Long-interval Intracortical Inhibition Research Articles

The effects of inhibitory and facilitatory intracortical circuits on interhemispheric inhibition in the human motor cortex

Inhibitory and facilitatory intracortical pathways regulating motor cortical output can be studied non-invasively in humans with transcranial magnetic stimulation. These circuits include short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Stimulation of the motor cortex also inhibits the contralateral motor cortex (interhemispheric inhibition, IHI) at short (approximately 10 ms, IHI10) or long intervals (approximately 40 ms, IHI40). We investigated how SICI, ICF, and LICI influence IHI10 and IHI40. We hypothesize that intracortical circuits will have similar effects on IHI and cortical output neurons: SICI and LICI will decrease IHI, and ICF will increase it. Motor evoked potentials were recorded from the first dorsal interosseous muscles bilaterally in 10 healthy subjects. We compared IHI10 and IHI40 alone to IHI10 and IHI40 elicited in the presence of SICI, ICF, or LICI. Our results showed that SICI and LICI reduced IHI10, IHI40 and corticospinal output to a similar degree. ICF increased corticospinal output but had no effect on either IHI10 or IHI40. The different effects of ICF on corticospinal excitability and IHI suggest the transcallosal fibres mediating IHI and the corticospinal output system arise from different neuronal populations. SICI and LICI produce more global inhibition with similar effects on the transcallosal and descending corticospinal circuits.

P.1.007 Semantic structure of emotion concepts in patients with schizophrenia

A growing body of evidence suggests that deficits in GABAergic inhibitory and glutamatergic excitatory neurotransmission may be involved in the core pathophysiology of generalized anxiety disorder (GAD), a disease characterized by pathological anxious worrying. The aim of the present study was to measure motor cortical excitability by paired-pulse transcranial magnetic stimulation (ppTMS) in patients with GAD.ppTMS measurements of excitation and inhibition from bilateral motor cortices were investigated in 26 right-handed GAD patients who were drug-naïve (half of them with a comorbidity of major depressive disorder) and 35 right-handed age- and sex-matched healthy controls. Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) were studied; evidence indicated that these are mainly mediated by GABA-A receptors, glutamate receptors, and GABA-B receptors, respectively.After correcting for multiple comparisons, GAD patients had significantly lower left ICF (p < 0.001, Cohen's d = 1.348) and right ICF (p = 0.001, Cohen's d = 0.963), but not SICI and LICI, than did healthy controls. No significant difference of the ICF values was found between GAD with and without depressive disorders. Multivariate linear regression analysis revealed that left ICF (B = −4.990, 95% CI = −8.821 to −1.039, p = 0.007) and group (B = 13.179, 95% CI = 10.208 to 16.149, p = 0.001) predicted anxiety symptoms significantly.The present study provided direct evidence to support that generalized anxiety disorder is characterized by impaired intra-cortical facilitation of motor cortex, suggesting glutamate-related excitatory dysfunction may play a key role in pathological anxiety.

Cortical inhibition and excitation in abstinent cocaine-dependent patients: a transcranial magnetic stimulation study

Prior transcranial magnetic stimulation studies showed that resting motor threshold is elevated in abstinent cocaine-dependent patients, suggesting a decrease in axonal excitability. In contrast, the increased incidence of seizures and psychosis in this group suggests increased excitability or decreased inhibition. Here, we studied long-interval intracortical facilitation and long-interval intracortical inhibition, paired-pulse transcranial magnetic stimulation measures that are more directly linked to glutamatergic cortical facilitation and GABAergic inhibition, respectively. Ten cocaine-dependent and 10 healthy controls were examined. Resting motor threshold, long-interval intracortical facilitation and long-interval intracortical inhibition were tested from the left motor cortex. The cocaine group showed an elevated resting motor threshold and an increased long-interval intracortical facilitation, whereas long-interval intracortical inhibition was normal. Although the increase in long-interval intracortical facilitation suggests exaggerated cortical glutamatergic excitability, the increase in resting motor threshold may signify a protective mechanism against seizures and psychosis.

