Mechanisms of cortical reorganization in lower-limb amputees

Abstract

The human motor system undergoes reorganization after amputation, but the site of motor reorganization and the mechanisms involved are unknown. We studied the site and mechanisms of motor reorganization in 16 subjects with traumatic lower-limb amputation. Stimulation at different levels in the CNS was used to determine the site of reorganization. The mechanisms involved were evaluated by measuring the thresholds for transcranial magnetic stimulation (TMS) and by testing intracortical inhibition and facilitation. With TMS, the threshold for muscle activation on the amputated side was lower than that of the intact side, but with transcranial electrical stimulation there was no difference in motor threshold between the two sides. TMS at the maximal output of the stimulator activated a higher percentage of the motor neuron pool (%MNP) on the amputated side than on the intact side. The %MNP activated by spinal electrical stimulation was similar on the two sides. Paired TMS study showed significantly less intracortical inhibition on the amputated side. Our findings suggest that motor reorganization after lower-limb amputation occurs predominately at the cortical level. The mechanisms involved are likely to include reduction of GABAergic inhibition.

Fig. 1.

Motor threshold for transcranial magnetic stimulation (A; n = 14) and transcranial electrical stimulation (B;n = 7). Each line represents one subject, and each error bar represents 1 SEM.

Fig. 2.

A, Maximum amplitudes produced by TMS (n = 14), TES (n = 13), SES (n = 13), and FNS (n = 14).B, Percentage of motor neuron pool activated with TMS (n = 14), TES (n = 13), and SES (n = 13). MEP, Motor-evoked potential; TMS, transcranial magnetic stimulation;TES, transcranial electrical stimulation;SES, spinal electrical stimulation; FNS, femoral nerve stimulation. Asterisks indicate a significant difference between the amputated and intact sides. Error bar indicates 1 SEM.

Fig. 3.

Paired TMS study. Interstimulus interval (ISI) of 0 represents the MEP amplitude of the test pulse alone, which is defined as 100%. Each point represents an average of 11 subjects for the amputated side, seven subjects for the intact side, and seven normal subjects. On the intact side and in normal subjects, there was inhibition at ISIs of 2 and 4 msec and facilitation at ISIs of 6–30 msec. On the amputated side, there was more facilitation than on the intact side at all ISIs. Error bar indicates 1 SEM.

Fig. 4.

A, Average MEP amplitude for inhibitory ISIs of 2 and 4 msec and facilitatory ISIs of 10 and 15 msec. B, Maximum inhibition and facilitation among all ISIs. The asterisk indicates a significant difference between the amputated and intact sides, and plus signsindicate a significant difference between the amputated side and normal subjects.

Fig. 5.

A subthreshold conditioning TMS was followed by either a suprathreshold test TMS (paired TMS) or electrical stimulation of the femoral nerve to elicit an H-reflex (femoral H-reflex). The ISI indicated for the femoral nerve H-reflex study reflects the potential arrival time of the stimuli at the spinal cord. The actual ISIs between TMS and femoral nerve stimulation were adjusted in each subject according to the TMS and H-reflex latencies. A, Results from six normal subjects. There was significant inhibition of the TMS test response at the ISI of 2 msec and facilitation at the ISI of 10 msec, but the femoral H-reflex amplitude was unchanged at all ISIs.B, Results from the amputated side of three lower-limb amputees. Each line represents one subject. The TMS test responses were inhibited (2 amputees) or facilitated (1 amputee) at the ISI of 2 msec and was facilitated at the ISI of 10 msec. The femoral H-reflex amplitude was unchanged at all ISIs.