Cortical reorganization in motor cortex after graft of both hands

ief communications© 2001 Nature Publishing Group http://neurosci.nature.com© 2001 Nature Publishing Group http://neurosci.nature.comTable 1. Time course of the center of gravity of M1 activations for the hand and elbow, for the different exams.Movement Before surgery 2 months 4 months 6 months Change in distance (before surgeryx y z x y z x y z x y z versus 6 months afterward)Right hand –42 –22 40 –40 –25 46 –39 –25 45 –39 –27 48 10 mmLeft hand 36 –18 46 33 –23 49 38 –21 48 33 –22 49 6 mmRight elbow –34 –29 49 –26 –33 54 –30 –31 52 –28 –32 54 8 mmLeft elbow 31 –23 47 29 –28 51 30 –26 52 30 –26 54 7 mmValues are in Talairach coordinates.of either elbow activated a contralateral central region of M1 thatcorresponds to the hand motor map (Fig. 2a). Six months afterward,elbow activations migrated toward the upper part of thelimb representation, classically defined as the arm region 6 . DifferentM1 cortical maps were observed before and six monthsafter surgery: before the graft, a central region, and afterward, anew superior medial area (Fig. 2c). As for hand movements, thenew superior locus of activation was apparent at two months (versusbefore surgery; Z > 10; cluster size, 236) for right elbow movements.The signal strength had increased significantly at 4 months(versus 2 months; Z = 5.2; cluster size, 26) but did not increasefurther at 6 months. For left elbow movements, the most significantsignal changes occurred between 4 and 6 months (Z = 6.9;cluster size, 67). The COGs along the four examinations underwenta progressive shift from the central to the superior part ofM1 (right elbow, 8 mm; left elbow, 7 mm; Fig. 2b; Table 1).The changes observed within the motor cortex for hand andelbow representations seemed to be strongly correlated in bothabtime and space. Across the different examinations, the distancebetween COGs remained fairly constant for the two types ofmovements (Table 1). Hand and elbow activations showed a highdegree of overlap, the extent of which increased from beforesurgery through the examinations after surgery.Parallel changes were also recorded in somatosensory cortex.Hand and elbow movements activated S1 in all four examinationsand their pattern was similar to that of the motor cortex activations.These results show that grafted hands come to be recognizedand activated normally by sensorimotor cortex. The displacementof the cortical activity from lateral to medial along the precentralgyrus is remarkably similar for hand and elbowmovements. These cortical maps covered in the same amount oftime a similar distance, as revealed by the trajectory of the activationCOGs. This suggests that new peripheral inputs alloweda global remodeling of the limb cortical map and reversed thefunctional reorganization induced by the amputation. The spatialtrajectory of these activations in time further indicates that thecortical rearrangement occurs in an orderly manner; the handand arm representations tend to return to their original corticallocus. Hence, brain plasticity is accomplished with reference toa previous pre-amputation somatotopic body representation.What are the mechanisms underlying this cortical reversibility?In monkeys with amputated segments, severed efferentmotoneurons preserve their functional efficacy by targeting newmuscles 7 . As efferent and afferent central pathway neurons surviveafter they are cut, the sensorimotor circuit may be functionallyready after the graft; this could explain why activity shifts areobserved as early as two months after surgery. The intrinsicchanges within M1 may result from a shift in the strengths of activationsamong existing connections. If we assume that hand andelbow had preexisting connections, the elbow activation in thephase before surgery may emerge as a change in the weight ofthese connections; that is, the elbow connection may be enhancedat the expense of the deprived hand region. The hand transplantmay have restored the efficacy of the original connections at theexpense, this time, of the elbow representation, thus allowing typicalfeatures of cortical organization to reappear in the motor map.cACKNOWLEDGEMENTSThis work was supported by a CNRS grant to A.S.RECEIVED 5 FEBRUARY; ACCEPTED 30 APRIL 2001Fig. 2. Activation maps in M1 obtained in the elbow movement condition.(a–c) Same as in Fig.1.1. Kaas, J. H. in The Organization of the Cerebral Cortex (eds. Schmitt, F. O.,Worden, F. G., Adelman, G. & Dennis, S. G.) 223–236 (MIT Press,Cambridge, Massachusetts, 1981).2. Roricht S., Meyer, B. U., Niehaus, L. & Brandt, S. A. Neurology 53, 106–111(1999).3. Dubernard J. M. et al. Lancet 353, 1315–1320 (1999).4. Ramachandran, V. S., Rogers-Ramachandran, D. & Stewart, M. Science 258,1159–1160 (1992).5. Yousry, T. A. et al. Brain 120, 141–157 (1997).6. Penfield W. The Cerebral Cortex of the Man (MacMillan, New York, 1950).7. Wu, C. W. & Kaas, J. H. Neuron 28, 967–978 (2000).692 nature neuroscience • volume 4 no 7 • july 2001