Differential changes in long-interval intracortical inhibition and silent period duration during fatiguing hand exercise

During fatiguing exercise corticomotor excitability increases as force declines, which may serve to increase motor output to the exercising muscle, but paradoxically at the same time there is an increase in silent period (SP) duration which is thought to represent a build-up of intracortical inhibition. Paired-pulse TMS at long interstimulus intervals can also be used to derive an index of long-interval cortical inhibition (LICI), however this has not yet been investigated in fatigue. Our aim was to measure LICI during and after a fatiguing exercise and determine if the changes in the index of LICI parallel the changes in SP duration. To do this, we used single and paired-pulse TMS to measure motor evoked potential (MEP) amplitude, LICI and SP duration during, and for 10 min after, a 10-min intermittent maximal fatiguing exercise of the index finger, designed to fatigue the first dorsal interosseous (FDI) muscle (force after 10-min of exercise 64 +/- 7% of baseline, P < 0.05). Single-pulse MEP amplitude and SP duration were increased during fatiguing exercise (minute 10; 179 +/- 24% and 128 +/- 9% of baseline, respectively, P < 0.05), in contrast the measure of LICI was reduced compared to baseline (minute 10; 0.45 +/- 0.17 vs. baseline; 0.70 +/- 0.10, P < 0.05). These results suggest that SP duration and LICI may reflect processes occurring in different neuronal populations. The increased SP duration may correspond to processes of central fatigue in centres 'upstream' of primary motor cortex (M1), whereas the decrease in LICI, together with increased MEP amplitude, are consistent with an increase in M1 output during fatigue that may serve to compensate for reduced central drive.

FC45.3 Effect of paired associative stimulation (PAS) on the interaction between afferent stimulation and long interval intracortical inhibition (LICI)

FC45.3 Effect of paired associative stimulation (PAS) on the interaction between afferent stimulation and long interval intracortical inhibition (LICI)

Pregabalin Exerts Oppositional Effects on Different Inhibitory Circuits in Human Motor Cortex: A Double‐blind, Placebo‐controlled Transcranial Magnetic Stimulation Study

To explore acute effects of pregabalin (PGB) on human motor cortex excitability with transcranial magnetic stimulation (TMS). PGB, 600 mg/day, was orally administered in 19 healthy subjects twice daily in a randomized, double-blind, placebo-controlled crossover design. Several measures of motor cortex excitability were tested with single- and paired-pulse TMS. Mean short-interval intracortical inhibition (SICI) was reduced after PGB (74 +/- 7% of unconditioned response) compared with placebo (60 +/- 6% of unconditioned response). In contrast, mean long-interval intracortical inhibition (LICI) was increased by PGB (26 +/- 4% of unconditioned response) compared with placebo (45 +/- 8% of unconditioned response), and mean cortical silent period (CSP) showed an increase from 139 +/- 8 ms or 145 +/- 8 ms after placebo to 162 +/- 7 ms or 161 +/- 10 ms after PGB. Motor thresholds, intracortical facilitation, and corticospinal excitability were unaffected. The observed excitability changes with oppositional effects on SICI and LICI or CSP suggest gamma-aminobutyric acid (GABA)B-receptor activation. They are markedly distinct from those induced by gabapentin, although both PGB and gabapentin are thought to mediate their function by binding to the alpha2-delta subunit of voltage-gated calcium channels. Conversely, the TMS profile of PGB shows striking similarities with the pattern evoked by the GABA-reuptake inhibitor tiagabine.

Cortical and spinal abnormalities in psychogenic dystonia

The pathophysiology of psychogenic dystonia has not been examined, but a growing body of literature suggests that abnormal sensory input from repetitive movements can lead to plastic cortical changes. Reduced cortical and spinal inhibition is well documented in organic dystonia. We tested the hypothesis that aberrant sensory input associated with abnormal posture may cause similar abnormalities by testing patients with psychogenic dystonia. We assessed cortical and spinal inhibitory circuits and cortical activity associated with voluntary movement in 10 patients with clinically definite psychogenic dystonia, 8 patients with organic dystonia, and 12 age-matched healthy control subjects. Three measures of cortical inhibition, resting short- and long-interval intracortical inhibition and cortical silent period, were reduced in both psychogenic dystonia and organic dystonia. Cutaneous silent period mediated by spinal circuitries was increased in psychogenic and organic dystonia. Forearm spinal reciprocal inhibition was reduced in psychogenic dystonia. Psychogenic and organic dystonia share similar physiological abnormalities. Previous findings of abnormal cortical and spinal excitability in organic dystonia may, in part, be a consequence rather than a cause of dystonia. Alternatively, these findings may represent endophenotypic abnormalities that predispose to both types of dystonia.

