Changes In SICI Research Articles

Single joint fatiguing exercise decreases long but not short-interval intracortical inhibition in older adults.

Ageing is accompanied by neuromuscular changes which may alter fatigue in older adults. These changes may include changes in corticospinal excitatory and inhibitory processes. Previous research has suggested that single joint fatiguing exercise decreases short-(SICI) and long-(LICI) interval intracortical inhibition in young adults. However, this is yet to be established in older adults. In 19 young (23 ± 4years) and 18 older (69 ± 5years) adults, SICI (2ms interstimulus interval; ISI) and LICI (100ms ISI) were measured in a resting first dorsal interosseous (FDI) muscle using transcranial magnetic stimulation (TMS) before and after a 15min sustained submaximal contraction at 25% of their maximum EMG. Subsequent ten 2-min contractions held at 25% EMG were also performed to sustain fatigue for a total of 30min, while SICI and LICI were taken immediately after each contraction. There was no change in SICI post-fatiguing exercise compared to baseline in both young and older adults (P = 0.4). Although there was no change in LICI post-fatiguing exercise in younger adults (P = 1.0), LICI was attenuated in older adults immediately post-fatiguing exercise and remained attenuated post-fatigue (PF)1 and PF2 (P < 0.05). Contrary to previous studies, the lack of change in SICI and LICI in young adults following a sustained submaximal EMG contraction suggests that GABA modulation may be dependent on the type of fatiguing task performed. The reduction in LICI in older adults post-fatiguing exercise suggests an age-related decrease in GABAB-mediated activity with sustained submaximal fatiguing exercise.

SICI during changing brain states: Differences in methodology can lead to different conclusions

BackgroundShort-latency intracortical inhibition (SICI) is extensively used to probe GABAergic inhibitory mechanisms in M1. Task-related changes in SICI are presumed to reflect changes in the central excitability of GABAergic pathways. Usually, the level of SICI is evaluated using a single intensity of conditioning stimulus so that inhibition can be compared in different brain states. ObjectiveHere, we show that this approach may sometimes be inadequate since distinct conclusions can be drawn if a different CS intensity is used. MethodsWe measured SICI using a range of CS intensities at rest and during a warned simple reaction time task. ConclusionsOur results show that SICI changes that occurred during the task could be either larger or smaller than at rest depending on the intensity of the CS. These findings indicate that careful interpretation of results are needed when a single intensity of CS is used to measure task-related physiological changes.

Neurophysiological responses and adaptation following repeated bouts of maximal lengthening contractions in young and older adults

A bout of maximal lengthening contractions is known to produce muscle damage, but confers protection against subsequent damaging bouts, with both tending to be lower in older adults. Neural factors contribute to this adaptation, but the role of the corticospinal pathway remains unclear. Twelve young (27 ± 5 yr) and 11 older adults (66 ± 4 yr) performed two bouts of 60 maximal lengthening dorsiflexions 2 weeks apart. Neuromuscular responses were measured preexercise, immediately postexercise, and at 24 and 72 h following both bouts. The initial bout resulted in prolonged reductions in maximal voluntary torque (MVC; immediately postexercise onward, P < 0.001) and increased creatine kinase (from 24 h onward, P = 0.001), with both responses being attenuated following the second bout (P < 0.015), demonstrating adaptation. Smaller reductions in MVC following both bouts occurred in older adults (P = 0.005). Intracortical facilitation showed no changes (P ≥ 0.245). Motor-evoked potentials increased 24 and 72 h postexercise in young (P ≤ 0.038). Torque variability (P ≤ 0.041) and H-reflex size (P = 0.024) increased, while short-interval intracortical inhibition (SICI; P = 0.019) and the silent period duration (SP) decreased (P = 0.001) in both groups immediately postexercise. The SP decrease was smaller following the second bout (P = 0.021), and there was an association between the change in SICI and reduction in MVC 24 h postexercise in young adults (R = -0.47, P = 0.036). Changes in neurophysiological responses were mostly limited to immediately postexercise, suggesting a modest role in adaptation. In young adults, neural inhibitory changes are linked to the extent of MVC reduction, possibly mediated by the muscle damage-related afferent feedback. Older adults incurred less muscle damage, which has implications for exercise prescription.NEW & NOTEWORTHY This is the first study to have collectively assessed the role of corticospinal, spinal, and intracortical activity in muscle damage attenuation following repeated bouts of exercise in young and older adults. Lower levels of muscle damage in older adults are not related to their neurophysiological responses. Neural inhibition transiently changed, which might be related to the extent of muscle damage; however, the role of processes along the corticospinal pathway in the adaptive response is limited.

