Limb amputation results in plasticity of connections between the brain and muscles, with the cortical motor representation of the missing limb seemingly shrinking, to the presumed benefit of remaining body parts that have cortical representations adjacent to the now-missing limb. Surprisingly, the corresponding perceptual representation does not suffer a similar fate but instead persists as a phantom limb endowed with sensory and motor qualities. How can cortical reorganization after amputation be reconciled with the maintenance of a motor representation of the phantom limb in the brain? In an attempt to answer this question we explored the relationship between the cortical representation of the remaining arm muscles and that of phantom movements. Using transcranial magnetic stimulation (TMS) we systematically mapped phantom movement perceptions while simultaneously recording stump muscle activity in three above-elbow amputees. TMS elicited sensations of movement in the phantom hand when applied over the presumed hand area of the motor cortex. In one subject the amplitude of the perceived movement was positively correlated with the intensity of stimulation. Interestingly, phantom limb movements that the patient could not produce voluntarily were easily triggered by TMS, suggesting that the inability to voluntarily move the phantom is not equivalent to a loss of the corresponding movement representation. We suggest that hand movement representations survive in the reorganized motor area of amputees even when these cannot be directly accessed. The activation of these representations is probably necessary for the experience of phantom movement.

The human primary motor cortex (M1) undergoes considerable reorganization in response to traumatic upper limb amputation. The representations of the preserved arm muscles expand, invading portions of M1 previously dedicated to the hand, suggesting that former hand neurons are reassigned to the control of remaining proximal upper limb muscles. Hand allograft offers a unique opportunity to study the reversibility of such long-term cortical changes. We used transcranial magnetic stimulation in patient LB, who underwent bilateral hand transplantation 3 years after a traumatic amputation, to longitudinally track both the emergence of intrinsic (from the donor) hand muscles in M1 as well as changes in the representation of stump (upper arm and forearm) muscles. The same muscles were also mapped in patient CD, the first bilateral hand allograft recipient. Newly transplanted intrinsic muscles acquired a cortical representation in LB's M1 at 10 months postgraft for the left hand and at 26 months for the right hand. The appearance of a cortical representation of transplanted hand muscles in M1 coincided with the shrinkage of stump muscle representations for the left but not for the right side. In patient CD, transcranial magnetic stimulation performed at 51 months postgraft revealed a complete set of intrinsic hand-muscle representations for the left but not the right hand. Our findings show that newly transplanted muscles can be recognized and integrated into the patient's motor cortex.amputation ͉ longitudinal ͉ plasticity ͉ reorganization ͉ TMS I t is now well established that the adult brain is highly influenced by changes occurring at the body's periphery. Evidence from human and animal models show that, when deprived of its afferent sensory input and/or its motor effectors, the primary sensory (S1) and motor (M1) cortical regions undergo plastic modifications (1-10).Traumatic upper limb amputation in humans produces lifelong consequences. Patients often report a global feeling that the missing body part is still present. This feeling is frequently associated with specific sensory and kinesthetic sensations and pain in the missing limb. Many patients further describe that the phantom limb can be moved voluntarily (review in refs. 11 and 12).Functional investigation of human M1 reorganization after amputation has demonstrated that instead of becoming inactive, the hand area is now activated during proximal limb movements (5,13,14), and that cortical stimulation of this region evokes contraction of proximal upper limb muscles (4, 9, 15, 16). Face and forearm motor representations that surround the representation of the missing hand have also been shown to expand into the de-efferented cortex (16,17), with the expansion of lip movements into the former hand area correlating positively with the amount of phantom limb pain (18). Studies employing TMS paired-pulse protocols have shown less intracortical inhibition in the region corresponding to the amputated limb when compared with the intact limb's region (19,20), suggest...