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.

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.

Short-interval cortical inhibition and corticomotor excitability with fatiguing hand exercise: a central adaptation to fatigue?

The central processes occurring during fatiguing exercise are not well understood, however transcranial magnetic stimulation (TMS) studies have reported increases both in corticomotor excitability, as measured by the motor-evoked potential (MEP) amplitude, and in long-interval intracortical inhibition, as measured by the duration of the post-MEP silent period. To determine whether short-interval cortical inhibition (SICI) is modulated by fatiguing exercise, we used single and paired-pulse TMS to measure MEP amplitude and SICI for the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the hand during, and for 20 min after, a 10-min intermittent maximal voluntary abduction of the index finger designed to fatigue the FDI muscle. For the FDI, the index of SICI increased at the onset of exercise (from 0.25+/-0.05 to 0.55+/-0.11, P < 0.05) and then decreased progressively as force declined. At the beginning of recovery, SICI again increased (0.57+/-0.11, P < 0.05) and remained elevated for the 20-min recovery period. In contrast, SICI for ADM did not change during or after exercise. MEP amplitude for both the FDI and ADM increased above baseline during exercise and then decreased below baseline during the recovery period. These results demonstrate that there are significant changes in SICI during and after a fatiguing exercise protocol that are isolated to the representation of the fatigued muscle. The inter-relationship between the changes in excitation and inhibition suggests the presence of a measured and adaptive process of modulation in central excitation and inhibition acting to increase corticomotor drive to the exercising muscle as fatigue is developing.

Representation of facial muscles in human motor cortex

Whether there is a projection from the primary motor cortex (M1) to upper facial muscles and how the facial M1 area is modulated by intracortical inhibitory and facilitatory circuits remains controversial. To assess these issues, we applied transcranial magnetic stimulation (TMS) to the M1 and recorded from resting and active contralateral (C-OOc) and ipsilateral orbicularis oculi (I-OOc), and contralateral (C-Tr) and ipsilateral triangularis (I-Tr) muscles in 12 volunteers. In five subjects, the effects of stimulating at different scalp positions were assessed. Paired TMS at interstimulus intervals (ISIs) of 2 ms were used to elicit short interval intracortical inhibition (SICI) and ISI of 10 ms for intracortical facilitation (ICF). Long interval intracortical inhibition (LICI) was evaluated at ISIs between 50 and 200 ms, both at rest and during muscle activation. The silent period (SP) was also determined. C-OOc and I-OOc responses were recorded in all subjects. The optimal position for eliciting C-OOc responses was lateral to the hand representation in all subjects and MEP amplitude markedly diminished when the coil was placed 2 cm away from the optimal position. For the I-OOc, responses were present in more scalp sites and the latency decreased with more anterior placement of the coil. C-Tr response was recorded in 10 out of 12 subjects and the I-Tr muscle showed either no response or low amplitude response, probably due to volume conduction. SICI and ICF were present in the C-OOc and C-Tr, but not in the I-OOc muscle. Muscle activation attenuated SICI and ICF. LICI at rest showed facilitation at 50 ms ISI in all muscles, but there was no significant inhibition at other ISIs. There was no significant inhibition or facilitation with the LICI protocol during muscle contraction. The SP was present in the C-OOc, C-Tr and I-OOc muscles and the mean durations ranged from 92 to 104 ms. These findings suggest that the I-OOc muscle response is probably related to the first component (R1) of the blink reflex. There is M1 projection to the contralateral upper and lower facial muscles in humans and the facial M1 area is susceptible to cortical inhibition and facilitation, similar to limb muscles.

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.

