Simranjit K. Sidhu

Cortical voluntary activation of the human knee extensors can be reliably estimated using transcranial magnetic stimulation

The objective of this study was to determine if a transcranial magnetic stimulation (TMS) method of quantifying the degree to which the motor cortex drives the muscles during voluntary efforts can be reliably applied to the human knee extensors. Although the technique for estimating “cortical” voluntary activation (VA) is valid and reliable for elbow flexors and wrist extensors, evidence that it can be applied to muscles of the lower limb is necessary if twitch interpolation with TMS is to be widely used in research or clinical practice. Eight subjects completed two identical test sessions involving brief isometric knee extensions at forces ranging from rest to maximal voluntary contraction (MVC). Electromyographic (EMG) responses to TMS of the motor cortex and electrical stimulation of the femoral nerve were recorded from the rectus femoris (RF) and biceps femoris (BF) muscles, and knee extension twitch forces evoked by stimulation were measured. The amplitude of TMS‐evoked twitch forces decreased linearly between 25% and 100% MVC (r2 > 0.9), and produced reliable estimations of resting twitch and VA (ICC2,1 > 0.85). The reliability and size of cortical measures of VA were comparable to those derived from motor nerve stimulation when the resting twitches were estimated on the basis of as few as three TMS trials. Thus, TMS measures of VA may provide a reliable and valid tool in studies investigating central fatigue due to exercise and neurological deficits in neural drive in the lower limbs.

Motor cortex excitability does not increase during sustained cycling exercise to volitional exhaustion

The excitability of the motor cortex increases as fatigue develops during sustained single-joint contractions, but there are no previous reports on how corticospinal excitability is affected by sustained locomotor exercise. Here we addressed this issue by measuring spinal and cortical excitability changes during sustained cycling exercise. Vastus lateralis (VL) and rectus femoris (RF) muscle responses to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs) and electrical stimulation of the descending tracts (cervicomedullary evoked potentials, CMEPs) were recorded every 3 min from nine subjects during 30 min of cycling at 75% of maximum workload (W(max)), and every minute during subsequent exercise at 105% of W(max) until subjective task failure. Responses were also measured during nonfatiguing control bouts at 80% and 110% of W(max) prior to sustained exercise. There were no significant changes in MEPs or CMEPs (P > 0.05) during the sustained cycling exercise. These results suggest that, in contrast to sustained single-joint contractions, sustained cycling exercise does not increase the excitability of motor cortical neurons. The contrasting corticospinal responses to the two modes of exercise may be due to differences in their associated systemic physiological consequences.

Spinal μ-opioid receptor-sensitive lower limb muscle afferents determine corticospinal responsiveness and promote central fatigue in upper limb muscle

We aimed to elucidate the role of group III/IV locomotor muscle afferents in the development of central fatigue and the responsiveness of the corticospinal tract in relation to an unexercised arm muscle. Intrathecal fentanyl, a μ‐opioid receptor agonist, was employed to attenuate afferent feedback from the leg muscles during intense cycling exercise characterized by either no or severe peripheral locomotor muscle fatigue. In the absence of locomotor muscle fatigue, group III/IV‐mediated leg afferent feedback facilitates the responsiveness of the motor pathway to upper limb flexor muscles. By contrast, in the presence of leg fatigue, group III/IV locomotor muscle afferents facilitate supraspinal fatigue in a remote muscle not involved in the exercise and disfacilitate the responsiveness of associated corticospinal projections.

Corticospinal contributions to lower limb muscle activity during cycling in humans

The purpose of the current study was to investigate corticospinal contributions to locomotor drive to leg muscles involved in cycling. We studied 1) if activation of inhibitory interneurons in the cortex via subthreshold transcranial magnetic stimulation (TMS) caused a suppression of EMG and 2) how the responses to stimulation of the motor cortex via TMS and cervicomedullary stimulation (CMS) were modulated across the locomotor cycle. TMS at intensities subthreshold for activation of the corticospinal tract elicited suppression of EMG for approximately one-half of the subjects and muscles during cycling, and in matched static contractions in vastus lateralis. There was also significant modulation in the size of motor-evoked potentials (MEPs) elicited by TMS across the locomotor cycle (P < 0.001) that was strongly related to variation in background EMG in all muscles (r > 0.86; P < 0.05). When MEP and CMEP amplitudes were normalized to background EMG, they were relatively larger prior to the main EMG burst and smaller when background EMG was maximum. Since the pattern of modulation of normalized MEP and CMEP responses was similar, the data suggest that phase-dependent modulation of corticospinal responses during cycling in humans is driven mainly by spinal mechanisms. However, there were subtle differences in the degree to which normalized MEP and CMEP responses were facilitated prior to EMG burst, which might reflect small increases in cortical excitability prior to maximum muscle activation. The data demonstrate that the motor cortex contributes actively to locomotor drive, and that spinal factors dominate phase-dependent modulation of corticospinal excitability during cycling in humans.

