The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.
ProtocolAn input-output curve for the MEP amplitude evoked in the resting FDI by TMS was constructed. Ten TMS were delivered at each intensity, beginning 10-12 % below resting threshold and increasing incrementally in 3 % steps to either 100 % of stimulator output, or to a stimulus intensity where MEP amplitude had Age and sex differences in human motor cortex input-output characteristics Julia B. Pitcher, Kirstin M. Ogston and Timothy S. Miles Department of Physiology, The University of Adelaide, Adelaide, South Australia 5005, AustraliaStimulus-response curves for motor evoked potentials (MEPs) induced in a hand muscle by transcranial magnetic stimulation (TMS) were constructed for 42 subjects with the aim of identifying differences related to age and sex. There was no effect of age on the resting threshold to TMS, the maximal amplitude of the MEP that could be evoked (MEP max ) or the maximal slope of the stimulus-response curve. However, higher stimulus intensities were required to achieve both MEP max and the maximal slope in the older subjects. The trial-to-trial variability of MEPs was greater in the older subjects, particularly at intensities near threshold. There was a significant interaction between age, threshold and trial-to-trial variability of MEP amplitude. Overall, MEP variability fell markedly as stimulus intensity increased above threshold but less rapidly in older than in younger subjects. Females tended to have larger MEP variability than males, but age and threshold were much stronger modulators than sex. These differences in input-output characteristics are likely to be due either to a decreased number of spinal motoneurones being activated synchronously in older subjects, or to the activation of the same number of motoneurones in a less synchronous manner, leading to phase cancellation in the surface electromyogram. Journal of Physiologyreached a plateau. The MEPs evoked at each stimulus intensity were averaged on-line. The peak-to-peak amplitude and onset latency of these averages were then determined with customwritten software (LabVIEW, National Instruments, Austin, TX, USA). All MEP and M-wave data are presented as the ensemble averages of 10 trials.The amplitudes of the MEP averages were plotted against stimulus intensity in each subject, and the Marquardt-Levenberg algorithm for least squares convergence (Sigmaplot for Windows 5.0, 1986-1999; SPSS Inc., IL, USA) was used to calculate the best fit of the cortical stimulus-response curves of each subject. The calculation was based on the highest coefficient of determination, R 2 , and the resulting 5-parameter sigmoidal curve is described by the following equation:where the five parameters are the difference between the smallest and the largest MEP amplitudes observed, i.e. the range between the two asymptotes (a); the minimum MEP amplitude (y 0 ); the difference between the stimulus intensities at 75 % and 25 % of the maximum MEP amplitude (i.e. the width of the transition) (b); the stimulus intensity required to obtain an MEP that ...
Combined peripheral nerve and brain stimulation ("dual stimulation") induces changes in the excitability of normal motor cortex. The authors sought to establish whether dual stimulation would also induce motor cortex plasticity and associated functional improvements in nine stroke patients with chronic stable hemiparesis. Following 4 weeks of daily dual stimulation, improvements were seen in some neurophysiological and functional measures. This technique may offer therapeutic opportunities in some stroke patients.
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