Neuromuscular effects of dorsiflexor training with and without blood flow restriction

Blood flow restriction training (BFRT) has been proposed for elderly and clinical populations with weakness. Before being used in these populations it is important to understand the neurological effects of, and subject perceptions to, BFRT. Seventeen healthy subjects were recruited and performed 2 experimental sessions, BFRT and training without blood flow restriction (TR-only), on separate days. Four sets of concentric/eccentric dorsiflexion contractions against theraband resistance were performed. Surface electromyography of the tibialis anterior was recorded during exercise and for the electrophysiological measures. At baseline, immediately-post, 10-min-post and 20-min-post exercise, motor evoked potentials (MEPs) from single pulse transcranial magnetic stimulation (TMS), paired-pulse TMS with interstimulus intervals of 2-ms (SICI) and 15-ms (ICF), and the M-max amplitude were recorded in the resting TA. Following training, subjects provided a numerical rating of the levels of pain, discomfort, fatigue, focus and difficulty during training. Muscle activation was higher in the last 20 contractions during BFRT compared to TR. There was no difference (time × condition interaction) between BFRT and TR for single-pulse MEP, SICI, ICF or M-max amplitude. There was a significant main effect of timepoint for single-pulse MEP and M-max amplitudes with both significantly reduced for 20-min-post exercise. No reductions were observed for SICI and ICF amplitudes. Taken together, BFRT and TR-only were only different during exercise and both regimes induced similar significant reductions in M-Max and MEP-amplitude post-training. Due to the lack of changes in SICI and ICF, it is unlikely that changes occurred in cortical sites related to these pathways. The increased surface electromyography activity in the last 20 contractions, indicate that the training regimes are different and that BFRT possibly induces more fatigue than TR. As such, BFRT could be used as an adjunct to conventional training. However, as subjects perceived BFRT as more painful, difficult and uncomfortable than TR-only, people should be selected carefully to undertake BFRT.

Electrical Stimulation of Back Muscles Does Not Prime the Corticospinal Pathway

To investigate whether peripheral electrical stimulation (PES) of back extensor muscles changes excitability of the corticospinal pathway of the stimulated muscle and synergist trunk muscles. In 12 volunteers with no history of low back pain (LBP), intramuscular fine-wire electrodes recorded electromyography (EMG) from the deep multifidus (DM) and longissimus muscles. Surface electrodes recorded general EMG from the erector spinae and abdominal muscles. Single- and paired-pulse transcranial magnetic stimulation (TMS) paradigms tested corticospinal excitability, short-interval intracortical inhibition (SICI-2 and 3 ms), and intracortical facilitation (ICF) optimized for recordings of DM. Active motor threshold (aMT) to evoke a motor-evoked potential (MEP) in DM was determined and stimulation was applied at 120% of this intensity. PES was provided via electrodes placed over the right multifidus. The effect of 20-min PES (ramped motor activation) was studied. Mean aMT for DM was 42.7 ± 10% of the maximal stimulator output. No effects of PES were found on MEP amplitude (single-pulse TMS) for any trunk muscles examined. There was no evidence for changes in SICI or ICF; that is, conditioned MEP amplitude was not different between trials after PES. Results indicate that, unlike previous reports that show increased corticospinal excitability of limb muscles, PES of back muscles does not modify the corticospinal excitability. This difference in response of the motor pathway of back muscles to PES might be explained by the lesser importance of voluntary cortical drive to these muscles and the greater role of postural networks. Whether PES influences back muscle training remains unclear, yet the present results suggest that potential effects are unlikely to be explained by the effects of PES at corticospinal level with the parameters used in this study.