Group III/IV muscle afferents limit the intramuscular metabolic perturbation during whole body exercise in humans

The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise‐induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ‐opioid receptor‐sensitive locomotor muscle afferents during a 5 km cycling time trial. The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural ‘drive’ to working locomotor muscle and limits the exercise‐induced intramuscular metabolic perturbation. Therefore, the CNS might regulate the degree of metabolic perturbation within locomotor muscle and thereby limit peripheral fatigue. It appears that the group III/IV muscle afferents are an important neural link in this regulatory mechanism, which probably serves to protect locomotor muscle from the potentially severe functional impairment as a consequence of severe intramuscular metabolic disturbance.

Corticospinal responses to sustained locomotor exercises: moving beyond single-joint studies of central fatigue

There is substantial evidence that fatiguing exercise is accompanied by changes within the central nervous system that reduce the force that can be produced by working muscles. Here we review studies that used non-invasive neurophysiological techniques to show that sustained single-joint contractions have the capacity to increase corticospinal responsiveness and reduce motoneuronal responsiveness. We contrast these findings with new evidence from our laboratory regarding corticospinal responsiveness during sustained cycling exercise. There seems to be a similar increase in responsiveness of the intracortical inhibitory interneurons during sustained locomotor and single-joint exercise which might be due to acute exercise responses that are common to fatiguing exercise of any nature, such as local accumulation of fatigue metabolites. In contrast, the pattern of changes in corticospinal responsiveness is fundamentally different between the two modes of exercise which might be due to greater systemic fatigue responses to locomotor exercises.

Corticospinal modulation induced by sounds depends on action preparedness

•  Unexpected loud auditory stimuli can trigger the involuntary release of motor actions during preparation to move. •  Because acoustic stimulation can suppress motor cortex excitability during action, this early release could be independent of the motor cortex, and interpreted as pre‐planned action stored and triggered from subcortical areas. •  In contrast, we show that corticospinal excitability in response to the loud auditory stimuli was increased when people were highly prepared to move, and reduced otherwise. •  Our results also indicate that auditory stimuli can affect intracortical excitability by increasing intracortical facilitation and reducing short‐interval intracortical inhibition. •  Together, our findings demonstrate that the early release of motor responses by auditory stimuli involves the motor cortex.

Sustained Cycling Exercise Increases Intracortical Inhibition

PURPOSE In the current study, we measured EMG suppression induced by subthreshold transcranial magnetic stimulation (TMS) to investigate the effects of sustained cycling exercise on intracortical inhibition. METHODS Sixteen subjects cycled at 75% of their maximum workload (Wmax) for 30 min, during which subthreshold TMS was applied at a defined crank angle where vastus lateralis (VL) EMG amplitude was increasing and approximately 50% of its recorded maximum. Subthreshold TMS was also applied during nonfatiguing control cycling bouts at 75% and 37.5% of Wmaxbefore sustained cycling. RESULTS Although EMG in VL during control cycling at 37.5% Wmax was approximately half that during cycling at 75% Wmax (P ≤ 0.05), the amount of EMG suppression was not different between workloads (P > 0.05). EMG amplitude in VL recorded in the last 5 min of sustained cycling was not different from the first 5 min (P > 0.05), whereas the amount of EMG suppression at the end of the sustained cycling was significantly greater than that at the start (P ≤ 0.05). CONCLUSIONS The increase in TMS-evoked EMG suppression during sustained cycling implies an increase in the excitability of the intracortical inhibitory interneurons during the exercise. The observed increase in intracortical inhibition is similar to that observed during sustained single joint contractions, suggesting that changes in the responsiveness of intracortical inhibitory interneurons are similar during locomotor exercise and static single joint contractions.

Group III/IV locomotor muscle afferents alter motor cortical and corticospinal excitability and promote central fatigue during cycling exercise

OBJECTIVE To investigate the influence of group III/IV muscle afferents on the development of central fatigue and corticospinal excitability during exercise. METHODS Fourteen males performed cycling-exercise both under control-conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from leg muscle afferents. Transcranial magnetic- and cervicomedullary stimulation was used to monitor cortical versus spinal excitability. RESULTS While fentanyl-blockade during non-fatiguing cycling had no effect on motor-evoked potentials (MEPs), cervicomedullary-evoked motor potentials (CMEPs) were 13±3% higher (P<0.05), resulting in a decrease in MEP/CMEP (P<0.05). Although the pre- to post-exercise reduction in resting twitch was greater in FENT vs. CTRL (-53±3% vs. -39±3%; P<0.01), the reduction in voluntary muscle activation was smaller (-2±2% vs. -10±2%; P<0.05). Compared to the start of fatiguing exercise, MEPs and CMEPs were unchanged at exhaustion in CTRL. In contrast, MEPs and MEP/CMEP increased 13±3% and 25±6% in FENT (P<0.05). CONCLUSION During non-fatiguing exercise, group III/IV muscle afferents disfacilitate, or inhibit, spinal motoneurons and facilitate motor cortical cells. In contrast, during exhaustive exercise, group III/IV muscle afferents disfacilitate/inhibit the motor cortex and promote central fatigue. SIGNIFICANCE Group III/IV muscle afferents influence corticospinal excitability and central fatigue during whole-body exercise in humans.

Short-interval intracortical inhibition in knee extensors during locomotor cycling

Short‐interval intracortical inhibition (SICI) can provide information on changes in cortical responsiveness during voluntary contractions. It is, however, unknown whether the magnitude of SICI changes throughout the cycle of rhythmic movements such as leg cycling.