that SICI and SAI are mediated through two distinct and reciprocally connected subtypes of GABAergic inhibitory interneurons with convergent projections onto the corticospinal neurons. Furthermore, dominance of S1 over P is compatible with the notion that the SICI interneurons target the corticospinal neurons closer to their axon initial segment than the SAI interneurons.     

Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans

Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA_A receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA_A activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA_A activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI  ( F _3,9= 3.19, P = 0.039)  . In contrast to SICI, SAI was significantly reduced by lorazepam  ( F _3,9= 9.39, P = 0.0002)  . Our findings demonstrate that GABA_A activity enhancement determines a suppression of SAI and an increase of SICI.     

Rapid-rate paired associative stimulation of the median nerve and motor cortex can produce long-lasting changes in motor cortical excitability in humans

Repetitive transcranial magnetic stimulation (rTMS) or repetitive electrical peripheral nerve stimulation (rENS) can induce changes in the excitability of the human motor cortex (M1) that is often short-lasting and variable, and occurs only after prolonged periods of stimulation. In 10 healthy volunteers, we used a new repetitive paired associative stimulation (rPAS) protocol to facilitate and prolong the effects of rENS and rTMS on cortical excitability. Sub-motor threshold 5 Hz rENS of the right median nerve was synchronized with submotor threshold 5 Hz rTMS of the left M1 at a constant interval for 2 min. The interstimulus interval (ISI) between the peripheral stimulus and the transcranial stimulation was set at 10 ms (5 Hz rPAS_10ms) or 25 ms (5 Hz rPAS_25ms). TMS was given over the hot spot of the right abductor pollicis brevis (APB) muscle. Before and after rPAS, we measured the amplitude of the unconditioned motor evoked potential (MEP), intracortical inhibition (ICI) and facilitation (ICF), short- and long-latency afferent inhibition (SAI and LAI) in the conditioned M1. The 5 Hz rPAS_25ms protocol but not the 5 Hz rPAS10_ms protocol caused a somatotopically specific increase in mean MEP amplitudes in the relaxed APB muscle. The 5 Hz rPAS_25ms protocol also led to a loss of SAI, but there was no correlation between individual changes in SAI and corticospinal excitability. These after-effects were still present 6 h after 5 Hz rPAS_25ms. There was no consistent effect on ICI, ICF and LAI. The 5 Hz rENS and 5 Hz rTMS protocols failed to induce any change in corticospinal excitability when given alone. These findings show that 2 min of 5 Hz rPAS_25ms produce a long-lasting and somatotopically specific increase in corticospinal excitability, presumably by sensorimotor disinhibition.     

Different modulation of the cortical silent period by two phases of short interval intracortical inhibition

PURPOSE: To investigate the influence of 2 phases of short interval intracortical inhibition (SICI) on the cortical silent period (SP). MATERIALS AND METHODS: Single- and paired-pulse transcranial magnetic stimulations (TMSs) at 1 and 2.5ms interstimulus intervals (ISIs) were applied to the left motor cortex in 12 healthy subjects while their right hand muscles were moderately activated. Conditioning stimulation intensity was 90% of the active motor threshold (AMT). Test stimulation intensities were 120, 140, 160, 180, 200, 220, 240, 260% of the AMT and at 100% of the maximal stimulator output, the order of which was arranged randomly. The rectified electromyography area of motor evoked potential (MEP) and duration of the SP were measured off-line using a computerized program. RESULTS: At high-test stimulation intensities, MEP areas were saturated in both single- and paired-pulse stimulations, except that saturated MEPs were smaller for the paired-pulse TMS at 1ms ISI than for the other conditions. As the test stimulation intensity increased, SP was progressively prolonged in both single- and paired-pulse stimulations but was shorter in paired-pulse than single-pulse TMS. Overall, the ratio of SP duration/MEP area was comparable between single- and paired-pulse TMS except for the paired-pulse TMS at 1 ms ISI with a test stimulation intensity at 140-180% of the AMT, in which the ratio was significantly higher than in the single pulse TMS. CONCLUSION: These results suggest that 2 phases of SICI modulate MEP saturation and SP duration differently and provide additional evidence supporting the view that 2 phases of SICI are mediated by different inhibitory mechanisms.     

Widely distributed GABA-mediated afferent inhibition processes within the ventrobasal thalamus of rat and their possible relevance to pathological pain states and somatotopic plasticity

Summary We have recently described extensive inhibitory interactions between inputs to the ventroposterolateral (VPL) (Roberts and Wells 1990, 1991) and ventropos-teromedial (VPM) (Salt 1989) portions of the ventrobasal nucleus of the thalamus (VB). We wished to determine whether (i) the inhibition observed in the VPL was operating at the thalamic level, (ii) was dependant on GABA receptors, (iii) was demonstrable on neurons of the ventro-posteromedial nucleus of the thalamus (VPM) and (iv) was operant on test responses evoked by natural stimuli. Conditioning stimulation of sciatic nerve afferents caused inhibition of air jet evoked test responses of single VB neurons in urethane-anaesthetized rats. Both VPM and VPL neurons were subject to inhibition by conditioning stimulation of hindlimb afferents, indicating the widespread nature of the inhibitory process. This inhibition was reduced by the iontophoretic application of SR95531, a GABA_A receptor antagonist. We conclude that there is a widely distributed inhibitory system operating in the somatic thalamus which involves both the medial and lateral portions of the nucleus and is, at least in part, mediated by GABA_A receptors. The possible involvement of inhibitory processes and intrinsic membrane properties of thalamic neurones in the somatotopic plasticity of the sensory thalamus following deafferentation and in deaf-ferentation pain is discussed.     

Modulation of motor cortex excitability by median nerve and digit stimulation

We investigated the time course of changes in motor cortex excitability after median nerve and digit stimulation. Although previous studies showed periods of increased and decreased corticospinal excitability following nerve stimulation, changes in cortical excitability beyond 200 ms after peripheral nerve stimulation have not been reported. Magnetoencephalographic studies have shown an increase in the 20-Hz rolandic rhythm from 200 to 1000 ms after median nerve stimulation. We tested the hypothesis that this increase is associated with reduced motor cortex excitability. The right or left median nerve was stimulated and transcranial magnetic stimulation (TMS) was applied to left motor cortex at different conditioning-test (C-T) intervals. Motor-evoked potentials (MEPs) were recorded from the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), and extensor carpi radialis (ECR) muscles. Right median nerve stimulation reduced test MEP amplitude at C-T intervals from 400 to 1000 ms for APB, at C-T intervals from 200 to 1000 ms for FDI, and at C-T intervals of 200 and 600 ms for ECR, but had no effect on FDI F-wave amplitude at a C-T interval of 200 ms. Left median nerve (ipsilateral to TMS) stimulation resulted in less inhibition than right median nerve stimulation, but test MEP amplitude was significantly reduced at a C-T interval of 200 ms for all three muscles. Digit stimulation also reduced test MEP amplitude at C-T intervals of 200–600 ms. The time course for decreased motor cortex excitability following median nerve stimulation corresponds well to rebound of the 20-Hz cortical rhythm and supports the hypothesis that this increased power represents cortical deactivation. Received: 11 December 1998 / Accepted: 30 April 1999