Modulation of specific inhibitory networks in fatigued locomotor muscles of healthy males

Reduced maximal force capability of skeletal muscle, as a consequence of exercise, can be due to peripheral or central fatigue mechanisms. In upper-limb muscles, neuromuscular fatigue is concurrent with reduced corticospinal excitability and increased inhibition (lengthened corticospinal silent period [CSP]; reduced short-interval intracortical inhibition [SICI] ratio). However, it is unclear whether these adjustments occur in response to fatiguing exercise of locomotor muscles. This study examined the effect of fatiguing, maximal, knee-extensor exercise on motor cortical excitability and inhibition. Thirteen males performed three 30-s maximal, isometric contractions with the dominant knee-extensors (MVC1, MVC2 and MVC3), separated by 60 s. At the end of, and between each MVC, neuromuscular fatigue, corticospinal excitability, CSP and SICI were assessed with supramaximal stimulation of the femoral nerve, and motor cortical stimulation, respectively. Repeated MVCs caused progressive reductions in MVC (− 10, − 24 and − 29%, respectively, P ≤ 0.01), along with significant peripheral (reductions in potentiated twitch of − 23, −53 and − 60%, respectively, P < 0.001) and central (reductions in VA of − 10% and − 13% post-MVC2 and 3, respectively, P ≤ 0.01) fatigue. Following MVC1 corticospinal excitability was reduced, and remained depressed thereafter. CSP increased in duration and remained longer throughout the protocol; whereas, no change in SICI was observed. Repeated, sustained, maximal contractions of the knee-extensors elicited substantial peripheral and central fatigue that was accompanied by a concomitant reduction in corticospinal excitability. However, divergent responses exist between inhibitory networks within the motor cortex, the activity of inhibitory networks mediated by GABAB are increased, whereas those mediated by GABAA are not.

Relationship between intracortical inhibition and motor behavior; implications for incomplete spinal cord injury

The sensorimotor cortices of the human brain contain intracortical inhibitory circuits that influence the neural output to muscles. Intracortical circuits of short and long-interval intracortical inhibition (SICI and LICI) can be probed using paired-pulse TMS paradigms while recording activity from the muscles. We recently identified changes in SICI and LICI within the motor cortex in individuals with incomplete cervical spinal cord injury. Decreases in the range of intensities eliciting SICI recruitment were observed without a difference in the depth of SICI. Active LICI was increased at higher conditioning intensities relative to controls. These changes may be linked to plastic and physiological changes of GABAergic cortical systems with SCI. Here we discuss the role of SICI and LICI in motor behavior and how the observed changes in these measures that follow SCI may explain motor impairments seen in this population.

Short-term immobilization influences use-dependent cortical plasticity and fine motor performance

Short-term immobilization that reduces muscle use for 8–10h is known to influence cortical excitability and motor performance. However, the mechanisms through which this is achieved, and whether these changes can be used to modify cortical plasticity and motor skill learning, are not known. The purpose of this study was to investigate the influence of short-term immobilization on use-dependent cortical plasticity, motor learning and retention. Twenty-one adults were divided into control and immobilized groups, both of which underwent two experimental sessions on consecutive days. Within each session, transcranial magnetic stimulation (TMS) was used to assess motor-evoked potential (MEP) amplitudes, short- (SICI) and long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF) before and after a grooved pegboard task. Prior to the second training session, the immobilized group underwent 8h of left hand immobilization targeting the index finger, while control subjects were allowed normal limb use. Immobilization produced a reduction in MEP amplitudes, but no change in SICI, LICI or ICF. While motor performance improved for both groups in each session, the level of performance was greater 24-h later in control, but not immobilized subjects. Furthermore, training-related MEP facilitation was greater after, compared with before, immobilization. These results indicate that immobilization can modulate use-dependent plasticity and the retention of motor skills. They also suggest that changes in intracortical excitability are unlikely to contribute to the immobilization-induced modification of cortical excitability.

Balancing the excitability of M1 circuitry during movement observation without overt replication.

Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE), and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS) over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: (i) electric cervicomedullary stimulation (CMS), to test spinal excitability, (ii) paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition (SICI) and intracortical facilitation (ICF)], and (iii) continuous theta-burst stimulation (cTBS), to modulate the excitability of M1 cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500 ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.

Homeostatic metaplasticity of corticospinal excitatory and intracortical inhibitory neural circuits in human motor cortex