The effect of sensory input and attention on the sensorimotor organization of the hand area of the human motor cortex

Sensory input can remodel representations in the sensory cortex, and this effect is heavily influenced by attention to the stimulus. Here we ask whether pure sensory input can also influence the spatial distribution of sensory effects on motor cortical hand area (sensorimotor organization) and whether this is modulated by attention. Sensorimotor organization was tested by applying short (1.5 s) periods of low amplitude vibration to single intrinsic hand muscles and measuring motor cortex excitability with transcranial magnetic stimulation (TMS). In healthy subjects, sensorimotor organization in the hand is focal, with input from one hand muscle increasing motor-evoked potentials (MEPs), decreasing short and increasing long-interval intracortical inhibition (SICI and LICI) in the vibrated muscle ('homotopic' effects) and having opposite effects on neighbouring muscles ('heterotopic' effects). Here we show that a 15 min intervention of vibration applied simultaneously to two hand muscles can lead to long-term (> 30 min) changes in the spatial pattern of sensorimotor interaction. The amount and direction of the effects depended on the subject's attention during the intervention: if subjects attended to both muscles when they were receiving simultaneous vibration, subsequent short-term vibration applied to one of them produced 'homotopic' effects on both muscles. 'Heterotopic' effects on a muscle not vibrated during the intervention were unaffected. If subjects did not attend to simultaneous vibration, subsequent short-term vibration of the muscles involved in the intervention no longer had any effect on them although the 'heterotopic' effects on a muscle not involved in the intervention were unchanged. We conclude that a 15 min period of pure sensory input can remodel the way that subsequent sensory inputs interact with motor output, that the effects are specific for the motor output to muscles involved in the intervention and that they are modulated by the subject's attention.

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.

Interactions between inhibitory and excitatory circuits in the human motor cortex

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.

P.3.053 Primary anxiety disorders: Impact of treatment on subsequent depression and health outcomes

A growing body of evidence suggests that deficits in GABAergic inhibitory and glutamatergic excitatory neurotransmission may be involved in the core pathophysiology of generalized anxiety disorder (GAD), a disease characterized by pathological anxious worrying. The aim of the present study was to measure motor cortical excitability by paired-pulse transcranial magnetic stimulation (ppTMS) in patients with GAD.ppTMS measurements of excitation and inhibition from bilateral motor cortices were investigated in 26 right-handed GAD patients who were drug-naïve (half of them with a comorbidity of major depressive disorder) and 35 right-handed age- and sex-matched healthy controls. Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) were studied; evidence indicated that these are mainly mediated by GABA-A receptors, glutamate receptors, and GABA-B receptors, respectively.After correcting for multiple comparisons, GAD patients had significantly lower left ICF (p < 0.001, Cohen's d = 1.348) and right ICF (p = 0.001, Cohen's d = 0.963), but not SICI and LICI, than did healthy controls. No significant difference of the ICF values was found between GAD with and without depressive disorders. Multivariate linear regression analysis revealed that left ICF (B = −4.990, 95% CI = −8.821 to −1.039, p = 0.007) and group (B = 13.179, 95% CI = 10.208 to 16.149, p = 0.001) predicted anxiety symptoms significantly.The present study provided direct evidence to support that generalized anxiety disorder is characterized by impaired intra-cortical facilitation of motor cortex, suggesting glutamate-related excitatory dysfunction may play a key role in pathological anxiety.

Effects of peripheral sensory input on cortical inhibition in humans.

Cortical inhibitory systems play an important role in motor output. The motor cortex can be inhibited by intracortical mechanisms and by peripheral sensory inputs. We examined whether cortical inhibition from peripheral sensory input is mediated through previously identified intracortical inhibitory systems and how these inhibitory systems interact. Two types of intracortical inhibition were assessed by paired-pulse transcranial magnetic stimulation (TMS). Short-interval intracortical inhibition (SICI) was determined with a subthreshold conditioning stimulus (CS) followed by a test stimulus 2 ms later and long-interval intracortical inhibition (LICI) with suprathreshold conditioning and test stimuli 100 ms apart. Cortical inhibition from peripheral sensory input was induced by median nerve stimulation (MNS) of the right hand and followed by a suprathreshold TMS over the left motor cortex 200 ms later. The first set of experiments tested the effects of different test stimulus intensities on SICI, LICI and cortical inhibition induced by median nerve stimulation (MNSI). With higher test stimulus intensities, LICI and MNSI decreased whereas SICI showed a trend towards an increase. The extent of SICI, LICI and MNSI did not correlate. The second experiment assessed the interaction between MNSI and LICI. The results of applying MNSI and LICI simultaneously were compared with MNSI and LICI alone. MNSI was virtually abolished in the presence of LICI and LICI was also significantly decreased in the presence of MNSI. Thus, the effects of MNSI and LICI when applied together were much less than their expected additive effects when applied alone. The degree of interaction between MNSI and LICI was related to the combined strength of MNSI and LICI but not to the strength of LICI alone. The third experiment investigated the interaction between SICI and MNSI. MNSI and SICI were applied together and the results were compared with MNSI and SICI alone. SICI remained unchanged in the presence of MNSI. We conclude that MNSI is mediated by circuits distinct from those mediating LICI or SICI. The MNSI circuits seem to have an inhibitory interaction with the LICI circuits, whereas the SICI and MNSI circuits do not seem to interact.

