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.Key words: amputation; motor reorganization; mechanisms of plasticity; human; transcranial magnetic stimulation; motor cortexThe motor system undergoes reorganization after peripheral nerve lesions Sanes et al., 1990), spinal cord injuries (Lev y et al., 1990;Topka et al., 1991), cortical lesions (Jenkins and Merzenich, 1987;Benecke et al., 1991;Cohen et al., 1991b;Weiller et al., 1992;Nudo et al., 1996), amputations (Hall et al., 1990;Cohen et al., 1991a;Fuhr et al., 1992;Kew et al., 1994;Ridding and Rothwell, 1995), and transient deafferentation induced by ischemia (Brasil-Neto et al., 1992, 1993. The changes after spinal cord injury and transient deafferentation are more prominent with the target muscle at rest than during voluntary activation (Topka et al., 1991;Ridding and Rothwell, 1995). Using ischemic deafferentation of the forearm as a model for short-term plasticity in humans, we recently showed that plastic changes in the deafferented motor cortex can be upregulated by transcranial magnetic stimulation (TMS) to the deafferented cortex and downregulated by TMS to the contralateral motor cortex (Z iemann et al., 1998). Although experiments in animals have shown that reorganization can occur at multiple levels, including the cortex (Pons et al., 1988;Recanzone et al., 1992;Merzenich and Jenkins, 1993; Gilbert, 1994, 1995), thalamus (Garraghty and Kass, 1991;Pons et al., 1991;Nicolelis et al., 1993), brainstem (Pons et al., 1991;Florence and Kaas, 1995), and spinal cord (C arp and Wolpaw, 1994;Florence and Kaas, 1995), the site of motor reorganization in humans is not known. Whereas animal studies have shown that GABAergic (Hendry and Jones, 1986;Welker et al., 1989;Jacobs and Donoghue, 1991), glutaminergic (Anw yl, 1991;Garraghty et al., 1993;Conti et al., 1996), and...

Modulation of motor cortex excitability after upper limb immobilization

“…Previous TMS studies documented the role of ICI reduction and ICF potentiation in neuroplasticity of stump muscles after upper limb (Schwenkreis et al, 2000) and lower limb amputation (Chen et al, 1998). Our data suggest that similar changes take place in the cortical representation of muscles exposed to sensorimotor restriction.…”

“…The MEP recruitment curve at rest measures the extent to which the alpha-motoneuronal pool is activated with increasing TMS intensities. The curve was steeper on the immobilized sides, mimicking the findings in amputees (Chen et al, 1998) or during ischemic anesthesia (Ridding and Rothwell, 1997). Factors influencing the curve are complex and interactive.…”

“…One possible mechanism accounting for RMT lowering may involve changes in sodium channels (Chen et al, 1997;Ziemann et al, 1996), which have been implicated in some forms of plasticity (Halter et al, 1995). RMT was reduced after amputation (Chen et al, 1998;Cohen et al, 1991) but not after ischemic nerve block (Brasil-Neto et al, 1993;Ridding and Rothwell, 1997;Ziemann et al, 1998a), suggesting that changes in RMT may require long term deafferentation. This hypothesis is consistent with studies on rats with nerve lesions of different duration (Sanes et al, 1990).…”

“…Learning new motor skills (Pascual-Leone et al, 1995) and performing skilled motor activities result in an expansion of the representation of the muscles involved in the task. Complete long term sensorimotor deafferentation, as in the case of limb amputation (Chen et al, 1998;Cohen et al, 1991;Kew et al, 1994;Ridding and Rothwell, 1997;Wu and Kaas, 1999) and peripheral nerve lesions (Rijntjes et al, 1997;Tinazzi et al, 1998), as well as short term deafferentation secondary to ischemic nerve block (Brasil-Neto et al, 1993;Ridding and Rothwell, 1997;Ziemann et al, 1998a;Ziemann et al, 1998b), result in an expansion of the surrounding representations.…”

Occupational therapy and neuromotor interventions

“…Adaptive neuroplasticity is evident in enlargement of the cortical map of the reading fi nger in blind Braille readers (PascualLeone and Torres, 1993), while maladaptive changes may result in chronic pain (Quarterone et al, 2006). Change may be transient, as when an altered cortical map is observed with immobilization (Liepert et al, 1995) or long-lasting, as in amputation (Chen et al, 1998). Additionally, the regular performance of a highly skilled motor task can result in enlargement of the cortical representation of the muscles involved.…”