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.

Corticospinal excitability can be increased by a transcranial magnetic stimulation (TMS) intervention that delivers repeated paired TMS pulses at an I (indirect)-wave interval of 1.5 ms. This is thought to target excitatory synaptic events by reinforcing facilitatory I-wave interaction, however, it remains to be determined what effect this intervention has on the various I-wave components. In the present study we compared I-wave facilitation curves over a range of inter-pulse intervals (IPIs) encompassing the first three I-waves, before and after 15 min of a paired-pulse TMS intervention with an IPI of 1.5 ms. The three peaks in the I-wave facilitation curves occurred at the same IPIs pre- and post-intervention (1.3, 2.5 and 4.3 ms). The facilitation curves were increased in amplitude for all three I-wave peaks post-intervention (mean increase 33%), and the mean increase across all IPIs correlated with the post-intervention increase in single-pulse MEP amplitude (r = 0.77). Modelling showed that the changes in the post-intervention curves were consistent with an increase in amplitude and broadening of the individual I-wave peaks. We conclude that an iTMS intervention with an IPI of 1.5 ms is able to target multiple I-waves. The findings are consistent with existing models of I-wave generation and suggest that the intervention increases the efficacy of synaptic events associated with the generation of descending I-wave volleys.

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.

We have compared functional MRI signals in primary sensorimotor cortex (SM1) during a paced motor task of each hand before and after unimanual (right hand) fatiguing exercise. Our aims were to determine whether the degree of activation is different when a motor task is performed after a fatiguing exercise, and whether there are any differences in activation between movement of the fatigued and non-fatigued hands. There was a significant reduction in the number of voxels activated in SM1 in the hemisphere contralateral to movement of both the fatigued hand (38 +/- 5 pre-exercise versus 21 +/- 3 post-exercise; P<0.05) and the non-fatigued hand (32 +/- 4 pre-exercise vs 18 +/- 4 post-exercise; P<0.05). There was no significant difference in the magnitude of the functional magnetic resonance imaging signal before or after exercise, however, the variance increased significantly after exercise (6.0 +/- 0.5 pre-exercise vs 7.3 +/- 0.6 post-exercise; P<0.01). Reduced functional activation in SM1 may reflect increased variability in the activation rather than a reduction in activation of cortical motor networks after fatigue.

The aim of this study was to determine whether there were significant changes in the time course of the functional magnetic resonance imaging (fMRI) signal in motor and non-motor regions of both cerebral hemispheres during a unilateral fatiguing exercise of the hand. Twelve subjects performed a submaximal (30%) intermittent fatiguing handgrip exercise (3 s grip, 2 s release, left hand) for approximately 9 min during fMRI scanning. Regression analysis was used to measure changes in fMRI signal from primary sensorimotor cortex (SM1), premotor cortex and visual cortex (V1) in both hemispheres. Force declined to 77 +/- 3.6% of prefatigue maximal force (P < 0.05). The fMRI signal from SM1 contralateral to the fatiguing hand increased by 1.2 +/- 0.5% of baseline (P < 0.05). The fMRI signal from the ipsilateral SM1 did not change significantly. Premotor cortex showed a similar pattern but did not reach significance. The signal from V1 increased significantly for both hemispheres (contralateral 1.3 +/- 0.9%, ipsilateral 1.5 +/- 0.9% of baseline and P < 0.05). During the performance of a unimanual, submaximal fatiguing exercise there is an increase in activation of motor and non-motor regions. The results are in keeping with the notion of an increase in sensory processing and corticomotor drive during fatiguing exercise to maintain task performance as fatigue develops.

We have previously shown that following a period of unimanual fatiguing exercise, there is a reduction in primary sensorimotor cortex (SM1) activation with movement of either the fatigued or the non-fatigued hand by Benwell et al. (Exp Brain Res 167:160-164, 2005). In the present study we have investigated whether this reduction is confined to motor areas or is more widespread. Functional imaging was performed before and after a 10-minute fatiguing exercise of the left hand (30% of maximum handgrip strength) in seven normal subjects (4 M, mean age 25 years). The activating task was a handgrip against a low resistance (1 kg) in response to a visual cue (chequerboard reversal every 2 +/- 0.5 s). We compared activation in SM1, supplementary motor area (SMA), cerebellum (CB) and primary visual cortex (V1) before and after the fatiguing exercise. After exercise, contralateral SM1 activation was reduced by 33% (P < 0.05) compared to baseline for the fatigued hand and by 49% for the non-fatigued hand (P < 0.05). A similar pattern was seen for the bilateral SMA and ipsilateral CB following exercise (45 vs. 50% for SMA; 30 vs. 35% for CB; fatigued versus non-fatigued). Activation was also reduced in V1 but to a lesser extent than in motor areas (19 vs. 24%; fatigued versus non-fatigued). These results show that although the reduced functional activation during the recovery period after fatiguing exercise is more marked in motor areas, it also extends to non-motor areas such as the visual cortex, suggesting that there are more widespread changes in cerebral haemodynamic responses after fatigue.

Previous studies have shown that the motor evoked potential (MEP) amplitude increases as force declines during a fatiguing muscle contraction, indicating that there is an increase in corticomotor excitability. In spite of this there is a progressive reduction in voluntary motor drive, as shown by an increase in the interpolated twitch force as fatigue develops. The aim of this study was to determine whether, by further increasing corticomotor excitability using a paired-pulse rTMS protocol designed to induce I-wave facilitation (iTMS), force loss during a sustained voluntary contraction could be reduced. We designed a cross-over study incorporating a 15-min period of iTMS (ISI 1.5 ms; 0.2 Hz; approximately AMT), following which MEP amplitude (first dorsal interosseous muscle) increased to 194 +/- 38% of baseline (P < 0.05), compared to a control period of stimulation that did not increase MEP amplitude (single-pulse TMS; 0.2 Hz; approximately 1.2 AMT). Eight right-handed healthy subjects received both iTMS and control stimulation, in a randomized order, a week apart. We measured percentage force loss at the end of a 10-s maximum right hand key-pinch task, and compared force loss before and after stimulation. There was an improvement in task performance following iTMS, with a reduction in force loss compared to pre-stimulation baseline (11.3 +/- 2.0 vs. 17.6 +/- 2.4%; post vs. pre; P < 0.05). There was no significant difference in force loss before and after control stimulation. The results indicate that by increasing corticomotor excitability using paired-pulse rTMS at trans-synaptic intervals, maximum voluntary force can be sustained at a higher level during a brief fatiguing maximal voluntary contraction.

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