Effects of peripheral sensory input on cortical inhibition in humans

Cortical inhibitory systems play an important role in motor output. The motor cortex can be inhibited by intracortical mechanisms and by peripheral sensory inputs. We examined whether cortical inhibition from peripheral sensory input is mediated through previously identified intracortical inhibitory systems and how these inhibitory systems interact. Two types of intracortical inhibition were assessed by paired-pulse transcranial magnetic stimulation (TMS). Short-interval intracortical inhibition (SICI) was determined with a subthreshold conditioning stimulus (CS) followed by a test stimulus 2 ms later and long-interval intracortical inhibition (LICI) with suprathreshold conditioning and test stimuli 100 ms apart. Cortical inhibition from peripheral sensory input was induced by median nerve stimulation (MNS) of the right hand and followed by a suprathreshold TMS over the left motor cortex 200 ms later. The first set of experiments tested the effects of different test stimulus intensities on SICI, LICI and cortical inhibition induced by median nerve stimulation (MNSI). With higher test stimulus intensities, LICI and MNSI decreased whereas SICI showed a trend towards an increase. The extent of SICI, LICI and MNSI did not correlate. The second experiment assessed the interaction between MNSI and LICI. The results of applying MNSI and LICI simultaneously were compared with MNSI and LICI alone. MNSI was virtually abolished in the presence of LICI and LICI was also significantly decreased in the presence of MNSI. Thus, the effects of MNSI and LICI when applied together were much less than their expected additive effects when applied alone. The degree of interaction between MNSI and LICI was related to the combined strength of MNSI and LICI but not to the strength of LICI alone. The third experiment investigated the interaction between SICI and MNSI. MNSI and SICI were applied together and the results were compared with MNSI and SICI alone. SICI remained unchanged in the presence of MNSI. We conclude that MNSI is mediated by circuits distinct from those mediating LICI or SICI. The MNSI circuits seem to have an inhibitory interaction with the LICI circuits, whereas the SICI and MNSI circuits do not seem to interact.

Active control of central nervous activation in cycling prior to exertion and rest

Transcranial magnetic stimulation was used to examine the effect of voluntary contraction on the magnitude of long-interval intracortical inhibition (LICI) and the duration of the silent period in intrinsic hand muscles. The magnitude of LICI acting on the first dorsal interosseus (FDI) measured with a paired-pulse protocol with an inter-pulse interval of 100 ms decreased with increasing tonic level of voluntary abduction force generated by the index finger. LICI in abductor pollicis brevis (APB) decreased from the condition in which the index finger was at rest to the conditions in which it was abducted, whereas LICI in abductor digiti minimi (ADM) was unaffected by the level of index finger abduction. During voluntary abduction of the index finger, the magnitude of LICI was least in FDI, intermediate in ADM, and greatest in APB, suggesting that it may be a mechanism by which tonic activation of hand muscles is fractionated. The magnitude of LICI increased with conditioning stimulus intensity, but intensity did not interact with abduction force. The duration of the silent period (SP) in FDI decreased with the level of voluntary index finger abduction and increased with eliciting stimulus intensity. Within-subject correlations showed that the effects of voluntary drive on SP duration and motor-evoked potential amplitude did not covary, implying an indirect effect of voluntary drive on SP duration. It is proposed that whereas voluntary drive directly reduces the magnitude of slow-acting inhibition acting on the active movement representations and near neighbors, sensory feedback from the contracting muscle acts to limit its time course.