Homeostatic metaplasticity, a fundamental principle for maintaining overall synaptic weight in the physiological range in neuronal networks, was demonstrated at the cellular and systems level predominantly for excitatory synaptic neurotransmission. Although inhibitory networks are crucial for regulating excitability, it is largely unknown to what extent homeostatic metaplasticity of inhibition also exists. Here, we employed intermittent and continuous transcranial magnetic theta burst stimulation (iTBS, cTBS) of the primary motor cortex in healthy subjects for induction of long-term potentiation (LTP)-like and long-term depression (LTD)-like plasticity. We studied metaplasticity by testing the interactions of priming TBS with LTP/LTD-like plasticity induced by subsequent test TBS. Changes in excitatory neurotransmission were measured by the input-output curve of motor-evoked potentials (IO-MEP), and changes in GABA(A)ergic inhibitory neurotransmission by the IO of short-interval intracortical inhibition (IO-SICI, four conditioning stimulus intensities of 70-100% active motor threshold, interstimulus interval 2.0 ms). Non-primed iTBS increased IO-MEP, while non-primed cTBS decreased IO-MEP. Pairing of identical protocols (iTBSiTBS, cTBScTBS) resulted in suppression of the non-primed TBS effects on IO-MEP, and pairing of different protocols (cTBSiTBS, iTBScTBS) enhanced the test TBS effects on IO-MEP. While non-primed TBS did not result in significant changes of IO-SICI, iTBSiTBS resulted in IO-SICI decrease, and cTBScTBS in IO-SICI increase compared with the non-primed conditions. The changes in SICI induced by priming TBS correlated with the changes in MEP induced by subsequent test TBS. Findings demonstrate that plasticity in both excitatory and inhibitory circuits in the human motor cortex are regulated by homeostatic metaplasticity, and that priming effects on inhibition contribute to the homeostatic regulation of metaplasticity in excitatory circuits.

Excitability of intracortical inhibitory and facilitatory circuits during ischemic nerve block

The primary motor cortex is capable of rapid, reversible plastic changes and longer-term, more permanent reorganization. Ischemic nerve block (INB) is a model of deafferentation-induced short-term plasticity. We used transcranial magnetic stimulation to examine whether changes in the excitability of short- and/or long-interval intracortical inhibitory (SICI, LICI) or short-interval intracortical facilitatory (SICF) circuits underlie the corticospinal excitability increases observed during INB. SICI and LICI recruitment curves, obtained by varying conditioning stimulus intensity, and SICF were measured at multiple inter-stimulus intervals (ISIs). Forearm flexor MEP amplitude increased during INB at the wrist; this was not accompanied by changes in SICI at ISIs of 1 or 2 ms, in SICF at ISIs of 1.2, 2.7, or 4.4 ms, or in LICI at an ISI of 80 ms, but was accompanied by an increase in LICI at an ISI of 150 ms. The results suggest that (1) the increased excitability of forearm flexors is not due to reduced SICI or LICI or increased SICF, and (2) LICI measured at ISIs of 80 and 150 ms are distinct processes. We discuss the importance of identifying distinct processes of LICI and speculate regarding other mechanisms that could potentially underlie INB-induced plasticity.

Short latency intracortical inhibition: one of the most popular tools in human motor neurophysiology

Short latency intracortical inhibition: one of the most popular tools in human motor neurophysiology

Relaxation from a voluntary contraction is preceded by increased excitability of motor cortical inhibitory circuits.

Termination of a muscle contraction is as important a part of movement as muscle activation yet the mechanisms responsible are less well understood. In the present experiments we examined the possible role of intracortical inhibitory circuits in terminating a 20% maximum isometric contraction of the first dorsal interosseous muscle (FDI) in eight healthy subjects. Subjects performed the task simultaneously with both hands and received single or pairs (at an interstimulus interval of 3 ms to evaluate short interval intracortical inhibition, SICI) of transcranial magnetic stimuli (TMS) via a focal coil over the motor hand area of the left hemisphere at different times before and after the onset of relaxation. The amplitude of the motor-evoked potential (MEP) following a single or a pair of TMS pulses was measured in the right FDI and plotted relative to the onset of relaxation as estimated from the surface electromyogram (EMG) of the left FDI. MEPs were larger during contraction than after relaxation whereas SICI was absent during contraction and reappeared after relaxation. We found that in all subjects, the time course of MEP changes during relaxation was closely fitted by a Boltzmann sigmoidal curve which allowed us to estimate the mean MEP amplitudes as well as the ratio of the amplitudes after single or pairs of TMS pulses (i.e.%SICI) at any time in the task. The data showed that the amplitude of MEPs to single pulse TMS had started to decline at about the same time as the onset of EMG silence. Furthermore, the size of the MEPs evoked by paired pulses decreased up to 30 ms beforehand. The latter suggests that an increase in SICI occurs prior to the onset of MEP changes, and hence that increased cortical inhibition may play a role in suppressing corticospinal excitability during relaxation. A subsidiary experiment showed that the time relations of changes in SICI and MEP were unchanged by a period of 10 min training on the task.